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H pylori: ACG Guideline Advises New Approaches to Treatment
Helicobacter pylori is one of the most common human bacterial chronic infections globally. Its prevalence has actually decreased in North America in recent years, although its current range of approximately 30%-40% remains substantial given the potential clinical implications of infection.
Standards have changed considerably regarding the testing, treatment, and follow-up of H pylori. This is made clear by the just-published clinical practice guideline from the American College of Gastroenterology (ACG), which provides several new recommendations based on recent scientific evidence that should change your clinical approach to managing this common infection.
This discussion aims to synthesize and highlight key concepts from the ACG’s comprehensive publication.
Who Should Be Tested and Treated?
The cardinal diseases caused by H pylori have traditionally included peptic ulcer disease, marginal zone B-cell lymphoma, gastric adenocarcinoma, and dyspepsia.
Additional associations have been made with idiopathic thrombocytopenic purpura and otherwise unexplained iron deficiency.
New evidence suggests that patients taking long-term nonsteroidal anti-inflammatory drugs, including low-dose aspirin, are relatively more susceptible to infection.
The ACG’s guideline also recommends testing persons at an increased risk for gastric adenocarcinoma (eg, those with autoimmune gastritis, current or history of premalignant conditions, or first-degree relative with gastric cancer), as well as household members of patients with a positive nonserologic test for H pylori.
The authors note that those with an indication for testing should be offered treatment if determined to have an infection. These patients should also undergo a posttreatment test-of-cure, which should occur at least 4 weeks afterwards using a urea breath test, fecal antigen test, or gastric biopsy.
Caveats to Treatment
Patients with H pylori infections are advised to undergo treatment for a duration of 14 days. Some of the commercial prepackaged H pylori treatment options (eg, Pylera, which contains bismuth subcitrate/metronidazole/tetracycline) are dispensed in regimens lasting only 10 days and currently are viewed as inadequate.
In the United States, the patterns of antibiotic resistance for the previously used standard drugs in the treatment of H pylori have increased considerably. They range from 32% for clarithromycin, 38% for levofloxacin, and 42% for metronidazole, in contrast to 3% for amoxicillin, 1% for tetracycline, and 0% for rifabutin.
Clarithromycin- and levofloxacin-containing treatments should be avoided in treatment-naive patients unless specifically directed following the results of susceptibility tests with either a phenotypic method (culture-based) or a molecular method (polymerase chain reaction or next-generation sequencing). Notably, the mutations responsible for both clarithromycin and levofloxacin resistance may be detectable by stool-based testing.
Maintenance of intragastric acid suppression is key to H pylori eradication, as elevated intragastric pH promotes active replication of H pylori and makes it more susceptible to bactericidal antibiotics.
Therefore, the use of histamine-2 receptors is not recommended, as they are inadequate for achieving acid suppression. Instead, a dual-based therapy of either the potassium-competitive acid blocker (PCAB) vonoprazan (20 mg) or a high-dose proton pump inhibitor (PPI) and amoxicillin, administered twice daily, is effective, although this finding is based on limited evidence.
Treatment-Naive Patients
In treatment-naive patients without penicillin allergy and for whom antibiotic susceptibility testing has not been obtained, the guideline offers its strongest recommendation for bismuth quadruple therapy. This therapy typically consists of a PPI, bismuth subcitrate or subsalicylate, tetracycline, and metronidazole.
Among those with a penicillin allergy, bismuth quadruple therapy is also the primary treatment choice. The authors suggest that patients with a suspected allergy are referred to an allergist for possible penicillin desensitization, given that less than 1% of the population is thought to present with a “true” allergy.
The guideline also presented conditional recommendations, based on low- to moderate-quality evidence, for using a rifabutin-based triple regimen of omeprazole, amoxicillin, and rifabutin (Talicia); a PCAB-based dual regimen of vonoprazan and amoxicillin (Voquezna Dual Pak); and a PCAB-based triple regimen of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak). In patients with unknown clarithromycin susceptibility, the PCAB-based triple therapy is preferred over PPI-clarithromycin triple therapy.
Although probiotics have been suggested to possibly lead to increased effectiveness or tolerability for H pylori eradication, this was based on studies with significant heterogeneity in their designs. At present, no high-quality data support probiotic therapy.
Clinicians may substitute doxycycline for tetracycline due to availability or cost, and also may prescribe metronidazole at a lower dose than recommended (1.5-2 g/d) to limit side effects. Both modifications have been associated with lower rates of H pylori eradication and are not recommended.
Treatment-Experienced Patients
Quadruple bismuth therapy is the optimal approach among treatment-experienced patients with persistent H pylori infection who have not previously received this therapy. However, this recommendation was rated as conditional, given that it was based on a low quality of evidence.
The guideline offered other recommendations for treatment-experienced patients with persistent infection who had received bismuth quadruple therapy — also conditionally based on a low quality of evidence.
In such patients, it is recommended to consider the use of a rifabutin-based triple therapy (ie, a PPI standard to double dose, amoxicillin, and rifabutin) and a levofloxacin-based triple therapy (ie, a PPI standard dose, levofloxacin, and amoxicillin or metronidazole).
Although significant evidence gaps prevented the authors from providing formal recommendations, they included a PCAB-based triple therapy of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak) and a high-dose dual therapy of either vonoprazan (20 mg) or PPI (double dose) and amoxicillin among their suggested salvage regimens for these patients.
A New Standard
We must recognize, however, that there are still substantial evidence gaps, particularly around the use of a PCAB-based regimen and its relative advantages over a standard or high-dose PPI-based regimen. This may be of particular importance based on the variable prevalence of cytochrome P450 2C19 (CYP2C19) polymorphisms in the specific patient populations, as PCABs are not metabolized by CYP2C19.
Reviewing the entirety of the ACG’s clinical guideline is encouraged for additional details about the management of H pylori beyond what is highlighted herein.
Dr. Johnson, Professor of Medicine, Chief of Gastroenterology, Eastern Virginia Medical School, Norfolk, Virginia, disclosed ties with ISOTHRIVE and Johnson & Johnson.
A version of this article appeared on Medscape.com.
Helicobacter pylori is one of the most common human bacterial chronic infections globally. Its prevalence has actually decreased in North America in recent years, although its current range of approximately 30%-40% remains substantial given the potential clinical implications of infection.
Standards have changed considerably regarding the testing, treatment, and follow-up of H pylori. This is made clear by the just-published clinical practice guideline from the American College of Gastroenterology (ACG), which provides several new recommendations based on recent scientific evidence that should change your clinical approach to managing this common infection.
This discussion aims to synthesize and highlight key concepts from the ACG’s comprehensive publication.
Who Should Be Tested and Treated?
The cardinal diseases caused by H pylori have traditionally included peptic ulcer disease, marginal zone B-cell lymphoma, gastric adenocarcinoma, and dyspepsia.
Additional associations have been made with idiopathic thrombocytopenic purpura and otherwise unexplained iron deficiency.
New evidence suggests that patients taking long-term nonsteroidal anti-inflammatory drugs, including low-dose aspirin, are relatively more susceptible to infection.
The ACG’s guideline also recommends testing persons at an increased risk for gastric adenocarcinoma (eg, those with autoimmune gastritis, current or history of premalignant conditions, or first-degree relative with gastric cancer), as well as household members of patients with a positive nonserologic test for H pylori.
The authors note that those with an indication for testing should be offered treatment if determined to have an infection. These patients should also undergo a posttreatment test-of-cure, which should occur at least 4 weeks afterwards using a urea breath test, fecal antigen test, or gastric biopsy.
Caveats to Treatment
Patients with H pylori infections are advised to undergo treatment for a duration of 14 days. Some of the commercial prepackaged H pylori treatment options (eg, Pylera, which contains bismuth subcitrate/metronidazole/tetracycline) are dispensed in regimens lasting only 10 days and currently are viewed as inadequate.
In the United States, the patterns of antibiotic resistance for the previously used standard drugs in the treatment of H pylori have increased considerably. They range from 32% for clarithromycin, 38% for levofloxacin, and 42% for metronidazole, in contrast to 3% for amoxicillin, 1% for tetracycline, and 0% for rifabutin.
Clarithromycin- and levofloxacin-containing treatments should be avoided in treatment-naive patients unless specifically directed following the results of susceptibility tests with either a phenotypic method (culture-based) or a molecular method (polymerase chain reaction or next-generation sequencing). Notably, the mutations responsible for both clarithromycin and levofloxacin resistance may be detectable by stool-based testing.
Maintenance of intragastric acid suppression is key to H pylori eradication, as elevated intragastric pH promotes active replication of H pylori and makes it more susceptible to bactericidal antibiotics.
Therefore, the use of histamine-2 receptors is not recommended, as they are inadequate for achieving acid suppression. Instead, a dual-based therapy of either the potassium-competitive acid blocker (PCAB) vonoprazan (20 mg) or a high-dose proton pump inhibitor (PPI) and amoxicillin, administered twice daily, is effective, although this finding is based on limited evidence.
Treatment-Naive Patients
In treatment-naive patients without penicillin allergy and for whom antibiotic susceptibility testing has not been obtained, the guideline offers its strongest recommendation for bismuth quadruple therapy. This therapy typically consists of a PPI, bismuth subcitrate or subsalicylate, tetracycline, and metronidazole.
Among those with a penicillin allergy, bismuth quadruple therapy is also the primary treatment choice. The authors suggest that patients with a suspected allergy are referred to an allergist for possible penicillin desensitization, given that less than 1% of the population is thought to present with a “true” allergy.
The guideline also presented conditional recommendations, based on low- to moderate-quality evidence, for using a rifabutin-based triple regimen of omeprazole, amoxicillin, and rifabutin (Talicia); a PCAB-based dual regimen of vonoprazan and amoxicillin (Voquezna Dual Pak); and a PCAB-based triple regimen of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak). In patients with unknown clarithromycin susceptibility, the PCAB-based triple therapy is preferred over PPI-clarithromycin triple therapy.
Although probiotics have been suggested to possibly lead to increased effectiveness or tolerability for H pylori eradication, this was based on studies with significant heterogeneity in their designs. At present, no high-quality data support probiotic therapy.
Clinicians may substitute doxycycline for tetracycline due to availability or cost, and also may prescribe metronidazole at a lower dose than recommended (1.5-2 g/d) to limit side effects. Both modifications have been associated with lower rates of H pylori eradication and are not recommended.
Treatment-Experienced Patients
Quadruple bismuth therapy is the optimal approach among treatment-experienced patients with persistent H pylori infection who have not previously received this therapy. However, this recommendation was rated as conditional, given that it was based on a low quality of evidence.
The guideline offered other recommendations for treatment-experienced patients with persistent infection who had received bismuth quadruple therapy — also conditionally based on a low quality of evidence.
In such patients, it is recommended to consider the use of a rifabutin-based triple therapy (ie, a PPI standard to double dose, amoxicillin, and rifabutin) and a levofloxacin-based triple therapy (ie, a PPI standard dose, levofloxacin, and amoxicillin or metronidazole).
Although significant evidence gaps prevented the authors from providing formal recommendations, they included a PCAB-based triple therapy of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak) and a high-dose dual therapy of either vonoprazan (20 mg) or PPI (double dose) and amoxicillin among their suggested salvage regimens for these patients.
A New Standard
We must recognize, however, that there are still substantial evidence gaps, particularly around the use of a PCAB-based regimen and its relative advantages over a standard or high-dose PPI-based regimen. This may be of particular importance based on the variable prevalence of cytochrome P450 2C19 (CYP2C19) polymorphisms in the specific patient populations, as PCABs are not metabolized by CYP2C19.
Reviewing the entirety of the ACG’s clinical guideline is encouraged for additional details about the management of H pylori beyond what is highlighted herein.
Dr. Johnson, Professor of Medicine, Chief of Gastroenterology, Eastern Virginia Medical School, Norfolk, Virginia, disclosed ties with ISOTHRIVE and Johnson & Johnson.
A version of this article appeared on Medscape.com.
Helicobacter pylori is one of the most common human bacterial chronic infections globally. Its prevalence has actually decreased in North America in recent years, although its current range of approximately 30%-40% remains substantial given the potential clinical implications of infection.
Standards have changed considerably regarding the testing, treatment, and follow-up of H pylori. This is made clear by the just-published clinical practice guideline from the American College of Gastroenterology (ACG), which provides several new recommendations based on recent scientific evidence that should change your clinical approach to managing this common infection.
This discussion aims to synthesize and highlight key concepts from the ACG’s comprehensive publication.
Who Should Be Tested and Treated?
The cardinal diseases caused by H pylori have traditionally included peptic ulcer disease, marginal zone B-cell lymphoma, gastric adenocarcinoma, and dyspepsia.
Additional associations have been made with idiopathic thrombocytopenic purpura and otherwise unexplained iron deficiency.
New evidence suggests that patients taking long-term nonsteroidal anti-inflammatory drugs, including low-dose aspirin, are relatively more susceptible to infection.
The ACG’s guideline also recommends testing persons at an increased risk for gastric adenocarcinoma (eg, those with autoimmune gastritis, current or history of premalignant conditions, or first-degree relative with gastric cancer), as well as household members of patients with a positive nonserologic test for H pylori.
The authors note that those with an indication for testing should be offered treatment if determined to have an infection. These patients should also undergo a posttreatment test-of-cure, which should occur at least 4 weeks afterwards using a urea breath test, fecal antigen test, or gastric biopsy.
Caveats to Treatment
Patients with H pylori infections are advised to undergo treatment for a duration of 14 days. Some of the commercial prepackaged H pylori treatment options (eg, Pylera, which contains bismuth subcitrate/metronidazole/tetracycline) are dispensed in regimens lasting only 10 days and currently are viewed as inadequate.
In the United States, the patterns of antibiotic resistance for the previously used standard drugs in the treatment of H pylori have increased considerably. They range from 32% for clarithromycin, 38% for levofloxacin, and 42% for metronidazole, in contrast to 3% for amoxicillin, 1% for tetracycline, and 0% for rifabutin.
Clarithromycin- and levofloxacin-containing treatments should be avoided in treatment-naive patients unless specifically directed following the results of susceptibility tests with either a phenotypic method (culture-based) or a molecular method (polymerase chain reaction or next-generation sequencing). Notably, the mutations responsible for both clarithromycin and levofloxacin resistance may be detectable by stool-based testing.
Maintenance of intragastric acid suppression is key to H pylori eradication, as elevated intragastric pH promotes active replication of H pylori and makes it more susceptible to bactericidal antibiotics.
Therefore, the use of histamine-2 receptors is not recommended, as they are inadequate for achieving acid suppression. Instead, a dual-based therapy of either the potassium-competitive acid blocker (PCAB) vonoprazan (20 mg) or a high-dose proton pump inhibitor (PPI) and amoxicillin, administered twice daily, is effective, although this finding is based on limited evidence.
Treatment-Naive Patients
In treatment-naive patients without penicillin allergy and for whom antibiotic susceptibility testing has not been obtained, the guideline offers its strongest recommendation for bismuth quadruple therapy. This therapy typically consists of a PPI, bismuth subcitrate or subsalicylate, tetracycline, and metronidazole.
Among those with a penicillin allergy, bismuth quadruple therapy is also the primary treatment choice. The authors suggest that patients with a suspected allergy are referred to an allergist for possible penicillin desensitization, given that less than 1% of the population is thought to present with a “true” allergy.
The guideline also presented conditional recommendations, based on low- to moderate-quality evidence, for using a rifabutin-based triple regimen of omeprazole, amoxicillin, and rifabutin (Talicia); a PCAB-based dual regimen of vonoprazan and amoxicillin (Voquezna Dual Pak); and a PCAB-based triple regimen of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak). In patients with unknown clarithromycin susceptibility, the PCAB-based triple therapy is preferred over PPI-clarithromycin triple therapy.
Although probiotics have been suggested to possibly lead to increased effectiveness or tolerability for H pylori eradication, this was based on studies with significant heterogeneity in their designs. At present, no high-quality data support probiotic therapy.
Clinicians may substitute doxycycline for tetracycline due to availability or cost, and also may prescribe metronidazole at a lower dose than recommended (1.5-2 g/d) to limit side effects. Both modifications have been associated with lower rates of H pylori eradication and are not recommended.
Treatment-Experienced Patients
Quadruple bismuth therapy is the optimal approach among treatment-experienced patients with persistent H pylori infection who have not previously received this therapy. However, this recommendation was rated as conditional, given that it was based on a low quality of evidence.
The guideline offered other recommendations for treatment-experienced patients with persistent infection who had received bismuth quadruple therapy — also conditionally based on a low quality of evidence.
In such patients, it is recommended to consider the use of a rifabutin-based triple therapy (ie, a PPI standard to double dose, amoxicillin, and rifabutin) and a levofloxacin-based triple therapy (ie, a PPI standard dose, levofloxacin, and amoxicillin or metronidazole).
Although significant evidence gaps prevented the authors from providing formal recommendations, they included a PCAB-based triple therapy of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak) and a high-dose dual therapy of either vonoprazan (20 mg) or PPI (double dose) and amoxicillin among their suggested salvage regimens for these patients.
A New Standard
We must recognize, however, that there are still substantial evidence gaps, particularly around the use of a PCAB-based regimen and its relative advantages over a standard or high-dose PPI-based regimen. This may be of particular importance based on the variable prevalence of cytochrome P450 2C19 (CYP2C19) polymorphisms in the specific patient populations, as PCABs are not metabolized by CYP2C19.
Reviewing the entirety of the ACG’s clinical guideline is encouraged for additional details about the management of H pylori beyond what is highlighted herein.
Dr. Johnson, Professor of Medicine, Chief of Gastroenterology, Eastern Virginia Medical School, Norfolk, Virginia, disclosed ties with ISOTHRIVE and Johnson & Johnson.
A version of this article appeared on Medscape.com.
What You Need to Know About Oropouche Virus Disease
The European Centre for Disease Prevention and Control (ECDC) has issued a warning to travelers in areas in South and Central America and the Caribbean affected by a current outbreak of Oropouche virus (OROV) disease. The ECDC said that there had been more than 8000 cases reported in these areas since January, with 19 imported cases reported in Europe for the first time in June and July. Of these, 12 were in Spain, five were in Italy, and two were in Germany.
The ECDC’s Threat Assessment Brief of Aug. 9 said that one of those affected had traveled to Brazil and the other 18 to Cuba; however, outbreaks have also been reported this year in Bolivia, Colombia, and Peru. Though the overall risk for infection to European travelers to OROV-epidemic countries was assessed as moderate, it was higher in the more affected municipalities of the northern states of Brazil and/or the Amazon region, and/or if personal protection measures are not taken.
An editorial published Aug. 8 in The Lancet Infectious Diseases described OROV as a “mysterious threat,” which there is limited knowledge about despite some half a million cases recorded since it was first detected in Trinidad and Tobago in 1955.
OROV is transmitted primarily through bites from infected midges (Culicoides paraensis). However, some mosquitoes species can also spread the virus, which causes symptoms very similar to other arbovirus diseases from the same regions, such as dengue, chikungunya, and Zika virus infection.
Most cases are mild, but meningitis and encephalitis can occur as well as possible fetal death and deformities after infection in pregnancy. Last month, the first fatal cases were reported in two young Brazilian women who, concerningly, had no comorbidities.
This news organization asked Jan Felix Drexler, MD, of the Institute of Virology at Charité – Universitätsmedizin in Berlin, Germany, who has studied the emergence of Oropouche fever in Latin America, what clinicians should know about OROV disease.
What are the main symptoms of OROV disease for which clinicians should be alert?
The main symptoms are not different from other arboviral infections, ie, fever, maybe joint and muscle pain, maybe rash. The problem is that we do not know how often severe disease may occur because we do not know whether the severe cases that have been postulated, including death in apparently healthy people and congenital infection, are due to increased testing; an altered virus; or an altered, more intense circulation (so that many more infections simply lead to rare severe cases appearing). Be alert and ask for testing in your patients.
What is the differential diagnosis if a recent traveler to affected regions presents with symptoms? Are there any clues to suggest whether the disease is Oropouche as opposed to Zika, etc.?
The main message is: Do not assume a particular infection based on clinical symptoms. If your patient is returning from or living in an endemic area, consider OROV disease in the differential diagnosis.
What personal protective measures should clinicians advise travelers in affected areas to take? Do these differ from normal mosquito precautions?
Repellents are extremely important as usual. However, there are differences. Mosquito nets’ hole sizes need to be smaller than those used against the vectors of malaria or dengue; in other words, they need to have a higher mesh. The problem is that nets with high mesh are complicated in very hot and humid conditions because they also limit ventilation. Travelers should discuss with local suppliers about the best trade-off.
The risk for midge bites is likely highest at dawn and dusk in still and humid conditions. So on the one hand, one could recommend avoiding those areas and being outside during those times of the day. On the other hand, specific recommendations cannot be made robustly because we cannot exclude other invertebrate vectors at current knowledge. Some studies have implicated that mosquitoes may also transmit the virus. If that holds true, then we are back to reducing any bite.
Should pregnant women be advised to avoid travel to affected regions?
Not immediately, but caution must be taken. We simply do not have sufficient data to gauge the risk for potential congenital infection. Much more epidemiologic data and controlled infection experiments will be required to make evidence-based recommendations.
All the cases reported in Europe so far were imported from Cuba and Brazil. Is there any risk for local transmission, eg, via midges/mosquitoes that might hitch a ride on an aircraft, as in cases of airport malaria?
Not immediately, but it cannot be excluded. We know very little about the infection intensity in the vectors. Controlled infection experiments, including robustness of vectors against commonly used insecticides in airplanes, need to be done.
What is the risk for an animal reservoir emerging in Europe?
We do not know, but there is also no reason for ringing the alarm bells. Controlled infection experiments and surveillance will be required.
Is treatment purely supportive or are there any specific agents worth trying in case of severe symptoms/neurologic involvement?
No specific treatment can be recommended as is. However, severe dengue illustrates the relevance of supportive treatment, which is hugely effective in reducing mortality.
The Lancet paper states: “Several laboratory tests have been developed but robust commercial tests are hardly available.” How likely is it that laboratories in Europe will have the capability to test for the Oropouche organism?
European laboratory networks have already taken action, and testing is now available at least in the major and reference laboratories. If a clinician asks for OROV testing, they will probably get a robust answer in a reasonable timespan. Of course, that can be improved once we have more cases and more laboratories will be equipped for testing.
Is there anything else you think clinicians should be aware of?
The most important is to think beyond the textbooks we know from medical school. Things change rapidly in a connected world under altered climate conditions.
Dr. Drexler has no conflicts of interest to declare.
A version of this article first appeared on Medscape.com.
The European Centre for Disease Prevention and Control (ECDC) has issued a warning to travelers in areas in South and Central America and the Caribbean affected by a current outbreak of Oropouche virus (OROV) disease. The ECDC said that there had been more than 8000 cases reported in these areas since January, with 19 imported cases reported in Europe for the first time in June and July. Of these, 12 were in Spain, five were in Italy, and two were in Germany.
The ECDC’s Threat Assessment Brief of Aug. 9 said that one of those affected had traveled to Brazil and the other 18 to Cuba; however, outbreaks have also been reported this year in Bolivia, Colombia, and Peru. Though the overall risk for infection to European travelers to OROV-epidemic countries was assessed as moderate, it was higher in the more affected municipalities of the northern states of Brazil and/or the Amazon region, and/or if personal protection measures are not taken.
An editorial published Aug. 8 in The Lancet Infectious Diseases described OROV as a “mysterious threat,” which there is limited knowledge about despite some half a million cases recorded since it was first detected in Trinidad and Tobago in 1955.
OROV is transmitted primarily through bites from infected midges (Culicoides paraensis). However, some mosquitoes species can also spread the virus, which causes symptoms very similar to other arbovirus diseases from the same regions, such as dengue, chikungunya, and Zika virus infection.
Most cases are mild, but meningitis and encephalitis can occur as well as possible fetal death and deformities after infection in pregnancy. Last month, the first fatal cases were reported in two young Brazilian women who, concerningly, had no comorbidities.
This news organization asked Jan Felix Drexler, MD, of the Institute of Virology at Charité – Universitätsmedizin in Berlin, Germany, who has studied the emergence of Oropouche fever in Latin America, what clinicians should know about OROV disease.
What are the main symptoms of OROV disease for which clinicians should be alert?
The main symptoms are not different from other arboviral infections, ie, fever, maybe joint and muscle pain, maybe rash. The problem is that we do not know how often severe disease may occur because we do not know whether the severe cases that have been postulated, including death in apparently healthy people and congenital infection, are due to increased testing; an altered virus; or an altered, more intense circulation (so that many more infections simply lead to rare severe cases appearing). Be alert and ask for testing in your patients.
What is the differential diagnosis if a recent traveler to affected regions presents with symptoms? Are there any clues to suggest whether the disease is Oropouche as opposed to Zika, etc.?
The main message is: Do not assume a particular infection based on clinical symptoms. If your patient is returning from or living in an endemic area, consider OROV disease in the differential diagnosis.
What personal protective measures should clinicians advise travelers in affected areas to take? Do these differ from normal mosquito precautions?
Repellents are extremely important as usual. However, there are differences. Mosquito nets’ hole sizes need to be smaller than those used against the vectors of malaria or dengue; in other words, they need to have a higher mesh. The problem is that nets with high mesh are complicated in very hot and humid conditions because they also limit ventilation. Travelers should discuss with local suppliers about the best trade-off.
The risk for midge bites is likely highest at dawn and dusk in still and humid conditions. So on the one hand, one could recommend avoiding those areas and being outside during those times of the day. On the other hand, specific recommendations cannot be made robustly because we cannot exclude other invertebrate vectors at current knowledge. Some studies have implicated that mosquitoes may also transmit the virus. If that holds true, then we are back to reducing any bite.
Should pregnant women be advised to avoid travel to affected regions?
Not immediately, but caution must be taken. We simply do not have sufficient data to gauge the risk for potential congenital infection. Much more epidemiologic data and controlled infection experiments will be required to make evidence-based recommendations.
All the cases reported in Europe so far were imported from Cuba and Brazil. Is there any risk for local transmission, eg, via midges/mosquitoes that might hitch a ride on an aircraft, as in cases of airport malaria?
Not immediately, but it cannot be excluded. We know very little about the infection intensity in the vectors. Controlled infection experiments, including robustness of vectors against commonly used insecticides in airplanes, need to be done.
What is the risk for an animal reservoir emerging in Europe?
We do not know, but there is also no reason for ringing the alarm bells. Controlled infection experiments and surveillance will be required.
Is treatment purely supportive or are there any specific agents worth trying in case of severe symptoms/neurologic involvement?
No specific treatment can be recommended as is. However, severe dengue illustrates the relevance of supportive treatment, which is hugely effective in reducing mortality.
The Lancet paper states: “Several laboratory tests have been developed but robust commercial tests are hardly available.” How likely is it that laboratories in Europe will have the capability to test for the Oropouche organism?
European laboratory networks have already taken action, and testing is now available at least in the major and reference laboratories. If a clinician asks for OROV testing, they will probably get a robust answer in a reasonable timespan. Of course, that can be improved once we have more cases and more laboratories will be equipped for testing.
Is there anything else you think clinicians should be aware of?
The most important is to think beyond the textbooks we know from medical school. Things change rapidly in a connected world under altered climate conditions.
Dr. Drexler has no conflicts of interest to declare.
A version of this article first appeared on Medscape.com.
The European Centre for Disease Prevention and Control (ECDC) has issued a warning to travelers in areas in South and Central America and the Caribbean affected by a current outbreak of Oropouche virus (OROV) disease. The ECDC said that there had been more than 8000 cases reported in these areas since January, with 19 imported cases reported in Europe for the first time in June and July. Of these, 12 were in Spain, five were in Italy, and two were in Germany.
The ECDC’s Threat Assessment Brief of Aug. 9 said that one of those affected had traveled to Brazil and the other 18 to Cuba; however, outbreaks have also been reported this year in Bolivia, Colombia, and Peru. Though the overall risk for infection to European travelers to OROV-epidemic countries was assessed as moderate, it was higher in the more affected municipalities of the northern states of Brazil and/or the Amazon region, and/or if personal protection measures are not taken.
An editorial published Aug. 8 in The Lancet Infectious Diseases described OROV as a “mysterious threat,” which there is limited knowledge about despite some half a million cases recorded since it was first detected in Trinidad and Tobago in 1955.
OROV is transmitted primarily through bites from infected midges (Culicoides paraensis). However, some mosquitoes species can also spread the virus, which causes symptoms very similar to other arbovirus diseases from the same regions, such as dengue, chikungunya, and Zika virus infection.
Most cases are mild, but meningitis and encephalitis can occur as well as possible fetal death and deformities after infection in pregnancy. Last month, the first fatal cases were reported in two young Brazilian women who, concerningly, had no comorbidities.
This news organization asked Jan Felix Drexler, MD, of the Institute of Virology at Charité – Universitätsmedizin in Berlin, Germany, who has studied the emergence of Oropouche fever in Latin America, what clinicians should know about OROV disease.
What are the main symptoms of OROV disease for which clinicians should be alert?
The main symptoms are not different from other arboviral infections, ie, fever, maybe joint and muscle pain, maybe rash. The problem is that we do not know how often severe disease may occur because we do not know whether the severe cases that have been postulated, including death in apparently healthy people and congenital infection, are due to increased testing; an altered virus; or an altered, more intense circulation (so that many more infections simply lead to rare severe cases appearing). Be alert and ask for testing in your patients.
What is the differential diagnosis if a recent traveler to affected regions presents with symptoms? Are there any clues to suggest whether the disease is Oropouche as opposed to Zika, etc.?
The main message is: Do not assume a particular infection based on clinical symptoms. If your patient is returning from or living in an endemic area, consider OROV disease in the differential diagnosis.
What personal protective measures should clinicians advise travelers in affected areas to take? Do these differ from normal mosquito precautions?
Repellents are extremely important as usual. However, there are differences. Mosquito nets’ hole sizes need to be smaller than those used against the vectors of malaria or dengue; in other words, they need to have a higher mesh. The problem is that nets with high mesh are complicated in very hot and humid conditions because they also limit ventilation. Travelers should discuss with local suppliers about the best trade-off.
The risk for midge bites is likely highest at dawn and dusk in still and humid conditions. So on the one hand, one could recommend avoiding those areas and being outside during those times of the day. On the other hand, specific recommendations cannot be made robustly because we cannot exclude other invertebrate vectors at current knowledge. Some studies have implicated that mosquitoes may also transmit the virus. If that holds true, then we are back to reducing any bite.
Should pregnant women be advised to avoid travel to affected regions?
Not immediately, but caution must be taken. We simply do not have sufficient data to gauge the risk for potential congenital infection. Much more epidemiologic data and controlled infection experiments will be required to make evidence-based recommendations.
All the cases reported in Europe so far were imported from Cuba and Brazil. Is there any risk for local transmission, eg, via midges/mosquitoes that might hitch a ride on an aircraft, as in cases of airport malaria?
Not immediately, but it cannot be excluded. We know very little about the infection intensity in the vectors. Controlled infection experiments, including robustness of vectors against commonly used insecticides in airplanes, need to be done.
What is the risk for an animal reservoir emerging in Europe?
We do not know, but there is also no reason for ringing the alarm bells. Controlled infection experiments and surveillance will be required.
Is treatment purely supportive or are there any specific agents worth trying in case of severe symptoms/neurologic involvement?
No specific treatment can be recommended as is. However, severe dengue illustrates the relevance of supportive treatment, which is hugely effective in reducing mortality.
The Lancet paper states: “Several laboratory tests have been developed but robust commercial tests are hardly available.” How likely is it that laboratories in Europe will have the capability to test for the Oropouche organism?
European laboratory networks have already taken action, and testing is now available at least in the major and reference laboratories. If a clinician asks for OROV testing, they will probably get a robust answer in a reasonable timespan. Of course, that can be improved once we have more cases and more laboratories will be equipped for testing.
Is there anything else you think clinicians should be aware of?
The most important is to think beyond the textbooks we know from medical school. Things change rapidly in a connected world under altered climate conditions.
Dr. Drexler has no conflicts of interest to declare.
A version of this article first appeared on Medscape.com.
Shortage of Blood Bottles Could Disrupt Care
Hospitals and laboratories across the United States are grappling with a shortage of Becton Dickinson BACTEC blood culture bottles that threatens to extend at least until September.
In a health advisory, the Centers for Disease Control and Prevention (CDC) warned that the critical shortage could lead to “delays in diagnosis, misdiagnosis, or other challenges” in the management of patients with infectious diseases.
Healthcare providers, laboratories, healthcare facility administrators, and state, tribal, local, and territorial health departments affected by the shortage “should immediately begin to assess their situations and develop plans and options to mitigate the potential impact,” according to the health advisory.
What to Do
To reduce the impact of the shortage, facilities are urged to:
- Determine the type of blood culture bottles they have
- Optimize the use of blood cultures at their facility
- Take steps to prevent blood culture contamination
- Ensure that the appropriate volume of blood is collected for culture
- Assess alternate options for blood cultures
- Work with a nearby facility or send samples to another laboratory
Health departments are advised to contact hospitals and laboratories in their jurisdictions to determine whether the shortage will affect them. Health departments are also encouraged to educate others on the supply shortage, optimal use of blood cultures, and mechanisms for reporting supply chain shortages or interruptions to the Food and Drug Administration (FDA), as well as to help with communication between laboratories and facilities willing to assist others in need.
To further assist affected providers, the CDC, in collaboration with the Infectious Diseases Society of America, hosted a webinar with speakers from Johns Hopkins University, Massachusetts General Hospital, and Vanderbilt University, who shared what their institutions are doing to cope with the shortage and protect patients.
Why It Happened
In June, Becton Dickinson warned its customers that they may experience “intermittent delays” in the supply of some BACTEC blood culture media over the coming months because of reduced availability of plastic bottles from its supplier.
In a July 22 update, the company said the supplier issues were “more complex” than originally communicated and it is taking steps to “resolve this challenge as quickly as possible.”
In July, the FDA published a letter to healthcare providers acknowledging the supply disruptions and recommended strategies to preserve the supply for patients at highest risk.
Becton Dickinson has promised an update by September to this “dynamic and evolving situation.”
A version of this article appeared on Medscape.com.
Hospitals and laboratories across the United States are grappling with a shortage of Becton Dickinson BACTEC blood culture bottles that threatens to extend at least until September.
In a health advisory, the Centers for Disease Control and Prevention (CDC) warned that the critical shortage could lead to “delays in diagnosis, misdiagnosis, or other challenges” in the management of patients with infectious diseases.
Healthcare providers, laboratories, healthcare facility administrators, and state, tribal, local, and territorial health departments affected by the shortage “should immediately begin to assess their situations and develop plans and options to mitigate the potential impact,” according to the health advisory.
What to Do
To reduce the impact of the shortage, facilities are urged to:
- Determine the type of blood culture bottles they have
- Optimize the use of blood cultures at their facility
- Take steps to prevent blood culture contamination
- Ensure that the appropriate volume of blood is collected for culture
- Assess alternate options for blood cultures
- Work with a nearby facility or send samples to another laboratory
Health departments are advised to contact hospitals and laboratories in their jurisdictions to determine whether the shortage will affect them. Health departments are also encouraged to educate others on the supply shortage, optimal use of blood cultures, and mechanisms for reporting supply chain shortages or interruptions to the Food and Drug Administration (FDA), as well as to help with communication between laboratories and facilities willing to assist others in need.
To further assist affected providers, the CDC, in collaboration with the Infectious Diseases Society of America, hosted a webinar with speakers from Johns Hopkins University, Massachusetts General Hospital, and Vanderbilt University, who shared what their institutions are doing to cope with the shortage and protect patients.
Why It Happened
In June, Becton Dickinson warned its customers that they may experience “intermittent delays” in the supply of some BACTEC blood culture media over the coming months because of reduced availability of plastic bottles from its supplier.
In a July 22 update, the company said the supplier issues were “more complex” than originally communicated and it is taking steps to “resolve this challenge as quickly as possible.”
In July, the FDA published a letter to healthcare providers acknowledging the supply disruptions and recommended strategies to preserve the supply for patients at highest risk.
Becton Dickinson has promised an update by September to this “dynamic and evolving situation.”
A version of this article appeared on Medscape.com.
Hospitals and laboratories across the United States are grappling with a shortage of Becton Dickinson BACTEC blood culture bottles that threatens to extend at least until September.
In a health advisory, the Centers for Disease Control and Prevention (CDC) warned that the critical shortage could lead to “delays in diagnosis, misdiagnosis, or other challenges” in the management of patients with infectious diseases.
Healthcare providers, laboratories, healthcare facility administrators, and state, tribal, local, and territorial health departments affected by the shortage “should immediately begin to assess their situations and develop plans and options to mitigate the potential impact,” according to the health advisory.
What to Do
To reduce the impact of the shortage, facilities are urged to:
- Determine the type of blood culture bottles they have
- Optimize the use of blood cultures at their facility
- Take steps to prevent blood culture contamination
- Ensure that the appropriate volume of blood is collected for culture
- Assess alternate options for blood cultures
- Work with a nearby facility or send samples to another laboratory
Health departments are advised to contact hospitals and laboratories in their jurisdictions to determine whether the shortage will affect them. Health departments are also encouraged to educate others on the supply shortage, optimal use of blood cultures, and mechanisms for reporting supply chain shortages or interruptions to the Food and Drug Administration (FDA), as well as to help with communication between laboratories and facilities willing to assist others in need.
To further assist affected providers, the CDC, in collaboration with the Infectious Diseases Society of America, hosted a webinar with speakers from Johns Hopkins University, Massachusetts General Hospital, and Vanderbilt University, who shared what their institutions are doing to cope with the shortage and protect patients.
Why It Happened
In June, Becton Dickinson warned its customers that they may experience “intermittent delays” in the supply of some BACTEC blood culture media over the coming months because of reduced availability of plastic bottles from its supplier.
In a July 22 update, the company said the supplier issues were “more complex” than originally communicated and it is taking steps to “resolve this challenge as quickly as possible.”
In July, the FDA published a letter to healthcare providers acknowledging the supply disruptions and recommended strategies to preserve the supply for patients at highest risk.
Becton Dickinson has promised an update by September to this “dynamic and evolving situation.”
A version of this article appeared on Medscape.com.
Dengue Surge in US Cases This Year
Federal health officials with the US Centers for Disease Control and Prevention (CDC) have issued an alert, warning health professionals and the public about an increased risk for dengue virus infections in the United States.
The global incidence of dengue in 2024 is the highest on record, reported the agency.
In the United States, Puerto Rico has declared a public health emergency, with 1498 dengue cases reported so far and a “higher-than-expected” number of dengue cases having been identified among US travelers in the first half of this year at 745 cases, according to the alert.
The CDC reports 197 dengue cases in Florida, 134 in New York, 50 in Massachusetts, 40 in California, 14 in Colorado, nine in Arizona, and eight in the District of Columbia, among others.
Transmitted by infected Aedes genus mosquitoes, dengue is the most common arboviral disease globally and is a nationally notifiable disease in the United States.
The six US territories and freely associated states with frequent or continuous dengue transmission are Puerto Rico, American Samoa, the US Virgin Islands, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau.
Monitoring for Dengue
With rising global and domestic cases of dengue, the CDC urges healthcare providers to monitor for dengue:
- Maintain a high index of suspicion in patients with fever who have been in areas with frequent or continuous dengue transmission within 14 days before illness onset.
- Order diagnostic tests for acute dengue infection such as reverse transcription polymerase chain reaction and immunoglobulin M (IgM) antibody tests or nonstructural protein 1 antigen tests and IgM antibody tests.
- Ensure timely reporting of dengue cases to public health authorities.
- Promote mosquito bite prevention measures among people living in or visiting areas with frequent or continuous dengue transmission.
Roughly one in four dengue virus infections are symptomatic and can be mild or severe. Symptoms begin after an incubation period of about 5-7 days.
Symptoms include fever accompanied by nonspecific signs and symptoms such as nausea, vomiting, rash, muscle aches, joint pain, bone pain, pain behind the eyes, headache, or low white blood cell counts.
Disease Progression
Warning signs that may predict progression to severe disease include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, and progressive increase in hematocrit or liver enlargement.
One in 20 people with symptomatic dengue will develop severe disease, with bleeding, shock, or respiratory distress caused by plasma leakage or end-organ impairment.
Infants aged a year or younger, pregnant people, adults aged 65 years or older, people with certain medical conditions, and those with previous dengue infections are at increased risk for severe dengue.
“Healthcare providers should be prepared to recognize, diagnose, manage, and report dengue cases to health authorities; public health partners should investigate cases and disseminate clear prevention messages to the public,” the alert stated.
The CDC is actively implementing several strategies to address the increase in cases of dengue in the United States. In early April, the agency launched a program-led emergency response and is providing monthly situational updates on dengue to partners, stakeholders, and jurisdictions.
The CDC is also expanding laboratory capacity to improve laboratory testing approaches; collaborating with state, tribal, local, and territorial health departments to strengthen dengue surveillance and recommend prevention strategies; and working to educate the public on dengue prevention.
A version of this article first appeared on Medscape.com.
Federal health officials with the US Centers for Disease Control and Prevention (CDC) have issued an alert, warning health professionals and the public about an increased risk for dengue virus infections in the United States.
The global incidence of dengue in 2024 is the highest on record, reported the agency.
In the United States, Puerto Rico has declared a public health emergency, with 1498 dengue cases reported so far and a “higher-than-expected” number of dengue cases having been identified among US travelers in the first half of this year at 745 cases, according to the alert.
The CDC reports 197 dengue cases in Florida, 134 in New York, 50 in Massachusetts, 40 in California, 14 in Colorado, nine in Arizona, and eight in the District of Columbia, among others.
Transmitted by infected Aedes genus mosquitoes, dengue is the most common arboviral disease globally and is a nationally notifiable disease in the United States.
The six US territories and freely associated states with frequent or continuous dengue transmission are Puerto Rico, American Samoa, the US Virgin Islands, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau.
Monitoring for Dengue
With rising global and domestic cases of dengue, the CDC urges healthcare providers to monitor for dengue:
- Maintain a high index of suspicion in patients with fever who have been in areas with frequent or continuous dengue transmission within 14 days before illness onset.
- Order diagnostic tests for acute dengue infection such as reverse transcription polymerase chain reaction and immunoglobulin M (IgM) antibody tests or nonstructural protein 1 antigen tests and IgM antibody tests.
- Ensure timely reporting of dengue cases to public health authorities.
- Promote mosquito bite prevention measures among people living in or visiting areas with frequent or continuous dengue transmission.
Roughly one in four dengue virus infections are symptomatic and can be mild or severe. Symptoms begin after an incubation period of about 5-7 days.
Symptoms include fever accompanied by nonspecific signs and symptoms such as nausea, vomiting, rash, muscle aches, joint pain, bone pain, pain behind the eyes, headache, or low white blood cell counts.
Disease Progression
Warning signs that may predict progression to severe disease include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, and progressive increase in hematocrit or liver enlargement.
One in 20 people with symptomatic dengue will develop severe disease, with bleeding, shock, or respiratory distress caused by plasma leakage or end-organ impairment.
Infants aged a year or younger, pregnant people, adults aged 65 years or older, people with certain medical conditions, and those with previous dengue infections are at increased risk for severe dengue.
“Healthcare providers should be prepared to recognize, diagnose, manage, and report dengue cases to health authorities; public health partners should investigate cases and disseminate clear prevention messages to the public,” the alert stated.
The CDC is actively implementing several strategies to address the increase in cases of dengue in the United States. In early April, the agency launched a program-led emergency response and is providing monthly situational updates on dengue to partners, stakeholders, and jurisdictions.
The CDC is also expanding laboratory capacity to improve laboratory testing approaches; collaborating with state, tribal, local, and territorial health departments to strengthen dengue surveillance and recommend prevention strategies; and working to educate the public on dengue prevention.
A version of this article first appeared on Medscape.com.
Federal health officials with the US Centers for Disease Control and Prevention (CDC) have issued an alert, warning health professionals and the public about an increased risk for dengue virus infections in the United States.
The global incidence of dengue in 2024 is the highest on record, reported the agency.
In the United States, Puerto Rico has declared a public health emergency, with 1498 dengue cases reported so far and a “higher-than-expected” number of dengue cases having been identified among US travelers in the first half of this year at 745 cases, according to the alert.
The CDC reports 197 dengue cases in Florida, 134 in New York, 50 in Massachusetts, 40 in California, 14 in Colorado, nine in Arizona, and eight in the District of Columbia, among others.
Transmitted by infected Aedes genus mosquitoes, dengue is the most common arboviral disease globally and is a nationally notifiable disease in the United States.
The six US territories and freely associated states with frequent or continuous dengue transmission are Puerto Rico, American Samoa, the US Virgin Islands, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau.
Monitoring for Dengue
With rising global and domestic cases of dengue, the CDC urges healthcare providers to monitor for dengue:
- Maintain a high index of suspicion in patients with fever who have been in areas with frequent or continuous dengue transmission within 14 days before illness onset.
- Order diagnostic tests for acute dengue infection such as reverse transcription polymerase chain reaction and immunoglobulin M (IgM) antibody tests or nonstructural protein 1 antigen tests and IgM antibody tests.
- Ensure timely reporting of dengue cases to public health authorities.
- Promote mosquito bite prevention measures among people living in or visiting areas with frequent or continuous dengue transmission.
Roughly one in four dengue virus infections are symptomatic and can be mild or severe. Symptoms begin after an incubation period of about 5-7 days.
Symptoms include fever accompanied by nonspecific signs and symptoms such as nausea, vomiting, rash, muscle aches, joint pain, bone pain, pain behind the eyes, headache, or low white blood cell counts.
Disease Progression
Warning signs that may predict progression to severe disease include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, and progressive increase in hematocrit or liver enlargement.
One in 20 people with symptomatic dengue will develop severe disease, with bleeding, shock, or respiratory distress caused by plasma leakage or end-organ impairment.
Infants aged a year or younger, pregnant people, adults aged 65 years or older, people with certain medical conditions, and those with previous dengue infections are at increased risk for severe dengue.
“Healthcare providers should be prepared to recognize, diagnose, manage, and report dengue cases to health authorities; public health partners should investigate cases and disseminate clear prevention messages to the public,” the alert stated.
The CDC is actively implementing several strategies to address the increase in cases of dengue in the United States. In early April, the agency launched a program-led emergency response and is providing monthly situational updates on dengue to partners, stakeholders, and jurisdictions.
The CDC is also expanding laboratory capacity to improve laboratory testing approaches; collaborating with state, tribal, local, and territorial health departments to strengthen dengue surveillance and recommend prevention strategies; and working to educate the public on dengue prevention.
A version of this article first appeared on Medscape.com.
Vaccine ‘Will Not Curb’ Dengue Epidemic, Says PAHO
The current tetravalent dengue vaccine TAK-003, from the Japanese laboratory Takeda, is not likely to control the ongoing epidemic, according to the Pan American Health Organization (PAHO). The organization emphasized the need to better understand the vaccine’s effectiveness against different serotypes and its safety under real-world clinical conditions.
The Americas are experiencing a record increase in dengue cases. Three times as many cases have been identified during 2024 (3.5 million) than were reported for the same period in 2023.
“The vaccine we have available will not curb the dengue epidemic; it should be used complementarily with other actions. The most important actions are field operations, vector control, prevention, and education,” said Daniel Salas, MD, executive manager of the PAHO Comprehensive Immunization Program, during a press conference on March 28.
“The vaccines we currently have are not the best response to reduce transmission and prevent deaths,” added Jarbas Barbosa, MD, PhD, PAHO’s director. The fatality rate remains below 0.05%, but this figure could be hard to maintain if the situation becomes more uncontrolled.
The TAK-003 regimen consists of two doses with a 3-month interval between applications, so “it is not a tool to control transmission at this moment. Studies have shown that only 8 years of [population-level] vaccination would have a significant impact on dengue transmission,” said Dr. Barbosa.
A new vaccine developed in Brazil in partnership with the company MSD, Butantan-DV, is in phase 3 trials and has the advantage of being a single-dose application, which could facilitate its use in situations with accelerated transmission. “But this vaccine will likely only be available in 2025,” said Dr. Barbosa.
PAHO officials also highlighted the need to better characterize the vaccine’s effectiveness and safety in the real world. They observed, for example, that when TAK-003 was investigated, the circulation of dengue serotype 3 was almost nonexistent, so the efficacy data against that serotype “are very limited.”
“The producer, Takeda, has very limited production capacity. Brazil is the country that uses this vaccine the most, followed by Argentina. Given that these countries have a good epidemiological surveillance system and adverse effect registration, they can conduct studies on how the vaccine performs in real life, which will greatly increase our knowledge about it. For example, we will see its effectiveness against serotype 3,” said Dr. Barbosa.
The PAHO Technical Advisory Group (TAG) on vaccine-preventable diseases recommended that any country using these vaccines have surveillance systems in place because it is important to promptly report and investigate any adverse events, said Dr. Salas. The organization also suggested that vaccination should ideally be administered in a “more controlled environment,” a phase 4 study, “to complete the safety and efficacy profile, especially in those who have not had dengue before and for dengue 3 and 4,” said Dr. Salas in response to a question from this news organization.
“People cannot expect that just because they were vaccinated, they will not get dengue. The vaccine has limited reach,” he emphasized.
Other research strategies for vector control, such as the use of the Wolbachia bacteria and mosquito sterilization, are future strategies and “not tools to control this outbreak,” noted Sylvain Aldighieri, MD, director of the Department of Prevention, Control, and Elimination of Transmissible Diseases at PAHO.
In his opening remarks, Dr. Barbosa urged the intensification of efforts with tools that are already available. These approaches include eliminating mosquito breeding sites (“80% are in or near homes”) and protecting against mosquito bites, preparing health services for early diagnosis and timely clinical management, and educating the population about dengue symptoms so they seek medical attention immediately.
Although dengue is increasing throughout Latin America and the Caribbean, the most affected countries are Brazil (83%), Paraguay (5.3%), and Argentina (3.7%), which account for 92% of the cases and 87% of the deaths, PAHO reported.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com .
The current tetravalent dengue vaccine TAK-003, from the Japanese laboratory Takeda, is not likely to control the ongoing epidemic, according to the Pan American Health Organization (PAHO). The organization emphasized the need to better understand the vaccine’s effectiveness against different serotypes and its safety under real-world clinical conditions.
The Americas are experiencing a record increase in dengue cases. Three times as many cases have been identified during 2024 (3.5 million) than were reported for the same period in 2023.
“The vaccine we have available will not curb the dengue epidemic; it should be used complementarily with other actions. The most important actions are field operations, vector control, prevention, and education,” said Daniel Salas, MD, executive manager of the PAHO Comprehensive Immunization Program, during a press conference on March 28.
“The vaccines we currently have are not the best response to reduce transmission and prevent deaths,” added Jarbas Barbosa, MD, PhD, PAHO’s director. The fatality rate remains below 0.05%, but this figure could be hard to maintain if the situation becomes more uncontrolled.
The TAK-003 regimen consists of two doses with a 3-month interval between applications, so “it is not a tool to control transmission at this moment. Studies have shown that only 8 years of [population-level] vaccination would have a significant impact on dengue transmission,” said Dr. Barbosa.
A new vaccine developed in Brazil in partnership with the company MSD, Butantan-DV, is in phase 3 trials and has the advantage of being a single-dose application, which could facilitate its use in situations with accelerated transmission. “But this vaccine will likely only be available in 2025,” said Dr. Barbosa.
PAHO officials also highlighted the need to better characterize the vaccine’s effectiveness and safety in the real world. They observed, for example, that when TAK-003 was investigated, the circulation of dengue serotype 3 was almost nonexistent, so the efficacy data against that serotype “are very limited.”
“The producer, Takeda, has very limited production capacity. Brazil is the country that uses this vaccine the most, followed by Argentina. Given that these countries have a good epidemiological surveillance system and adverse effect registration, they can conduct studies on how the vaccine performs in real life, which will greatly increase our knowledge about it. For example, we will see its effectiveness against serotype 3,” said Dr. Barbosa.
The PAHO Technical Advisory Group (TAG) on vaccine-preventable diseases recommended that any country using these vaccines have surveillance systems in place because it is important to promptly report and investigate any adverse events, said Dr. Salas. The organization also suggested that vaccination should ideally be administered in a “more controlled environment,” a phase 4 study, “to complete the safety and efficacy profile, especially in those who have not had dengue before and for dengue 3 and 4,” said Dr. Salas in response to a question from this news organization.
“People cannot expect that just because they were vaccinated, they will not get dengue. The vaccine has limited reach,” he emphasized.
Other research strategies for vector control, such as the use of the Wolbachia bacteria and mosquito sterilization, are future strategies and “not tools to control this outbreak,” noted Sylvain Aldighieri, MD, director of the Department of Prevention, Control, and Elimination of Transmissible Diseases at PAHO.
In his opening remarks, Dr. Barbosa urged the intensification of efforts with tools that are already available. These approaches include eliminating mosquito breeding sites (“80% are in or near homes”) and protecting against mosquito bites, preparing health services for early diagnosis and timely clinical management, and educating the population about dengue symptoms so they seek medical attention immediately.
Although dengue is increasing throughout Latin America and the Caribbean, the most affected countries are Brazil (83%), Paraguay (5.3%), and Argentina (3.7%), which account for 92% of the cases and 87% of the deaths, PAHO reported.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com .
The current tetravalent dengue vaccine TAK-003, from the Japanese laboratory Takeda, is not likely to control the ongoing epidemic, according to the Pan American Health Organization (PAHO). The organization emphasized the need to better understand the vaccine’s effectiveness against different serotypes and its safety under real-world clinical conditions.
The Americas are experiencing a record increase in dengue cases. Three times as many cases have been identified during 2024 (3.5 million) than were reported for the same period in 2023.
“The vaccine we have available will not curb the dengue epidemic; it should be used complementarily with other actions. The most important actions are field operations, vector control, prevention, and education,” said Daniel Salas, MD, executive manager of the PAHO Comprehensive Immunization Program, during a press conference on March 28.
“The vaccines we currently have are not the best response to reduce transmission and prevent deaths,” added Jarbas Barbosa, MD, PhD, PAHO’s director. The fatality rate remains below 0.05%, but this figure could be hard to maintain if the situation becomes more uncontrolled.
The TAK-003 regimen consists of two doses with a 3-month interval between applications, so “it is not a tool to control transmission at this moment. Studies have shown that only 8 years of [population-level] vaccination would have a significant impact on dengue transmission,” said Dr. Barbosa.
A new vaccine developed in Brazil in partnership with the company MSD, Butantan-DV, is in phase 3 trials and has the advantage of being a single-dose application, which could facilitate its use in situations with accelerated transmission. “But this vaccine will likely only be available in 2025,” said Dr. Barbosa.
PAHO officials also highlighted the need to better characterize the vaccine’s effectiveness and safety in the real world. They observed, for example, that when TAK-003 was investigated, the circulation of dengue serotype 3 was almost nonexistent, so the efficacy data against that serotype “are very limited.”
“The producer, Takeda, has very limited production capacity. Brazil is the country that uses this vaccine the most, followed by Argentina. Given that these countries have a good epidemiological surveillance system and adverse effect registration, they can conduct studies on how the vaccine performs in real life, which will greatly increase our knowledge about it. For example, we will see its effectiveness against serotype 3,” said Dr. Barbosa.
The PAHO Technical Advisory Group (TAG) on vaccine-preventable diseases recommended that any country using these vaccines have surveillance systems in place because it is important to promptly report and investigate any adverse events, said Dr. Salas. The organization also suggested that vaccination should ideally be administered in a “more controlled environment,” a phase 4 study, “to complete the safety and efficacy profile, especially in those who have not had dengue before and for dengue 3 and 4,” said Dr. Salas in response to a question from this news organization.
“People cannot expect that just because they were vaccinated, they will not get dengue. The vaccine has limited reach,” he emphasized.
Other research strategies for vector control, such as the use of the Wolbachia bacteria and mosquito sterilization, are future strategies and “not tools to control this outbreak,” noted Sylvain Aldighieri, MD, director of the Department of Prevention, Control, and Elimination of Transmissible Diseases at PAHO.
In his opening remarks, Dr. Barbosa urged the intensification of efforts with tools that are already available. These approaches include eliminating mosquito breeding sites (“80% are in or near homes”) and protecting against mosquito bites, preparing health services for early diagnosis and timely clinical management, and educating the population about dengue symptoms so they seek medical attention immediately.
Although dengue is increasing throughout Latin America and the Caribbean, the most affected countries are Brazil (83%), Paraguay (5.3%), and Argentina (3.7%), which account for 92% of the cases and 87% of the deaths, PAHO reported.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com .
European Scientists Assess Avian Flu Pandemic Risk
As avian influenza continues to spread among wild bird populations in the European Union (EU), scientists have described a wide range of factors that could drive the virus to spread efficiently among humans, thereby increasing its pandemic potential.
Although transmission of avian influenza A(H5N1) from infected birds to humans is rare, “new strains carrying potential mutations for mammalian adaptation” could occur, according to a report issued on April 3 by the European Centre for Disease Prevention and Control and the European Food Safety Authority. The analysis identified a threat of strains currently circulating outside Europe that could enter the EU and the wider European Economic Area (EEA).
“If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defenses against H5 viruses in humans,” the report warned.
Evolution of Avian Influenza Remains Hard to Predict
However, despite many occurrences of human exposure to avian influenza since 2020, “no symptomatic or productive infection in a human has been identified in the EU/EEA,” the scientists stated. Furthermore, after almost three decades of human exposure to the A(H5N1) virus of the Gs/GD lineage, the virus has not yet acquired the mutations required for airborne transmissibility between humans. However, it remains “difficult to predict the evolutionary direction the virus will take in the future,” the scientists assessed.
“Clearly, humans are being exposed in the current USA cattle outbreak,” Professor James Wood, infectious disease epidemiologist at the University of Cambridge, United Kingdom, told this news organization. “But, arguably, what is more significant is how few cases there have been with this virus lineage and its close relatives, despite massive global exposures over the last 3 years. All diagnosed human cases seem to have been singletons, with no evidence of human-to-human transmission.”
Ian Jones, professor of virology at the University of Reading, United Kingdom, sees no evidence of an imminent spillover of avian influenza from birds. But he told this news organization: “The trouble is, the clock resets every minute. Every time the virus has come out of a bird and gone somewhere, the clock is reset. So you can never say that just because it hasn’t happened since whenever, it’s never going to happen.”
Preventive Measures Recommended
The European report recommended a range of cautionary measures that included enhanced surveillance, access to rapid diagnostics, and sharing of genetic sequence data. It urged EU authorities to work together, adopting a One Health perspective, to limit the exposure of mammals, including humans, to avian influenza viruses.
Sarah Pitt, a microbiologist at the University of Brighton, United Kingdom, said the emphasis on authorities taking a One Health approach was sound. “You’re looking at humans, animals, plants, and the environment and how they’re all closely interacted,” she told this news organization. “Putting all those things together is actually going to be good for human health. So they’ve mentioned One Health a lot and I’m sure that’s on purpose because it’s the latest buzzword, and presumably it’s a way of getting governments to take it seriously.”
Overall, Dr. Pitt believes the document is designed to move zoonotic infectious diseases a bit higher up the agenda. “They should have been higher up the agenda before COVID,” she said.
The report also called for consideration of preventative measures, such as vaccination of poultry flocks.
Overall, Dr. Jones assesses the European report as “a reworking of what’s been pretty well covered over the years.” Despite extensive work by scientists in the field, he said: “I’m not sure we’re any better at predicting an emerging virus than we’ve ever been. I would point out that we didn’t spot SARS-CoV-2 coming, even though we had SARS-CoV-1 a few years earlier. Nobody spotted the 2009 pandemic from influenza, even though there was a lot of surveillance around at the time.”
A version of this article appeared on Medscape.com.
As avian influenza continues to spread among wild bird populations in the European Union (EU), scientists have described a wide range of factors that could drive the virus to spread efficiently among humans, thereby increasing its pandemic potential.
Although transmission of avian influenza A(H5N1) from infected birds to humans is rare, “new strains carrying potential mutations for mammalian adaptation” could occur, according to a report issued on April 3 by the European Centre for Disease Prevention and Control and the European Food Safety Authority. The analysis identified a threat of strains currently circulating outside Europe that could enter the EU and the wider European Economic Area (EEA).
“If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defenses against H5 viruses in humans,” the report warned.
Evolution of Avian Influenza Remains Hard to Predict
However, despite many occurrences of human exposure to avian influenza since 2020, “no symptomatic or productive infection in a human has been identified in the EU/EEA,” the scientists stated. Furthermore, after almost three decades of human exposure to the A(H5N1) virus of the Gs/GD lineage, the virus has not yet acquired the mutations required for airborne transmissibility between humans. However, it remains “difficult to predict the evolutionary direction the virus will take in the future,” the scientists assessed.
“Clearly, humans are being exposed in the current USA cattle outbreak,” Professor James Wood, infectious disease epidemiologist at the University of Cambridge, United Kingdom, told this news organization. “But, arguably, what is more significant is how few cases there have been with this virus lineage and its close relatives, despite massive global exposures over the last 3 years. All diagnosed human cases seem to have been singletons, with no evidence of human-to-human transmission.”
Ian Jones, professor of virology at the University of Reading, United Kingdom, sees no evidence of an imminent spillover of avian influenza from birds. But he told this news organization: “The trouble is, the clock resets every minute. Every time the virus has come out of a bird and gone somewhere, the clock is reset. So you can never say that just because it hasn’t happened since whenever, it’s never going to happen.”
Preventive Measures Recommended
The European report recommended a range of cautionary measures that included enhanced surveillance, access to rapid diagnostics, and sharing of genetic sequence data. It urged EU authorities to work together, adopting a One Health perspective, to limit the exposure of mammals, including humans, to avian influenza viruses.
Sarah Pitt, a microbiologist at the University of Brighton, United Kingdom, said the emphasis on authorities taking a One Health approach was sound. “You’re looking at humans, animals, plants, and the environment and how they’re all closely interacted,” she told this news organization. “Putting all those things together is actually going to be good for human health. So they’ve mentioned One Health a lot and I’m sure that’s on purpose because it’s the latest buzzword, and presumably it’s a way of getting governments to take it seriously.”
Overall, Dr. Pitt believes the document is designed to move zoonotic infectious diseases a bit higher up the agenda. “They should have been higher up the agenda before COVID,” she said.
The report also called for consideration of preventative measures, such as vaccination of poultry flocks.
Overall, Dr. Jones assesses the European report as “a reworking of what’s been pretty well covered over the years.” Despite extensive work by scientists in the field, he said: “I’m not sure we’re any better at predicting an emerging virus than we’ve ever been. I would point out that we didn’t spot SARS-CoV-2 coming, even though we had SARS-CoV-1 a few years earlier. Nobody spotted the 2009 pandemic from influenza, even though there was a lot of surveillance around at the time.”
A version of this article appeared on Medscape.com.
As avian influenza continues to spread among wild bird populations in the European Union (EU), scientists have described a wide range of factors that could drive the virus to spread efficiently among humans, thereby increasing its pandemic potential.
Although transmission of avian influenza A(H5N1) from infected birds to humans is rare, “new strains carrying potential mutations for mammalian adaptation” could occur, according to a report issued on April 3 by the European Centre for Disease Prevention and Control and the European Food Safety Authority. The analysis identified a threat of strains currently circulating outside Europe that could enter the EU and the wider European Economic Area (EEA).
“If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defenses against H5 viruses in humans,” the report warned.
Evolution of Avian Influenza Remains Hard to Predict
However, despite many occurrences of human exposure to avian influenza since 2020, “no symptomatic or productive infection in a human has been identified in the EU/EEA,” the scientists stated. Furthermore, after almost three decades of human exposure to the A(H5N1) virus of the Gs/GD lineage, the virus has not yet acquired the mutations required for airborne transmissibility between humans. However, it remains “difficult to predict the evolutionary direction the virus will take in the future,” the scientists assessed.
“Clearly, humans are being exposed in the current USA cattle outbreak,” Professor James Wood, infectious disease epidemiologist at the University of Cambridge, United Kingdom, told this news organization. “But, arguably, what is more significant is how few cases there have been with this virus lineage and its close relatives, despite massive global exposures over the last 3 years. All diagnosed human cases seem to have been singletons, with no evidence of human-to-human transmission.”
Ian Jones, professor of virology at the University of Reading, United Kingdom, sees no evidence of an imminent spillover of avian influenza from birds. But he told this news organization: “The trouble is, the clock resets every minute. Every time the virus has come out of a bird and gone somewhere, the clock is reset. So you can never say that just because it hasn’t happened since whenever, it’s never going to happen.”
Preventive Measures Recommended
The European report recommended a range of cautionary measures that included enhanced surveillance, access to rapid diagnostics, and sharing of genetic sequence data. It urged EU authorities to work together, adopting a One Health perspective, to limit the exposure of mammals, including humans, to avian influenza viruses.
Sarah Pitt, a microbiologist at the University of Brighton, United Kingdom, said the emphasis on authorities taking a One Health approach was sound. “You’re looking at humans, animals, plants, and the environment and how they’re all closely interacted,” she told this news organization. “Putting all those things together is actually going to be good for human health. So they’ve mentioned One Health a lot and I’m sure that’s on purpose because it’s the latest buzzword, and presumably it’s a way of getting governments to take it seriously.”
Overall, Dr. Pitt believes the document is designed to move zoonotic infectious diseases a bit higher up the agenda. “They should have been higher up the agenda before COVID,” she said.
The report also called for consideration of preventative measures, such as vaccination of poultry flocks.
Overall, Dr. Jones assesses the European report as “a reworking of what’s been pretty well covered over the years.” Despite extensive work by scientists in the field, he said: “I’m not sure we’re any better at predicting an emerging virus than we’ve ever been. I would point out that we didn’t spot SARS-CoV-2 coming, even though we had SARS-CoV-1 a few years earlier. Nobody spotted the 2009 pandemic from influenza, even though there was a lot of surveillance around at the time.”
A version of this article appeared on Medscape.com.
Hepatitis E Vaccine Shows Long-Term Efficacy
The hepatitis E virus (HEV) is among the leading global causes of acute viral hepatitis. Molecular studies of HEV strains have identified four main genotypes. Genotypes 1 and 2 are limited to humans and are transmitted through contaminated water in resource-limited countries, mainly in Asia. Genotypes 3 and 4 are zoonotic, causing sporadic indigenous hepatitis E in nearly all countries.
Each year, approximately 20 million HEV infections occur worldwide, resulting in around 3.3 million symptomatic infections and 70,000 deaths. Despite this toll, HEV infection remains underestimated, and Western countries are likely not immune to the virus. To date, two recombinant vaccines against hepatitis E, based on genotype 1, have been developed and approved in China, but further studies are needed to determine the duration of vaccination protection.
Ten-Year Results
This study is an extension of a randomized, double-blind, placebo-controlled phase 3 clinical trial of the Hecolin hepatitis E vaccine that was conducted in Dongtai County, Jiangsu, China. In the initial trial, healthy adults aged 16-65 years were recruited, stratified by age and sex, and randomly assigned in a 1:1 ratio to receive three doses of intramuscular hepatitis E vaccine or placebo at months 0, 1, and 6.
A hepatitis E surveillance system, including 205 clinical sentinels covering the entire study region, was established before the study began and maintained for 10 years after vaccination to identify individuals with suspected hepatitis. In addition, an external control cohort was formed to assess vaccine efficacy. The primary endpoint was the vaccine’s efficacy in preventing confirmed hepatitis E occurring at least 30 days after the administration of the third vaccine dose.
Follow-up occurred every 3 months. Participants with hepatitis symptoms for 3 days or more underwent alanine aminotransferase (ALT) concentration measurement. Patients with ALT concentrations ≥ 2.5 times the upper limit of normal were considered to have acute hepatitis. A diagnosis of HEV-confirmed infection was made for patients with acute hepatitis presenting with at least two of the following markers: Presence of HEV RNA, presence of positive anti-HEV immunoglobulin (Ig) M antibodies, and at least fourfold increase in anti-HEV IgG concentrations.
For the efficacy analysis, a Poisson regression model was used to estimate the relative risk and its 95% CI of incidence between groups. Incidence was reported as the number of patients with hepatitis E per 10,000 person-years.
Immunogenicity persistence was assessed by measuring anti-HEV IgG in participants. Serum samples were collected at months 0, 7, 13, 19, 31, 43, 55, 79, and 103 for Qingdao district participants and at months 0, 7, 19, 31, 43, 67, and 91 for Anfeng district participants.
Efficacy and Duration
The follow-up period extended from 2007 to 2017. In total, 97,356 participants completed the three-dose regimen and were included in the per-protocol population (48,693 in the vaccine group and 48,663 in the placebo group), and 178,236 residents from the study region participated in the external control cohort. During the study period, 90 cases of hepatitis E were identified, with 13 in the vaccine group (0.2 per 10,000 person-years) and 77 in the placebo group (1.4 per 10,000 person-years). This indicated a vaccine efficacy of 86.6% in the per-protocol analysis.
In the subgroups evaluated for immunogenicity persistence, among those who were initially seronegative and received three doses of hepatitis E vaccine, 254 out of 291 vaccinated participants (87.3%) in Qingdao after 8.5 years and 1270 (73.0%) out of 1740 vaccinated participants in Anfeng after 7.5 years maintained detectable antibody concentrations.
The identification of infections despite vaccination is notable, especially with eight cases occurring beyond the fourth year following the last dose. This information is crucial for understanding potential immunity decline over time and highlights the importance of exploring various vaccination strategies to optimize protection.
An ongoing phase 4 clinical trial in Bangladesh, exploring different administration schedules and target populations, could help optimize vaccination strategies. The remarkable efficacy (100%) observed over a 30-month period for the two-dose schedule (doses are administered 1 month apart) is promising.
The observation of higher IgG antibody avidity in participants with infections despite vaccination underscores the importance of robust antibody responses to mitigate disease severity and duration. Several study limitations, such as lack of data on deaths and emigrations, a single-center study design, predominance of genotype 4 infections, and the risk for bias in the external control cohort, should be acknowledged.
In conclusion, this study provides compelling evidence of sustained protection of the hepatitis E vaccine over a decade. The observed persistence of induced antibodies for at least 8.5 years supports the long-term efficacy of the vaccine. Diverse global trials, further investigation into the impact of natural infections on vaccine-induced antibodies, and confirmation of inter-genotypic protection are needed.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
The hepatitis E virus (HEV) is among the leading global causes of acute viral hepatitis. Molecular studies of HEV strains have identified four main genotypes. Genotypes 1 and 2 are limited to humans and are transmitted through contaminated water in resource-limited countries, mainly in Asia. Genotypes 3 and 4 are zoonotic, causing sporadic indigenous hepatitis E in nearly all countries.
Each year, approximately 20 million HEV infections occur worldwide, resulting in around 3.3 million symptomatic infections and 70,000 deaths. Despite this toll, HEV infection remains underestimated, and Western countries are likely not immune to the virus. To date, two recombinant vaccines against hepatitis E, based on genotype 1, have been developed and approved in China, but further studies are needed to determine the duration of vaccination protection.
Ten-Year Results
This study is an extension of a randomized, double-blind, placebo-controlled phase 3 clinical trial of the Hecolin hepatitis E vaccine that was conducted in Dongtai County, Jiangsu, China. In the initial trial, healthy adults aged 16-65 years were recruited, stratified by age and sex, and randomly assigned in a 1:1 ratio to receive three doses of intramuscular hepatitis E vaccine or placebo at months 0, 1, and 6.
A hepatitis E surveillance system, including 205 clinical sentinels covering the entire study region, was established before the study began and maintained for 10 years after vaccination to identify individuals with suspected hepatitis. In addition, an external control cohort was formed to assess vaccine efficacy. The primary endpoint was the vaccine’s efficacy in preventing confirmed hepatitis E occurring at least 30 days after the administration of the third vaccine dose.
Follow-up occurred every 3 months. Participants with hepatitis symptoms for 3 days or more underwent alanine aminotransferase (ALT) concentration measurement. Patients with ALT concentrations ≥ 2.5 times the upper limit of normal were considered to have acute hepatitis. A diagnosis of HEV-confirmed infection was made for patients with acute hepatitis presenting with at least two of the following markers: Presence of HEV RNA, presence of positive anti-HEV immunoglobulin (Ig) M antibodies, and at least fourfold increase in anti-HEV IgG concentrations.
For the efficacy analysis, a Poisson regression model was used to estimate the relative risk and its 95% CI of incidence between groups. Incidence was reported as the number of patients with hepatitis E per 10,000 person-years.
Immunogenicity persistence was assessed by measuring anti-HEV IgG in participants. Serum samples were collected at months 0, 7, 13, 19, 31, 43, 55, 79, and 103 for Qingdao district participants and at months 0, 7, 19, 31, 43, 67, and 91 for Anfeng district participants.
Efficacy and Duration
The follow-up period extended from 2007 to 2017. In total, 97,356 participants completed the three-dose regimen and were included in the per-protocol population (48,693 in the vaccine group and 48,663 in the placebo group), and 178,236 residents from the study region participated in the external control cohort. During the study period, 90 cases of hepatitis E were identified, with 13 in the vaccine group (0.2 per 10,000 person-years) and 77 in the placebo group (1.4 per 10,000 person-years). This indicated a vaccine efficacy of 86.6% in the per-protocol analysis.
In the subgroups evaluated for immunogenicity persistence, among those who were initially seronegative and received three doses of hepatitis E vaccine, 254 out of 291 vaccinated participants (87.3%) in Qingdao after 8.5 years and 1270 (73.0%) out of 1740 vaccinated participants in Anfeng after 7.5 years maintained detectable antibody concentrations.
The identification of infections despite vaccination is notable, especially with eight cases occurring beyond the fourth year following the last dose. This information is crucial for understanding potential immunity decline over time and highlights the importance of exploring various vaccination strategies to optimize protection.
An ongoing phase 4 clinical trial in Bangladesh, exploring different administration schedules and target populations, could help optimize vaccination strategies. The remarkable efficacy (100%) observed over a 30-month period for the two-dose schedule (doses are administered 1 month apart) is promising.
The observation of higher IgG antibody avidity in participants with infections despite vaccination underscores the importance of robust antibody responses to mitigate disease severity and duration. Several study limitations, such as lack of data on deaths and emigrations, a single-center study design, predominance of genotype 4 infections, and the risk for bias in the external control cohort, should be acknowledged.
In conclusion, this study provides compelling evidence of sustained protection of the hepatitis E vaccine over a decade. The observed persistence of induced antibodies for at least 8.5 years supports the long-term efficacy of the vaccine. Diverse global trials, further investigation into the impact of natural infections on vaccine-induced antibodies, and confirmation of inter-genotypic protection are needed.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
The hepatitis E virus (HEV) is among the leading global causes of acute viral hepatitis. Molecular studies of HEV strains have identified four main genotypes. Genotypes 1 and 2 are limited to humans and are transmitted through contaminated water in resource-limited countries, mainly in Asia. Genotypes 3 and 4 are zoonotic, causing sporadic indigenous hepatitis E in nearly all countries.
Each year, approximately 20 million HEV infections occur worldwide, resulting in around 3.3 million symptomatic infections and 70,000 deaths. Despite this toll, HEV infection remains underestimated, and Western countries are likely not immune to the virus. To date, two recombinant vaccines against hepatitis E, based on genotype 1, have been developed and approved in China, but further studies are needed to determine the duration of vaccination protection.
Ten-Year Results
This study is an extension of a randomized, double-blind, placebo-controlled phase 3 clinical trial of the Hecolin hepatitis E vaccine that was conducted in Dongtai County, Jiangsu, China. In the initial trial, healthy adults aged 16-65 years were recruited, stratified by age and sex, and randomly assigned in a 1:1 ratio to receive three doses of intramuscular hepatitis E vaccine or placebo at months 0, 1, and 6.
A hepatitis E surveillance system, including 205 clinical sentinels covering the entire study region, was established before the study began and maintained for 10 years after vaccination to identify individuals with suspected hepatitis. In addition, an external control cohort was formed to assess vaccine efficacy. The primary endpoint was the vaccine’s efficacy in preventing confirmed hepatitis E occurring at least 30 days after the administration of the third vaccine dose.
Follow-up occurred every 3 months. Participants with hepatitis symptoms for 3 days or more underwent alanine aminotransferase (ALT) concentration measurement. Patients with ALT concentrations ≥ 2.5 times the upper limit of normal were considered to have acute hepatitis. A diagnosis of HEV-confirmed infection was made for patients with acute hepatitis presenting with at least two of the following markers: Presence of HEV RNA, presence of positive anti-HEV immunoglobulin (Ig) M antibodies, and at least fourfold increase in anti-HEV IgG concentrations.
For the efficacy analysis, a Poisson regression model was used to estimate the relative risk and its 95% CI of incidence between groups. Incidence was reported as the number of patients with hepatitis E per 10,000 person-years.
Immunogenicity persistence was assessed by measuring anti-HEV IgG in participants. Serum samples were collected at months 0, 7, 13, 19, 31, 43, 55, 79, and 103 for Qingdao district participants and at months 0, 7, 19, 31, 43, 67, and 91 for Anfeng district participants.
Efficacy and Duration
The follow-up period extended from 2007 to 2017. In total, 97,356 participants completed the three-dose regimen and were included in the per-protocol population (48,693 in the vaccine group and 48,663 in the placebo group), and 178,236 residents from the study region participated in the external control cohort. During the study period, 90 cases of hepatitis E were identified, with 13 in the vaccine group (0.2 per 10,000 person-years) and 77 in the placebo group (1.4 per 10,000 person-years). This indicated a vaccine efficacy of 86.6% in the per-protocol analysis.
In the subgroups evaluated for immunogenicity persistence, among those who were initially seronegative and received three doses of hepatitis E vaccine, 254 out of 291 vaccinated participants (87.3%) in Qingdao after 8.5 years and 1270 (73.0%) out of 1740 vaccinated participants in Anfeng after 7.5 years maintained detectable antibody concentrations.
The identification of infections despite vaccination is notable, especially with eight cases occurring beyond the fourth year following the last dose. This information is crucial for understanding potential immunity decline over time and highlights the importance of exploring various vaccination strategies to optimize protection.
An ongoing phase 4 clinical trial in Bangladesh, exploring different administration schedules and target populations, could help optimize vaccination strategies. The remarkable efficacy (100%) observed over a 30-month period for the two-dose schedule (doses are administered 1 month apart) is promising.
The observation of higher IgG antibody avidity in participants with infections despite vaccination underscores the importance of robust antibody responses to mitigate disease severity and duration. Several study limitations, such as lack of data on deaths and emigrations, a single-center study design, predominance of genotype 4 infections, and the risk for bias in the external control cohort, should be acknowledged.
In conclusion, this study provides compelling evidence of sustained protection of the hepatitis E vaccine over a decade. The observed persistence of induced antibodies for at least 8.5 years supports the long-term efficacy of the vaccine. Diverse global trials, further investigation into the impact of natural infections on vaccine-induced antibodies, and confirmation of inter-genotypic protection are needed.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Oral Transmission of Chagas Disease Has Severe Effects
Thanks to decades of successful vector control strategies, vector-borne transmission of Chagas disease has significantly decreased in many regions. Oral ingestion of Trypanosoma cruzi through contaminated food and beverages, however, is increasing. Unlike vector transmission, oral transmission of Chagas disease entails high lethality in pediatric and adult populations.
“The oral transmission of Chagas disease is becoming a much more recognized route, and it is crucial to understand that people can die from this type of transmission,” Norman L. Beatty, MD, assistant professor of infectious diseases and global medicine at the University of Florida College of Medicine in Gainesville, Florida, told this news organization. Dr. Beatty is the lead author of a recent article on the subject.
In regions where the parasite circulates in the environment, people are consuming foods, fruit juices, and possibly wild animal meat that may be contaminated. “As we experience changes in our environment and in the way we consume food, it is crucial to consider how food preparation is carried out in areas where T cruzi transmission occurs in the environment,” said Dr. Beatty. “And as organic farming methods without insecticides become increasingly common, more research is needed in these areas, both in Latin America and in the United States, to understand if oral transmission of T cruzi is occurring.”
In the Amazon basin, foodborne transmission is already the leading cause of acute Chagas disease. It has been described in Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, and Venezuela.
Dr. Beatty’s colleagues recently treated a Brazilian patient at the hospital in Florida. “He came to our hospital very ill, with acute myocarditis after consuming contaminated açaí.” Clarifying that there is widespread awareness about oral transmission in Brazil, he stated, “We are concerned that it may not be recognized in other areas of Latin America.”
Mexico and regions of Central America have little to no information on oral transmission, but it is likely occurring, and cases may be going undetected in the region, said Dr. Beatty.
He investigated the issue in Colombia as part of an international collaboration involving the University of Antioquia, aiming to find ways to mitigate oral transmission and create a model that can be used throughout Latin America and the United States. For the Colombia study, they reviewed all cases reported to the Ministry of Health and Social Protection, and oral transmission turned out to be more common than the research group expected. “Still, I imagine that in certain areas with limited resources…there are many more cases that are not being reported.
“A myth I would like to dispel is that Chagas disease is not being transmitted in the United States,” Dr. Beatty added. He mentioned that at least 30 American states have vectors, and in Florida, it was documented that triatomines invaded homes and bit residents. In addition, 30% of these insects are infected with T cruzi. Research is underway to determine whether Floridians are becoming infected and if they are also at risk of contracting Chagas disease orally, said Dr. Beatty. “In the United States, we know very little about how many people are infected and what the infection routes are. Much more research is needed.”
Roberto Chuit, MD, PhD, a doctor in public health and an external consultant for the Pan American Health Organization (PAHO), agreed that this route of food contamination, which occurs because of vector-borne parasites, was until recently masked or hidden by the predominance of vector presence. Just as it began to gain importance as other transmission routes were controlled, “it now has extremely high importance in the Americas, as does vertical transmission,” he said.
In 2023, more than 50 years after the first description of oral transmission, the PAHO expert meeting proposed to alert health services and the broader community about the severity and potential lethality of oral Chagas disease outbreaks to elicit immediate responses and mitigation measures. The body also proposed conducting studies to provide detailed information on the contamination source and the wild vectors present in oral transmission foci.
Unique Clinical Manifestations
The exacerbated signs and symptoms of oral infection (see sidebar) are attributed to the high parasite loads in contaminated food and beverages. A single crushed triatomine along with a food or beverage harboring T cruzi can contain an estimated 600,000 metacyclic trypomastigotes, compared with 3000-4000 per µL when infection occurs by triatomine fecal matter. The robust systemic immune response observed in patients with acute oral Chagas disease is thought to result from more efficient transmission after penetration through the oral, pharyngeal, and gastric mucosae.
Seven Things to Know About Orally Transmitted Chagas Disease
1. It presents with exacerbated symptoms and rapid disease progression in immunocompetent individuals. This presentation is not common in vector-borne, congenital, or transfusion-related transmission. It can cause fulminant myocarditis and heart failure, meningoencephalitis, or potentially fatal shock due to parasitemia.
2. Most patients (71%-100%) with acute oral Chagas present with fever.
3. Electrocardiographic abnormalities, specifically ventricular depolarization alterations and pericardial involvement, are observed in most patients.
4. Facial edema, which typically affects the entire face and parts of the lips, is present in 57%-100% of patients with acute oral Chagas disease. In those with acute symptoms from vector transmission, unilateral periorbital swelling (Romaña’s sign) is more common.
5. Other notable systemic symptoms include edema of the lower extremities, myalgia, generalized lymphadenopathy, abdominal discomfort, dyspnea, vomiting, diarrhea, hepatomegaly, splenomegaly, headache, chest pain, cutaneous erythematous rash, jaundice, arthralgia, epistaxis, hematemesis, melena, and palpitations.
6. The incubation period after oral ingestion of products contaminated with Trypanosoma cruzi is approximately 3-22 days, in contrast to 4-15 days for vector-borne transmission and 8-160 days for transfusion and transplant-related transmission.
7. Patients need antiparasitic drugs immediately.
Thinking Epidemiologically
Dr. Chuit recalled that suspicion of food contamination should be based on epidemiology, especially in outbreaks affecting several people and in regions where Chagas vectors have been described. Sometimes, however, a single careless tourist consumes contaminated products.
“The difficulty is that many times it is not considered, and if it is not considered, the search for the parasite is not requested,” said Dr. Chuit. He added that it is common for the professional to consider Chagas disease only if viral and bacterial isolation tests are negative. Clinicians sometimes consider Chagas disease because the patient has not responded to regular treatments for other causes, such as antibiotics and hydration.
Epidemiology is important, especially when Chagas disease is diagnosed in groups or a family, because they are usually not isolated cases but outbreaks of 3-40 cases, according to Dr. Chuit. “Under these conditions, it must be quickly considered…that this parasite may be involved.”
One of the difficulties is that the source of these oral transmissions is not recognized most of the time. In general, the sources are usually foods that are more likely to be contaminated by insects or insect feces, such as orange juice or sugarcane. But in fact, any food or beverage left unattended could be contaminated by vectors or possible secretions from infected marsupial odoriferous glands.
An analysis of 32 outbreaks from 1965 to 2022 showed that the main foods involved in oral transmission were homemade fruit juices. But different vector species were identified, and the reservoirs were mainly dogs, rodents, and large American opossums (Didelphis).
The largest oral Chagas outbreak was linked to the consumption of contaminated guava juice in a primary school in Caracas, Venezuela. Nonindustrially produced açaí is a common source of orally acquired Chagas disease in Brazil. In Colombia, Chagas disease has been associated with the consumption of palm wine, sugar cane, and tangerine juice. Other oral transmission routes include consuming meat from wild animals and ingesting blood from infected armadillos, which is related to a traditional medicine practice.
Deadly Yet Easily Treatable
In the outbreak of 119 confirmed and suspected cases in Venezuela, 20.3% required hospitalization, and a 5-year-old child died of acute myocarditis. These percentages differ from those reported in vector transmission, which is asymptomatic in the acute phase for 95%-99% of cases or will only develop a mild febrile illness that resolves on its own.
“Not all cases will present as severe, because depending on the inoculum, there may be individuals with subclinical situations. But any food poisoning that occurs in endemic areas, where food is not properly controlled, and these street foods are associated with processes in jungle areas, raises the possibility that T cruzi is involved and should be considered as a differential diagnosis,» noted Dr. Chuit. “The treatment is highly effective, and people recover quickly.”
“The most important thing about oral transmission of Chagas is that someone infected in this way needs antiparasitic drugs immediately. We can cure them if we treat them immediately,” said Dr. Beatty, adding that treatment is sometimes delayed due to lack of access to appropriate antiparasitic drugs. “Here in the United States and in Latin America, it is quite common for healthcare professionals not to understand the differences between vector, vertical, and oral transmission. By not treating these patients, they become ill quickly.”
Dr. Beatty and Dr. Chuit declared no relevant financial conflicts of interest.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Thanks to decades of successful vector control strategies, vector-borne transmission of Chagas disease has significantly decreased in many regions. Oral ingestion of Trypanosoma cruzi through contaminated food and beverages, however, is increasing. Unlike vector transmission, oral transmission of Chagas disease entails high lethality in pediatric and adult populations.
“The oral transmission of Chagas disease is becoming a much more recognized route, and it is crucial to understand that people can die from this type of transmission,” Norman L. Beatty, MD, assistant professor of infectious diseases and global medicine at the University of Florida College of Medicine in Gainesville, Florida, told this news organization. Dr. Beatty is the lead author of a recent article on the subject.
In regions where the parasite circulates in the environment, people are consuming foods, fruit juices, and possibly wild animal meat that may be contaminated. “As we experience changes in our environment and in the way we consume food, it is crucial to consider how food preparation is carried out in areas where T cruzi transmission occurs in the environment,” said Dr. Beatty. “And as organic farming methods without insecticides become increasingly common, more research is needed in these areas, both in Latin America and in the United States, to understand if oral transmission of T cruzi is occurring.”
In the Amazon basin, foodborne transmission is already the leading cause of acute Chagas disease. It has been described in Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, and Venezuela.
Dr. Beatty’s colleagues recently treated a Brazilian patient at the hospital in Florida. “He came to our hospital very ill, with acute myocarditis after consuming contaminated açaí.” Clarifying that there is widespread awareness about oral transmission in Brazil, he stated, “We are concerned that it may not be recognized in other areas of Latin America.”
Mexico and regions of Central America have little to no information on oral transmission, but it is likely occurring, and cases may be going undetected in the region, said Dr. Beatty.
He investigated the issue in Colombia as part of an international collaboration involving the University of Antioquia, aiming to find ways to mitigate oral transmission and create a model that can be used throughout Latin America and the United States. For the Colombia study, they reviewed all cases reported to the Ministry of Health and Social Protection, and oral transmission turned out to be more common than the research group expected. “Still, I imagine that in certain areas with limited resources…there are many more cases that are not being reported.
“A myth I would like to dispel is that Chagas disease is not being transmitted in the United States,” Dr. Beatty added. He mentioned that at least 30 American states have vectors, and in Florida, it was documented that triatomines invaded homes and bit residents. In addition, 30% of these insects are infected with T cruzi. Research is underway to determine whether Floridians are becoming infected and if they are also at risk of contracting Chagas disease orally, said Dr. Beatty. “In the United States, we know very little about how many people are infected and what the infection routes are. Much more research is needed.”
Roberto Chuit, MD, PhD, a doctor in public health and an external consultant for the Pan American Health Organization (PAHO), agreed that this route of food contamination, which occurs because of vector-borne parasites, was until recently masked or hidden by the predominance of vector presence. Just as it began to gain importance as other transmission routes were controlled, “it now has extremely high importance in the Americas, as does vertical transmission,” he said.
In 2023, more than 50 years after the first description of oral transmission, the PAHO expert meeting proposed to alert health services and the broader community about the severity and potential lethality of oral Chagas disease outbreaks to elicit immediate responses and mitigation measures. The body also proposed conducting studies to provide detailed information on the contamination source and the wild vectors present in oral transmission foci.
Unique Clinical Manifestations
The exacerbated signs and symptoms of oral infection (see sidebar) are attributed to the high parasite loads in contaminated food and beverages. A single crushed triatomine along with a food or beverage harboring T cruzi can contain an estimated 600,000 metacyclic trypomastigotes, compared with 3000-4000 per µL when infection occurs by triatomine fecal matter. The robust systemic immune response observed in patients with acute oral Chagas disease is thought to result from more efficient transmission after penetration through the oral, pharyngeal, and gastric mucosae.
Seven Things to Know About Orally Transmitted Chagas Disease
1. It presents with exacerbated symptoms and rapid disease progression in immunocompetent individuals. This presentation is not common in vector-borne, congenital, or transfusion-related transmission. It can cause fulminant myocarditis and heart failure, meningoencephalitis, or potentially fatal shock due to parasitemia.
2. Most patients (71%-100%) with acute oral Chagas present with fever.
3. Electrocardiographic abnormalities, specifically ventricular depolarization alterations and pericardial involvement, are observed in most patients.
4. Facial edema, which typically affects the entire face and parts of the lips, is present in 57%-100% of patients with acute oral Chagas disease. In those with acute symptoms from vector transmission, unilateral periorbital swelling (Romaña’s sign) is more common.
5. Other notable systemic symptoms include edema of the lower extremities, myalgia, generalized lymphadenopathy, abdominal discomfort, dyspnea, vomiting, diarrhea, hepatomegaly, splenomegaly, headache, chest pain, cutaneous erythematous rash, jaundice, arthralgia, epistaxis, hematemesis, melena, and palpitations.
6. The incubation period after oral ingestion of products contaminated with Trypanosoma cruzi is approximately 3-22 days, in contrast to 4-15 days for vector-borne transmission and 8-160 days for transfusion and transplant-related transmission.
7. Patients need antiparasitic drugs immediately.
Thinking Epidemiologically
Dr. Chuit recalled that suspicion of food contamination should be based on epidemiology, especially in outbreaks affecting several people and in regions where Chagas vectors have been described. Sometimes, however, a single careless tourist consumes contaminated products.
“The difficulty is that many times it is not considered, and if it is not considered, the search for the parasite is not requested,” said Dr. Chuit. He added that it is common for the professional to consider Chagas disease only if viral and bacterial isolation tests are negative. Clinicians sometimes consider Chagas disease because the patient has not responded to regular treatments for other causes, such as antibiotics and hydration.
Epidemiology is important, especially when Chagas disease is diagnosed in groups or a family, because they are usually not isolated cases but outbreaks of 3-40 cases, according to Dr. Chuit. “Under these conditions, it must be quickly considered…that this parasite may be involved.”
One of the difficulties is that the source of these oral transmissions is not recognized most of the time. In general, the sources are usually foods that are more likely to be contaminated by insects or insect feces, such as orange juice or sugarcane. But in fact, any food or beverage left unattended could be contaminated by vectors or possible secretions from infected marsupial odoriferous glands.
An analysis of 32 outbreaks from 1965 to 2022 showed that the main foods involved in oral transmission were homemade fruit juices. But different vector species were identified, and the reservoirs were mainly dogs, rodents, and large American opossums (Didelphis).
The largest oral Chagas outbreak was linked to the consumption of contaminated guava juice in a primary school in Caracas, Venezuela. Nonindustrially produced açaí is a common source of orally acquired Chagas disease in Brazil. In Colombia, Chagas disease has been associated with the consumption of palm wine, sugar cane, and tangerine juice. Other oral transmission routes include consuming meat from wild animals and ingesting blood from infected armadillos, which is related to a traditional medicine practice.
Deadly Yet Easily Treatable
In the outbreak of 119 confirmed and suspected cases in Venezuela, 20.3% required hospitalization, and a 5-year-old child died of acute myocarditis. These percentages differ from those reported in vector transmission, which is asymptomatic in the acute phase for 95%-99% of cases or will only develop a mild febrile illness that resolves on its own.
“Not all cases will present as severe, because depending on the inoculum, there may be individuals with subclinical situations. But any food poisoning that occurs in endemic areas, where food is not properly controlled, and these street foods are associated with processes in jungle areas, raises the possibility that T cruzi is involved and should be considered as a differential diagnosis,» noted Dr. Chuit. “The treatment is highly effective, and people recover quickly.”
“The most important thing about oral transmission of Chagas is that someone infected in this way needs antiparasitic drugs immediately. We can cure them if we treat them immediately,” said Dr. Beatty, adding that treatment is sometimes delayed due to lack of access to appropriate antiparasitic drugs. “Here in the United States and in Latin America, it is quite common for healthcare professionals not to understand the differences between vector, vertical, and oral transmission. By not treating these patients, they become ill quickly.”
Dr. Beatty and Dr. Chuit declared no relevant financial conflicts of interest.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Thanks to decades of successful vector control strategies, vector-borne transmission of Chagas disease has significantly decreased in many regions. Oral ingestion of Trypanosoma cruzi through contaminated food and beverages, however, is increasing. Unlike vector transmission, oral transmission of Chagas disease entails high lethality in pediatric and adult populations.
“The oral transmission of Chagas disease is becoming a much more recognized route, and it is crucial to understand that people can die from this type of transmission,” Norman L. Beatty, MD, assistant professor of infectious diseases and global medicine at the University of Florida College of Medicine in Gainesville, Florida, told this news organization. Dr. Beatty is the lead author of a recent article on the subject.
In regions where the parasite circulates in the environment, people are consuming foods, fruit juices, and possibly wild animal meat that may be contaminated. “As we experience changes in our environment and in the way we consume food, it is crucial to consider how food preparation is carried out in areas where T cruzi transmission occurs in the environment,” said Dr. Beatty. “And as organic farming methods without insecticides become increasingly common, more research is needed in these areas, both in Latin America and in the United States, to understand if oral transmission of T cruzi is occurring.”
In the Amazon basin, foodborne transmission is already the leading cause of acute Chagas disease. It has been described in Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, and Venezuela.
Dr. Beatty’s colleagues recently treated a Brazilian patient at the hospital in Florida. “He came to our hospital very ill, with acute myocarditis after consuming contaminated açaí.” Clarifying that there is widespread awareness about oral transmission in Brazil, he stated, “We are concerned that it may not be recognized in other areas of Latin America.”
Mexico and regions of Central America have little to no information on oral transmission, but it is likely occurring, and cases may be going undetected in the region, said Dr. Beatty.
He investigated the issue in Colombia as part of an international collaboration involving the University of Antioquia, aiming to find ways to mitigate oral transmission and create a model that can be used throughout Latin America and the United States. For the Colombia study, they reviewed all cases reported to the Ministry of Health and Social Protection, and oral transmission turned out to be more common than the research group expected. “Still, I imagine that in certain areas with limited resources…there are many more cases that are not being reported.
“A myth I would like to dispel is that Chagas disease is not being transmitted in the United States,” Dr. Beatty added. He mentioned that at least 30 American states have vectors, and in Florida, it was documented that triatomines invaded homes and bit residents. In addition, 30% of these insects are infected with T cruzi. Research is underway to determine whether Floridians are becoming infected and if they are also at risk of contracting Chagas disease orally, said Dr. Beatty. “In the United States, we know very little about how many people are infected and what the infection routes are. Much more research is needed.”
Roberto Chuit, MD, PhD, a doctor in public health and an external consultant for the Pan American Health Organization (PAHO), agreed that this route of food contamination, which occurs because of vector-borne parasites, was until recently masked or hidden by the predominance of vector presence. Just as it began to gain importance as other transmission routes were controlled, “it now has extremely high importance in the Americas, as does vertical transmission,” he said.
In 2023, more than 50 years after the first description of oral transmission, the PAHO expert meeting proposed to alert health services and the broader community about the severity and potential lethality of oral Chagas disease outbreaks to elicit immediate responses and mitigation measures. The body also proposed conducting studies to provide detailed information on the contamination source and the wild vectors present in oral transmission foci.
Unique Clinical Manifestations
The exacerbated signs and symptoms of oral infection (see sidebar) are attributed to the high parasite loads in contaminated food and beverages. A single crushed triatomine along with a food or beverage harboring T cruzi can contain an estimated 600,000 metacyclic trypomastigotes, compared with 3000-4000 per µL when infection occurs by triatomine fecal matter. The robust systemic immune response observed in patients with acute oral Chagas disease is thought to result from more efficient transmission after penetration through the oral, pharyngeal, and gastric mucosae.
Seven Things to Know About Orally Transmitted Chagas Disease
1. It presents with exacerbated symptoms and rapid disease progression in immunocompetent individuals. This presentation is not common in vector-borne, congenital, or transfusion-related transmission. It can cause fulminant myocarditis and heart failure, meningoencephalitis, or potentially fatal shock due to parasitemia.
2. Most patients (71%-100%) with acute oral Chagas present with fever.
3. Electrocardiographic abnormalities, specifically ventricular depolarization alterations and pericardial involvement, are observed in most patients.
4. Facial edema, which typically affects the entire face and parts of the lips, is present in 57%-100% of patients with acute oral Chagas disease. In those with acute symptoms from vector transmission, unilateral periorbital swelling (Romaña’s sign) is more common.
5. Other notable systemic symptoms include edema of the lower extremities, myalgia, generalized lymphadenopathy, abdominal discomfort, dyspnea, vomiting, diarrhea, hepatomegaly, splenomegaly, headache, chest pain, cutaneous erythematous rash, jaundice, arthralgia, epistaxis, hematemesis, melena, and palpitations.
6. The incubation period after oral ingestion of products contaminated with Trypanosoma cruzi is approximately 3-22 days, in contrast to 4-15 days for vector-borne transmission and 8-160 days for transfusion and transplant-related transmission.
7. Patients need antiparasitic drugs immediately.
Thinking Epidemiologically
Dr. Chuit recalled that suspicion of food contamination should be based on epidemiology, especially in outbreaks affecting several people and in regions where Chagas vectors have been described. Sometimes, however, a single careless tourist consumes contaminated products.
“The difficulty is that many times it is not considered, and if it is not considered, the search for the parasite is not requested,” said Dr. Chuit. He added that it is common for the professional to consider Chagas disease only if viral and bacterial isolation tests are negative. Clinicians sometimes consider Chagas disease because the patient has not responded to regular treatments for other causes, such as antibiotics and hydration.
Epidemiology is important, especially when Chagas disease is diagnosed in groups or a family, because they are usually not isolated cases but outbreaks of 3-40 cases, according to Dr. Chuit. “Under these conditions, it must be quickly considered…that this parasite may be involved.”
One of the difficulties is that the source of these oral transmissions is not recognized most of the time. In general, the sources are usually foods that are more likely to be contaminated by insects or insect feces, such as orange juice or sugarcane. But in fact, any food or beverage left unattended could be contaminated by vectors or possible secretions from infected marsupial odoriferous glands.
An analysis of 32 outbreaks from 1965 to 2022 showed that the main foods involved in oral transmission were homemade fruit juices. But different vector species were identified, and the reservoirs were mainly dogs, rodents, and large American opossums (Didelphis).
The largest oral Chagas outbreak was linked to the consumption of contaminated guava juice in a primary school in Caracas, Venezuela. Nonindustrially produced açaí is a common source of orally acquired Chagas disease in Brazil. In Colombia, Chagas disease has been associated with the consumption of palm wine, sugar cane, and tangerine juice. Other oral transmission routes include consuming meat from wild animals and ingesting blood from infected armadillos, which is related to a traditional medicine practice.
Deadly Yet Easily Treatable
In the outbreak of 119 confirmed and suspected cases in Venezuela, 20.3% required hospitalization, and a 5-year-old child died of acute myocarditis. These percentages differ from those reported in vector transmission, which is asymptomatic in the acute phase for 95%-99% of cases or will only develop a mild febrile illness that resolves on its own.
“Not all cases will present as severe, because depending on the inoculum, there may be individuals with subclinical situations. But any food poisoning that occurs in endemic areas, where food is not properly controlled, and these street foods are associated with processes in jungle areas, raises the possibility that T cruzi is involved and should be considered as a differential diagnosis,» noted Dr. Chuit. “The treatment is highly effective, and people recover quickly.”
“The most important thing about oral transmission of Chagas is that someone infected in this way needs antiparasitic drugs immediately. We can cure them if we treat them immediately,” said Dr. Beatty, adding that treatment is sometimes delayed due to lack of access to appropriate antiparasitic drugs. “Here in the United States and in Latin America, it is quite common for healthcare professionals not to understand the differences between vector, vertical, and oral transmission. By not treating these patients, they become ill quickly.”
Dr. Beatty and Dr. Chuit declared no relevant financial conflicts of interest.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Curbing Antibiotic Use Works
, revealed the fourth joint interagency antimicrobial consumption and resistance analysis report.
The report was published by the European Centre for Disease Prevention and Control, the European Food Safety Authority, and the European Medicines Agency. Its findings were derived from an integrated analysis of the potential relationship between antimicrobial consumption (AMC) by humans and animals and the occurrence of antimicrobial resistance (AMR) using data collected between 2019 and 2021.
A Real Threat
AMR poses a significant threat to public and animal health, causing more than 35,000 deaths annually in the European Union (EU) and the European Economic Area. It also imposes a substantial economic burden on European healthcare systems, amounting to approximately €11.7 billion per year.
To address this challenge, the Council of the European Union recommended concerted and sustained efforts to achieve a 20% reduction in AMC in humans (compared with 2019 levels) and a 50% reduction in food-producing animals (compared with 2018 levels) by 2030. These targets are outlined in the European Commission’s Farm to Fork strategy.
It Really Works
Analysis of the trends of AMC and AMR in Escherichia coli from humans and food-producing animals, conducted for the first time, revealed that the susceptibility of E coli to antimicrobials in humans and animals increases with an overall decrease in the consumption of antibiotics.
Concurrent trends in AMC and AMR from 2014 to 2021 were also assessed. AMC in both human and animal sectors, measured in mg/kg of estimated biomass, was compared at country and European levels. In 2021, human AMC totaled 125.0 mg/kg of biomass, while food-producing animals registered 92.6 mg/kg of biomass.
Over the 2014-2021 period, total AMC in food-producing animals decreased by 44%, while in humans, it remained relatively stable. The consumption of certain antimicrobials was positively associated with resistance to those substances in bacteria from both humans and food-producing animals.
The report also highlighted that E coli resistance is linked in humans to the use of carbapenems, third- and fourth-generation cephalosporins, and quinolones and in food-producing animals to the administration of quinolones, polymyxins, aminopenicillins, and tetracyclines. Further, a connection exists between bacterial resistance in humans and food-producing animals, particularly for bacterial species such as Campylobacter jejuni and C coli.
The findings suggest that measures to reduce AMC in both food-producing animals and humans have been effective in many countries. However, reinforcing these measures is crucial to maintain and further advance reductions in AMC.
More Work
Aligned with the European Commission’s One Health holistic and coordinated approach to managing the human and veterinary sectors together, the European agencies advocate for:
- Sustained efforts to combat AMR at national, EU, and global levels.
- Coordinated surveillance of antibiotic use and AMR in both human and animal sectors.
- Continued research in the field of AMR.
The statistical code used to conduct these analyses was made publicly available in order to support further research analyses.
A version of this article appeared on Medscape.com.
, revealed the fourth joint interagency antimicrobial consumption and resistance analysis report.
The report was published by the European Centre for Disease Prevention and Control, the European Food Safety Authority, and the European Medicines Agency. Its findings were derived from an integrated analysis of the potential relationship between antimicrobial consumption (AMC) by humans and animals and the occurrence of antimicrobial resistance (AMR) using data collected between 2019 and 2021.
A Real Threat
AMR poses a significant threat to public and animal health, causing more than 35,000 deaths annually in the European Union (EU) and the European Economic Area. It also imposes a substantial economic burden on European healthcare systems, amounting to approximately €11.7 billion per year.
To address this challenge, the Council of the European Union recommended concerted and sustained efforts to achieve a 20% reduction in AMC in humans (compared with 2019 levels) and a 50% reduction in food-producing animals (compared with 2018 levels) by 2030. These targets are outlined in the European Commission’s Farm to Fork strategy.
It Really Works
Analysis of the trends of AMC and AMR in Escherichia coli from humans and food-producing animals, conducted for the first time, revealed that the susceptibility of E coli to antimicrobials in humans and animals increases with an overall decrease in the consumption of antibiotics.
Concurrent trends in AMC and AMR from 2014 to 2021 were also assessed. AMC in both human and animal sectors, measured in mg/kg of estimated biomass, was compared at country and European levels. In 2021, human AMC totaled 125.0 mg/kg of biomass, while food-producing animals registered 92.6 mg/kg of biomass.
Over the 2014-2021 period, total AMC in food-producing animals decreased by 44%, while in humans, it remained relatively stable. The consumption of certain antimicrobials was positively associated with resistance to those substances in bacteria from both humans and food-producing animals.
The report also highlighted that E coli resistance is linked in humans to the use of carbapenems, third- and fourth-generation cephalosporins, and quinolones and in food-producing animals to the administration of quinolones, polymyxins, aminopenicillins, and tetracyclines. Further, a connection exists between bacterial resistance in humans and food-producing animals, particularly for bacterial species such as Campylobacter jejuni and C coli.
The findings suggest that measures to reduce AMC in both food-producing animals and humans have been effective in many countries. However, reinforcing these measures is crucial to maintain and further advance reductions in AMC.
More Work
Aligned with the European Commission’s One Health holistic and coordinated approach to managing the human and veterinary sectors together, the European agencies advocate for:
- Sustained efforts to combat AMR at national, EU, and global levels.
- Coordinated surveillance of antibiotic use and AMR in both human and animal sectors.
- Continued research in the field of AMR.
The statistical code used to conduct these analyses was made publicly available in order to support further research analyses.
A version of this article appeared on Medscape.com.
, revealed the fourth joint interagency antimicrobial consumption and resistance analysis report.
The report was published by the European Centre for Disease Prevention and Control, the European Food Safety Authority, and the European Medicines Agency. Its findings were derived from an integrated analysis of the potential relationship between antimicrobial consumption (AMC) by humans and animals and the occurrence of antimicrobial resistance (AMR) using data collected between 2019 and 2021.
A Real Threat
AMR poses a significant threat to public and animal health, causing more than 35,000 deaths annually in the European Union (EU) and the European Economic Area. It also imposes a substantial economic burden on European healthcare systems, amounting to approximately €11.7 billion per year.
To address this challenge, the Council of the European Union recommended concerted and sustained efforts to achieve a 20% reduction in AMC in humans (compared with 2019 levels) and a 50% reduction in food-producing animals (compared with 2018 levels) by 2030. These targets are outlined in the European Commission’s Farm to Fork strategy.
It Really Works
Analysis of the trends of AMC and AMR in Escherichia coli from humans and food-producing animals, conducted for the first time, revealed that the susceptibility of E coli to antimicrobials in humans and animals increases with an overall decrease in the consumption of antibiotics.
Concurrent trends in AMC and AMR from 2014 to 2021 were also assessed. AMC in both human and animal sectors, measured in mg/kg of estimated biomass, was compared at country and European levels. In 2021, human AMC totaled 125.0 mg/kg of biomass, while food-producing animals registered 92.6 mg/kg of biomass.
Over the 2014-2021 period, total AMC in food-producing animals decreased by 44%, while in humans, it remained relatively stable. The consumption of certain antimicrobials was positively associated with resistance to those substances in bacteria from both humans and food-producing animals.
The report also highlighted that E coli resistance is linked in humans to the use of carbapenems, third- and fourth-generation cephalosporins, and quinolones and in food-producing animals to the administration of quinolones, polymyxins, aminopenicillins, and tetracyclines. Further, a connection exists between bacterial resistance in humans and food-producing animals, particularly for bacterial species such as Campylobacter jejuni and C coli.
The findings suggest that measures to reduce AMC in both food-producing animals and humans have been effective in many countries. However, reinforcing these measures is crucial to maintain and further advance reductions in AMC.
More Work
Aligned with the European Commission’s One Health holistic and coordinated approach to managing the human and veterinary sectors together, the European agencies advocate for:
- Sustained efforts to combat AMR at national, EU, and global levels.
- Coordinated surveillance of antibiotic use and AMR in both human and animal sectors.
- Continued research in the field of AMR.
The statistical code used to conduct these analyses was made publicly available in order to support further research analyses.
A version of this article appeared on Medscape.com.
Europe Needs to Get on Top of Its Measles Outbreak
“Measles should be a memory, not a present risk,” Quique Bassat, MBBS, PhD, director general of the Barcelona Institute of Global Health, told this news organization.
That is certainly not the case right now in some parts of Europe.
“What we are seeing currently is an almost 45-fold rise in measles cases in the WHO European Region,” Siddhartha Datta, MD, European regional advisor on vaccine-preventable diseases and immunization for the WHO, told this news organization. “In 2022, there were 940 cases, and in 2023 till November, it was around 42,000 plus. Between 2020 and 2022, we have seen 1.8 million children who have missed their measles vaccine doses.”
Lapses in Vaccinations
The overriding reason for the resurgence of measles is a backslide in vaccination coverage during the COVID-19 pandemic.
“During the COVID pandemic, we had a 5% decrease in coverage for most of the vaccines, and we are still seeing the consequences,” explained Dr. Bassat. “Measles is the perfect example of when you have a small drop of coverage you get outbreaks, as it’s extremely infectious and complicated to control.”
Reported national coverage with the first dose of measles-containing vaccine in the European Region fell from 96% in 2019 to 93% in 2022. Second-dose coverage fell from 92% in 2019 to 91% in 2022.
“You need to have 95% of the population vaccinated if you want herd immunity,” Dr. Bassat said.
Variation Across Europe
The WHO European Region comprises 53 countries, including Russia and some countries in central Asia. Its figures show Kazakhstan had the most recorded cases of measles last year, at more than 13,000, followed by the Russian Federation.
Romania declared a national epidemic in December 2023. Dr. Datta said there have also been outbreaks in Austria and France.
The UK Health Security Agency declared a major incident in January 2024 because of a surge in cases. From October 2023 to January 2024, there were 347 lab-confirmed cases of measles in England, with 127 of these confirmed in January. The West Midlands is an area of particular concern.
“It was not as though everything was rosy before COVID,” said Dr. Datta. “We saw wide variation in the coverage rates before the pandemic. Some countries weren’t doing as well. More particularly between some communities or municipalities, there were wide variations, and COVID-19 exacerbated the inequities in coverage. What we are seeing now is a combination of gaps before and after the pandemic, so it’s a compound problem.”
Belgium has also seen a measles resurgence, but not as many cases as the year before the pandemic. Laura Cornelissen, MD, works at the Belgian Public Health Institute, Sciensano, where she leads a team working on vaccine-preventable diseases.
She told this news organization: “We did observe a significant rise in cases and several clusters in 2023, compared to the very low numbers that were observed during the COVID-19 years. Preliminary figures indicate 85 measles cases for Belgium in 2023, leading to at least 26 hospitalizations. This is compared with eight cases for 2022, seven in 2021, and 47 in 2020; but 480 cases in the pre-pandemic year 2019.”
Sabrina Bacci, MD, head of vaccine-preventable diseases and immunization at the European Centre of Disease Control, told this news organization: “There have been a high number of cases in Romania and smaller outbreaks in other countries. However, there are a number of European countries which haven’t seen measles. Even though we have this variation between the different European countries, the tools to respond to outbreaks are the same.”
Vaccine Hesitance
Vaccine hesitance or even refusal is on the rise in Europe and elsewhere in the world.
“We can see from behavioral insights that, during COVID, people’s trust on vaccines, healthcare systems, and the government in general has gone down,” said Dr. Datta. “There had been skepticism before about the MMR jab causing autism, which was proved wrong, but vaccine skepticism shown throughout COVID is now showing its head in routine vaccine systems.”
The rise of so-called anti-vaxxers and associated fake conspiracy theories, including a mistrust of Big Pharma, hasn’t been helpful for encouraging essential childhood vaccination uptake, like measles, mumps, and rubella (MMR).
But the MMR vaccine backslide does not only originate in the pandemic.
Vanessa Saliba, consultant epidemiologist at the UK Health Security Agency, said: “MMR vaccine coverage has been falling for the last decade, with 1 out of 10 children starting school in England not protected.”
It could be that some people have religious concerns about the use of pork gelatin as a stabilizer in MMR vaccines. An alternative vaccine that does not contain pork gelatin can be requested.
Doctors and others in healthcare have a pivotal role to play when it comes to getting on top of the surges and educating patients, according to Dr. Bacci. “Healthcare professionals are the most precious resource we have, as they are the ones on the frontline explaining the importance of vaccination to their patients. It’s a very important dialogue.”
Clinics and Catch-Up Campaigns
Intensified routine immunization clinics and catch-up campaigns have been established in countries across Europe where they are needed.
Countries with large outbreaks are carrying out case investigations, identifying and vaccinating susceptible contacts, and generally raising awareness and implementing outbreak response immunization.
“Countries are really making good efforts and are systematically catching up the children who have missed their doses in the last 2 years. But the recovery to the 2019 levels has been slow, and more efforts and energy [need] to be put into this. We understand healthcare systems are stretched out from COVID, but this is not the time to lower our guard,” Dr. Datta said.
“Some countries are more proactive than others,” added Dr. Bassat. “Measles is an example of a disease where you typically organize catch-up campaigns. Measles has one of the highest reproductive numbers, as in the absence of preventive measures one infected person infects 14-16 others.”
All countries, even if they haven’t yet experienced measles outbreaks, are being urged by European healthcare authorities to look at potential immunity gaps and address them immediately.
When Will It Get Back to Normal?
“Measles was a disease that was targeted for elimination, but because of these outbreaks, we are seeing it almost everywhere again. We need to be careful and get on top of this,” warned Dr. Bassat.
Dr. Datta said it’s up to member states, decision-makers, healthcare leaders, and parents to come together to raise the immunity profiles of the European population. “Vaccination is a shared responsibility. The tools are effective. We just need to be ahead of the virus, and that is the challenge.”
Dr. Bacci added, “We have to remember we are entering the spring, which is a season when, traditionally, the disease can spread more easily, and it can find its way when people are susceptible. The vaccine is the tool that can help, and we have to act now and make sure it’s offered on time.”
A version of this article appeared on Medscape.com.
“Measles should be a memory, not a present risk,” Quique Bassat, MBBS, PhD, director general of the Barcelona Institute of Global Health, told this news organization.
That is certainly not the case right now in some parts of Europe.
“What we are seeing currently is an almost 45-fold rise in measles cases in the WHO European Region,” Siddhartha Datta, MD, European regional advisor on vaccine-preventable diseases and immunization for the WHO, told this news organization. “In 2022, there were 940 cases, and in 2023 till November, it was around 42,000 plus. Between 2020 and 2022, we have seen 1.8 million children who have missed their measles vaccine doses.”
Lapses in Vaccinations
The overriding reason for the resurgence of measles is a backslide in vaccination coverage during the COVID-19 pandemic.
“During the COVID pandemic, we had a 5% decrease in coverage for most of the vaccines, and we are still seeing the consequences,” explained Dr. Bassat. “Measles is the perfect example of when you have a small drop of coverage you get outbreaks, as it’s extremely infectious and complicated to control.”
Reported national coverage with the first dose of measles-containing vaccine in the European Region fell from 96% in 2019 to 93% in 2022. Second-dose coverage fell from 92% in 2019 to 91% in 2022.
“You need to have 95% of the population vaccinated if you want herd immunity,” Dr. Bassat said.
Variation Across Europe
The WHO European Region comprises 53 countries, including Russia and some countries in central Asia. Its figures show Kazakhstan had the most recorded cases of measles last year, at more than 13,000, followed by the Russian Federation.
Romania declared a national epidemic in December 2023. Dr. Datta said there have also been outbreaks in Austria and France.
The UK Health Security Agency declared a major incident in January 2024 because of a surge in cases. From October 2023 to January 2024, there were 347 lab-confirmed cases of measles in England, with 127 of these confirmed in January. The West Midlands is an area of particular concern.
“It was not as though everything was rosy before COVID,” said Dr. Datta. “We saw wide variation in the coverage rates before the pandemic. Some countries weren’t doing as well. More particularly between some communities or municipalities, there were wide variations, and COVID-19 exacerbated the inequities in coverage. What we are seeing now is a combination of gaps before and after the pandemic, so it’s a compound problem.”
Belgium has also seen a measles resurgence, but not as many cases as the year before the pandemic. Laura Cornelissen, MD, works at the Belgian Public Health Institute, Sciensano, where she leads a team working on vaccine-preventable diseases.
She told this news organization: “We did observe a significant rise in cases and several clusters in 2023, compared to the very low numbers that were observed during the COVID-19 years. Preliminary figures indicate 85 measles cases for Belgium in 2023, leading to at least 26 hospitalizations. This is compared with eight cases for 2022, seven in 2021, and 47 in 2020; but 480 cases in the pre-pandemic year 2019.”
Sabrina Bacci, MD, head of vaccine-preventable diseases and immunization at the European Centre of Disease Control, told this news organization: “There have been a high number of cases in Romania and smaller outbreaks in other countries. However, there are a number of European countries which haven’t seen measles. Even though we have this variation between the different European countries, the tools to respond to outbreaks are the same.”
Vaccine Hesitance
Vaccine hesitance or even refusal is on the rise in Europe and elsewhere in the world.
“We can see from behavioral insights that, during COVID, people’s trust on vaccines, healthcare systems, and the government in general has gone down,” said Dr. Datta. “There had been skepticism before about the MMR jab causing autism, which was proved wrong, but vaccine skepticism shown throughout COVID is now showing its head in routine vaccine systems.”
The rise of so-called anti-vaxxers and associated fake conspiracy theories, including a mistrust of Big Pharma, hasn’t been helpful for encouraging essential childhood vaccination uptake, like measles, mumps, and rubella (MMR).
But the MMR vaccine backslide does not only originate in the pandemic.
Vanessa Saliba, consultant epidemiologist at the UK Health Security Agency, said: “MMR vaccine coverage has been falling for the last decade, with 1 out of 10 children starting school in England not protected.”
It could be that some people have religious concerns about the use of pork gelatin as a stabilizer in MMR vaccines. An alternative vaccine that does not contain pork gelatin can be requested.
Doctors and others in healthcare have a pivotal role to play when it comes to getting on top of the surges and educating patients, according to Dr. Bacci. “Healthcare professionals are the most precious resource we have, as they are the ones on the frontline explaining the importance of vaccination to their patients. It’s a very important dialogue.”
Clinics and Catch-Up Campaigns
Intensified routine immunization clinics and catch-up campaigns have been established in countries across Europe where they are needed.
Countries with large outbreaks are carrying out case investigations, identifying and vaccinating susceptible contacts, and generally raising awareness and implementing outbreak response immunization.
“Countries are really making good efforts and are systematically catching up the children who have missed their doses in the last 2 years. But the recovery to the 2019 levels has been slow, and more efforts and energy [need] to be put into this. We understand healthcare systems are stretched out from COVID, but this is not the time to lower our guard,” Dr. Datta said.
“Some countries are more proactive than others,” added Dr. Bassat. “Measles is an example of a disease where you typically organize catch-up campaigns. Measles has one of the highest reproductive numbers, as in the absence of preventive measures one infected person infects 14-16 others.”
All countries, even if they haven’t yet experienced measles outbreaks, are being urged by European healthcare authorities to look at potential immunity gaps and address them immediately.
When Will It Get Back to Normal?
“Measles was a disease that was targeted for elimination, but because of these outbreaks, we are seeing it almost everywhere again. We need to be careful and get on top of this,” warned Dr. Bassat.
Dr. Datta said it’s up to member states, decision-makers, healthcare leaders, and parents to come together to raise the immunity profiles of the European population. “Vaccination is a shared responsibility. The tools are effective. We just need to be ahead of the virus, and that is the challenge.”
Dr. Bacci added, “We have to remember we are entering the spring, which is a season when, traditionally, the disease can spread more easily, and it can find its way when people are susceptible. The vaccine is the tool that can help, and we have to act now and make sure it’s offered on time.”
A version of this article appeared on Medscape.com.
“Measles should be a memory, not a present risk,” Quique Bassat, MBBS, PhD, director general of the Barcelona Institute of Global Health, told this news organization.
That is certainly not the case right now in some parts of Europe.
“What we are seeing currently is an almost 45-fold rise in measles cases in the WHO European Region,” Siddhartha Datta, MD, European regional advisor on vaccine-preventable diseases and immunization for the WHO, told this news organization. “In 2022, there were 940 cases, and in 2023 till November, it was around 42,000 plus. Between 2020 and 2022, we have seen 1.8 million children who have missed their measles vaccine doses.”
Lapses in Vaccinations
The overriding reason for the resurgence of measles is a backslide in vaccination coverage during the COVID-19 pandemic.
“During the COVID pandemic, we had a 5% decrease in coverage for most of the vaccines, and we are still seeing the consequences,” explained Dr. Bassat. “Measles is the perfect example of when you have a small drop of coverage you get outbreaks, as it’s extremely infectious and complicated to control.”
Reported national coverage with the first dose of measles-containing vaccine in the European Region fell from 96% in 2019 to 93% in 2022. Second-dose coverage fell from 92% in 2019 to 91% in 2022.
“You need to have 95% of the population vaccinated if you want herd immunity,” Dr. Bassat said.
Variation Across Europe
The WHO European Region comprises 53 countries, including Russia and some countries in central Asia. Its figures show Kazakhstan had the most recorded cases of measles last year, at more than 13,000, followed by the Russian Federation.
Romania declared a national epidemic in December 2023. Dr. Datta said there have also been outbreaks in Austria and France.
The UK Health Security Agency declared a major incident in January 2024 because of a surge in cases. From October 2023 to January 2024, there were 347 lab-confirmed cases of measles in England, with 127 of these confirmed in January. The West Midlands is an area of particular concern.
“It was not as though everything was rosy before COVID,” said Dr. Datta. “We saw wide variation in the coverage rates before the pandemic. Some countries weren’t doing as well. More particularly between some communities or municipalities, there were wide variations, and COVID-19 exacerbated the inequities in coverage. What we are seeing now is a combination of gaps before and after the pandemic, so it’s a compound problem.”
Belgium has also seen a measles resurgence, but not as many cases as the year before the pandemic. Laura Cornelissen, MD, works at the Belgian Public Health Institute, Sciensano, where she leads a team working on vaccine-preventable diseases.
She told this news organization: “We did observe a significant rise in cases and several clusters in 2023, compared to the very low numbers that were observed during the COVID-19 years. Preliminary figures indicate 85 measles cases for Belgium in 2023, leading to at least 26 hospitalizations. This is compared with eight cases for 2022, seven in 2021, and 47 in 2020; but 480 cases in the pre-pandemic year 2019.”
Sabrina Bacci, MD, head of vaccine-preventable diseases and immunization at the European Centre of Disease Control, told this news organization: “There have been a high number of cases in Romania and smaller outbreaks in other countries. However, there are a number of European countries which haven’t seen measles. Even though we have this variation between the different European countries, the tools to respond to outbreaks are the same.”
Vaccine Hesitance
Vaccine hesitance or even refusal is on the rise in Europe and elsewhere in the world.
“We can see from behavioral insights that, during COVID, people’s trust on vaccines, healthcare systems, and the government in general has gone down,” said Dr. Datta. “There had been skepticism before about the MMR jab causing autism, which was proved wrong, but vaccine skepticism shown throughout COVID is now showing its head in routine vaccine systems.”
The rise of so-called anti-vaxxers and associated fake conspiracy theories, including a mistrust of Big Pharma, hasn’t been helpful for encouraging essential childhood vaccination uptake, like measles, mumps, and rubella (MMR).
But the MMR vaccine backslide does not only originate in the pandemic.
Vanessa Saliba, consultant epidemiologist at the UK Health Security Agency, said: “MMR vaccine coverage has been falling for the last decade, with 1 out of 10 children starting school in England not protected.”
It could be that some people have religious concerns about the use of pork gelatin as a stabilizer in MMR vaccines. An alternative vaccine that does not contain pork gelatin can be requested.
Doctors and others in healthcare have a pivotal role to play when it comes to getting on top of the surges and educating patients, according to Dr. Bacci. “Healthcare professionals are the most precious resource we have, as they are the ones on the frontline explaining the importance of vaccination to their patients. It’s a very important dialogue.”
Clinics and Catch-Up Campaigns
Intensified routine immunization clinics and catch-up campaigns have been established in countries across Europe where they are needed.
Countries with large outbreaks are carrying out case investigations, identifying and vaccinating susceptible contacts, and generally raising awareness and implementing outbreak response immunization.
“Countries are really making good efforts and are systematically catching up the children who have missed their doses in the last 2 years. But the recovery to the 2019 levels has been slow, and more efforts and energy [need] to be put into this. We understand healthcare systems are stretched out from COVID, but this is not the time to lower our guard,” Dr. Datta said.
“Some countries are more proactive than others,” added Dr. Bassat. “Measles is an example of a disease where you typically organize catch-up campaigns. Measles has one of the highest reproductive numbers, as in the absence of preventive measures one infected person infects 14-16 others.”
All countries, even if they haven’t yet experienced measles outbreaks, are being urged by European healthcare authorities to look at potential immunity gaps and address them immediately.
When Will It Get Back to Normal?
“Measles was a disease that was targeted for elimination, but because of these outbreaks, we are seeing it almost everywhere again. We need to be careful and get on top of this,” warned Dr. Bassat.
Dr. Datta said it’s up to member states, decision-makers, healthcare leaders, and parents to come together to raise the immunity profiles of the European population. “Vaccination is a shared responsibility. The tools are effective. We just need to be ahead of the virus, and that is the challenge.”
Dr. Bacci added, “We have to remember we are entering the spring, which is a season when, traditionally, the disease can spread more easily, and it can find its way when people are susceptible. The vaccine is the tool that can help, and we have to act now and make sure it’s offered on time.”
A version of this article appeared on Medscape.com.