What’s Eating You? Sand Flies

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What’s Eating You? Sand Flies

Identification

Phlebotomine sand flies are the only member of the Psychodidae family that are capable of taking blood.1 The mouthparts of the sand fly are toothed distally, and the maxilla and mandible are utilized in a sawtooth fashion to take a bloodmeal.2 The flies are very small (ie, only 1.5–3.5 mm in length), which makes their identification difficult.1 Sand flies can be distinguished by the appearance of their wings, which often are covered in hair and extend across the back in a V shape.3 The adult sand fly is hairy with a 6- to 8-segmented abdomen, and the color can range from gray to yellow to brown.2 Phlebotomine sand flies can be further identified by their long antennae, dark eyes, and small heads (Figure).2

Sand fly anatomy.

As is the case with all Diptera, the sand fly goes through 4 complete life stages from egg to larva to pupa to adult.3 Female sand flies will lay their eggs following a blood meal and have been found to take multiple blood meals in a single cycle.2 On average, the eggs will hatch in 6 to 17 days but are temperature dependent.3 The subsequent larvae and pupa stages last 20 to 30 days and 6 to 13 days, respectively.1 The larvae are white in color with short antennae and dark heads.4 Sand flies prefer to lay their eggs in areas where adequate resting places are available and where their larvae will thrive.4,5 The larvae require warm moist environments to succeed and thus are commonly found in animal burrows.3 Once fully developed, the adult sand fly can live up to 6 weeks.2

Sand Fly Vector

Although it is more common in rural forested areas, the sand fly also can be found in urban areas, including heavily populated cities in Brazil.6 Sand flies are most active during hot humid seasons but depending on the local climate may remain active year-round.1,7 For example, in tropical regions of Asia, the number of sand flies increases substantially during the monsoon season compared to the dry season.2 Phlebotomine sand flies are most active at dusk and during the night5 but may become agitated during the daytime if their environment is disturbed.1

Host selection usually is broad and includes a wide variety of vertebrates.2 In the United States, host species are thought to include small rodents, foxes, armadillos, and opossums.8 One study found that visceral leishmaniasis in foxhounds is able to develop fully in sand flies, thus posing an emerging risk to the American population.9

Distribution

The Phlebotominae family contains approximately 700 different species of sand flies but only 21 are known vectors of disease.10 The great majority belong to 1 of 3 genuses: Phlebotomus, Sergentomyia, and Lutzomyia.11 The vectors are commonly divided into Old World species, dominated by the Phlebotomus genus, and New World species, which exclusively refers to the Lutzomyia genus.3 The Old World and New World distinction helps to classify the various vectors and subsequently the diseases they transmit. Old World refers to those vectors found in Southwest and Central Asia, the Indian subcontinent, the Middle East, and East Africa, as well as Southern Europe.6 New World refers to vectors found predominantly in Brazil and other parts of Latin America but also Mexico and the United States.6 Sand flies are found to be endemic in 90 countries and on each continent, except Australia.5 Although the vector can be found in a variety of environments, sand flies prefer moist environments that typify tropical and subtropical climates, thus it is not surprising that the highest diversity of Phlebotominae in the world can be found in the Amazon basin.12

 

 

Disease Transmission

Leishmania refers to a genus of intracellular protozoa found in both the Old World and the New World that causes a variety of clinical syndromes.5 Approximately 20 Leishmania species are known to cause human disease that includes localized cutaneous, diffuse cutaneous, mucosal cutaneous, and visceral infections.13 Cases of all forms of leishmaniasis worldwide have increased rapidly over the last few decades from multiple factors including war in endemic regions, increased numbers of immunodeficient individuals, and increased travel to endemic areas.14 In the United States, leishmaniasis is caused by both imported and autochthonous forms of transmission and often mirrors recent travel and immigration patterns.14,15

Sand flies also serve as vectors for sandfly fever, also known as Pappataci fever. Although sandfly fever commonly causes a mild febrile illness, it has been shown to be a considerable cause of aseptic meningitis.16 A number of novel Phleboviruses have been isolated as causes of sandfly fever, including Massilia virus, Granada virus, and Punique virus.16-18 A form of sandfly fever caused by the Toscana virus has a predilection for the nervous system and can cause encephalitis.19 Sandfly fever can be found in both the Old World and New World and thus poses a global risk.2 Additionally, Phlebotominae also have been found to transmit the Changuinola virus, a type of bunyavirus that is known to cause febrile illness in Panama.20 Vesicular stomatitis, also carried by sand flies, is a known cause of febrile disease in North and South America, including the United States.2 In 2013, the Niakha virus, a novel type of Rhabdoviridae, was isolated from Phlebotominae in Senegal.21 The sand fly is noted to transmit another type of Rhabdoviridae in India and Africa, known as the Chandipura virus.22 Although originally thought to cause mild febrile disease, it was the primary cause of multiple outbreaks of fatal encephalitis in India in 200323,24 and again in 2012.22

Sand flies also are known to serve as vectors for the bacterium Bartonella bacilliformis, which is responsible for bartonellosis.25 The disease is divided into 2 forms, which can occur separately or in succession, and is endemic to the Andes region of Peru, Ecuador, and Colombia. The first form is Oroya fever, an acute febrile hemolytic anemia that is fatal in 40% to 88% of cases without intervention.25 This bacterium also causes verruga peruana, an endemic form of bacillary angiomatosis that can persist for years.2 Two reports suggested that bartonellosis also can be caused by Bartonella rochalimae and Candidatus Bartonella ancashi.26,27

Vector Control

Prevention is key to reducing the risk of the various diseases caused by the Phlebotominae vector. Vector control often falls into a few categories, including residual sprays, barriers, and topical repellants.3 It appears that residual sprays applied to houses and animal shelters are the most utilized and effective form of control, with the pyrethroid insecticides having the highest sand fly–specific toxicity.3,28 Insecticides also have been applied to animal burrows where sand flies are known to reproduce; one study in Kenya showed a 90% reduction in the sand fly population following treatment of termite and animal burrows with a pyrethroid spray.29 Studies by Perich et al30,31 in 1995 and 2003 showed that using barrier sprays can be an effective protective measure. The investigators applied a 100-m barrier using a pyrethroid spray on vegetation and reported a notable decrease in sand flies for over an 80-day period.30,31

For personal protection, barrier methods are important adjunct methods of preventing individual exposures. Due to the small size of sand flies, ordinary bed nets are not effective and those treated with insecticides should be used,15 which may ultimately prove to be the most sustainable way to prevent sand fly–borne disease.32 Protective attire also should be worn, as sand flies are not able to penetrate clothing.2 N,N-diethyl-meta-toluamide (DEET)–based repellants should be applied to exposed skin.15 Finally, it is important to avoid exposure from dusk to dawn when sand flies are most active.15

Rise in Autochthonous Cutaneous Leishmaniasis in the United States

With the increased amount of worldwide tourism, especially to endemic areas, providers will continue to see rising numbers of leishmaniasis in the United States. It is difficult to determine the incidence of the disease in the United States, but one study has shown that leishmaniasis accounts for 143 of every 1000 dermatologic diseases acquired by South American tourists.33,34 In addition, the number of autochthonous cases reported in the United States continues to grow. Although only 29 cases were reported between 1903 and 1996, 13 cases were reported between 2000 and 2008.35 Another report in 2013 described an additional 3 cases in the states of Texas and Oklahoma.35 The cases have continued to move in a northeasterly pattern, suggesting a possible shift in the location of sand fly populations. Each of these cases in which a specific species of Leishmania was identified showed transmission of Leishmania mexicana.35 Most cases of cutaneous disease have occurred in Texas and Oklahoma. The first known case outside of this region was reported in 2014 in North Dakota.8 Leishmania donovani, brought into the United States with European foxhounds, also is spreading.8 One species of sand fly, Leishmania shannoni, has now been discovered in 16 states,36-42 where it serves as a potential vector for L mexicana.43,44

References
  1. European Centre for Disease Prevention and Control. Phlebotomine sand flies—factsheet for experts. https://ecdc.europa.eu/en/disease-vectors/facts/phlebotomine-sand-flies. Accessed January 24, 2018.
  2. Durden L, Mullen G. Moth flies and sand flies (Psychodidae). Medical And Veterinary Entomology. San Diego, CA: Academic Press; 2002.
  3. Claborn DM. The biology and control of leishmaniasis vectors. J Glob Infect Dis. 2010;2:127-134.
  4. Young DG, Duncan MA. Guide to the identification and geographic distribution of Lutzomyia sand flies in Mexico, the West Indies, Central and South America (Diptera: Psychodidae). Mem Am Entomol Inst. 1994;54:1-881.
  5. Wolff K, Johnson R, Saavedra AP. Systemic parasitic infections. In: Wolff K, Johnson R, Saavedra AP, eds. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 7th ed. New York, NY: McGraw-Hill; 2013.
  6. Herwaldt BL, Magill AJ. Leishmaniasis, visceral. In: Centers for Disease Control and Prevention. CDC Yellow Book. https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/leishmaniasis-visceral. Updated May 31, 2017. Accessed January 24, 2018.
  7. Lawyer PG, Perkins PV. Leishmaniasis and trypanosomiasis. In: Eldridge BF, Edman JD, eds. Medical Entomology. Dordrecht, Netherlands: Kluwer Academic; 2000.
  8. Douvoyiannis M, Khromachou T, Byers N, et al. Cutaneous leishmaniasis in North Dakota. Clin Infect Dis. 2014;59:73-75.
  9. Schaut RG, Robles-Murguia M, Juelsgaard R, et al. Vectorborne transmission of Leishmania infantum from hounds, United States. Emerg Infect Dis. 2015;21:2209-2212 .
  10. Hennings C, Bloch K, Miller J, et al. What is your diagnosis? New World cutaneous leishmaniasis. Cutis. 2015;95:208, 229-230.
  11. Lewis DJ. Phlebotomid sandflies. Bull World Health Organ. 1971;44:535-551.
  12. Alves VR, Freitas RA, Santos FL, et al. Sand flies (Diptera, Psychodidae, Phlebotominae) from Central Amazonia and four new records for the Amazonas state, Brazil. Rev Bras Entomol. 2012;56:220-227.
  13. Hashiguchi Y, Gomez EL, Kato H, et al. Diffuse and disseminated cutaneous leishmaniasis: clinical cases experienced in Ecuador and a brief review. Trop Med Health. 2016;44:2.
  14. Shaw J. The leishmaniases—survival and expansion in a changing world. a mini-review. Mem Inst Oswaldo Cruz. 2007;102:541-547.
  15. Centers for Disease Control and Prevention. CDC Health Information for International Travel 2016. New York, NY: Oxford University Press; 2016.
  16. Zhioua E, Moureau G, Chelbi I, et al. Punique virus, a novel phlebovirus, related to sandfly fever Naples virus, isolated from sandflies collected in Tunisia. J Gen Virol. 2010;91:1275-1283.
  17. Charrel RN, Moureau G, Temmam S, et al. Massilia virus, a novel phlebovirus (Bunyaviridae) isolated from sandflies in the Mediterranean. Vector Borne Zoonotic Dis. 2009;9:519-530.
  18. Collao X, Palacios G, de Ory F, et al. SecoGranada virus: a natural phlebovirus reassortant of the sandfly fever Naples serocomplex with low seroprevalence in humans. Am J Trop Med Hyg. 2010;83:760-765.
  19. Alkan C, Bichaud L, de Lamballerie X, et al. Sandfly-borne phleboviruses of Eurasia and Africa: epidemiology, genetic diversity, geographic range, control measures. Antiviral Res. 2013;100:54-74.
  20. Travassos da Rosa AP, Tesh RB, Pinheiro FP, et al. Characterization of the Changuinola serogroup viruses (Reoviridae: Orbivirus). Intervirology. 1984;21:38-49.
  21. Vasilakis N, Widen S, Mayer SV, et al. Niakha virus: a novel member of the family Rhabdoviridae isolated from phlebotomine sandflies in Senegal. Virology. 2013;444:80-89.
  22. Sudeep AB, Bondre VP, Gurav YK, et al. Isolation of Chandipura virus (Vesiculovirus: Rhabdoviridae) from Sergentomyia species of sandflies from Nagpur, Maharashtra, India. Indian J Med Res. 2014;139:769-772.
  23. Rao BL, Basu A, Wairagkar NS, et al. A large outbreak of acute encephalitis with high fatality rate in children in Andhra Pradesh, India, in 2003, associated with Chandipura virus. Lancet. 2004;364:869-874.
  24. Chadha MS, Arankalle VA, Jadi RS, et al. An outbreak of Chandipura virus encephalitis in the eastern districts of Gujarat state, India. Am J Trop Med Hyg. 2005;73:566-570.
  25. Minnick MF, Anderson BE, Lima A, et al. Oroya fever and verruga peruana: bartonelloses unique to South America. PLoS Negl Trop Dis. 2014;8:E2919.
  26. Eremeeva ME, Gerns HL, Lydy SL, et al. Bacteremia, fever, and splenomegaly caused by a newly recognized bartonella species. N Engl J Med. 2007;356:2381-2387.
  27. Blazes DL, Mullins K, Smoak BL, et al. Novel bartonella agent as cause of verruga peruana. Emerg Infect Dis. 2013;19:1111-1114.
  28. Tetreault GE, Zayed AB, Hanafi HA, et al. Suseptibility of sand flies to selected insecticides in North Africa and the Middle East. J Am Mosq Control Assoc. 2001;17:23-27.
  29. Robert LL, Perich MJ. Phlebotomine sand fly (Diptera:Psychodidae) control using a residual pyrethroid insecticide. J Am Mosq Control Assoc. 1995;11:195-199.
  30. Perich MJ, Hoch AL, Rizzo N, et al. Insecticide barrier spraying for the control of sandfly vectors of cutaneous leishmaniasis in rural Guatemala. Am J Trop Med Hyg. 1995;52:485-488.
  31. Perich MJ, Kardec A, Braga IA, et al. Field evaluation of a lethal ovitrap against dengue vectors in Brazil. Med Vet Entomol. 2003;17:205-210.
  32. Alexander B, Maroli M. Control of phlebotomine sandflies. Medical and Veterinary Entomology. 2003;17:1-18.
  33. Freedman DO, Weld LH, Kozarsky PE, et al. Spectrum of disease and relation to place of exposure among ill returned travelers. New Engl J Med. 2006;354:119-130.
  34. Ergen EN, King AH, Tull M. Cutaneous leishmaniasis: an emerging infectious disease in travelers. Cutis. 2015;96:E22-E26.
  35. Clarke CF, Bradley KK, Wright JH, et al. Emergence of autochthonous cutaneous leishmaniasis in northeastern Texas and southeastern Oklahoma. Am J Trop Med Hyg. 2013;88:157-161.
  36. Young DG, Perkins PV. Phlebotomine sand flies of North America (Diptera:Psychodidae). Mosq News. 1984;44:263-304.
  37. Comer JA, Tesh RB, Modi GB, et al. Vesicular stomatitis virus, New Jersey serotype: replication in and transmission by Lutzomyia shannoni (Diptera: Psychodidae). Am J Trop Med Hyg. 1990;42:483-490.
  38. Haddow A, Curler G, Moulton J. New records of Lutzomyia shannoni and Lutzomyia vexator (Diptera: Psychodidae) in eastern Tennessee. J Vector Ecol. 2008;33:393-396.
  39. Claborn DM, Rowton ED, Lawyer PG, et al. Species diversity and relative abundance of phlebotomine sand flies (Diptera: Psychodidae) on three Army installations in the southern United States and susceptibility of a domestic sand fly to infection with Old World Leishmania major. Mil Med. 2009;174:1203-1208.
  40. Minter L, Kovacic B, Claborn DM, et al. New state records for Lutzomyia shannoni (Dyar) and Lutzomyia vexator (Coquillett). J Med Entomol. 2009;46:965-968.
  41. Price DC, Gunther DE, Gaugler R. First collection records of phlebotomine sand flies (Diptera: Psychodidae) from New Jersey. J Med Entomol. 2011;48:476-478.
  42. Weng J, Young SL, Gordon DM, et al. First report of phlebotomine sand flies (Diptera: Psychodidae) in Kansas and Missouri, and a PCR method to distinguish Lutzomyia shannoni from Lutzomyia vexator. J Med Entomol. 2012;49:1460-1465.
  43. Pech-May A, Escobedo-Ortegón FJ, Berzunza-Cruz M, et al. Incrimination of four sandfly species previously unrecognized as vectors of leishmania parasites in Mexico. Med Vet Entomol. 2010;24:150-161.
  44. González C, Rebollar-Téllez EA, Ibáñez-Bernal S, et al. Current knowledge of leishmania vectors in Mexico: how geographic distributions of species relate to transmission areas. Am J Trop Med Hyg. 2011;85:839-846.
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Dr. Willenbrink is from the Transitional Year Program, Spartanburg Regional Medical Center, South Carolina. Dr. Elston is from the Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston.

The authors report no conflict of interest.

The image is in the public domain.

Correspondence: Tyler J. Willenbrink, MD, Transitional Year Program, 101 E Wood St, Spartanburg, SC 29303 (T.J.Willenbrink@gmail.com).

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Correspondence: Tyler J. Willenbrink, MD, Transitional Year Program, 101 E Wood St, Spartanburg, SC 29303 (T.J.Willenbrink@gmail.com).

Author and Disclosure Information

Dr. Willenbrink is from the Transitional Year Program, Spartanburg Regional Medical Center, South Carolina. Dr. Elston is from the Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston.

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The image is in the public domain.

Correspondence: Tyler J. Willenbrink, MD, Transitional Year Program, 101 E Wood St, Spartanburg, SC 29303 (T.J.Willenbrink@gmail.com).

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Identification

Phlebotomine sand flies are the only member of the Psychodidae family that are capable of taking blood.1 The mouthparts of the sand fly are toothed distally, and the maxilla and mandible are utilized in a sawtooth fashion to take a bloodmeal.2 The flies are very small (ie, only 1.5–3.5 mm in length), which makes their identification difficult.1 Sand flies can be distinguished by the appearance of their wings, which often are covered in hair and extend across the back in a V shape.3 The adult sand fly is hairy with a 6- to 8-segmented abdomen, and the color can range from gray to yellow to brown.2 Phlebotomine sand flies can be further identified by their long antennae, dark eyes, and small heads (Figure).2

Sand fly anatomy.

As is the case with all Diptera, the sand fly goes through 4 complete life stages from egg to larva to pupa to adult.3 Female sand flies will lay their eggs following a blood meal and have been found to take multiple blood meals in a single cycle.2 On average, the eggs will hatch in 6 to 17 days but are temperature dependent.3 The subsequent larvae and pupa stages last 20 to 30 days and 6 to 13 days, respectively.1 The larvae are white in color with short antennae and dark heads.4 Sand flies prefer to lay their eggs in areas where adequate resting places are available and where their larvae will thrive.4,5 The larvae require warm moist environments to succeed and thus are commonly found in animal burrows.3 Once fully developed, the adult sand fly can live up to 6 weeks.2

Sand Fly Vector

Although it is more common in rural forested areas, the sand fly also can be found in urban areas, including heavily populated cities in Brazil.6 Sand flies are most active during hot humid seasons but depending on the local climate may remain active year-round.1,7 For example, in tropical regions of Asia, the number of sand flies increases substantially during the monsoon season compared to the dry season.2 Phlebotomine sand flies are most active at dusk and during the night5 but may become agitated during the daytime if their environment is disturbed.1

Host selection usually is broad and includes a wide variety of vertebrates.2 In the United States, host species are thought to include small rodents, foxes, armadillos, and opossums.8 One study found that visceral leishmaniasis in foxhounds is able to develop fully in sand flies, thus posing an emerging risk to the American population.9

Distribution

The Phlebotominae family contains approximately 700 different species of sand flies but only 21 are known vectors of disease.10 The great majority belong to 1 of 3 genuses: Phlebotomus, Sergentomyia, and Lutzomyia.11 The vectors are commonly divided into Old World species, dominated by the Phlebotomus genus, and New World species, which exclusively refers to the Lutzomyia genus.3 The Old World and New World distinction helps to classify the various vectors and subsequently the diseases they transmit. Old World refers to those vectors found in Southwest and Central Asia, the Indian subcontinent, the Middle East, and East Africa, as well as Southern Europe.6 New World refers to vectors found predominantly in Brazil and other parts of Latin America but also Mexico and the United States.6 Sand flies are found to be endemic in 90 countries and on each continent, except Australia.5 Although the vector can be found in a variety of environments, sand flies prefer moist environments that typify tropical and subtropical climates, thus it is not surprising that the highest diversity of Phlebotominae in the world can be found in the Amazon basin.12

 

 

Disease Transmission

Leishmania refers to a genus of intracellular protozoa found in both the Old World and the New World that causes a variety of clinical syndromes.5 Approximately 20 Leishmania species are known to cause human disease that includes localized cutaneous, diffuse cutaneous, mucosal cutaneous, and visceral infections.13 Cases of all forms of leishmaniasis worldwide have increased rapidly over the last few decades from multiple factors including war in endemic regions, increased numbers of immunodeficient individuals, and increased travel to endemic areas.14 In the United States, leishmaniasis is caused by both imported and autochthonous forms of transmission and often mirrors recent travel and immigration patterns.14,15

Sand flies also serve as vectors for sandfly fever, also known as Pappataci fever. Although sandfly fever commonly causes a mild febrile illness, it has been shown to be a considerable cause of aseptic meningitis.16 A number of novel Phleboviruses have been isolated as causes of sandfly fever, including Massilia virus, Granada virus, and Punique virus.16-18 A form of sandfly fever caused by the Toscana virus has a predilection for the nervous system and can cause encephalitis.19 Sandfly fever can be found in both the Old World and New World and thus poses a global risk.2 Additionally, Phlebotominae also have been found to transmit the Changuinola virus, a type of bunyavirus that is known to cause febrile illness in Panama.20 Vesicular stomatitis, also carried by sand flies, is a known cause of febrile disease in North and South America, including the United States.2 In 2013, the Niakha virus, a novel type of Rhabdoviridae, was isolated from Phlebotominae in Senegal.21 The sand fly is noted to transmit another type of Rhabdoviridae in India and Africa, known as the Chandipura virus.22 Although originally thought to cause mild febrile disease, it was the primary cause of multiple outbreaks of fatal encephalitis in India in 200323,24 and again in 2012.22

Sand flies also are known to serve as vectors for the bacterium Bartonella bacilliformis, which is responsible for bartonellosis.25 The disease is divided into 2 forms, which can occur separately or in succession, and is endemic to the Andes region of Peru, Ecuador, and Colombia. The first form is Oroya fever, an acute febrile hemolytic anemia that is fatal in 40% to 88% of cases without intervention.25 This bacterium also causes verruga peruana, an endemic form of bacillary angiomatosis that can persist for years.2 Two reports suggested that bartonellosis also can be caused by Bartonella rochalimae and Candidatus Bartonella ancashi.26,27

Vector Control

Prevention is key to reducing the risk of the various diseases caused by the Phlebotominae vector. Vector control often falls into a few categories, including residual sprays, barriers, and topical repellants.3 It appears that residual sprays applied to houses and animal shelters are the most utilized and effective form of control, with the pyrethroid insecticides having the highest sand fly–specific toxicity.3,28 Insecticides also have been applied to animal burrows where sand flies are known to reproduce; one study in Kenya showed a 90% reduction in the sand fly population following treatment of termite and animal burrows with a pyrethroid spray.29 Studies by Perich et al30,31 in 1995 and 2003 showed that using barrier sprays can be an effective protective measure. The investigators applied a 100-m barrier using a pyrethroid spray on vegetation and reported a notable decrease in sand flies for over an 80-day period.30,31

For personal protection, barrier methods are important adjunct methods of preventing individual exposures. Due to the small size of sand flies, ordinary bed nets are not effective and those treated with insecticides should be used,15 which may ultimately prove to be the most sustainable way to prevent sand fly–borne disease.32 Protective attire also should be worn, as sand flies are not able to penetrate clothing.2 N,N-diethyl-meta-toluamide (DEET)–based repellants should be applied to exposed skin.15 Finally, it is important to avoid exposure from dusk to dawn when sand flies are most active.15

Rise in Autochthonous Cutaneous Leishmaniasis in the United States

With the increased amount of worldwide tourism, especially to endemic areas, providers will continue to see rising numbers of leishmaniasis in the United States. It is difficult to determine the incidence of the disease in the United States, but one study has shown that leishmaniasis accounts for 143 of every 1000 dermatologic diseases acquired by South American tourists.33,34 In addition, the number of autochthonous cases reported in the United States continues to grow. Although only 29 cases were reported between 1903 and 1996, 13 cases were reported between 2000 and 2008.35 Another report in 2013 described an additional 3 cases in the states of Texas and Oklahoma.35 The cases have continued to move in a northeasterly pattern, suggesting a possible shift in the location of sand fly populations. Each of these cases in which a specific species of Leishmania was identified showed transmission of Leishmania mexicana.35 Most cases of cutaneous disease have occurred in Texas and Oklahoma. The first known case outside of this region was reported in 2014 in North Dakota.8 Leishmania donovani, brought into the United States with European foxhounds, also is spreading.8 One species of sand fly, Leishmania shannoni, has now been discovered in 16 states,36-42 where it serves as a potential vector for L mexicana.43,44

Identification

Phlebotomine sand flies are the only member of the Psychodidae family that are capable of taking blood.1 The mouthparts of the sand fly are toothed distally, and the maxilla and mandible are utilized in a sawtooth fashion to take a bloodmeal.2 The flies are very small (ie, only 1.5–3.5 mm in length), which makes their identification difficult.1 Sand flies can be distinguished by the appearance of their wings, which often are covered in hair and extend across the back in a V shape.3 The adult sand fly is hairy with a 6- to 8-segmented abdomen, and the color can range from gray to yellow to brown.2 Phlebotomine sand flies can be further identified by their long antennae, dark eyes, and small heads (Figure).2

Sand fly anatomy.

As is the case with all Diptera, the sand fly goes through 4 complete life stages from egg to larva to pupa to adult.3 Female sand flies will lay their eggs following a blood meal and have been found to take multiple blood meals in a single cycle.2 On average, the eggs will hatch in 6 to 17 days but are temperature dependent.3 The subsequent larvae and pupa stages last 20 to 30 days and 6 to 13 days, respectively.1 The larvae are white in color with short antennae and dark heads.4 Sand flies prefer to lay their eggs in areas where adequate resting places are available and where their larvae will thrive.4,5 The larvae require warm moist environments to succeed and thus are commonly found in animal burrows.3 Once fully developed, the adult sand fly can live up to 6 weeks.2

Sand Fly Vector

Although it is more common in rural forested areas, the sand fly also can be found in urban areas, including heavily populated cities in Brazil.6 Sand flies are most active during hot humid seasons but depending on the local climate may remain active year-round.1,7 For example, in tropical regions of Asia, the number of sand flies increases substantially during the monsoon season compared to the dry season.2 Phlebotomine sand flies are most active at dusk and during the night5 but may become agitated during the daytime if their environment is disturbed.1

Host selection usually is broad and includes a wide variety of vertebrates.2 In the United States, host species are thought to include small rodents, foxes, armadillos, and opossums.8 One study found that visceral leishmaniasis in foxhounds is able to develop fully in sand flies, thus posing an emerging risk to the American population.9

Distribution

The Phlebotominae family contains approximately 700 different species of sand flies but only 21 are known vectors of disease.10 The great majority belong to 1 of 3 genuses: Phlebotomus, Sergentomyia, and Lutzomyia.11 The vectors are commonly divided into Old World species, dominated by the Phlebotomus genus, and New World species, which exclusively refers to the Lutzomyia genus.3 The Old World and New World distinction helps to classify the various vectors and subsequently the diseases they transmit. Old World refers to those vectors found in Southwest and Central Asia, the Indian subcontinent, the Middle East, and East Africa, as well as Southern Europe.6 New World refers to vectors found predominantly in Brazil and other parts of Latin America but also Mexico and the United States.6 Sand flies are found to be endemic in 90 countries and on each continent, except Australia.5 Although the vector can be found in a variety of environments, sand flies prefer moist environments that typify tropical and subtropical climates, thus it is not surprising that the highest diversity of Phlebotominae in the world can be found in the Amazon basin.12

 

 

Disease Transmission

Leishmania refers to a genus of intracellular protozoa found in both the Old World and the New World that causes a variety of clinical syndromes.5 Approximately 20 Leishmania species are known to cause human disease that includes localized cutaneous, diffuse cutaneous, mucosal cutaneous, and visceral infections.13 Cases of all forms of leishmaniasis worldwide have increased rapidly over the last few decades from multiple factors including war in endemic regions, increased numbers of immunodeficient individuals, and increased travel to endemic areas.14 In the United States, leishmaniasis is caused by both imported and autochthonous forms of transmission and often mirrors recent travel and immigration patterns.14,15

Sand flies also serve as vectors for sandfly fever, also known as Pappataci fever. Although sandfly fever commonly causes a mild febrile illness, it has been shown to be a considerable cause of aseptic meningitis.16 A number of novel Phleboviruses have been isolated as causes of sandfly fever, including Massilia virus, Granada virus, and Punique virus.16-18 A form of sandfly fever caused by the Toscana virus has a predilection for the nervous system and can cause encephalitis.19 Sandfly fever can be found in both the Old World and New World and thus poses a global risk.2 Additionally, Phlebotominae also have been found to transmit the Changuinola virus, a type of bunyavirus that is known to cause febrile illness in Panama.20 Vesicular stomatitis, also carried by sand flies, is a known cause of febrile disease in North and South America, including the United States.2 In 2013, the Niakha virus, a novel type of Rhabdoviridae, was isolated from Phlebotominae in Senegal.21 The sand fly is noted to transmit another type of Rhabdoviridae in India and Africa, known as the Chandipura virus.22 Although originally thought to cause mild febrile disease, it was the primary cause of multiple outbreaks of fatal encephalitis in India in 200323,24 and again in 2012.22

Sand flies also are known to serve as vectors for the bacterium Bartonella bacilliformis, which is responsible for bartonellosis.25 The disease is divided into 2 forms, which can occur separately or in succession, and is endemic to the Andes region of Peru, Ecuador, and Colombia. The first form is Oroya fever, an acute febrile hemolytic anemia that is fatal in 40% to 88% of cases without intervention.25 This bacterium also causes verruga peruana, an endemic form of bacillary angiomatosis that can persist for years.2 Two reports suggested that bartonellosis also can be caused by Bartonella rochalimae and Candidatus Bartonella ancashi.26,27

Vector Control

Prevention is key to reducing the risk of the various diseases caused by the Phlebotominae vector. Vector control often falls into a few categories, including residual sprays, barriers, and topical repellants.3 It appears that residual sprays applied to houses and animal shelters are the most utilized and effective form of control, with the pyrethroid insecticides having the highest sand fly–specific toxicity.3,28 Insecticides also have been applied to animal burrows where sand flies are known to reproduce; one study in Kenya showed a 90% reduction in the sand fly population following treatment of termite and animal burrows with a pyrethroid spray.29 Studies by Perich et al30,31 in 1995 and 2003 showed that using barrier sprays can be an effective protective measure. The investigators applied a 100-m barrier using a pyrethroid spray on vegetation and reported a notable decrease in sand flies for over an 80-day period.30,31

For personal protection, barrier methods are important adjunct methods of preventing individual exposures. Due to the small size of sand flies, ordinary bed nets are not effective and those treated with insecticides should be used,15 which may ultimately prove to be the most sustainable way to prevent sand fly–borne disease.32 Protective attire also should be worn, as sand flies are not able to penetrate clothing.2 N,N-diethyl-meta-toluamide (DEET)–based repellants should be applied to exposed skin.15 Finally, it is important to avoid exposure from dusk to dawn when sand flies are most active.15

Rise in Autochthonous Cutaneous Leishmaniasis in the United States

With the increased amount of worldwide tourism, especially to endemic areas, providers will continue to see rising numbers of leishmaniasis in the United States. It is difficult to determine the incidence of the disease in the United States, but one study has shown that leishmaniasis accounts for 143 of every 1000 dermatologic diseases acquired by South American tourists.33,34 In addition, the number of autochthonous cases reported in the United States continues to grow. Although only 29 cases were reported between 1903 and 1996, 13 cases were reported between 2000 and 2008.35 Another report in 2013 described an additional 3 cases in the states of Texas and Oklahoma.35 The cases have continued to move in a northeasterly pattern, suggesting a possible shift in the location of sand fly populations. Each of these cases in which a specific species of Leishmania was identified showed transmission of Leishmania mexicana.35 Most cases of cutaneous disease have occurred in Texas and Oklahoma. The first known case outside of this region was reported in 2014 in North Dakota.8 Leishmania donovani, brought into the United States with European foxhounds, also is spreading.8 One species of sand fly, Leishmania shannoni, has now been discovered in 16 states,36-42 where it serves as a potential vector for L mexicana.43,44

References
  1. European Centre for Disease Prevention and Control. Phlebotomine sand flies—factsheet for experts. https://ecdc.europa.eu/en/disease-vectors/facts/phlebotomine-sand-flies. Accessed January 24, 2018.
  2. Durden L, Mullen G. Moth flies and sand flies (Psychodidae). Medical And Veterinary Entomology. San Diego, CA: Academic Press; 2002.
  3. Claborn DM. The biology and control of leishmaniasis vectors. J Glob Infect Dis. 2010;2:127-134.
  4. Young DG, Duncan MA. Guide to the identification and geographic distribution of Lutzomyia sand flies in Mexico, the West Indies, Central and South America (Diptera: Psychodidae). Mem Am Entomol Inst. 1994;54:1-881.
  5. Wolff K, Johnson R, Saavedra AP. Systemic parasitic infections. In: Wolff K, Johnson R, Saavedra AP, eds. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 7th ed. New York, NY: McGraw-Hill; 2013.
  6. Herwaldt BL, Magill AJ. Leishmaniasis, visceral. In: Centers for Disease Control and Prevention. CDC Yellow Book. https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/leishmaniasis-visceral. Updated May 31, 2017. Accessed January 24, 2018.
  7. Lawyer PG, Perkins PV. Leishmaniasis and trypanosomiasis. In: Eldridge BF, Edman JD, eds. Medical Entomology. Dordrecht, Netherlands: Kluwer Academic; 2000.
  8. Douvoyiannis M, Khromachou T, Byers N, et al. Cutaneous leishmaniasis in North Dakota. Clin Infect Dis. 2014;59:73-75.
  9. Schaut RG, Robles-Murguia M, Juelsgaard R, et al. Vectorborne transmission of Leishmania infantum from hounds, United States. Emerg Infect Dis. 2015;21:2209-2212 .
  10. Hennings C, Bloch K, Miller J, et al. What is your diagnosis? New World cutaneous leishmaniasis. Cutis. 2015;95:208, 229-230.
  11. Lewis DJ. Phlebotomid sandflies. Bull World Health Organ. 1971;44:535-551.
  12. Alves VR, Freitas RA, Santos FL, et al. Sand flies (Diptera, Psychodidae, Phlebotominae) from Central Amazonia and four new records for the Amazonas state, Brazil. Rev Bras Entomol. 2012;56:220-227.
  13. Hashiguchi Y, Gomez EL, Kato H, et al. Diffuse and disseminated cutaneous leishmaniasis: clinical cases experienced in Ecuador and a brief review. Trop Med Health. 2016;44:2.
  14. Shaw J. The leishmaniases—survival and expansion in a changing world. a mini-review. Mem Inst Oswaldo Cruz. 2007;102:541-547.
  15. Centers for Disease Control and Prevention. CDC Health Information for International Travel 2016. New York, NY: Oxford University Press; 2016.
  16. Zhioua E, Moureau G, Chelbi I, et al. Punique virus, a novel phlebovirus, related to sandfly fever Naples virus, isolated from sandflies collected in Tunisia. J Gen Virol. 2010;91:1275-1283.
  17. Charrel RN, Moureau G, Temmam S, et al. Massilia virus, a novel phlebovirus (Bunyaviridae) isolated from sandflies in the Mediterranean. Vector Borne Zoonotic Dis. 2009;9:519-530.
  18. Collao X, Palacios G, de Ory F, et al. SecoGranada virus: a natural phlebovirus reassortant of the sandfly fever Naples serocomplex with low seroprevalence in humans. Am J Trop Med Hyg. 2010;83:760-765.
  19. Alkan C, Bichaud L, de Lamballerie X, et al. Sandfly-borne phleboviruses of Eurasia and Africa: epidemiology, genetic diversity, geographic range, control measures. Antiviral Res. 2013;100:54-74.
  20. Travassos da Rosa AP, Tesh RB, Pinheiro FP, et al. Characterization of the Changuinola serogroup viruses (Reoviridae: Orbivirus). Intervirology. 1984;21:38-49.
  21. Vasilakis N, Widen S, Mayer SV, et al. Niakha virus: a novel member of the family Rhabdoviridae isolated from phlebotomine sandflies in Senegal. Virology. 2013;444:80-89.
  22. Sudeep AB, Bondre VP, Gurav YK, et al. Isolation of Chandipura virus (Vesiculovirus: Rhabdoviridae) from Sergentomyia species of sandflies from Nagpur, Maharashtra, India. Indian J Med Res. 2014;139:769-772.
  23. Rao BL, Basu A, Wairagkar NS, et al. A large outbreak of acute encephalitis with high fatality rate in children in Andhra Pradesh, India, in 2003, associated with Chandipura virus. Lancet. 2004;364:869-874.
  24. Chadha MS, Arankalle VA, Jadi RS, et al. An outbreak of Chandipura virus encephalitis in the eastern districts of Gujarat state, India. Am J Trop Med Hyg. 2005;73:566-570.
  25. Minnick MF, Anderson BE, Lima A, et al. Oroya fever and verruga peruana: bartonelloses unique to South America. PLoS Negl Trop Dis. 2014;8:E2919.
  26. Eremeeva ME, Gerns HL, Lydy SL, et al. Bacteremia, fever, and splenomegaly caused by a newly recognized bartonella species. N Engl J Med. 2007;356:2381-2387.
  27. Blazes DL, Mullins K, Smoak BL, et al. Novel bartonella agent as cause of verruga peruana. Emerg Infect Dis. 2013;19:1111-1114.
  28. Tetreault GE, Zayed AB, Hanafi HA, et al. Suseptibility of sand flies to selected insecticides in North Africa and the Middle East. J Am Mosq Control Assoc. 2001;17:23-27.
  29. Robert LL, Perich MJ. Phlebotomine sand fly (Diptera:Psychodidae) control using a residual pyrethroid insecticide. J Am Mosq Control Assoc. 1995;11:195-199.
  30. Perich MJ, Hoch AL, Rizzo N, et al. Insecticide barrier spraying for the control of sandfly vectors of cutaneous leishmaniasis in rural Guatemala. Am J Trop Med Hyg. 1995;52:485-488.
  31. Perich MJ, Kardec A, Braga IA, et al. Field evaluation of a lethal ovitrap against dengue vectors in Brazil. Med Vet Entomol. 2003;17:205-210.
  32. Alexander B, Maroli M. Control of phlebotomine sandflies. Medical and Veterinary Entomology. 2003;17:1-18.
  33. Freedman DO, Weld LH, Kozarsky PE, et al. Spectrum of disease and relation to place of exposure among ill returned travelers. New Engl J Med. 2006;354:119-130.
  34. Ergen EN, King AH, Tull M. Cutaneous leishmaniasis: an emerging infectious disease in travelers. Cutis. 2015;96:E22-E26.
  35. Clarke CF, Bradley KK, Wright JH, et al. Emergence of autochthonous cutaneous leishmaniasis in northeastern Texas and southeastern Oklahoma. Am J Trop Med Hyg. 2013;88:157-161.
  36. Young DG, Perkins PV. Phlebotomine sand flies of North America (Diptera:Psychodidae). Mosq News. 1984;44:263-304.
  37. Comer JA, Tesh RB, Modi GB, et al. Vesicular stomatitis virus, New Jersey serotype: replication in and transmission by Lutzomyia shannoni (Diptera: Psychodidae). Am J Trop Med Hyg. 1990;42:483-490.
  38. Haddow A, Curler G, Moulton J. New records of Lutzomyia shannoni and Lutzomyia vexator (Diptera: Psychodidae) in eastern Tennessee. J Vector Ecol. 2008;33:393-396.
  39. Claborn DM, Rowton ED, Lawyer PG, et al. Species diversity and relative abundance of phlebotomine sand flies (Diptera: Psychodidae) on three Army installations in the southern United States and susceptibility of a domestic sand fly to infection with Old World Leishmania major. Mil Med. 2009;174:1203-1208.
  40. Minter L, Kovacic B, Claborn DM, et al. New state records for Lutzomyia shannoni (Dyar) and Lutzomyia vexator (Coquillett). J Med Entomol. 2009;46:965-968.
  41. Price DC, Gunther DE, Gaugler R. First collection records of phlebotomine sand flies (Diptera: Psychodidae) from New Jersey. J Med Entomol. 2011;48:476-478.
  42. Weng J, Young SL, Gordon DM, et al. First report of phlebotomine sand flies (Diptera: Psychodidae) in Kansas and Missouri, and a PCR method to distinguish Lutzomyia shannoni from Lutzomyia vexator. J Med Entomol. 2012;49:1460-1465.
  43. Pech-May A, Escobedo-Ortegón FJ, Berzunza-Cruz M, et al. Incrimination of four sandfly species previously unrecognized as vectors of leishmania parasites in Mexico. Med Vet Entomol. 2010;24:150-161.
  44. González C, Rebollar-Téllez EA, Ibáñez-Bernal S, et al. Current knowledge of leishmania vectors in Mexico: how geographic distributions of species relate to transmission areas. Am J Trop Med Hyg. 2011;85:839-846.
References
  1. European Centre for Disease Prevention and Control. Phlebotomine sand flies—factsheet for experts. https://ecdc.europa.eu/en/disease-vectors/facts/phlebotomine-sand-flies. Accessed January 24, 2018.
  2. Durden L, Mullen G. Moth flies and sand flies (Psychodidae). Medical And Veterinary Entomology. San Diego, CA: Academic Press; 2002.
  3. Claborn DM. The biology and control of leishmaniasis vectors. J Glob Infect Dis. 2010;2:127-134.
  4. Young DG, Duncan MA. Guide to the identification and geographic distribution of Lutzomyia sand flies in Mexico, the West Indies, Central and South America (Diptera: Psychodidae). Mem Am Entomol Inst. 1994;54:1-881.
  5. Wolff K, Johnson R, Saavedra AP. Systemic parasitic infections. In: Wolff K, Johnson R, Saavedra AP, eds. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 7th ed. New York, NY: McGraw-Hill; 2013.
  6. Herwaldt BL, Magill AJ. Leishmaniasis, visceral. In: Centers for Disease Control and Prevention. CDC Yellow Book. https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/leishmaniasis-visceral. Updated May 31, 2017. Accessed January 24, 2018.
  7. Lawyer PG, Perkins PV. Leishmaniasis and trypanosomiasis. In: Eldridge BF, Edman JD, eds. Medical Entomology. Dordrecht, Netherlands: Kluwer Academic; 2000.
  8. Douvoyiannis M, Khromachou T, Byers N, et al. Cutaneous leishmaniasis in North Dakota. Clin Infect Dis. 2014;59:73-75.
  9. Schaut RG, Robles-Murguia M, Juelsgaard R, et al. Vectorborne transmission of Leishmania infantum from hounds, United States. Emerg Infect Dis. 2015;21:2209-2212 .
  10. Hennings C, Bloch K, Miller J, et al. What is your diagnosis? New World cutaneous leishmaniasis. Cutis. 2015;95:208, 229-230.
  11. Lewis DJ. Phlebotomid sandflies. Bull World Health Organ. 1971;44:535-551.
  12. Alves VR, Freitas RA, Santos FL, et al. Sand flies (Diptera, Psychodidae, Phlebotominae) from Central Amazonia and four new records for the Amazonas state, Brazil. Rev Bras Entomol. 2012;56:220-227.
  13. Hashiguchi Y, Gomez EL, Kato H, et al. Diffuse and disseminated cutaneous leishmaniasis: clinical cases experienced in Ecuador and a brief review. Trop Med Health. 2016;44:2.
  14. Shaw J. The leishmaniases—survival and expansion in a changing world. a mini-review. Mem Inst Oswaldo Cruz. 2007;102:541-547.
  15. Centers for Disease Control and Prevention. CDC Health Information for International Travel 2016. New York, NY: Oxford University Press; 2016.
  16. Zhioua E, Moureau G, Chelbi I, et al. Punique virus, a novel phlebovirus, related to sandfly fever Naples virus, isolated from sandflies collected in Tunisia. J Gen Virol. 2010;91:1275-1283.
  17. Charrel RN, Moureau G, Temmam S, et al. Massilia virus, a novel phlebovirus (Bunyaviridae) isolated from sandflies in the Mediterranean. Vector Borne Zoonotic Dis. 2009;9:519-530.
  18. Collao X, Palacios G, de Ory F, et al. SecoGranada virus: a natural phlebovirus reassortant of the sandfly fever Naples serocomplex with low seroprevalence in humans. Am J Trop Med Hyg. 2010;83:760-765.
  19. Alkan C, Bichaud L, de Lamballerie X, et al. Sandfly-borne phleboviruses of Eurasia and Africa: epidemiology, genetic diversity, geographic range, control measures. Antiviral Res. 2013;100:54-74.
  20. Travassos da Rosa AP, Tesh RB, Pinheiro FP, et al. Characterization of the Changuinola serogroup viruses (Reoviridae: Orbivirus). Intervirology. 1984;21:38-49.
  21. Vasilakis N, Widen S, Mayer SV, et al. Niakha virus: a novel member of the family Rhabdoviridae isolated from phlebotomine sandflies in Senegal. Virology. 2013;444:80-89.
  22. Sudeep AB, Bondre VP, Gurav YK, et al. Isolation of Chandipura virus (Vesiculovirus: Rhabdoviridae) from Sergentomyia species of sandflies from Nagpur, Maharashtra, India. Indian J Med Res. 2014;139:769-772.
  23. Rao BL, Basu A, Wairagkar NS, et al. A large outbreak of acute encephalitis with high fatality rate in children in Andhra Pradesh, India, in 2003, associated with Chandipura virus. Lancet. 2004;364:869-874.
  24. Chadha MS, Arankalle VA, Jadi RS, et al. An outbreak of Chandipura virus encephalitis in the eastern districts of Gujarat state, India. Am J Trop Med Hyg. 2005;73:566-570.
  25. Minnick MF, Anderson BE, Lima A, et al. Oroya fever and verruga peruana: bartonelloses unique to South America. PLoS Negl Trop Dis. 2014;8:E2919.
  26. Eremeeva ME, Gerns HL, Lydy SL, et al. Bacteremia, fever, and splenomegaly caused by a newly recognized bartonella species. N Engl J Med. 2007;356:2381-2387.
  27. Blazes DL, Mullins K, Smoak BL, et al. Novel bartonella agent as cause of verruga peruana. Emerg Infect Dis. 2013;19:1111-1114.
  28. Tetreault GE, Zayed AB, Hanafi HA, et al. Suseptibility of sand flies to selected insecticides in North Africa and the Middle East. J Am Mosq Control Assoc. 2001;17:23-27.
  29. Robert LL, Perich MJ. Phlebotomine sand fly (Diptera:Psychodidae) control using a residual pyrethroid insecticide. J Am Mosq Control Assoc. 1995;11:195-199.
  30. Perich MJ, Hoch AL, Rizzo N, et al. Insecticide barrier spraying for the control of sandfly vectors of cutaneous leishmaniasis in rural Guatemala. Am J Trop Med Hyg. 1995;52:485-488.
  31. Perich MJ, Kardec A, Braga IA, et al. Field evaluation of a lethal ovitrap against dengue vectors in Brazil. Med Vet Entomol. 2003;17:205-210.
  32. Alexander B, Maroli M. Control of phlebotomine sandflies. Medical and Veterinary Entomology. 2003;17:1-18.
  33. Freedman DO, Weld LH, Kozarsky PE, et al. Spectrum of disease and relation to place of exposure among ill returned travelers. New Engl J Med. 2006;354:119-130.
  34. Ergen EN, King AH, Tull M. Cutaneous leishmaniasis: an emerging infectious disease in travelers. Cutis. 2015;96:E22-E26.
  35. Clarke CF, Bradley KK, Wright JH, et al. Emergence of autochthonous cutaneous leishmaniasis in northeastern Texas and southeastern Oklahoma. Am J Trop Med Hyg. 2013;88:157-161.
  36. Young DG, Perkins PV. Phlebotomine sand flies of North America (Diptera:Psychodidae). Mosq News. 1984;44:263-304.
  37. Comer JA, Tesh RB, Modi GB, et al. Vesicular stomatitis virus, New Jersey serotype: replication in and transmission by Lutzomyia shannoni (Diptera: Psychodidae). Am J Trop Med Hyg. 1990;42:483-490.
  38. Haddow A, Curler G, Moulton J. New records of Lutzomyia shannoni and Lutzomyia vexator (Diptera: Psychodidae) in eastern Tennessee. J Vector Ecol. 2008;33:393-396.
  39. Claborn DM, Rowton ED, Lawyer PG, et al. Species diversity and relative abundance of phlebotomine sand flies (Diptera: Psychodidae) on three Army installations in the southern United States and susceptibility of a domestic sand fly to infection with Old World Leishmania major. Mil Med. 2009;174:1203-1208.
  40. Minter L, Kovacic B, Claborn DM, et al. New state records for Lutzomyia shannoni (Dyar) and Lutzomyia vexator (Coquillett). J Med Entomol. 2009;46:965-968.
  41. Price DC, Gunther DE, Gaugler R. First collection records of phlebotomine sand flies (Diptera: Psychodidae) from New Jersey. J Med Entomol. 2011;48:476-478.
  42. Weng J, Young SL, Gordon DM, et al. First report of phlebotomine sand flies (Diptera: Psychodidae) in Kansas and Missouri, and a PCR method to distinguish Lutzomyia shannoni from Lutzomyia vexator. J Med Entomol. 2012;49:1460-1465.
  43. Pech-May A, Escobedo-Ortegón FJ, Berzunza-Cruz M, et al. Incrimination of four sandfly species previously unrecognized as vectors of leishmania parasites in Mexico. Med Vet Entomol. 2010;24:150-161.
  44. González C, Rebollar-Téllez EA, Ibáñez-Bernal S, et al. Current knowledge of leishmania vectors in Mexico: how geographic distributions of species relate to transmission areas. Am J Trop Med Hyg. 2011;85:839-846.
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Practice Points

  • Sand flies cause a wide array of cutaneous and systemic diseases worldwide.
  • Identification and treatment of leishmaniasis and other diseases transmitted by sand flies requires a high degree of clinical suspicion.
  • With the increase in global travel and the rise of autochthonous disease in the United States, American physicians must increase their awareness of diseases for which sand flies serve as vectors.
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The Effects of Sunscreen on Marine Environments

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The Effects of Sunscreen on Marine Environments

Coastal travel accounts for 80% of all tourism worldwide, a number that continues to grow. The number of travelers to the Mediterranean Sea alone is expected to rise to 350 million individuals per year within the next 20 years.1 As the number of tourists visiting the world’s oceans increases, the rate of sunscreen unintentionally washed into these marine environments also rises. One study estimated that approximately one-quarter of the sunscreen applied to the skin is washed off over a 20-minute period spent in the water.2 Four of the most common sunscreen agents—benzophenone-3 (BP-3), 4-methylbenzylidene camphor (4-MBC), and the nanoparticles titanium dioxide and zinc oxide—have been considered to be risks to marine environments. As this topic has received increasing media scrutiny over the last few years, we summarize the general conclusions that can be drawn from current research and note the questions that still remain to better address patient concerns.

Benzophenone-3

Benzophenone-3, or oxybenzone, is a widely studied UV filter and its effects on marine ecosystems have received the media’s attention over the last few years. Benzophenone-3 is known to cause a bleaching effect to coral, which can inhibit growth and possibly kill the organism.3 Further, oxybenzone sunscreens can promote viral infections in coral, resulting in additional bleaching events.2 In a recent study, exposure to BP-3 caused mobile planulae, the larval form of coral, to become clearly deformed, trapped within its own calcium carbonate skeleton.3 The concentration of BP-3 needed to induce these physiological changes is as small as 62 parts per trillion, which is the equivalent of a single drop of water in 6.5 Olympic-sized swimming pools. Levels of BP-3 contamination in the waters off of the US Virgin Islands’ beaches have been recorded as high as 1.4 parts per million, with average concentrations closer to 250 parts per billion.3 High BP-3 concentrations have also been recorded in the waters off the Canary Islands,4 Hawaii,3 and South Carolina.5

4-Methylbenzylidene Camphor

Environmental concerns have also been raised about another common chemical UV filter: 4-MBC, or enzacamene. In laboratory studies, 4-MBC has been shown to cause oxidative stress to Tetrahymena thermophila, an aquatic protozoan, which results in inhibited growth. At higher concentrations, damage to the cellular membrane was seen as soon as 4 hours after exposure.6 In embryonic zebrafish, elevated 4-MBC levels were correlated to improper nerve and muscular development, resulting in developmental defects.7 Another study demonstrated that 4-MBC was toxic to Mytilus galloprovincialis, known as the Mediterranean mussel, and Paracentrotus lividus, a species of sea urchin.8 Although these studies utilized highly controlled laboratory settings, further studies are needed to examine the effects of 4-MBC on these species at environmentally relevant concentrations.

Physical Sunscreens

Physical sunscreens, as compared to the chemical filters referenced above, use either zinc or titanium to protect the skin from the sun’s rays. Nanoparticles, in particular, are preferred because they do not leave a white film on the skin.9 Both titanium dioxide and zinc oxide nanoparticles have been found to inhibit the growth and photosynthesis of marine phytoplankton, the most abundant primary producers on Earth.10,11 These metal contaminants can be transferred to organisms of higher trophic levels, including zooplankton,12 and filter-feeding organisms, including marine abalone13 and the Mediterranean mussel.14 These nanoparticles have been shown to cause oxidative stress to these organisms, making them less fit to withstand environmental stressors. It is difficult to show their true impact, however, as it is challenging to accurately detect and quantify nanoparticle concentrations in vivo.15

Final Thoughts

A recent study showed that 7% of consumers (N=325) regarded environmental agencies’ recommendations as an important factor in their sunscreen purchase.16 When treating patients with these concerns, the ability to provide sound and informed advice will likely impact their sunscreen use and future sun protection behaviors. Although studies have shown the potential for sunscreen pollution to cause environmental harm, it is important to note that a portion of this research is not correlated to in vivo findings, and further work is required to determine the magnitude and importance of these studies.15 Regardless, legislation has already been submitted in both Hawaii and the European Union calling for a ban on oxybenzone-containing sunscreens, so knowledge of the subject is prudent when counseling patients.17 One potential solution may be to recommend sun-protective clothing during water-intensive activities to both increase skin protection and reduce the environmental impact. Furthermore, recommendations could be tailored to specific settings, such as coastal resorts and populated beaches, where these sunscreen ingredients are found in much higher concentrations. At this time, more data must be collected before making any definitive claims or recommendations, but knowledge of the current research will be an important tool in educating patients going forward.

References
  1. Marine problems: tourism & coastal development. World Wide Fund for Nature website. http://wwf.panda.org/about_our_earth/blue_planet/problems/tourism/. Published 2017. Accessed November 14, 2017.
  2. Danovaro R, Bongiorni L, Corinaldesi C, et al. Sunscreens cause coral bleaching by promoting viral infections. Environ Health Perspect. 2008;116:441-447.
  3. Downs C, Kramarsky-Winter E, Segal R, et al. Toxicopathological effects of the sunscreen UV filter, oxybenzone (benzophenone-3), on coral planulae and cultured primary cells and its environmental contamination in Hawaii and the US Virgin Islands. Arch Environ Contam Toxicol. 2016;70:265-288.
  4. Sánchez Rodríguez A, Rodrigo Sanz M, Betancort Rodríguez JR. Occurrence of eight UV filters in beaches of Gran Canaria (Canary Islands)[published online March 17, 2015]. Chemosphere. 2015;131:85-90.
  5. Bratkovics S, Sapozhnikova Y. Determination of seven commonly used organic UV filters in fresh and saline waters by liquid chromatography-tandem mass spectrometry. Analytical Methods. 2011;3:2943-2950.
  6. Gao L, Yuan T, Zhou C, et al. Effects of four commonly used UV filters on the growth, cell viability and oxidative stress responses of the Tetrahymena thermophila. Chemosphere. 2013;93:2507-2513.
  7. Li VW, Tsui MP, Chen X, et al. Effects of 4-methylbenzylidene camphor (4-MBC) on neuronal and muscular development in zebrafish (Danio rerio) embryos [published online February 18, 2016]. Environ Sci Pollut Res Int. 2016;23:8275-8285.
  8. Paredes E, Perez S, Rodil R, et al. Ecotoxicological evaluation of four UV filters using marine organisms from different trophic levels Isochrysis galbana, Mytilus galloprovincialis, Paracentrotus lividus, and Siriella armata. Chemosphere. 2014;104:44-50.
  9. Osterwalder U, Sohn M, Herzog B. Global state of sunscreens. Photodermatol Photoimmunol Photomed. 2014;30:62-80.
  10. Miller RJ, Bennett S, Keller AA, et al. TiO2 nanoparticles are phototoxic to marine phytoplankton. PloS One. 2012;7:E30321.
  11. Spisni E. Toxicity Assessment of Industrial- and Sunscreen-derived ZnO Nanoparticles [master’s thesis]. Coral Gables, FL: University of Miami Libraries Scholarly Repository; 2016. http://scholarlyrepository.miami.edu/cgi/viewcontent.cgi?article=1625&context=oa_theses. Accessed November 10, 2017.
  12. Jarvis TA, Miller RJ, Lenihan HS, et al. Toxicity of ZnO nanoparticles to the copepod Acartia tonsa, exposed through a phytoplankton diet [published online April 15, 2013]. Environ Toxicol Chem. 2013;32:1264-1269.
  13. Zhu X, Zhou J, Cai Z. The toxicity and oxidative stress of TiO2 nanoparticles in marine abalone (Haliotis diversicolor supertexta). Mar Pollut Bull. 2011;63:334-338.
  14. Barmo C, Ciacci C, Canonico B, et al. In vivo effects of n-TiO2 on digestive gland and immune function of the marine bivalve Mytilus galloprovincialis. Aquatic Toxicol. 2013;132:9-18.
  15. Sánchez-Quiles D, Tovar-Sánchez A. Are sunscreens a new environmental risk associated with coastal tourism? Environ Int. 2015;83:158-170.
  16. Xu S, Kwa M, Agarwal A, et al. Sunscreen product performance and other determinants of consumer preferences. JAMA Dermatol. 2016;152:920-927.
  17. Vesper I. Hawaii seeks to ban ‘reef-unfriendly’ sunscreen. Nature. February 3, 2017. https://www.nature.com/news/hawaii-seeks-to-ban-reef-unfriendly-sunscreen-1.21332. Accessed November 16, 2017.
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Dr. Willenbrink is from the Transitional Year Program, Spartanburg Regional Medical Center, South Carolina. Ms. Barker is from the United States National Park Service, National Park of American Samoa, Pago Pago. Dr. Diven is from the Department of Dermatology, University of Texas, Dell School of Medicine, Austin.

The authors report no conflict of interest.

Correspondence: Tyler J. Willenbrink, MD, Transitional Year Program, 101 E Wood St, Spartanburg, SC 29303 (T.J.Willenbrink@gmail.com).

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Dr. Willenbrink is from the Transitional Year Program, Spartanburg Regional Medical Center, South Carolina. Ms. Barker is from the United States National Park Service, National Park of American Samoa, Pago Pago. Dr. Diven is from the Department of Dermatology, University of Texas, Dell School of Medicine, Austin.

The authors report no conflict of interest.

Correspondence: Tyler J. Willenbrink, MD, Transitional Year Program, 101 E Wood St, Spartanburg, SC 29303 (T.J.Willenbrink@gmail.com).

Author and Disclosure Information

Dr. Willenbrink is from the Transitional Year Program, Spartanburg Regional Medical Center, South Carolina. Ms. Barker is from the United States National Park Service, National Park of American Samoa, Pago Pago. Dr. Diven is from the Department of Dermatology, University of Texas, Dell School of Medicine, Austin.

The authors report no conflict of interest.

Correspondence: Tyler J. Willenbrink, MD, Transitional Year Program, 101 E Wood St, Spartanburg, SC 29303 (T.J.Willenbrink@gmail.com).

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Coastal travel accounts for 80% of all tourism worldwide, a number that continues to grow. The number of travelers to the Mediterranean Sea alone is expected to rise to 350 million individuals per year within the next 20 years.1 As the number of tourists visiting the world’s oceans increases, the rate of sunscreen unintentionally washed into these marine environments also rises. One study estimated that approximately one-quarter of the sunscreen applied to the skin is washed off over a 20-minute period spent in the water.2 Four of the most common sunscreen agents—benzophenone-3 (BP-3), 4-methylbenzylidene camphor (4-MBC), and the nanoparticles titanium dioxide and zinc oxide—have been considered to be risks to marine environments. As this topic has received increasing media scrutiny over the last few years, we summarize the general conclusions that can be drawn from current research and note the questions that still remain to better address patient concerns.

Benzophenone-3

Benzophenone-3, or oxybenzone, is a widely studied UV filter and its effects on marine ecosystems have received the media’s attention over the last few years. Benzophenone-3 is known to cause a bleaching effect to coral, which can inhibit growth and possibly kill the organism.3 Further, oxybenzone sunscreens can promote viral infections in coral, resulting in additional bleaching events.2 In a recent study, exposure to BP-3 caused mobile planulae, the larval form of coral, to become clearly deformed, trapped within its own calcium carbonate skeleton.3 The concentration of BP-3 needed to induce these physiological changes is as small as 62 parts per trillion, which is the equivalent of a single drop of water in 6.5 Olympic-sized swimming pools. Levels of BP-3 contamination in the waters off of the US Virgin Islands’ beaches have been recorded as high as 1.4 parts per million, with average concentrations closer to 250 parts per billion.3 High BP-3 concentrations have also been recorded in the waters off the Canary Islands,4 Hawaii,3 and South Carolina.5

4-Methylbenzylidene Camphor

Environmental concerns have also been raised about another common chemical UV filter: 4-MBC, or enzacamene. In laboratory studies, 4-MBC has been shown to cause oxidative stress to Tetrahymena thermophila, an aquatic protozoan, which results in inhibited growth. At higher concentrations, damage to the cellular membrane was seen as soon as 4 hours after exposure.6 In embryonic zebrafish, elevated 4-MBC levels were correlated to improper nerve and muscular development, resulting in developmental defects.7 Another study demonstrated that 4-MBC was toxic to Mytilus galloprovincialis, known as the Mediterranean mussel, and Paracentrotus lividus, a species of sea urchin.8 Although these studies utilized highly controlled laboratory settings, further studies are needed to examine the effects of 4-MBC on these species at environmentally relevant concentrations.

Physical Sunscreens

Physical sunscreens, as compared to the chemical filters referenced above, use either zinc or titanium to protect the skin from the sun’s rays. Nanoparticles, in particular, are preferred because they do not leave a white film on the skin.9 Both titanium dioxide and zinc oxide nanoparticles have been found to inhibit the growth and photosynthesis of marine phytoplankton, the most abundant primary producers on Earth.10,11 These metal contaminants can be transferred to organisms of higher trophic levels, including zooplankton,12 and filter-feeding organisms, including marine abalone13 and the Mediterranean mussel.14 These nanoparticles have been shown to cause oxidative stress to these organisms, making them less fit to withstand environmental stressors. It is difficult to show their true impact, however, as it is challenging to accurately detect and quantify nanoparticle concentrations in vivo.15

Final Thoughts

A recent study showed that 7% of consumers (N=325) regarded environmental agencies’ recommendations as an important factor in their sunscreen purchase.16 When treating patients with these concerns, the ability to provide sound and informed advice will likely impact their sunscreen use and future sun protection behaviors. Although studies have shown the potential for sunscreen pollution to cause environmental harm, it is important to note that a portion of this research is not correlated to in vivo findings, and further work is required to determine the magnitude and importance of these studies.15 Regardless, legislation has already been submitted in both Hawaii and the European Union calling for a ban on oxybenzone-containing sunscreens, so knowledge of the subject is prudent when counseling patients.17 One potential solution may be to recommend sun-protective clothing during water-intensive activities to both increase skin protection and reduce the environmental impact. Furthermore, recommendations could be tailored to specific settings, such as coastal resorts and populated beaches, where these sunscreen ingredients are found in much higher concentrations. At this time, more data must be collected before making any definitive claims or recommendations, but knowledge of the current research will be an important tool in educating patients going forward.

Coastal travel accounts for 80% of all tourism worldwide, a number that continues to grow. The number of travelers to the Mediterranean Sea alone is expected to rise to 350 million individuals per year within the next 20 years.1 As the number of tourists visiting the world’s oceans increases, the rate of sunscreen unintentionally washed into these marine environments also rises. One study estimated that approximately one-quarter of the sunscreen applied to the skin is washed off over a 20-minute period spent in the water.2 Four of the most common sunscreen agents—benzophenone-3 (BP-3), 4-methylbenzylidene camphor (4-MBC), and the nanoparticles titanium dioxide and zinc oxide—have been considered to be risks to marine environments. As this topic has received increasing media scrutiny over the last few years, we summarize the general conclusions that can be drawn from current research and note the questions that still remain to better address patient concerns.

Benzophenone-3

Benzophenone-3, or oxybenzone, is a widely studied UV filter and its effects on marine ecosystems have received the media’s attention over the last few years. Benzophenone-3 is known to cause a bleaching effect to coral, which can inhibit growth and possibly kill the organism.3 Further, oxybenzone sunscreens can promote viral infections in coral, resulting in additional bleaching events.2 In a recent study, exposure to BP-3 caused mobile planulae, the larval form of coral, to become clearly deformed, trapped within its own calcium carbonate skeleton.3 The concentration of BP-3 needed to induce these physiological changes is as small as 62 parts per trillion, which is the equivalent of a single drop of water in 6.5 Olympic-sized swimming pools. Levels of BP-3 contamination in the waters off of the US Virgin Islands’ beaches have been recorded as high as 1.4 parts per million, with average concentrations closer to 250 parts per billion.3 High BP-3 concentrations have also been recorded in the waters off the Canary Islands,4 Hawaii,3 and South Carolina.5

4-Methylbenzylidene Camphor

Environmental concerns have also been raised about another common chemical UV filter: 4-MBC, or enzacamene. In laboratory studies, 4-MBC has been shown to cause oxidative stress to Tetrahymena thermophila, an aquatic protozoan, which results in inhibited growth. At higher concentrations, damage to the cellular membrane was seen as soon as 4 hours after exposure.6 In embryonic zebrafish, elevated 4-MBC levels were correlated to improper nerve and muscular development, resulting in developmental defects.7 Another study demonstrated that 4-MBC was toxic to Mytilus galloprovincialis, known as the Mediterranean mussel, and Paracentrotus lividus, a species of sea urchin.8 Although these studies utilized highly controlled laboratory settings, further studies are needed to examine the effects of 4-MBC on these species at environmentally relevant concentrations.

Physical Sunscreens

Physical sunscreens, as compared to the chemical filters referenced above, use either zinc or titanium to protect the skin from the sun’s rays. Nanoparticles, in particular, are preferred because they do not leave a white film on the skin.9 Both titanium dioxide and zinc oxide nanoparticles have been found to inhibit the growth and photosynthesis of marine phytoplankton, the most abundant primary producers on Earth.10,11 These metal contaminants can be transferred to organisms of higher trophic levels, including zooplankton,12 and filter-feeding organisms, including marine abalone13 and the Mediterranean mussel.14 These nanoparticles have been shown to cause oxidative stress to these organisms, making them less fit to withstand environmental stressors. It is difficult to show their true impact, however, as it is challenging to accurately detect and quantify nanoparticle concentrations in vivo.15

Final Thoughts

A recent study showed that 7% of consumers (N=325) regarded environmental agencies’ recommendations as an important factor in their sunscreen purchase.16 When treating patients with these concerns, the ability to provide sound and informed advice will likely impact their sunscreen use and future sun protection behaviors. Although studies have shown the potential for sunscreen pollution to cause environmental harm, it is important to note that a portion of this research is not correlated to in vivo findings, and further work is required to determine the magnitude and importance of these studies.15 Regardless, legislation has already been submitted in both Hawaii and the European Union calling for a ban on oxybenzone-containing sunscreens, so knowledge of the subject is prudent when counseling patients.17 One potential solution may be to recommend sun-protective clothing during water-intensive activities to both increase skin protection and reduce the environmental impact. Furthermore, recommendations could be tailored to specific settings, such as coastal resorts and populated beaches, where these sunscreen ingredients are found in much higher concentrations. At this time, more data must be collected before making any definitive claims or recommendations, but knowledge of the current research will be an important tool in educating patients going forward.

References
  1. Marine problems: tourism & coastal development. World Wide Fund for Nature website. http://wwf.panda.org/about_our_earth/blue_planet/problems/tourism/. Published 2017. Accessed November 14, 2017.
  2. Danovaro R, Bongiorni L, Corinaldesi C, et al. Sunscreens cause coral bleaching by promoting viral infections. Environ Health Perspect. 2008;116:441-447.
  3. Downs C, Kramarsky-Winter E, Segal R, et al. Toxicopathological effects of the sunscreen UV filter, oxybenzone (benzophenone-3), on coral planulae and cultured primary cells and its environmental contamination in Hawaii and the US Virgin Islands. Arch Environ Contam Toxicol. 2016;70:265-288.
  4. Sánchez Rodríguez A, Rodrigo Sanz M, Betancort Rodríguez JR. Occurrence of eight UV filters in beaches of Gran Canaria (Canary Islands)[published online March 17, 2015]. Chemosphere. 2015;131:85-90.
  5. Bratkovics S, Sapozhnikova Y. Determination of seven commonly used organic UV filters in fresh and saline waters by liquid chromatography-tandem mass spectrometry. Analytical Methods. 2011;3:2943-2950.
  6. Gao L, Yuan T, Zhou C, et al. Effects of four commonly used UV filters on the growth, cell viability and oxidative stress responses of the Tetrahymena thermophila. Chemosphere. 2013;93:2507-2513.
  7. Li VW, Tsui MP, Chen X, et al. Effects of 4-methylbenzylidene camphor (4-MBC) on neuronal and muscular development in zebrafish (Danio rerio) embryos [published online February 18, 2016]. Environ Sci Pollut Res Int. 2016;23:8275-8285.
  8. Paredes E, Perez S, Rodil R, et al. Ecotoxicological evaluation of four UV filters using marine organisms from different trophic levels Isochrysis galbana, Mytilus galloprovincialis, Paracentrotus lividus, and Siriella armata. Chemosphere. 2014;104:44-50.
  9. Osterwalder U, Sohn M, Herzog B. Global state of sunscreens. Photodermatol Photoimmunol Photomed. 2014;30:62-80.
  10. Miller RJ, Bennett S, Keller AA, et al. TiO2 nanoparticles are phototoxic to marine phytoplankton. PloS One. 2012;7:E30321.
  11. Spisni E. Toxicity Assessment of Industrial- and Sunscreen-derived ZnO Nanoparticles [master’s thesis]. Coral Gables, FL: University of Miami Libraries Scholarly Repository; 2016. http://scholarlyrepository.miami.edu/cgi/viewcontent.cgi?article=1625&context=oa_theses. Accessed November 10, 2017.
  12. Jarvis TA, Miller RJ, Lenihan HS, et al. Toxicity of ZnO nanoparticles to the copepod Acartia tonsa, exposed through a phytoplankton diet [published online April 15, 2013]. Environ Toxicol Chem. 2013;32:1264-1269.
  13. Zhu X, Zhou J, Cai Z. The toxicity and oxidative stress of TiO2 nanoparticles in marine abalone (Haliotis diversicolor supertexta). Mar Pollut Bull. 2011;63:334-338.
  14. Barmo C, Ciacci C, Canonico B, et al. In vivo effects of n-TiO2 on digestive gland and immune function of the marine bivalve Mytilus galloprovincialis. Aquatic Toxicol. 2013;132:9-18.
  15. Sánchez-Quiles D, Tovar-Sánchez A. Are sunscreens a new environmental risk associated with coastal tourism? Environ Int. 2015;83:158-170.
  16. Xu S, Kwa M, Agarwal A, et al. Sunscreen product performance and other determinants of consumer preferences. JAMA Dermatol. 2016;152:920-927.
  17. Vesper I. Hawaii seeks to ban ‘reef-unfriendly’ sunscreen. Nature. February 3, 2017. https://www.nature.com/news/hawaii-seeks-to-ban-reef-unfriendly-sunscreen-1.21332. Accessed November 16, 2017.
References
  1. Marine problems: tourism & coastal development. World Wide Fund for Nature website. http://wwf.panda.org/about_our_earth/blue_planet/problems/tourism/. Published 2017. Accessed November 14, 2017.
  2. Danovaro R, Bongiorni L, Corinaldesi C, et al. Sunscreens cause coral bleaching by promoting viral infections. Environ Health Perspect. 2008;116:441-447.
  3. Downs C, Kramarsky-Winter E, Segal R, et al. Toxicopathological effects of the sunscreen UV filter, oxybenzone (benzophenone-3), on coral planulae and cultured primary cells and its environmental contamination in Hawaii and the US Virgin Islands. Arch Environ Contam Toxicol. 2016;70:265-288.
  4. Sánchez Rodríguez A, Rodrigo Sanz M, Betancort Rodríguez JR. Occurrence of eight UV filters in beaches of Gran Canaria (Canary Islands)[published online March 17, 2015]. Chemosphere. 2015;131:85-90.
  5. Bratkovics S, Sapozhnikova Y. Determination of seven commonly used organic UV filters in fresh and saline waters by liquid chromatography-tandem mass spectrometry. Analytical Methods. 2011;3:2943-2950.
  6. Gao L, Yuan T, Zhou C, et al. Effects of four commonly used UV filters on the growth, cell viability and oxidative stress responses of the Tetrahymena thermophila. Chemosphere. 2013;93:2507-2513.
  7. Li VW, Tsui MP, Chen X, et al. Effects of 4-methylbenzylidene camphor (4-MBC) on neuronal and muscular development in zebrafish (Danio rerio) embryos [published online February 18, 2016]. Environ Sci Pollut Res Int. 2016;23:8275-8285.
  8. Paredes E, Perez S, Rodil R, et al. Ecotoxicological evaluation of four UV filters using marine organisms from different trophic levels Isochrysis galbana, Mytilus galloprovincialis, Paracentrotus lividus, and Siriella armata. Chemosphere. 2014;104:44-50.
  9. Osterwalder U, Sohn M, Herzog B. Global state of sunscreens. Photodermatol Photoimmunol Photomed. 2014;30:62-80.
  10. Miller RJ, Bennett S, Keller AA, et al. TiO2 nanoparticles are phototoxic to marine phytoplankton. PloS One. 2012;7:E30321.
  11. Spisni E. Toxicity Assessment of Industrial- and Sunscreen-derived ZnO Nanoparticles [master’s thesis]. Coral Gables, FL: University of Miami Libraries Scholarly Repository; 2016. http://scholarlyrepository.miami.edu/cgi/viewcontent.cgi?article=1625&context=oa_theses. Accessed November 10, 2017.
  12. Jarvis TA, Miller RJ, Lenihan HS, et al. Toxicity of ZnO nanoparticles to the copepod Acartia tonsa, exposed through a phytoplankton diet [published online April 15, 2013]. Environ Toxicol Chem. 2013;32:1264-1269.
  13. Zhu X, Zhou J, Cai Z. The toxicity and oxidative stress of TiO2 nanoparticles in marine abalone (Haliotis diversicolor supertexta). Mar Pollut Bull. 2011;63:334-338.
  14. Barmo C, Ciacci C, Canonico B, et al. In vivo effects of n-TiO2 on digestive gland and immune function of the marine bivalve Mytilus galloprovincialis. Aquatic Toxicol. 2013;132:9-18.
  15. Sánchez-Quiles D, Tovar-Sánchez A. Are sunscreens a new environmental risk associated with coastal tourism? Environ Int. 2015;83:158-170.
  16. Xu S, Kwa M, Agarwal A, et al. Sunscreen product performance and other determinants of consumer preferences. JAMA Dermatol. 2016;152:920-927.
  17. Vesper I. Hawaii seeks to ban ‘reef-unfriendly’ sunscreen. Nature. February 3, 2017. https://www.nature.com/news/hawaii-seeks-to-ban-reef-unfriendly-sunscreen-1.21332. Accessed November 16, 2017.
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