ABSTRACT

Objectives.

To present the state-of-the-knowledge on the epidemiology of tungiasis in the Region of the Americas.

Methods.

A search of publications on the epidemiology of tungiasis in the Americas was performed in PubMed and LILACS databases from January 2007 to June 2021. In addition, a manual literature search on articles on the epidemiology of tungiasis was performed.

Results.

A total of 83 articles were analyzed which contained relevant information on tungiasis cases and their geographical distribution, prevalence and risk factors, life cycle, sites where transmission takes place, and zoonotic aspects. The on-host and off-host life cycles have been researched in detail. In certain contexts, the whole life cycle is completed indoors enabling transmission around the whole year. Cases were reported from 10 countries; 71% of them were from Brazil. In the general population, the prevalence varied between 1.0% and 82.6% according to the settings. Age-specific prevalence indicated that children and the elderly bear the highest disease burden. Risk factor studies indicate that tungiasis is associated with severe poverty.

Conclusions.

In the Americas, there are important gaps in information and knowledge of tungiasis. Understanding the burden, epidemiology, distribution, magnitude, related risk factors, and reservoirs, among others, is needed to develop and implement integrated control measures tailored to the context and patterns of transmission in the affected communities.

Keywords
Tungiasis; skin diseases; epidemiology; Americas

RESUMEN

Objetivos.

Presentar el estado del conocimiento sobre las características epidemiológicas de la tungiasis en la Región de las Américas.

Métodos.

Se hizo una búsqueda de publicaciones sobre las características epidemiológicas de la tungiasis en la Región en las bases de datos PubMed y LILACS en el período comprendido entre enero del 2007 y junio del 2021. Además, se realizó una búsqueda bibliográfica manual de artículos sobre las características epidemiológicas de la tungiasis.

Resultados.

Se analizaron en total 83 artículos que contenían información pertinente sobre casos de tungiasis y su distribución geográfica, prevalencia y factores de riesgo, ciclo de vida, lugares donde se produce la transmisión y aspectos zoonóticos. Se investigaron en detalle los ciclos de vida dentro y fuera del huésped. En ciertos contextos, la totalidad del ciclo de vida se completa en espacios cerrados, lo que permite la transmisión durante todo el año. Se notificaron casos en 10 países, con 71% de los casos notificados en Brasil. En la población general, la prevalencia varió entre 1,0% y 82,6% según el entorno. La prevalencia específica por edad indica que la población infantil y las personas mayores tienen la mayor carga de morbilidad. Los estudios relativos a los factores de riesgo indican que la tungiasis está relacionada con la pobreza extrema.

Conclusiones.

En la Región, hay lagunas importantes en la información y el conocimiento sobre la tungiasis. Es necesario comprender la carga, las características epidemiológicas, la distribución, la magnitud, los factores de riesgo relacionados y los reservorios, entre otros factores, para elaborar y aplicar medidas de control integradas adaptadas al contexto y los patrones de transmisión en las comunidades afectadas.

Palabras clave
Tungiasis; enfermedades de la piel; epidemiología; Américas

RESUMO

Objetivos.

Apresentar o estado do conhecimento sobre a epidemiologia da tungíase na Região das Américas.

Métodos.

Realizou-se uma pesquisa de estudos publicados de janeiro de 2007 a junho de 2021 sobre a epidemiologia da tungíase nas Américas nas bases de dados PubMed e LILACS, bem como uma pesquisa bibliográfica manual de artigos sobre a epidemiologia da tungíase.

Resultados.

Analisou-se um total de 83 artigos com informações de interesse sobre casos de tungíase e sua distribuição geográfica, prevalência e fatores de risco, ciclo vital, locais de transmissão e aspectos zoonóticos. Os ciclos vitais dentro e fora do hospedeiro foram pesquisados em detalhes. Em determinados contextos, todo o ciclo vital ocorre em ambientes fechados, o que possibilita a transmissão durante todo o ano. Relataram-se casos de 10 países; 71% deles no Brasil. Na população em geral, a prevalência variou de 1,0% a 82,6%, de acordo com o local. A prevalência específica por idade mostrou que a maior carga de doença ocorre em crianças e pessoas idosas. Estudos dos fatores de risco indicam que a tungíase está associada à extrema pobreza.

Conclusões.

Nas Américas, existem importantes lacunas de informação e conhecimento sobre a tungíase. É necessário compreender fatores como carga, epidemiologia, distribuição, magnitude, fatores de risco relacionados e reservatórios, entre outros, para desenvolver e implementar medidas integradas de controle adequadas ao contexto e aos padrões de transmissão nas comunidades afetadas.

Palavras-chave
Tungíase; dermatopatias; epidemiologia; América

Tungiasis is a parasitic disease of the skin caused by the female sand flea Tunga penetrans, which is the only multi-cellular parasite originated and spread in the Americas and transferred to sub-Saharan Africa in the 19^th century (¹1. Linardi PM, de Avelar DM. Neosomes of tungid fleas on wild and domestic animals. Parasitol Res [Internet]. 2014 Sep 25 [cited 2022 Mar 29];113(10):3517. Available from: /pmc/articles/PMC4172993/
/pmc/articles/PMC4172993/... ). Tungiasis is considered a neglected tropical disease and is caused by the penetration of the female flea into the skin (usually on the feet), causing an intense inflammatory response leading to itching and pain. In endemic areas, the disease occurs with acute weakening and chronic morbidity that can even progress to deformation and mutilation (²2. Elson L, Wright K, Swift J, Feldmeier H. Control of Tungiasis in Absence of a Roadmap: Grassroots and Global Approaches. Trop Med Infect Dis [Internet]. 2017 Jul 27 [cited 2022 Mar 29];2(3). Available from: /pmc/articles/PMC6082108/
/pmc/articles/PMC6082108/... ).

There is convincing evidence that tungiasis was present and common in the Americas in pre-Hispanic times (³3. Maco V, Tantaleán M, Gotuzzo E. Evidence of Tungiasis in Pre-Hispanic America. Emerg Infect Dis [Internet]. 2011 [cited 2022 Mar 29];17(5):855. Available from: /pmc/articles/PMC3321756/
/pmc/articles/PMC3321756/... ). The disease is still common in several countries in Central and South America and the Caribbean, although the precise spatial distribution is not known (⁴4. Feldmeier H, Heukelbach J, Ugbomoiko US, Sentongo E, Mbabazi P, von Samson-Himmelstjerna G, et al. Tungiasis--a neglected disease with many challenges for global public health. PLoS Negl Trop Dis [Internet]. 2014 Oct 30;8(10):e3133–e3133. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25356978
https://www.ncbi.nlm.nih.gov/pubmed/2535... ). Tungiasis thrives where living conditions are precarious, including in shantytowns, rural communities in the hinterland, as well as, in villages along the coast of the Atlantic Ocean (⁴4. Feldmeier H, Heukelbach J, Ugbomoiko US, Sentongo E, Mbabazi P, von Samson-Himmelstjerna G, et al. Tungiasis--a neglected disease with many challenges for global public health. PLoS Negl Trop Dis [Internet]. 2014 Oct 30;8(10):e3133–e3133. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25356978
https://www.ncbi.nlm.nih.gov/pubmed/2535... ). Tungiasis is one of the neglected tropical diseases included in the Road Map for neglected tropical diseases 2021-2030 of the World Health Organization (WHO) for which integrated interventions should be implemented to reduce the burden (⁵5. World Health Organization. Ending the neglect to attain the Sustainable Development Goals A road map for neglected tropical diseases 2021-2030 [Internet]. Geneva; 2020 [cited 2021 Feb 22]. Available from: https://www.who.int/publications/i/item/9789240010352.
https://www.who.int/publications/i/item/... ). Data on prevalence, risk factors, and zoonotic aspects of tungiasis in the Americas are scarce and have never been analyzed systematically. The objective of this study is to present the state-of-the-knowledge on the epidemiology of tungiasis in the Region of the Americas.

METHODS

A search of studies reporting data on tungiasis cases and their geographical distribution, prevalence and risk factors, life cycle, sites where transmission takes place, and zoonotic aspects was performed restricted to countries in the Region of the Americas. The search was conducted in PubMed and LILACS databases for studies published from January 2007 to June 2021. One of the authors (HF) had performed an identical literature search in December 2006 and had read and analyzed all publications on tungiasis in the Americas published before 2006.

First, it was checked whether entries existed for at least one of the many local terms and designations reported or in use for tungiasis in the Americas: aagrani, aju, atten, bicho del pie, bicho de pé, bicho do porco, catebuco, chego, chegoe, chik, chica, chicque, chigger, chigoe flea, ckicke, jatecuba, jigger, jiggers, kuti, nigua, nihua, niua, pico, pigue, piki, pique, piqui, puce-chique, puce de sable, pulga de areia, sand flea, sandflea disease, seccec, sicca, sico, sike, tchike, tom, tschike, tungay, tungiase, tungose, tü, wenca, xique.

Second, a search was performed using the keyword [tungiasis] OR [any of the local designations identified in step one] for studies of the Americas. This approach was used since a preliminary search using epidemiology-related keywords, such as life cycle, transmission, disease occurrence, prevalence, incidence, risk factor AND tungiasis did not retrieve any relevant publication. No language restrictions were applied for the search in PubMed. The search in LILACS was limited to Spanish and Portuguese.

In addition, we searched the grey literature by seeking doctorate theses and other types of research not published in scientific journals by contacting scientists known to have worked on tungiasis in the Americas. For this search, no time restrictions were applied. Finally, reference lists of articles published between 2007 and 2021 were hand-searched for publications with relevant information according to the objective of this study. Here, too, no time restrictions were applied.

Since analytical studies were scarce, case series and case reports, and descriptive studies on the life cycle, transmission, and zoonotic aspects of tungiasis, were also included. The abstracts of publications from the Americas were reviewed for relevance by one of the authors (HF). An article was considered relevant for analysis if in the abstract and keywords one of the following terms were mentioned: life cycle, transmission, disease occurrence, prevalence, incidence, seasonal variation, risk factor, zoonosis, or animal reservoir. Since the great majority of the published studies contained qualitative rather than quantitative data, a narrative style was used to summarize the current knowledge on the epidemiology of tungiasis in the Americas.

RESULTS

The initial search identified a total of 119 publications. After an initial screening, 36 were considered not relevant for the objective of the study, and 83 were included for analysis (Figure 1). Six publications were studies performed before 2000, 40 between 2000 and 2010, and 37 between 2011 and 2021.

Parasite, life cycle, and transmission

Almost all the existing data on the life cycle of T. penetrans has been generated in the Region of Americas. T. penetrans parasitizes at least 26 species of domestic, sylvatic, and synanthropic animals (¹1. Linardi PM, de Avelar DM. Neosomes of tungid fleas on wild and domestic animals. Parasitol Res [Internet]. 2014 Sep 25 [cited 2022 Mar 29];113(10):3517. Available from: /pmc/articles/PMC4172993/
/pmc/articles/PMC4172993/... ) (Table 1). The remarkably broad host-specificity of T. penetrans is reflected by animals as different as anteaters and armadillos, on one side of the host spectrum, and monkeys and jaguars on the other side (⁶6. Linardi PM, Beaucournu JC, de Avelar DM, Belaz S. Notes on the genus Tunga (Siphonaptera: Tungidae) II – neosomes, morphology, classification, and other taxonomic notes. Parasite [Internet]. 2014 [cited 2022 Mar 29];21. Available from: /pmc/articles/PMC4270284/
/pmc/articles/PMC4270284/... ). In contrast, T. trimamillata and T. hexalobulata parasitize only a limited number of animal species and the spatial occurrence of these Tunga species is restricted (⁷7. Linardi PM, de Avelar DM, Facury Filho EJ. Establishment of Tunga trimamillata (Siphonaptera: Tungidae) in Brazil. Parasitol Res [Internet]. 2013 Sep [cited 2022 Mar 29];112(9):3239–42. Available from: https://pubmed.ncbi.nlm.nih.gov/23797275/
https://pubmed.ncbi.nlm.nih.gov/23797275... ).

In the on-host cycle, non-fertilized sand flea females penetrate the epidermis of their host, where they hypertrophy by a factor of 2 000 within a week. Through its last abdominal segments, the flea remains in contact with the environment to breathe, defecate, copulate, and expel eggs. After expelling about 100 eggs, it dies in situ within four to six weeks (⁸8. Eisele M, Heukelbach J, van Marck E, Mehlhorn H, Meckes O, Franck S, et al. Investigations on the biology, epidemiology, pathology and control of Tunga penetrans in Brazil: I. Natural history of tungiasis in man. Parasitol Res [Internet]. 2003 Jun [cited 2018 Aug 23];90(2):87–99. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12756541
http://www.ncbi.nlm.nih.gov/pubmed/12756... ). The on-host development is well understood, and a staging system was developed, named the Fortaleza classification (⁸8. Eisele M, Heukelbach J, van Marck E, Mehlhorn H, Meckes O, Franck S, et al. Investigations on the biology, epidemiology, pathology and control of Tunga penetrans in Brazil: I. Natural history of tungiasis in man. Parasitol Res [Internet]. 2003 Jun [cited 2018 Aug 23];90(2):87–99. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12756541
http://www.ncbi.nlm.nih.gov/pubmed/12756... ). Stages I-III of the Fortaleza classification reflect the presence of a viable parasite, stage IV indicates a dying/decaying parasite and stage V is a residual lesion (⁸8. Eisele M, Heukelbach J, van Marck E, Mehlhorn H, Meckes O, Franck S, et al. Investigations on the biology, epidemiology, pathology and control of Tunga penetrans in Brazil: I. Natural history of tungiasis in man. Parasitol Res [Internet]. 2003 Jun [cited 2018 Aug 23];90(2):87–99. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12756541
http://www.ncbi.nlm.nih.gov/pubmed/12756... ).

The off-host cycle is similar to other siphonaptera, requiring a dry environment and soil shielded from direct sunlight (⁹9. Linardi PM, Calheiros CML, Campelo-Junior EB, Duarte EM, Heukelbach J, Feldmeier H. Occurrence of the off-host life stages of Tunga penetrans (Siphonaptera) in various environments in Brazil. Ann Trop Med Parasitol [Internet]. 2010 Jun 1 [cited 2022 Mar 29];104(4):337–45. Available from: https://pubmed.ncbi.nlm.nih.gov/20659395/
https://pubmed.ncbi.nlm.nih.gov/20659395... ). Under ideal circumstances, the off-host phase of T. penetrans is completed within 20 days (⁹9. Linardi PM, Calheiros CML, Campelo-Junior EB, Duarte EM, Heukelbach J, Feldmeier H. Occurrence of the off-host life stages of Tunga penetrans (Siphonaptera) in various environments in Brazil. Ann Trop Med Parasitol [Internet]. 2010 Jun 1 [cited 2022 Mar 29];104(4):337–45. Available from: https://pubmed.ncbi.nlm.nih.gov/20659395/
https://pubmed.ncbi.nlm.nih.gov/20659395... ,¹⁰10. Nagy N, Abari E, D‘Haese J, Calheiros C, Heukelbach J, Mencke N, et al. Investigations on the life cycle and morphology of Tunga penetrans in Brazil. Parasitol Res [Internet]. 2007 Sep [cited 2022 Mar 29];101 Suppl 2(SUPPLEMENT 2). Available from: https://pubmed.ncbi.nlm.nih.gov/17823833/
https://pubmed.ncbi.nlm.nih.gov/17823833... ). In dwellings without a solid floor, the whole life cycle can be completed indoors: eggs expelled during sleep may fall directly down to the floor, or when shaking the bedding or turning a mat or mattress. Eggs are transferred to crevices and holes when the floor is swept with a broom. The larvae feed on the organic material present in cracks and holes (⁹9. Linardi PM, Calheiros CML, Campelo-Junior EB, Duarte EM, Heukelbach J, Feldmeier H. Occurrence of the off-host life stages of Tunga penetrans (Siphonaptera) in various environments in Brazil. Ann Trop Med Parasitol [Internet]. 2010 Jun 1 [cited 2022 Mar 29];104(4):337–45. Available from: https://pubmed.ncbi.nlm.nih.gov/20659395/
https://pubmed.ncbi.nlm.nih.gov/20659395... ). Adult females attach to and penetrate the skin when a person places their feet or other parts of the body on the contaminated floor (¹¹11. Miller H, Ocampo J, Ayala A, Trujillo J, Feldmeierid H. Very severe tungiasis in Amerindians in the Amazon lowland of Colombia: A case series. PLoS Negl Trop Dis [Internet]. 2019;13(2). Available from: https://doi.org/10.1371/journal.pntd.0007068
https://doi.org/10.1371/journal.pntd.000... ). In resource-poor settings, school classrooms without a solid floor may also constitute breeding and transmission sites (⁴4. Feldmeier H, Heukelbach J, Ugbomoiko US, Sentongo E, Mbabazi P, von Samson-Himmelstjerna G, et al. Tungiasis--a neglected disease with many challenges for global public health. PLoS Negl Trop Dis [Internet]. 2014 Oct 30;8(10):e3133–e3133. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25356978
https://www.ncbi.nlm.nih.gov/pubmed/2535... ).

In a tropical environment, four life cycles exist: human, domestic, synanthropic, and sylvatic animal (⁴4. Feldmeier H, Heukelbach J, Ugbomoiko US, Sentongo E, Mbabazi P, von Samson-Himmelstjerna G, et al. Tungiasis--a neglected disease with many challenges for global public health. PLoS Negl Trop Dis [Internet]. 2014 Oct 30;8(10):e3133–e3133. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25356978
https://www.ncbi.nlm.nih.gov/pubmed/2535... ) (Figure 2). These cycles may overlap, partially or totally, depending on the context. In the human and domestic cycles, the transmission usually occurs peridomiciliary, but under favorable circumstances, it will also be intradomiciliary. In Brazil, for instance, intradomiciliary transmission was shown to occur in resource-poor urban settings where the floors of the houses consisted of sand (⁹9. Linardi PM, Calheiros CML, Campelo-Junior EB, Duarte EM, Heukelbach J, Feldmeier H. Occurrence of the off-host life stages of Tunga penetrans (Siphonaptera) in various environments in Brazil. Ann Trop Med Parasitol [Internet]. 2010 Jun 1 [cited 2022 Mar 29];104(4):337–45. Available from: https://pubmed.ncbi.nlm.nih.gov/20659395/
https://pubmed.ncbi.nlm.nih.gov/20659395... ,¹²12. Calheiros CML. Aspectos biológicos e ecológicos de Tunga penetrans (L.,1758) (Siphonaptera: Tungidae) em áreas endêmicas brasileiras [Internet]. Belo Horizonte; 2007 [cited 2022 Mar 29]. Available from: https://www.lareferencia.info/vufind/Record/BR_60e5a9dfe8b86caf87b3b2ac44a5fac0/Description#tabnav
https://www.lareferencia.info/vufind/Rec... ). By placing flea traps on the floors in a resource-poor town in Rio de Janeiro State, Brazil, adult T. penetrans fleas were caught in 35 out of 100 traps placed overnight indicating that intradomiciliary transmission was common (¹³13. de Carvalho RW, de Almeida AB, Barbosa-Silva SC, Amorim M, Ribeiro PC, Serra-Freire NM. The patterns of tungiasis in Araruama township, state of Rio de Janeiro, Brazil. Mem Inst Cruz [Internet]. 2003 [cited 2022 Mar 29];98(1):31–6. Available from: http://www.scielo.br/j/mioc/a/kVw4RzPLD7zTdCrghF6MPPd/?lang=en
http://www.scielo.br/j/mioc/a/kVw4RzPLD7... ). In traditional Amerindian communities in the Amazon lowlands, transmission seems to predominantly occur intradomiciliary (¹¹11. Miller H, Ocampo J, Ayala A, Trujillo J, Feldmeierid H. Very severe tungiasis in Amerindians in the Amazon lowland of Colombia: A case series. PLoS Negl Trop Dis [Internet]. 2019;13(2). Available from: https://doi.org/10.1371/journal.pntd.0007068
https://doi.org/10.1371/journal.pntd.000... ,¹⁴14. Miller H, Rodríguez G, Rodríguez G. Tungiasis en población indígena del departamento de Vaupés: epidemiología, clínica, tratamiento y prevención. Biomedica [Internet]. 2010 Oct 1 [cited 2018 Aug 23];30(2):215. Available from: http://www.revistabiomedica.org/index.php/biomedica/article/view/185
http://www.revistabiomedica.org/index.ph... ) (Table 2). When the transmission is mainly indoors, incident cases will appear the whole year round (²2. Elson L, Wright K, Swift J, Feldmeier H. Control of Tungiasis in Absence of a Roadmap: Grassroots and Global Approaches. Trop Med Infect Dis [Internet]. 2017 Jul 27 [cited 2022 Mar 29];2(3). Available from: /pmc/articles/PMC6082108/
/pmc/articles/PMC6082108/... ,¹⁴14. Miller H, Rodríguez G, Rodríguez G. Tungiasis en población indígena del departamento de Vaupés: epidemiología, clínica, tratamiento y prevención. Biomedica [Internet]. 2010 Oct 1 [cited 2018 Aug 23];30(2):215. Available from: http://www.revistabiomedica.org/index.php/biomedica/article/view/185
http://www.revistabiomedica.org/index.ph... ).

Exactly where transmission occurs can be assessed by placing laboratory-raised Wistar rats in cages on the ground and monitoring the animals for infection (¹⁵15. Witt L, Heukelbach J, Schwalfenberg S, Ribeiro RA, Harms G, Feldmeier H. Infestation of Wistar rats with Tunga penetrans in different microenvironments. Am J Trop Med Hyg [Internet]. 2007 Apr 1 [cited 2022 Mar 29];76(4):666–8. Available from: https://www.ajtmh.org/view/journals/tpmd/76/4/article-p666.xml
https://www.ajtmh.org/view/journals/tpmd... ). In a study in a resource-poor rural community in Ceará State, Northeast Brazil, transmission took place at the far end of the compound where waste was deposited and rodents were common (¹⁵15. Witt L, Heukelbach J, Schwalfenberg S, Ribeiro RA, Harms G, Feldmeier H. Infestation of Wistar rats with Tunga penetrans in different microenvironments. Am J Trop Med Hyg [Internet]. 2007 Apr 1 [cited 2022 Mar 29];76(4):666–8. Available from: https://www.ajtmh.org/view/journals/tpmd/76/4/article-p666.xml
https://www.ajtmh.org/view/journals/tpmd... ).

Under certain circumstances, the transmission of adult females from person to person may occur when a health care provider comes into close contact with a patient who has free-running sand fleas on the skin such as during examination and treatment (¹⁶16. Krüger GM, Takita LC, Loro LS, Hans Filho G. Disseminated tungiasis. An Bras Dermatol [Internet]. 2017 Sep 1 [cited 2022 Mar 29];92(5):727. Available from: /pmc/articles/PMC5674713/
/pmc/articles/PMC5674713/... ,¹⁷17. Elson L, Thielecke M, Fillinger U, Feldmeier H. Infection with tungiasis through interhost movement of adult female sand fleas, Tunga penetrans. Trans R Soc Trop Med Hyg [Internet]. 2022 Feb 1 [cited 2022 Mar 29];116(2):85–6. Available from: https://pubmed.ncbi.nlm.nih.gov/34352892/
https://pubmed.ncbi.nlm.nih.gov/34352892... ).

Disease occurrence and spatial distribution

No systematic studies on the spatial distribution of tungiasis in the Americas were identified. Therefore, case reports and case series of travelers returning from a circumscribed area, migrants originating from an endemic area, and tungiasis in people who never left a certain geographic area in their home country, were analyzed to provide hints on the spatial distribution of tungiasis.

Between 2003 and 2021 a total of 135 cases were reported for which the geographical origin of tungiasis was known. Ninety-six out of the 135 cases (71%) were reported from Brazil (¹⁸18. Santos RP, Resende C, da Luz Duarte M, Brito C. Tungiasis: a poorly-known diagnosis in Europe. Two paradigmatic cases from Portugal. Acta Dermatovenerol Alp Pannonica Adriat [Internet]. 2017 [cited 2022 Mar 29];26(4):115–7. Available from: https://pubmed.ncbi.nlm.nih.gov/29264904/
https://pubmed.ncbi.nlm.nih.gov/29264904... –³³33. Leiro V, Novac V, Olivares L, Maronna E. Tungiasis inusual: forma clínica ampollar. Dermatol Argent. 2010 Sep;16(5):344–8.). In Brazil, cases were reported from Amazonas and Roraima States in the North of the country to Rio Grande do Sul State in the extreme South. Cases were also reported, in decreasing order of frequency, from Venezuela (³⁴34. Navas AM. Tungiasis. Medicina Interna. 2013;29(1):42.–³⁸38. Veraldi S, Camozzi S, Scarabelli G. Tungiasis presenting with sterile pustular lesions on the hand. Acta Derm Venereol [Internet]. 1996 [cited 2022 Mar 29];76(6):495. Available from: https://pubmed.ncbi.nlm.nih.gov/8982425/
https://pubmed.ncbi.nlm.nih.gov/8982425/... ), Ecuador (³⁹39. Wolf R, Orion E, Matz H. Stowaways with wings: Two case reports on high-flying insects. Dermatol Online J. 2003;9(3):128–33.–⁴²42. Calvopiña M, Bezemer J. Case Report: Evidence of Tungiasis in the Amazon Rain Forest of Ecuador. Am J Trop Med Hyg [Internet]. 2021 Sep 1 [cited 2022 Mar 29];105(3):698–700. Available from: https://pubmed.ncbi.nlm.nih.gov/34252050/
https://pubmed.ncbi.nlm.nih.gov/34252050... ), Argentina (⁴³43. Menghi CI, Comunale E, Gatta CL. Tungiosis adquirida en la provincia del Chaco, Argentina [Tungiasis acquired in Chaco Province, Argentina]. Rev Argent Microbiol [Internet]. 2009;41:148–50. Available from: http://www.cfnavarra.es/
http://www.cfnavarra.es/... –⁴⁵45. Bollea L, Vacas A, Enz P, de Luca D, Ferrario D, Mazzuoccolo L. Serie parasitosis en Dermatología Tungiasis. Rev del Hosp Ital Buenos Aires. 2017;37(3):112–5.), Peru (⁴⁶46. Maco V, Maco VP, Gotuzzo E. Case Report: An Ectopic Case of Tunga spp. Infection in Peru. Am J Trop Med Hyg [Internet]. 2010 Jun [cited 2022 Mar 29];82(6):1076. Available from: /pmc/articles/PMC2877413/
/pmc/articles/PMC2877413/... ,⁴⁷47. Maco V, Maco VP, Tantalean ME, Gotuzzo E. Case Report: Histopathological Features of Tungiasis in Peru. Am J Trop Med Hyg [Internet]. 2013 Jun [cited 2022 Mar 29];88(6):1212. Available from: /pmc/articles/PMC3752826/
/pmc/articles/PMC3752826/... ), Mexico (⁴⁸48. Ferreyra V, Martinetti C, Natinzon R, Rojas G, Zandoni J, Medin I, et al. Tungiasis: Reporte de un caso clínico con evolución inesperada. Fenómeno isotópico. Rev Argent Dermatol [Internet]. 2019 [cited 2022 Mar 29];100(4):31–40. Available from: http://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S1851-300X2019000400031&lng=es&nrm=iso&tlng=es
http://www.scielo.org.ar/scielo.php?scri... ,⁴⁹49. Ibáñez-Bernal S, Velasco-Castrejón O. New records of human tungiasis in Mexico (Siphonaptera:Tungidae). J Med Entomol [Internet]. 1996 [cited 2022 Mar 29];33(6):988–9. Available from: https://pubmed.ncbi.nlm.nih.gov/8961652/
https://pubmed.ncbi.nlm.nih.gov/8961652/... ), Paraguay (⁵⁰50. Fich F, del Barrio-Díaz P, Kam S, Celle V, Concha M, Kolbach M, et al. [Tungiasis, an emerging tropical disease in Chile: three imported cases reports]. Rev Chilena Infectol [Internet]. 2013 Dec [cited 2022 Mar 29];30(6):676–9. Available from: https://pubmed.ncbi.nlm.nih.gov/24522316/
https://pubmed.ncbi.nlm.nih.gov/24522316... ), Barbados (³²32. Veraldi S, Valsecchi M. Imported tungiasis: a report of 19 cases and review of the literature. Int J Dermatol [Internet]. 2007 Oct [cited 2022 Mar 29];46(10):1061–6. Available from: https://pubmed.ncbi.nlm.nih.gov/17910715/
https://pubmed.ncbi.nlm.nih.gov/17910715... ), Colombia (⁵¹51. Díaz CJ, Escandón-Vargas K. Tungiasis in a Colombian patient. Braz J Infect Dis [Internet]. 2017 Jul 1 [cited 2022 Mar 29];21(4):484–5. Available from: http://bjid.elsevier.es/en-tungiasis-in-colombian-patient-articulo-S141386701630602X
http://bjid.elsevier.es/en-tungiasis-in-... ,⁵²52. Ortega-Narváez A, Vásquez-Arteaga LR, Cujar-Otero O, Madroñero-Daza J, Cabra-Bautista G. Tungiasis en el área urbana de Popayán, Colombia: reporte de caso. Biomedica [Internet]. 2021 May 31 [cited 2022 Mar 29];41(Supl. 1):8–16. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/5851
https://revistabiomedica.org/index.php/b... ), and Bolivia (⁵³53. Greenfield Oliver. In quest of the unicorn bird. 1st ed. London: Michael Joseph; 1992. 211 pp.). In a study of international travelers who stayed one to three weeks at beaches near Fortaleza, Northeast Brazil, 3.2% of the travelers acquired tungiasis (²⁶26. Heukelbach J, Gomide M, Araújo F, Pinto NSR, Santana RD, Brito JRM, et al. Cutaneous larva migrans and tungiasis in international travelers exiting Brazil: an airport survey. J Travel Med [Internet]. 2007 Nov [cited 2022 Mar 29];14(6):374–80. Available from: https://pubmed.ncbi.nlm.nih.gov/17995532/
https://pubmed.ncbi.nlm.nih.gov/17995532... ).

Recently, a geostatistical approach was used to map the spatial distribution of tungiasis based on an ecological niche model (⁵⁴54. Deka MA, Heukelbach J. Distribution of tungiasis in Latin America: Identification of areas for potential disease transmission using an ecological niche model. Lancet Reg Health Am. 2022 Jan 1;5:100080.). The authors identified Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guyana, Guatemala, Haiti, Mexico, Paraguay, Peru, Trinidad and Tobago, and Venezuela as countries in which tungiasis may occur or probably occurs.

Prevalence

Population-based studies were performed in Argentina (⁵⁵55. Oscherov EB, Milano AMF, Roque Bar A. Percepciones y comportamiento de la población de un área endémica de Argentina en relación a la transmisión de Tunga penetrans (Siphonaptera: Tungidae). Bol Malariol Salud Ambient [Internet]. 2008 [cited 2022 Mar 29];48(1):53–60. Available from: http://ve.scielo.org/scielo.php?script=sci_arttext&pid=S1690-46482008000100006&lng=en&nrm=iso&tlng=
http://ve.scielo.org/scielo.php?script=s... ), Brazil (¹³13. de Carvalho RW, de Almeida AB, Barbosa-Silva SC, Amorim M, Ribeiro PC, Serra-Freire NM. The patterns of tungiasis in Araruama township, state of Rio de Janeiro, Brazil. Mem Inst Cruz [Internet]. 2003 [cited 2022 Mar 29];98(1):31–6. Available from: http://www.scielo.br/j/mioc/a/kVw4RzPLD7zTdCrghF6MPPd/?lang=en
http://www.scielo.br/j/mioc/a/kVw4RzPLD7... ,⁵⁶56. Matias RS. Epidemia de tungíase no Rio Grande do Sul. Rev Soc Bras Med Trop [Internet]. 1989 [cited 2022 Mar 29];22(3):137–42. Available from: http://www.scielo.br/j/rsbmt/a/tYdYvjn86vvdgYDfwxP9KHf/?lang=pt
http://www.scielo.br/j/rsbmt/a/tYdYvjn86... –⁶⁵65. Lütkepohl AC. Prävalenz und Risikofaktoren von Ektoparasitosen und Dermatomykosen in einer ländlichen Siedlung im brasilianischen Amazonasgebiet [Prevalence and risk factors of ectoparasitic skin diseases and dermatomycoses in a rural community in Amazonia, Brazil]. Berlin; 2016.), Haiti (⁶⁶66. Louis SJ, Bronsnick T, Louis FJ, Rao B. Tungiasis in Haiti: a case series of 383 patients. Int J Dermatol [Internet]. 2014 [cited 2022 Mar 29];53(8):999–1004. Available from: https://pubmed.ncbi.nlm.nih.gov/24601858/
https://pubmed.ncbi.nlm.nih.gov/24601858... ,⁶⁷67. Joseph JK, Bazile J, Mutter J, Shin S, Ruddle A, Ivers L, et al. Tungiasis in rural Haiti: a community-based response. Trans R Soc Trop Med Hyg [Internet]. 2006 Oct 1 [cited 2022 Mar 29];100(10):970–4. Available from: https://academic.oup.com/trstmh/article/100/10/970/1913208
https://academic.oup.com/trstmh/article/... ), Trinidad and Tobago (⁶⁸68. Chadee D. Distribution patterns of Tunga penetrans within a community in Trinidad, West Indies. J Trop Med Hyg. 1994;97(3):167–70.,⁶⁹69. Chadee DD. Tungiasis among five communities in South-western Trinidad, West Indies. Ann Trop Med Parasitol [Internet]. 1998 [cited 2022 Mar 29];92(1):107–13. Available from: https://pubmed.ncbi.nlm.nih.gov/9614460/
https://pubmed.ncbi.nlm.nih.gov/9614460/... ), and Venezuela (⁷⁰70. Franco-Salazar N, González B, Franco-Salazar V, Chinchilla O, Caraballo RV, García OR. Tungiasis en habitantes de Cañifle, municipio Sucre, estado Sucre, Venezuela [tungiasis in Cañifle residents, Sucre municipality, Sucre state, Venezuela]. Saber. 2016;28(1):90–8.). Prevalence ranged between 1.0% in the general population in a rural town in Amazonas State, Brazil (⁶⁵65. Lütkepohl AC. Prävalenz und Risikofaktoren von Ektoparasitosen und Dermatomykosen in einer ländlichen Siedlung im brasilianischen Amazonasgebiet [Prevalence and risk factors of ectoparasitic skin diseases and dermatomycoses in a rural community in Amazonia, Brazil]. Berlin; 2016.) and 82.6% in a rural community in Rio Grande do Sul State, Brazil (⁵⁶56. Matias RS. Epidemia de tungíase no Rio Grande do Sul. Rev Soc Bras Med Trop [Internet]. 1989 [cited 2022 Mar 29];22(3):137–42. Available from: http://www.scielo.br/j/rsbmt/a/tYdYvjn86vvdgYDfwxP9KHf/?lang=pt
http://www.scielo.br/j/rsbmt/a/tYdYvjn86... ). However, except for six studies performed in Brazil (¹³13. de Carvalho RW, de Almeida AB, Barbosa-Silva SC, Amorim M, Ribeiro PC, Serra-Freire NM. The patterns of tungiasis in Araruama township, state of Rio de Janeiro, Brazil. Mem Inst Cruz [Internet]. 2003 [cited 2022 Mar 29];98(1):31–6. Available from: http://www.scielo.br/j/mioc/a/kVw4RzPLD7zTdCrghF6MPPd/?lang=en
http://www.scielo.br/j/mioc/a/kVw4RzPLD7... ,⁵⁷57. Wilcke T, Heukelbach J, César Sabóia Moura R, Regina Sansigolo Kerr-Pontes L, Feldmeier H. High prevalence of tungiasis in a poor neighbourhood in Fortaleza, Northeast Brazil. Acta Trop [Internet]. 2002 Sep [cited 2022 Mar 29];83(3):255–8. Available from: https://pubmed.ncbi.nlm.nih.gov/12204399/
https://pubmed.ncbi.nlm.nih.gov/12204399... –⁶⁰60. Heukelbach J, Wilcke T, Harms G, Feldmeier H. Seasonal variation of tungiasis in an endemic community. Am J Trop Med Hyg [Internet]. 2005 Feb 1 [cited 2022 Mar 29];72(2):145–9. Available from: https://www.ajtmh.org/view/journals/tpmd/72/2/article-p145.xml
https://www.ajtmh.org/view/journals/tpmd... ,⁶³63. Ariza L, Seidenschwang M, Buckendahl J, Gomide M, Feldmeier H, Heukelbach J. [Tungiasis: a neglected disease causing severe morbidity in a shantytown in Fortaleza, State of Ceará]. Rev Soc Bras Med Trop [Internet]. 2007 [cited 2022 Mar 29];40(1):63–7. Available from: https://pubmed.ncbi.nlm.nih.gov/17486257/
https://pubmed.ncbi.nlm.nih.gov/17486257... ), it remained unclear how the study population was selected, whether the sample examined was representative, and whether the study was performed in the dry or rainy season. In studies in which the age-specific prevalence was reported, children constantly showed the highest prevalence (¹³13. de Carvalho RW, de Almeida AB, Barbosa-Silva SC, Amorim M, Ribeiro PC, Serra-Freire NM. The patterns of tungiasis in Araruama township, state of Rio de Janeiro, Brazil. Mem Inst Cruz [Internet]. 2003 [cited 2022 Mar 29];98(1):31–6. Available from: http://www.scielo.br/j/mioc/a/kVw4RzPLD7zTdCrghF6MPPd/?lang=en
http://www.scielo.br/j/mioc/a/kVw4RzPLD7... ,⁵⁶56. Matias RS. Epidemia de tungíase no Rio Grande do Sul. Rev Soc Bras Med Trop [Internet]. 1989 [cited 2022 Mar 29];22(3):137–42. Available from: http://www.scielo.br/j/rsbmt/a/tYdYvjn86vvdgYDfwxP9KHf/?lang=pt
http://www.scielo.br/j/rsbmt/a/tYdYvjn86... –⁵⁸58. Muehlen M, Heukelbach J, Wilcke T, Winter B, Mehlhorn H, Feldmeier H. Investigations on the biology, epidemiology, pathology and control of Tunga penetrans in Brazil. II. Prevalence, parasite load and topographic distribution of lesions in the population of a traditional fishing village. Parasitol Res [Internet]. 2003 Aug 1 [cited 2022 Mar 29];90(6):449–55. Available from: https://pubmed.ncbi.nlm.nih.gov/12768415/
https://pubmed.ncbi.nlm.nih.gov/12768415... ,⁶⁰60. Heukelbach J, Wilcke T, Harms G, Feldmeier H. Seasonal variation of tungiasis in an endemic community. Am J Trop Med Hyg [Internet]. 2005 Feb 1 [cited 2022 Mar 29];72(2):145–9. Available from: https://www.ajtmh.org/view/journals/tpmd/72/2/article-p145.xml
https://www.ajtmh.org/view/journals/tpmd... ,⁶²62. Bonfim W de M, Cardoso MD, Cardoso V de A, Andreazze R. Tungíase em uma área de aglomerado subnormal de Natal-RN: prevalência e fatores associados. Epidemiol Serv Saude [Internet]. 2010 Dec [cited 2022 Mar 29];19(4):379–88. Available from: http://scielo.iec.pa.gov.br/http://scielo.php?script=sci_arttext&pid=S1679-49742010000400008&lng=en&nrm=iso&tlng=en
http://scielo.iec.pa.gov.br/http://sciel... ). It is important to note that a high prevalence at the community level was associated with a high intensity of infection and severe morbidity (⁵⁸58. Muehlen M, Heukelbach J, Wilcke T, Winter B, Mehlhorn H, Feldmeier H. Investigations on the biology, epidemiology, pathology and control of Tunga penetrans in Brazil. II. Prevalence, parasite load and topographic distribution of lesions in the population of a traditional fishing village. Parasitol Res [Internet]. 2003 Aug 1 [cited 2022 Mar 29];90(6):449–55. Available from: https://pubmed.ncbi.nlm.nih.gov/12768415/
https://pubmed.ncbi.nlm.nih.gov/12768415... ,⁷¹71. Kehr JD, Heukelbach J, Mehlhorn H, Feldmeier H. Morbidity assessment in sand flea disease (tungiasis). Parasitol Res [Internet]. 2007 Jan [cited 2022 Mar 29];100(2):413–21. Available from: https://pubmed.ncbi.nlm.nih.gov/17058108/
https://pubmed.ncbi.nlm.nih.gov/17058108... –⁷³73. Feldmeier H, Kehr JD, Poggensee G, Heukelbach J. High exposure to Tunga penetrans (Linnaeus, 1758) correlates with intensity of infestation. Mem Inst Cruz [Internet]. 2006 [cited 2022 Mar 29];101(1):65–9. Available from: http://www.scielo.br/j/mioc/a/csnpsRLq5FqY5MkQLf8GRjG/?lang=en
http://www.scielo.br/j/mioc/a/csnpsRLq5F... ).

A constant finding was an S-shaped age-specific prevalence curve with a peak in children 5 to 12 years and a second peak in people older than 60 years (¹³13. de Carvalho RW, de Almeida AB, Barbosa-Silva SC, Amorim M, Ribeiro PC, Serra-Freire NM. The patterns of tungiasis in Araruama township, state of Rio de Janeiro, Brazil. Mem Inst Cruz [Internet]. 2003 [cited 2022 Mar 29];98(1):31–6. Available from: http://www.scielo.br/j/mioc/a/kVw4RzPLD7zTdCrghF6MPPd/?lang=en
http://www.scielo.br/j/mioc/a/kVw4RzPLD7... ,⁵⁶56. Matias RS. Epidemia de tungíase no Rio Grande do Sul. Rev Soc Bras Med Trop [Internet]. 1989 [cited 2022 Mar 29];22(3):137–42. Available from: http://www.scielo.br/j/rsbmt/a/tYdYvjn86vvdgYDfwxP9KHf/?lang=pt
http://www.scielo.br/j/rsbmt/a/tYdYvjn86... ,⁵⁷57. Wilcke T, Heukelbach J, César Sabóia Moura R, Regina Sansigolo Kerr-Pontes L, Feldmeier H. High prevalence of tungiasis in a poor neighbourhood in Fortaleza, Northeast Brazil. Acta Trop [Internet]. 2002 Sep [cited 2022 Mar 29];83(3):255–8. Available from: https://pubmed.ncbi.nlm.nih.gov/12204399/
https://pubmed.ncbi.nlm.nih.gov/12204399... ,⁵⁹59. Heukelbach J, Jackson A, Ariza L, Calheiros C, Soares V, Feldmeier H. Epidemiology and clinical aspects of tungiasis (sand flea infestation) in Alagoas State. J Infect Dev Ctries. 2007 Oct;1:202–9.,⁶⁰60. Heukelbach J, Wilcke T, Harms G, Feldmeier H. Seasonal variation of tungiasis in an endemic community. Am J Trop Med Hyg [Internet]. 2005 Feb 1 [cited 2022 Mar 29];72(2):145–9. Available from: https://www.ajtmh.org/view/journals/tpmd/72/2/article-p145.xml
https://www.ajtmh.org/view/journals/tpmd... ,⁶²62. Bonfim W de M, Cardoso MD, Cardoso V de A, Andreazze R. Tungíase em uma área de aglomerado subnormal de Natal-RN: prevalência e fatores associados. Epidemiol Serv Saude [Internet]. 2010 Dec [cited 2022 Mar 29];19(4):379–88. Available from: http://scielo.iec.pa.gov.br/http://scielo.php?script=sci_arttext&pid=S1679-49742010000400008&lng=en&nrm=iso&tlng=en
http://scielo.iec.pa.gov.br/http://sciel... ,⁶⁸68. Chadee D. Distribution patterns of Tunga penetrans within a community in Trinidad, West Indies. J Trop Med Hyg. 1994;97(3):167–70.,⁷⁰70. Franco-Salazar N, González B, Franco-Salazar V, Chinchilla O, Caraballo RV, García OR. Tungiasis en habitantes de Cañifle, municipio Sucre, estado Sucre, Venezuela [tungiasis in Cañifle residents, Sucre municipality, Sucre state, Venezuela]. Saber. 2016;28(1):90–8.). Typically, women were less frequently infected than men, irrespective of age (⁵⁷57. Wilcke T, Heukelbach J, César Sabóia Moura R, Regina Sansigolo Kerr-Pontes L, Feldmeier H. High prevalence of tungiasis in a poor neighbourhood in Fortaleza, Northeast Brazil. Acta Trop [Internet]. 2002 Sep [cited 2022 Mar 29];83(3):255–8. Available from: https://pubmed.ncbi.nlm.nih.gov/12204399/
https://pubmed.ncbi.nlm.nih.gov/12204399...

58. Muehlen M, Heukelbach J, Wilcke T, Winter B, Mehlhorn H, Feldmeier H. Investigations on the biology, epidemiology, pathology and control of Tunga penetrans in Brazil. II. Prevalence, parasite load and topographic distribution of lesions in the population of a traditional fishing village. Parasitol Res [Internet]. 2003 Aug 1 [cited 2022 Mar 29];90(6):449–55. Available from: https://pubmed.ncbi.nlm.nih.gov/12768415/
https://pubmed.ncbi.nlm.nih.gov/12768415...

59. Heukelbach J, Jackson A, Ariza L, Calheiros C, Soares V, Feldmeier H. Epidemiology and clinical aspects of tungiasis (sand flea infestation) in Alagoas State. J Infect Dev Ctries. 2007 Oct;1:202–9.

60. Heukelbach J, Wilcke T, Harms G, Feldmeier H. Seasonal variation of tungiasis in an endemic community. Am J Trop Med Hyg [Internet]. 2005 Feb 1 [cited 2022 Mar 29];72(2):145–9. Available from: https://www.ajtmh.org/view/journals/tpmd/72/2/article-p145.xml
https://www.ajtmh.org/view/journals/tpmd...

61. Damazio ORDS, da Silva MV. Tungiasis in schoolchildren in Criciúma, Santa Catarina State, South Brazil. Rev Inst Med Trop Sao Paulo [Internet]. 2009 Mar [cited 2022 Mar 29];51(2):103–8. Available from: https://pubmed.ncbi.nlm.nih.gov/19390739/
https://pubmed.ncbi.nlm.nih.gov/19390739...

62. Bonfim W de M, Cardoso MD, Cardoso V de A, Andreazze R. Tungíase em uma área de aglomerado subnormal de Natal-RN: prevalência e fatores associados. Epidemiol Serv Saude [Internet]. 2010 Dec [cited 2022 Mar 29];19(4):379–88. Available from: http://scielo.iec.pa.gov.br/http://scielo.php?script=sci_arttext&pid=S1679-49742010000400008&lng=en&nrm=iso&tlng=en
http://scielo.iec.pa.gov.br/http://sciel...

63. Ariza L, Seidenschwang M, Buckendahl J, Gomide M, Feldmeier H, Heukelbach J. [Tungiasis: a neglected disease causing severe morbidity in a shantytown in Fortaleza, State of Ceará]. Rev Soc Bras Med Trop [Internet]. 2007 [cited 2022 Mar 29];40(1):63–7. Available from: https://pubmed.ncbi.nlm.nih.gov/17486257/
https://pubmed.ncbi.nlm.nih.gov/17486257... -⁶⁴64. Pilger D, Schwalfenberg S, Heukelbach J, Witt L, Mencke N, Khakban A, et al. Controlling Tungiasis in an Impoverished Community: An Intervention Study. PLoS Negl Trop Dis [Internet]. 2008 Jul [cited 2022 Mar 29];2(10):e324. Available from: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0000324
https://journals.plos.org/plosntds/artic... , ⁶⁹69. Chadee DD. Tungiasis among five communities in South-western Trinidad, West Indies. Ann Trop Med Parasitol [Internet]. 1998 [cited 2022 Mar 29];92(1):107–13. Available from: https://pubmed.ncbi.nlm.nih.gov/9614460/
https://pubmed.ncbi.nlm.nih.gov/9614460/... ). These findings suggest that children and the elderly are the most vulnerable population groups and bear the highest disease burden.

How intense transmission can be in a resource-poor setting is demonstrated by a study in a favela in Fortaleza, Northeast Brazil. All individuals who re-entered the community after being out of the endemic area for some time became infected within three weeks (⁷⁴74. Heukelbach J, Franck S, Feldmeier H. High attack rate of Tunga penetrans (Linnaeus 1758) infestation in an impoverished Brazilian community. Trans R Soc Trop Med Hyg [Internet]. 2004 Jul [cited 2022 Mar 29];98(7):431–4. Available from: https://pubmed.ncbi.nlm.nih.gov/15138080/
https://pubmed.ncbi.nlm.nih.gov/15138080... ). In this setting, an average of 15 new fleas penetrated each individual per week.

Seasonal variation

Three community-based studies performed in semi-arid Northeast Brazil indicate a characteristic variation of prevalence and incidence according to seasons of the year (⁶⁰60. Heukelbach J, Wilcke T, Harms G, Feldmeier H. Seasonal variation of tungiasis in an endemic community. Am J Trop Med Hyg [Internet]. 2005 Feb 1 [cited 2022 Mar 29];72(2):145–9. Available from: https://www.ajtmh.org/view/journals/tpmd/72/2/article-p145.xml
https://www.ajtmh.org/view/journals/tpmd... ,⁶⁴64. Pilger D, Schwalfenberg S, Heukelbach J, Witt L, Mencke N, Khakban A, et al. Controlling Tungiasis in an Impoverished Community: An Intervention Study. PLoS Negl Trop Dis [Internet]. 2008 Jul [cited 2022 Mar 29];2(10):e324. Available from: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0000324
https://journals.plos.org/plosntds/artic... ,⁷⁵75. Heukelbach J, Winter B, Wilcke T, Muehlen M, Albrecht S, Sales De Oliveira FA, et al. Selective mass treatment with ivermectin to control intestinal helminthiases and parasitic skin diseases in a severely affected population. Bull World Health Organ [Internet]. 2004 Aug [cited 2022 Mar 29];82(8):563. Available from: /pmc/articles/PMC2622929/?report=abstract
/pmc/articles/PMC2622929/?report=abstrac... ). There was a significant inverse correlation between precipitation and the prevalence of tungiasis (⁶⁰60. Heukelbach J, Wilcke T, Harms G, Feldmeier H. Seasonal variation of tungiasis in an endemic community. Am J Trop Med Hyg [Internet]. 2005 Feb 1 [cited 2022 Mar 29];72(2):145–9. Available from: https://www.ajtmh.org/view/journals/tpmd/72/2/article-p145.xml
https://www.ajtmh.org/view/journals/tpmd... ). Prevalence started to increase as soon as the rainy season ended and peaked at the end of the dry season whereafter it decreased. During the dry season, the prevalence can be three times as high as in the rainy season.

Risk factors

Very few studies attempted to identify risk factors for the presence of tungiasis and the severity of the disease (Table 3). Only two studies were adequately designed to allow the calculation of odds ratios after multiple regression analysis (⁶²62. Bonfim W de M, Cardoso MD, Cardoso V de A, Andreazze R. Tungíase em uma área de aglomerado subnormal de Natal-RN: prevalência e fatores associados. Epidemiol Serv Saude [Internet]. 2010 Dec [cited 2022 Mar 29];19(4):379–88. Available from: http://scielo.iec.pa.gov.br/http://scielo.php?script=sci_arttext&pid=S1679-49742010000400008&lng=en&nrm=iso&tlng=en
http://scielo.iec.pa.gov.br/http://sciel... ,⁷⁶76. Muehlen M, Feldmeier H, Wilcke T, Winter B, Heukelbach J. Identifying risk factors for tungiasis and heavy infestation in a resource-poor community in northeast Brazil. Trans R Soc Trop Med Hyg [Internet]. 2006 Apr [cited 2022 Mar 29];100(4):371–80. Available from: https://pubmed.ncbi.nlm.nih.gov/16297946/
https://pubmed.ncbi.nlm.nih.gov/16297946... ). Poor construction of the house, presence of animals on the compound, low level of education, and not using shoes regularly were the exposure variables with the highest odds ratio. Poor housing characteristics and the absence of a solid floor turned out to be independent risk factors for the presence of tungiasis and severe disease (⁷⁶76. Muehlen M, Feldmeier H, Wilcke T, Winter B, Heukelbach J. Identifying risk factors for tungiasis and heavy infestation in a resource-poor community in northeast Brazil. Trans R Soc Trop Med Hyg [Internet]. 2006 Apr [cited 2022 Mar 29];100(4):371–80. Available from: https://pubmed.ncbi.nlm.nih.gov/16297946/
https://pubmed.ncbi.nlm.nih.gov/16297946... ). Studies performed in rural Argentina and rural Venezuela, and in Santa Catarina State, Brazil described low economic status, presence of garbage on the compound, and lack of a solid floor as risk factors (⁵⁵55. Oscherov EB, Milano AMF, Roque Bar A. Percepciones y comportamiento de la población de un área endémica de Argentina en relación a la transmisión de Tunga penetrans (Siphonaptera: Tungidae). Bol Malariol Salud Ambient [Internet]. 2008 [cited 2022 Mar 29];48(1):53–60. Available from: http://ve.scielo.org/scielo.php?script=sci_arttext&pid=S1690-46482008000100006&lng=en&nrm=iso&tlng=
http://ve.scielo.org/scielo.php?script=s... ,⁶¹61. Damazio ORDS, da Silva MV. Tungiasis in schoolchildren in Criciúma, Santa Catarina State, South Brazil. Rev Inst Med Trop Sao Paulo [Internet]. 2009 Mar [cited 2022 Mar 29];51(2):103–8. Available from: https://pubmed.ncbi.nlm.nih.gov/19390739/
https://pubmed.ncbi.nlm.nih.gov/19390739... ,⁶²62. Bonfim W de M, Cardoso MD, Cardoso V de A, Andreazze R. Tungíase em uma área de aglomerado subnormal de Natal-RN: prevalência e fatores associados. Epidemiol Serv Saude [Internet]. 2010 Dec [cited 2022 Mar 29];19(4):379–88. Available from: http://scielo.iec.pa.gov.br/http://scielo.php?script=sci_arttext&pid=S1679-49742010000400008&lng=en&nrm=iso&tlng=en
http://scielo.iec.pa.gov.br/http://sciel... ,⁶⁴64. Pilger D, Schwalfenberg S, Heukelbach J, Witt L, Mencke N, Khakban A, et al. Controlling Tungiasis in an Impoverished Community: An Intervention Study. PLoS Negl Trop Dis [Internet]. 2008 Jul [cited 2022 Mar 29];2(10):e324. Available from: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0000324
https://journals.plos.org/plosntds/artic... ,⁷⁰70. Franco-Salazar N, González B, Franco-Salazar V, Chinchilla O, Caraballo RV, García OR. Tungiasis en habitantes de Cañifle, municipio Sucre, estado Sucre, Venezuela [tungiasis in Cañifle residents, Sucre municipality, Sucre state, Venezuela]. Saber. 2016;28(1):90–8.). However, these studies were not conceived as analytical studies and therefore do not allow a conclusion. There is circumstantial evidence that tungiasis is not only causally related to poverty but that it also perpetuates poverty (⁷⁷77. Feldmeier H, Heukelbach J. Epidermal parasitic skin diseases: a neglected category of poverty-associated plagues. Bull World Health Organ [Internet]. 2009 Feb [cited 2022 Mar 29];87(2):152–9. Available from: https://pubmed.ncbi.nlm.nih.gov/19274368/
https://pubmed.ncbi.nlm.nih.gov/19274368... ).

Zoonotic aspects of tungiasis

Recently, the zoonotic aspects of tungiasis in the Americas have been reviewed in detail (⁷⁸78. Harvey TV, Linardi PM, Carlos RSA, Heukelbach J. Tungiasis in domestic, wild, and synanthropic animals in Brazil. Acta Trop [Internet]. 2021 Oct 1 [cited 2022 Mar 29];222. Available from: https://pubmed.ncbi.nlm.nih.gov/34331896/
https://pubmed.ncbi.nlm.nih.gov/34331896... ). In Brazil alone, 11 species of domestic, sylvatic synanthropic animals are known to be hosts for T. penetrans (⁷⁸78. Harvey TV, Linardi PM, Carlos RSA, Heukelbach J. Tungiasis in domestic, wild, and synanthropic animals in Brazil. Acta Trop [Internet]. 2021 Oct 1 [cited 2022 Mar 29];222. Available from: https://pubmed.ncbi.nlm.nih.gov/34331896/
https://pubmed.ncbi.nlm.nih.gov/34331896... ). Presumably, in the Amazon rainforest, many other species serve as hosts for T. penetrans (¹1. Linardi PM, de Avelar DM. Neosomes of tungid fleas on wild and domestic animals. Parasitol Res [Internet]. 2014 Sep 25 [cited 2022 Mar 29];113(10):3517. Available from: /pmc/articles/PMC4172993/
/pmc/articles/PMC4172993/... ).

In urban areas, dogs kept as pet animals were found to be the most frequently infected animal species with a prevalence of up to 87% (⁷⁸78. Harvey TV, Linardi PM, Carlos RSA, Heukelbach J. Tungiasis in domestic, wild, and synanthropic animals in Brazil. Acta Trop [Internet]. 2021 Oct 1 [cited 2022 Mar 29];222. Available from: https://pubmed.ncbi.nlm.nih.gov/34331896/
https://pubmed.ncbi.nlm.nih.gov/34331896... ). Infected cats were identified as animal reservoirs in rural and urban resource-poor communities, with prevalence ranging between 8.3% and 45.6% (⁷⁸78. Harvey TV, Linardi PM, Carlos RSA, Heukelbach J. Tungiasis in domestic, wild, and synanthropic animals in Brazil. Acta Trop [Internet]. 2021 Oct 1 [cited 2022 Mar 29];222. Available from: https://pubmed.ncbi.nlm.nih.gov/34331896/
https://pubmed.ncbi.nlm.nih.gov/34331896... ). Pigs were the most frequently infected livestock animal with a prevalence between 16.6% and 78% (⁷⁸78. Harvey TV, Linardi PM, Carlos RSA, Heukelbach J. Tungiasis in domestic, wild, and synanthropic animals in Brazil. Acta Trop [Internet]. 2021 Oct 1 [cited 2022 Mar 29];222. Available from: https://pubmed.ncbi.nlm.nih.gov/34331896/
https://pubmed.ncbi.nlm.nih.gov/34331896... ). In a resource-poor urban community in Fortaleza, Northeast Brazil, 41.2% of Rattus rattus were found to be infected (⁷⁴74. Heukelbach J, Franck S, Feldmeier H. High attack rate of Tunga penetrans (Linnaeus 1758) infestation in an impoverished Brazilian community. Trans R Soc Trop Med Hyg [Internet]. 2004 Jul [cited 2022 Mar 29];98(7):431–4. Available from: https://pubmed.ncbi.nlm.nih.gov/15138080/
https://pubmed.ncbi.nlm.nih.gov/15138080... ).

To which extent the different animal species contribute to human infection seems to depend on the setting and sociocultural practices. A study in a rural community in Ceará State, Northeast Brazil, showed that of six mammal species suitable as hosts for T. penetrans, only cats and dogs were infected (⁷⁹79. Pilger D, Schwalfenberg S, Heukelbach J, Witt L, Mehlhorn H, Mencke N, et al. Investigations on the biology, epidemiology, pathology, and control of Tunga penetrans in Brazil: VII. The importance of animal reservoirs for human infestation. Parasitol Res [Internet]. 2008 Apr [cited 2022 Mar 29];102(5):875–80. Available from: https://pubmed.ncbi.nlm.nih.gov/18172688/
https://pubmed.ncbi.nlm.nih.gov/18172688... ). There was a positive correlation between the intensity of the infection in animals and that in humans. Living in a household with an infected dog or cat increased the odds of the presence of tungiasis in household members by 1.9 (95% CI 1.1-3.4) (⁷⁹79. Pilger D, Schwalfenberg S, Heukelbach J, Witt L, Mehlhorn H, Mencke N, et al. Investigations on the biology, epidemiology, pathology, and control of Tunga penetrans in Brazil: VII. The importance of animal reservoirs for human infestation. Parasitol Res [Internet]. 2008 Apr [cited 2022 Mar 29];102(5):875–80. Available from: https://pubmed.ncbi.nlm.nih.gov/18172688/
https://pubmed.ncbi.nlm.nih.gov/18172688... ).

DISCUSSION

Over the last two decades research performed in the Americas has substantially increased the knowledge of the epidemiology of tungiasis. Although data on the dynamics of transmission of tungiasis found in our study is limited to a few countries in the Americas, with most of the studies carried out in Brazil, the data highlight that the on-host and the off-host life cycle of T. penetrans are completed indoors in resource-poor settings. This causes cases to appear the whole year round, meaning that interventions need to be tailored to this type of transmission and sustained to reduce morbidity and prevent disabilities. However, it is also noticed that in some populations, transmission is seasonal. Understanding transmission patterns and dynamics in each context is fundamental to determining the type of interventions to reduce and hopefully interrupt transmission.

The number and diversity of animal species parasitized by T. penetrans and the remarkably broad host-specificity of sand flea in the Americas impose challenges to implementing control interventions for tungiasis in populations living already in vulnerable conditions. Integrated interventions must be based on a One Health approach and demand intersectoral work to reduce the burden of disease (⁸⁰80. Pan American Health Organization. 59th Directing Council. 73rd Session of the Regional committee of WHO for the Americas. One Health: A Comprehensive Approach for Addressing Health Threats at the Human-Animal-Environment Interface. Document 59/9 [Internet]. Washington, D.C.; 2021 [cited 2022 Mar 28]. Available from: https://www.paho.org/en/documents/cd599-one-health-comprehensive-approach-addressing-health-threats-human-animal
https://www.paho.org/en/documents/cd599-... ). Communities affected by tungiasis are commonly affected by other neglected tropical diseases, so integrated packages of interventions will benefit them and contribute to reducing their suffering caused by multiple diseases.

The extent of the geographical distribution of tungiasis in countries of the Region of the Americas is unknown. It is noticeable that the list of countries with reports of tungiasis in foreign travelers returning from endemic areas mirrored the list of countries where tungiasis may occur based on an ecological niche study (⁵⁴54. Deka MA, Heukelbach J. Distribution of tungiasis in Latin America: Identification of areas for potential disease transmission using an ecological niche model. Lancet Reg Health Am. 2022 Jan 1;5:100080.). This might suggest that at least 13 countries in the Americas (Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guyana, Guatemala, Haiti, Mexico, Paraguay, Peru, Trinidad and Tobago, and Venezuela) should implement tungiasis surveillance systems to determine the distribution and magnitude of tungiasis and implement interventions accordingly.

Tungiasis in travelers returning from countries in the Americas seems to be often reported especially during holidays. Reports of tungiasis in foreign travelers returning from an endemic area support the findings from the ecological niche model. A study from Fortaleza, a tourist hot spot in Northeast Brazil, showed that 3.2% of foreign travelers who spent holidays in communities located at a beach in Ceará State acquired tungiasis (²⁶26. Heukelbach J, Gomide M, Araújo F, Pinto NSR, Santana RD, Brito JRM, et al. Cutaneous larva migrans and tungiasis in international travelers exiting Brazil: an airport survey. J Travel Med [Internet]. 2007 Nov [cited 2022 Mar 29];14(6):374–80. Available from: https://pubmed.ncbi.nlm.nih.gov/17995532/
https://pubmed.ncbi.nlm.nih.gov/17995532... ). The risk to acquire tungiasis during holidays was four times as high as that for cutaneous larva migrans (²⁶26. Heukelbach J, Gomide M, Araújo F, Pinto NSR, Santana RD, Brito JRM, et al. Cutaneous larva migrans and tungiasis in international travelers exiting Brazil: an airport survey. J Travel Med [Internet]. 2007 Nov [cited 2022 Mar 29];14(6):374–80. Available from: https://pubmed.ncbi.nlm.nih.gov/17995532/
https://pubmed.ncbi.nlm.nih.gov/17995532... ). Hence, tungiasis should be considered a health risk for travelers to endemic areas.

Community-based studies done in Brazil, Venezuela and Haiti showed that prevalence in the general population varied between 1.0% and 82.6%. A similar broad range of prevalence is known from tungiasis-endemic areas in sub-Saharan Africa (⁴4. Feldmeier H, Heukelbach J, Ugbomoiko US, Sentongo E, Mbabazi P, von Samson-Himmelstjerna G, et al. Tungiasis--a neglected disease with many challenges for global public health. PLoS Negl Trop Dis [Internet]. 2014 Oct 30;8(10):e3133–e3133. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25356978
https://www.ncbi.nlm.nih.gov/pubmed/2535... ,⁸¹81. Ugbomoiko US, Ofoezie IE, Heukelbach J. Tungiasis: high prevalence, parasite load, and morbidity in a rural community in Lagos State, Nigeria. Int J Dermatol [Internet]. 2007 May [cited 2022 Mar 29];46(5):475–81. Available from: https://pubmed.ncbi.nlm.nih.gov/17472674/
https://pubmed.ncbi.nlm.nih.gov/17472674... ,⁸²82. Wiese S, Elson L, Reichert F, Mambo B, Feldmeier H. Prevalence, intensity and risk factors of tungiasis in Kilifi County, Kenya: I. Results from a community-based study. PLoS Negl Trop Dis [Internet]. 2017 Oct 9 [cited 2022 Mar 29];11(10):e0005925. Available from: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005925
https://journals.plos.org/plosntds/artic... ). The highly diverging prevalence may be attributed to the socio-economic characteristics of the communities, differences in the accuracy of the diagnostic methods applied, and the time of year the study was performed. Studies from Northeast Brazil, a region with a semi-arid climate, showed that prevalence in the dry season is 1.5 to 3-fold higher than in the rainy season (⁵⁹59. Heukelbach J, Jackson A, Ariza L, Calheiros C, Soares V, Feldmeier H. Epidemiology and clinical aspects of tungiasis (sand flea infestation) in Alagoas State. J Infect Dev Ctries. 2007 Oct;1:202–9.,⁶⁰60. Heukelbach J, Wilcke T, Harms G, Feldmeier H. Seasonal variation of tungiasis in an endemic community. Am J Trop Med Hyg [Internet]. 2005 Feb 1 [cited 2022 Mar 29];72(2):145–9. Available from: https://www.ajtmh.org/view/journals/tpmd/72/2/article-p145.xml
https://www.ajtmh.org/view/journals/tpmd... ). A rapid assessment method has been developed and validated which allows the examination of several hundred individuals in a single day (⁸³83. Ariza L, Wilcke T, Jackson A, Gomide M, Ugbomoiko US, Feldmeier H, et al. A simple method for rapid community assessment of tungiasis. Trop Med Int Health [Internet]. 2010 Jul [cited 2022 Mar 29];15(7):856–64. Available from: https://pubmed.ncbi.nlm.nih.gov/20497406/
https://pubmed.ncbi.nlm.nih.gov/20497406... ). If performed together with digital mapping technologies, disease occurrence and spatial distribution of tungiasis in a country can be reliably determined (²2. Elson L, Wright K, Swift J, Feldmeier H. Control of Tungiasis in Absence of a Roadmap: Grassroots and Global Approaches. Trop Med Infect Dis [Internet]. 2017 Jul 27 [cited 2022 Mar 29];2(3). Available from: /pmc/articles/PMC6082108/
/pmc/articles/PMC6082108/... ).

It is remarkable the finding of the S-shaped age-specific prevalence curve affecting children 5 to 12 years and the elderly of 60 years and over, and even more the finding of tungiasis affecting children ≤1 in Amerindian communities. This is surprising since children <1 year are usually carried on the hip or the back of their mother and should not have contact with the soil. Age-specific prevalence positively correlates with the intensity of tungiasis as measured by the number of embedded sand fleas (⁷⁶76. Muehlen M, Feldmeier H, Wilcke T, Winter B, Heukelbach J. Identifying risk factors for tungiasis and heavy infestation in a resource-poor community in northeast Brazil. Trans R Soc Trop Med Hyg [Internet]. 2006 Apr [cited 2022 Mar 29];100(4):371–80. Available from: https://pubmed.ncbi.nlm.nih.gov/16297946/
https://pubmed.ncbi.nlm.nih.gov/16297946... ). This allows the conclusion that children and the elderly are the most vulnerable part of the population and bear the highest disease burden. The S-shaped curve might indicate that in endemic areas with repeated re-infections a protective immunity against penetrating sand fleas does not develop, but in-depth studies on this aspect are needed for better characterization.

Tungiasis is a disease associated with poor living conditions, especially factors facilitating the transmission and reinfection as demonstrated in five of the six studies attempting to identify risk factors. However, only two studies from Brazil did allow to determine odds ratios (⁷⁵75. Heukelbach J, Winter B, Wilcke T, Muehlen M, Albrecht S, Sales De Oliveira FA, et al. Selective mass treatment with ivermectin to control intestinal helminthiases and parasitic skin diseases in a severely affected population. Bull World Health Organ [Internet]. 2004 Aug [cited 2022 Mar 29];82(8):563. Available from: /pmc/articles/PMC2622929/?report=abstract
/pmc/articles/PMC2622929/?report=abstrac... ). These studies showed that tungiasis transmission is maintained in communities with houses built from recycled material and without solid floors where families usually have a very low income diminishing their capacities to improve household conditions. This explains why within a country or region marginalized population groups bear the highest disease burden.

The findings of infection of jaguars and anteaters with T. penetrans in Brazil and Argentina (⁸⁴84. Widmer CE, Azevedo FCC. Tungiasis in a free-ranging jaguar (Panthera onca) population in Brazil. Parasitol Res [Internet]. 2012 Mar [cited 2022 Mar 29];110(3):1311–4. Available from: https://pubmed.ncbi.nlm.nih.gov/21863398/
https://pubmed.ncbi.nlm.nih.gov/21863398... –⁸⁶86. Frank R, Melaun C, Martins MM, Santos ALQ, Heukelbach J, Klimpel S. Tunga penetrans and further parasites in the giant anteater (Myrmecophaga tridactyla) from Minas Gerais, Brazil. Parasitol Res [Internet]. 2012 Nov [cited 2022 Mar 29];111(5):1907–12. Available from: https://pubmed.ncbi.nlm.nih.gov/22814770/
https://pubmed.ncbi.nlm.nih.gov/22814770... ), respectively, are indicative of ongoing transmission in natural environments and so of the risk of infection for tourists and residents entering those areas. Tungiasis in sylvatic environments is challenging for transmission interruption actions but information on preventive measures to avoid contact between the sand flea and the skin of humans is key in these areas.

Although this study did not meet the criteria for a systematic review, the authors followed a similar methodology to search for and analyze publications to better understand the current state of the knowledge on tungiasis epidemiology in the Region. This limitation may have affected the robustness of the findings, but it is clear the lack of knowledge of this neglected tropical disease in the Americas and the urgent need to support countries to implement surveillance of the disease and characterize the transmission in different contexts to tailor integrated interventions.

Our study showed that there are knowledge gaps on the distribution and magnitude of tungiasis in the Americas that prevent countries from implementing integrated actions to reduce morbidity. To close these gaps, combined efforts are urgently needed to understand important aspects such as:

• Identification of settings where tungiasis currently occurs including assessment of the burden of disease, knowledge of the age-specific and season-specific prevalence, and identification of the risk factors;

• Identification of most vulnerable population groups for severe disease and the predisposing risk factors;

• Identification of animal species that act as reservoirs/sources of infection in different settings;

• Development of entomological methods to better understand the transmission of T. penetrans in different settings; and

• Assessment of the socio-economic impact of tungiasis on the affected communities.

Understanding the transmission of tungiasis in the context of the affected communities will allow countries to develop One Health strategies to accelerate efforts toward reducing the burden of tungiasis as established in global and regional plans for neglected tropical diseases (⁵5. World Health Organization. Ending the neglect to attain the Sustainable Development Goals A road map for neglected tropical diseases 2021-2030 [Internet]. Geneva; 2020 [cited 2021 Feb 22]. Available from: https://www.who.int/publications/i/item/9789240010352.
https://www.who.int/publications/i/item/... ,⁸⁷87. Pan American Health Organization. 55th Directing Council. 68th Session of the Regional Committee of WHO for the Americas. Plan of Action for the Elimination of Neglected Infectious Diseases and Post-elimination Actions 2016-2022. Document CD55/15 [Internet]. Washington, D.C.; 2016 Sep [cited 2022 Apr 3]. Available from: https://www.paho.org/en/documents/cd5515-plan-action-elimination-neglected-infectious-diseases-and-post-elimination-actions
https://www.paho.org/en/documents/cd5515... ).

Conclusions

Research on T. penetrans and tungiasis performed in the Americas in the last two decades has substantially contributed to the current knowledge on the parasite and the disease. Nonetheless, there are important gaps in knowledge on the distribution and magnitude of the disease. Epidemiological surveillance of tungiasis in the Region of the Americas is urgently needed to identify the affected populations and the risk factors associated with its transmission in different settings. Implementation of affordable, integrated, and culturally accepted interventions to prevent tungiasis and reduce transmission in endemic communities is needed to reach the goals established in global and regional initiatives to eliminate neglected tropical diseases within which tungiasis is included.

Disclaimer.

Authors hold sole responsibility for the views expressed in the manuscript, which may not necessarily reflect the opinion or policy of the RPSP/PAJPH and/or those of the Pan American Health Organization (PAHO).

REFERENCES

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