Tropical Infections in the Context of Kidney Transplantation in Latin America.

Reports on tropical infections among kidney transplant (KT) recipients have increased in recent years, mainly because of the growing number of KT programs located in tropical and subtropical areas, and greater mobility or migration between different areas of the world. Endemic in emerging and developing regions, like most countries in Latin America, tropical infections are an important cause of morbidity and mortality in this population. Tropical infections in KT recipients may exhibit different pathways for acquisition compared with those in nonrecipients, such as transmission through a graft and reactivation of a latent infection triggered by immunosuppression. Clinical presentation may differ compared with that in immunocompetent patients, and there are also particularities in diagnostic aspects, treatment, and prognosis. KT patients must be screened for latent infections and immunized properly. Last, drug-drug interactions between immunosuppressive agents and drugs used to treat tropical infections are an additional challenge in KT patients. In this review, we summarize the management of tropical infections in KT patients.

Febre amarela / Yellow fever

A febre amarela é uma doença febril aguda de curta duração (no máximo 12 dias) e de gravidade variável. Apesar da erradicação da febre amarela urbana no Brasil, a febre amarela silvestre é endêmica em nosso país devido à manutenção do vírus na natureza, pela transmissão entre primatas não humanos (PNH) e mosquitos silvestres arbóreos. Acidentalmente, seres humanos susceptíveis são infectados ao penetrar o ciclo enzoótico natural. Por isso é importante atenção aos "eventos sentinela", situações em que um número maior de PNH adoece e morre alertando a comunidade na forma de epizootia. Nessa situação definem-se estratégias de intensificação da vacinação nos moradores das regiões afetadas (BRASIL, 2018).

Yellow fever is a short-term acute febrile disease (maximum 12 days) and of varying severity. Despite the eradication of urban yellow fever in Brazil, wild yellow fever is endemic in our country due to the maintenance of the virus in nature, due to the transmission between non-human primates (NHP) and wild tree mosquitoes. Accidentally, susceptible humans are infected by penetrating the natural enzootic cycle. Therefore, it is important to pay attention to "sentinel events", situations in which a greater number of NHP gets sick and dies alerting the community in the form of epizootics. This situation defines strategies for intensifying vaccination in residents of the affected regions (BRASIL, 2018).

Fiebre amarilla selvática con serología positiva para leptospira en un varon joven peruano / Jungle yellow fever with positive serology for leptospira in a young peruvian male

RESUMEN Fiebre amarilla (FA) y leptospirosis son zoonosis endémicas subdiagnosticadas de las regiones tropicales de África y Sudamérica. Ambas, pueden ser clínicamente indistinguibles y presentarse como síndrome febril icterohemorrágico agudo. Reportamos el caso de un varón de 20 años, procedente del departamento de Amazonas que se presentó con nueve días de enfermedad caracterizada por falla multiorgánica (compromiso neurológico, renal, hepático, respiratorio, y hematológico). Recibió tratamiento antibiótico, soporte transfusional, dialítico, hemodinámico, y ventilatorio; y a pesar de la gravedad del cuadro clínico, evolucionó favorablemente. Se confirmó FA por Rt-PCR y se obtuvo serología positiva para leptospira por ELISA y microaglutinación. Sin embargo, no se pudo demostrar, desde el punto de vista laboratorial, coinfección real por FA y leptospira. Este caso de FA severa con desenlace no fatal enfatiza la importancia del diagnóstico sindrómico adecuado, y un tratamiento de soporte precoz y agresivo que puede salvar la vida del paciente.

ABSTRACT Yellow fever (YF) and leptospirosis are under-diagnosed endemic zoonoses of the tropical regions of Africa and South America. Both may be clinically indistinguishable and present as an acute icterohemorrhagic febrile syndrome. We report the case of a 20-year-old male from the department of Amazonas who presented with nine days of disease characterized by multiorgan failure (neurological, renal, hepatic, respiratory, and hematological involvement). He received antibiotic treatment, as well as, transfusion, dialysis, hemodynamic, and ventilatory support. Despite the severity of the clinical condition, he evolved favorably. YF was confirmed by Rt-PCR and positive serology was obtained for leptospira by ELISA and microagglutination. However, from a laboratory point of view, real co-infection by yellow fever and leptospira could not be demonstrated. This case of severe YF with non-fatal outcome emphasizes the importance of adequate syndromic diagnosis, and early and aggressive supportive treatment that can save a patient's life.

Febre Amarela / Yellow Fever

A Febre Amarela é uma doença infecciosa aguda, caracterizada por febre. Não é transmissível e tem duração de no máximo 12 dias. As manifestações clínicas revelam as fases evolutivas da doença. Este trabalho consiste em um artigo de atualização, no qual foi realizado um estudo bibliográfico interpretativo e descritivo baseado na literatura atual sobre a Febre Amarela no Brasil. Esta doença é causada por um arbovírus que pertence à família Flaviviridae. A expansão da área de vacinação é muito discutida atualmente. Segundo o Ministério da Saúde, em 2016, foram confirmados seis casos de Febre Amarela no Brasil. Conforme a Sociedade Brasileira de Infectologia, a fisiopatologia desta doença é a mesma no ciclo urbano e no silvestre. O seu diagnóstico pode ser dividido em clínico e laboratorial, pois são as duas formas de confirmar a doença em indivíduos. As medidas preventivas consistem, principalmente, na imunização, medidas de proteção e no controle do vetor. Esta pesquisa fornece dados atuais em bases confiáveis, podendo ser utilizada para futuros trabalhos.

Yellow Fever is an acute infectious disease, characterized by fever. It is not transferable and lasts for a maximum of 12 days. The clinical manifestations reveal the evolutionary phases of the disease. This work consists of an update article, where an interpretative and descriptive bibliographic study was carried out based on the current literature on Yellow Fever in Brazil. This disease is caused by an arbovirus belonging to the family Flaviviridae. The expansion of the vaccination area is much discussed today. According to the Ministry of Health, in 2016, six cases of yellow fever were confirmed in Brazil. According to the Brazilian Society of Infectology, the pathophysiology of Yellow Fever is the same in the urban and wild cycle. The diagnosis of yellow fever can be divided into clinical and laboratory, as they are the two ways to confirm the disease in individuals. Preventive measures consist mainly of immunization, protective measures and vector control. This research provides current data on a reliable basis and can be used for future work

Infectious Disease: Mosquito-Borne Viral Illnesses.

Due to rapid globalization and ease of travel, mosquito-borne viral infections are now a concern for family physicians throughout the United States. Zika virus infection is one such concern. It is spread via mosquito bites or by sexual contact with an infected individual. Most patients are asymptomatic, and when symptoms occur, they are mild and nonspecific. The main concern is the potential of the infection to cause fetal anomalies. Dengue is another mosquito-borne viral infection. Symptoms of initial infection are mild, and may include arthralgias. Subsequent infection with a different serotype can cause life-threatening hemorrhagic fever or shock. Chikungunya virus infection is widespread in the Americas and symptoms are similar to those of dengue. However, it can cause a postviral chronic inflammatory rheumatism in up to half of patients. Yellow fever occurs mostly in sub-Saharan Africa and can cause hepatic failure. Encephalitis viruses, most commonly West Nile in the United States and others such as Japanese encephalitis virus, can cause neuroinvasive disease, most often in older adults. Vaccines are available for yellow fever and Japanese encephalitis viruses but the keys to prevention are insect avoidance, mosquito eradication, and use of mosquito repellants.

[Jungle yellow fever with positive serology for leptospira in a young peruvian male]. / Fiebre amarilla selvática con serología positiva para leptospira en un varon joven peruano.

Yellow fever (YF) and leptospirosis are under-diagnosed endemic zoonoses of the tropical regions of Africa and South America. Both may be clinically indistinguishable and present as an acute icterohemorrhagic febrile syndrome. We report the case of a 20-year-old male from the department of Amazonas who presented with nine days of disease characterized by multiorgan failure (neurological, renal, hepatic, respiratory, and hematological involvement). He received antibiotic treatment, as well as, transfusion, dialysis, hemodynamic, and ventilatory support. Despite the severity of the clinical condition, he evolved favorably. YF was confirmed by Rt-PCR and positive serology was obtained for leptospira by ELISA and microagglutination. However, from a laboratory point of view, real co-infection by yellow fever and leptospira could not be demonstrated. This case of severe YF with non-fatal outcome emphasizes the importance of adequate syndromic diagnosis, and early and aggressive supportive treatment that can save a patient's life.

Fiebre amarilla (FA) y leptospirosis son zoonosis endémicas subdiagnosticadas de las regiones tropicales de África y Sudamérica. Ambas, pueden ser clínicamente indistinguibles y presentarse como síndrome febril icterohemorrágico agudo. Reportamos el caso de un varón de 20 años, procedente del departamento de Amazonas que se presentó con nueve días de enfermedad caracterizada por falla multiorgánica (compromiso neurológico, renal, hepático, respiratorio, y hematológico). Recibió tratamiento antibiótico, soporte transfusional, dialítico, hemodinámico, y ventilatorio; y a pesar de la gravedad del cuadro clínico, evolucionó favorablemente. Se confirmó FA por Rt-PCR y se obtuvo serología positiva para leptospira por ELISA y microaglutinación. Sin embargo, no se pudo demostrar, desde el punto de vista laboratorial, coinfección real por FA y leptospira. Este caso de FA severa con desenlace no fatal enfatiza la importancia del diagnóstico sindrómico adecuado, y un tratamiento de soporte precoz y agresivo que puede salvar la vida del paciente.

Travelers' tropical skin diseases: Challenges and interventions.

Tropical regions receive a significant part of the traveling population. It is very important that health professionals are familiar with the main tropical skin diseases and able to advice patients appropriately. This article reviews the main tropical diseases of travelers, with an emphasis on diagnosis, management, and prevention. Among others, cutaneous larva migrans, myiasis, tungiasis, Chagas disease, Dengue fever, African trypanosomiasis, filariasis, and leishmaniasis are discussed. Increasing awareness among travelers and health care professionals can help reduce morbidity and mortality. Continued research on new drugs and vaccines is needed to reduce the risks of tropical diseases.

Lipase and factor V (but not viral load) are prognostic factors for the evolution of severe yellow fever cases

BACKGROUND Despite a highly efficacious vaccine, yellow fever (YF) is still a major threat in developing countries and a cause of outbreaks. In 2018, the Brazilian state of São Paulo witnessed a new YF outbreak in areas where the virus has not been detected before. OBJECTIVE The aim is to describe the clinical and laboratorial characteristics of severe cases of YF, evaluate viral to determine markers associated with fatal outcome. METHODS Acute severe YF cases (n = 62) were admitted to the Intensive Care Unit of a reference hospital and submitted to routine laboratorial evaluation on admission. YFV-RNA was detected in serum and urine by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and then sequenced. Patients were classified in two groups: survival or death. FINDINGS In the univariate analysis the following variables were associated with outcome: alanin aminotransferase (ALT), aspartat aminotransferase (AST), AST/ALT ratio, total bilirubin (TB), chronic kidney disease epidemiology collaboration (CKD-EPI), ammonia, lipase, factor V, international normalised ratio (INR), lactate and bicarbonate. Logistic regression model showed two independent variables associated with death: lipase [odds ratio (OR) 1.018, 95% confidence interval (CI) 1.007 to 1.030, p = 0.002], and factor V (OR -0.955, 95% CI 0.929 to 0.982, p = 0.001). The estimated lipase and factor V cut-off values that maximised sensitivity and specificity for death prediction were 147.5 U/L [area under the curve (AUC) = 0.879], and 56.5% (AUC = 0.913). MAIN CONCLUSIONS YF acute severe cases show a generalised involvement of different organs (liver, spleen, heart, kidneys, intestines and pancreas), and different parameters were related to outcome. Factor V and lipase are independent variables associated with death, reinforcing the importance of hemorrhagic events due to fulminant liver failure and pointing to pancreatitis as a relevant event in the outcome of the disease.

Combination of surveillance tools reveals that Yellow Fever virus can remain in the same Atlantic Forest area at least for three transmission seasons

BACKGROUND In Brazil, the Yellow Fever virus (YFV) is endemic in the Amazon, from where it eventually expands into epidemic waves. Coastal south-eastern (SE) Brazil, which has been a YFV-free region for eight decades, has reported a severe sylvatic outbreak since 2016. The virus spread from the north toward the south of the Rio de Janeiro (RJ) state, causing 307 human cases with 105 deaths during the 2016-2017 and 2017-2018 transmission seasons. It is unclear, however, whether the YFV would persist in the coastal Atlantic Forest of RJ during subsequent transmission seasons. OBJECTIVES To conduct a real-time surveillance and assess the potential persistence of YFV in the coastal Atlantic Forest of RJ during the 2018-2019 transmission season. METHODS We combined epizootic surveillance with fast diagnostic and molecular, phylogenetic, and evolutionary analyses. FINDINGS Using this integrative strategy, we detected the first evidence of YFV re-emergence in the third transmission season (2018-2019) in a dying howler monkey from the central region of the RJ state. The YFV detected in 2019 has the molecular signature associated with the current SE YFV outbreak and exhibited a close phylogenetic relationship with the YFV lineage that circulated in the same Atlantic Forest fragment during the past seasons. This lineage circulated along the coastal side of the Serra do Mar mountain chain, and its evolution seems to be mainly driven by genetic drift. The potential bridge vector Aedes albopictus was found probing on the recently dead howler monkey in the forest edge, very close to urban areas. MAIN CONCLUSIONS Collectively, our data revealed that YFV transmission persisted at the same Atlantic Forest area for at least three consecutive transmission seasons without the need of new introductions. Our real-time surveillance strategy permitted health authorities to take preventive actions within 48 h after the detection of the sick non-human primate. The local virus persistence and the proximity of the epizootic forest to urban areas reinforces the concern with regards to the risk of re-urbanisation and seasonal re-emergence of YFV, stressing the need for continuous effective surveillance and high vaccination coverage in the SE region, particularly in RJ, an important tourist location.

Unexpected healers: Chinese medicine in the age of global migration (Lima and California, 1850-1930). / Sanadores inesperados: medicina china en la era de migración global (Lima y California, 1850-1930).

The massive waves of Chinese migrants arriving in California and Lima in the second half of the nineteenth century played a crucial role in expanding Chinese medicine in both settings. From the late 1860s on, herbalists expanded their healing system beyond their ethnic community, transforming Chinese medicine into one of the healing practices most widely adopted by the local population. This article uses a comparative approach to examine the diverging trajectories of Chinese healers in Peru and the USA, as well as the social and political factors that determined how this foreign medical knowledge adapted to its new environments.

Sanadores inesperados: medicina china en la era de migración global (Lima y California, 1850-1930) / Unexpected healers: Chinese medicine in the age of global migration (Lima and California, 1850-1930)

Resumen Las masivas olas de migrantes chinos que llegaron a California y Lima en la segunda mitad del siglo XIX jugaron un rol clave en la expansión de la medicina china en ambos contextos. Desde fines de la década de 1860, los herbolarios expandieron su sistema de sanación más allá de su comunidad étnica, transformando la medicina china en una de las prácticas de sanación más adoptada por la población local. Desde una perspectiva comparada, este artículo examina las divergentes trayectorias de los sanadores chinos en Perú y EEUU, así como los factores sociales y políticos que determinaron la adaptación de este conocimiento médico, foráneo, en su nuevo entorno.

Abstract The massive waves of Chinese migrants arriving in California and Lima in the second half of the nineteenth century played a crucial role in expanding Chinese medicine in both settings. From the late 1860s on, herbalists expanded their healing system beyond their ethnic community, transforming Chinese medicine into one of the healing practices most widely adopted by the local population. This article uses a comparative approach to examine the diverging trajectories of Chinese healers in Peru and the USA, as well as the social and political factors that determined how this foreign medical knowledge adapted to its new environments.

Yellow fever outbreak in Brazil: the puzzle of rapid viral spread and challenges for immunisation

We discuss the complex eco-social factors involved in the puzzle of the unexpected rapid viral spread in the ongoing Brazilian yellow fever (YF) outbreak, which has increased the reurbanisation risk of a disease without urban cases in Brazil since 1942. Indeed, this rapid spatial viral dissemination to the Southeast and South regions, now circulating in the Atlantic Forest fragments close to peri-urban areas of the main Brazilian megalopolises (São Paulo and Rio de Janeiro) has led to an exponential increase in the number of yellow fever cases. In less than 18 months, 1,833 confirmed cases and 578 deaths were recorded most of them reported in the Southeast region (99,9%). Large epizooties in monkeys and other non-human primates (NHPs) were communicated in the country with 732 YF virus (YFV) laboratory confirmed events only in the 2017/2018 monitoring period. We also discuss the peculiarities and similarities of the current outbreak when compared with previous great epidemics, examining several hypotheses to explain the recent unexpected acceleration of epizootic waves in the sylvatic cycle of the YFV together with the role of human, NHPs and mosquito mobility with respect to viral spread. We conclude that the most feasible hypothesis to explain this rapidity would be related to human behavior combined with ecological changes that promoted a significant increase in mosquito and NHP densities and their contacts with humans. We emphasize the urgent need for an adequate response to this outbreak such as extending immunisation coverage to the whole Brazilian population and developing novel strategies for immunisation of NHPs confined in selected reserve areas and zoos. Finally, we stress the urgent need to improve the quality of response in order to prevent future outbreaks and a catastrophic reurbanisation of the disease in Brazil and other South American countries. Continuous monitoring of YFV receptivity and vulnerability conditions with effective control of the urban vector Aedes aegypti and significant investments in YF vaccine production capacity and research and development for reduction of adverse effects are of the highest priority.

Not a polar island: yellow fever, Spanish medical research, and the struggle for scientific and political hegemony in late nineteenth century Cuba / Não se trata de uma ilha polar: febre amarela, pesquisa médica espanhola, e a luta pela hegemonia científica e política em Cuba no final do século XIX

Abstract: This paper explores questions related to yellow fever and the political destiny of Cuba in the late nineteenth century. A forgotten therapeutic device to treat the disease invented in that period, the "polar chamber" (cámara polar), provides a useful standpoint for reconstructing the tradition of Spanish yellow fever research in Cuba, a topic largely neglected by the medical historiography. The failed history of this device can also illuminate the complex struggle for scientific hegemony between Spanish, Cuban, and US institutions and researchers. Finally, we focus on the politics of the polar chamber by analyzing how this invention intended to provide a particular solution for the complex, threefold struggle for Cuba's political future.

Resumo: Este artigo investiga perguntas relativas à febre amarela e ao destino político de Cuba no final do século XIX. Um dispositivo terapêutico usado para tratar a doença foi inventado nesse período - a câmara polar. Ela oferece uma perspectiva útil para reconstituir a tradição da pesquisa espanhola da febre amarela em Cuba, um tópico muito negligenciado pela histografia médica. A falta de registro histórico deste dispositivo explica, em parte, a complexa luta por hegemonia científica entre instituições e pesquisadores espanhóis, cubanos e norte-americanos. Finalmente, abordamos a política da câmara polar, analisando como esta invenção visava oferecer uma solução especial para a complexa luta tríplice pelo futuro político de Cuba.

Not a polar island: yellow fever, Spanish medical research, and the struggle for scientific and political hegemony in late nineteenth century Cuba

This paper explores questions related to yellow fever and the political destiny of Cuba in the late nineteenth century. A forgotten therapeutic device to treat the disease invented in that period, the “polar chamber” (cámara polar), provides a useful standpoint for reconstructing the tradition of Spanish yellow fever research in Cuba, a topic largely neglected by the medical historiography. The failed history of this device can also illuminate the complex struggle for scientific hegemony between Spanish, Cuban, and US institutions and researchers. Finally, we focus on the politics of the polar chamber by analyzing how this invention intended to provide a particular solution for the complex, threefold struggle for Cuba’s political future.(AU)

Animal models of yellow fever and their application in clinical research.

Yellow fever virus (YFV) is an arbovirus that causes significant human morbidity and mortality. This virus has been studied intensively over the past century, although there are still no treatment options for those who become infected. Periodic and unpredictable yellow fever (YF) outbreaks in Africa and South America continue to occur and underscore the ongoing need to further understand this viral disease and to develop additional countermeasures to prevent or treat cases of illness. The use of animal models of YF is critical to accomplishing this goal. There are several animal models of YF that replicate various aspects of clinical disease and have provided insight into pathogenic mechanisms of the virus. These typically include mice, hamsters and non-human primates (NHP). The utilities and shortcomings of the available animal models of YF are discussed. Information on recent discoveries that have been made in the field of YFV research is also included as well as important future directions in further ameliorating the morbidity and mortality that occur as a result of YFV infection. It is anticipated that these model systems will help facilitate further improvements in the understanding of this virus and in furthering countermeasures to prevent or treat infections.

A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 in vitro but does not protect a mouse model from disease.

The yellow fever virus (YFV) vaccine 17D-204 is considered safe and effective, yet rare severe adverse events (SAEs), some resulting in death, have been documented following vaccination. Individuals exhibiting post-vaccinal SAEs are ideal candidates for antiviral monoclonal antibody (MAb) therapy; the time until appearance of clinical signs post-exposure is usually short and patients are quickly hospitalized. We previously developed a murine-human chimeric monoclonal antibody (cMAb), 2C9-cIgG, reactive with both virulent YFV and 17D-204, and demonstrated its ability to prevent and treat YF disease in both AG129 mouse and hamster models of infection. To counteract possible selection of 17D-204 variants that escape neutralization by treatment with a single MAb (2C9-cIgG), we developed a second cMAb, 864-cIgG, for use in combination with 2C9-cIgG in post-vaccinal therapy. MAb 864-cIgG recognizes/neutralizes only YFV 17D-204 vaccine substrain and binds to domain III (DIII) of the viral envelope protein, which is different from the YFV type-specific binding site of 2C9-cIgG in DII. Although it neutralized 17D-204 in vitro, administration of 864-cIgG had no protective capacity in the interferon receptor-deficient AG129 mouse model of 17D-204 infection. The data presented here show that although DIII-specific 864-cIgG neutralizes virus infectivity in vitro, it does not have the ability to abrogate disease in vivo. Therefore, combination of 864-cIgG with 2C9-cIgG for treatment of YF vaccination SAEs does not appear to provide an improvement on 2C9-cIgG therapy alone.

Yellow fever virus: genetic and phenotypic diversity and implications for detection, prevention and therapy.

Yellow fever virus (YFV) is the prototypical hemorrhagic fever virus, yet our understanding of its phenotypic diversity and any molecular basis for observed differences in disease severity and epidemiology is lacking, when compared to other arthropod-borne and haemorrhagic fever viruses. This is, in part, due to the availability of safe and effective vaccines resulting in basic YFV research taking a back seat to those viruses for which no effective vaccine occurs. However, regular outbreaks occur in endemic areas, and the spread of the virus to new, previously unaffected, areas is possible. Analysis of isolates from endemic areas reveals a strong geographic association for major genotypes, and recent epidemics have demonstrated the emergence of novel sequence variants. This review aims to outline the current understanding of YFV genetic and phenotypic diversity and its sources, as well as the available animal models for characterizing these differences in vivo. The consequences of genetic diversity for detection and diagnosis of yellow fever and development of new vaccines and therapeutics are discussed.