Carlos Henrique Nery Costa

Mannan-Binding Lectin Enhances Susceptibility to Visceral Leishmaniasis

ABSTRACT Levels of the serum opsonin mannan-binding lectin (MBL) were directly correlated with the probability of developing visceral leishmaniasis. Monocytes infected with MBL-opsonized Leishmania chagasi promastigotes secreted higher levels of tumor necrosis factor alpha and interleukin-6 than cells infected with nonopsonized parasites. Our findings indicate that MBL can modulate the clinical outcome of infection with L. chagasi and the function of infected macrophages.

Changes in the control program of visceral leishmaniasis in Brazil

Endereço para correspondência: Dr. Carlos Henrique Nery Costa. Laboratório de Leishmanioses/Hospital de Doenças Infecto-Contagiosas. R. Gov. Artur de Vasconcelos 151-Sul, 64000-450 Teresina, PI, Brasil. Tel: 55 86 221-3413 Fax: 55 86 221-2424 e-mail: crlshncst@aol.com Recebido em 23/2/2001 Depois de duas décadas de tentativas de controle da leishmaniose visceral (LV) no Brasil, o número de casos no país aumentou nitidamente e invadiu áreas urbanas, onde encontrou-se com a AIDS27. A recente proposta do Ministério da Saúde de reavaliar os programas de controle de endemias, aliada ao reconhecimento da pouca eficiência do programa brasileiro para LV, levou à convocação de um comitê de consultores para analisar o programa atual e propor mudanças para o controle da doença no país. Foram realizadas algumas reuniões do grupo técnico, a última tendo ocorrido em 4 de dezembro de 2000 em Brasília. Esta reunião contou com a presença dos consultores da Ministerio da Saúde e Técnico da Fundação Nacional de Saúde: Almério de Castro Gomes (Universidade de São Paulo), Carlos Henrique Nery Costa ( Universidade Federal do Piauí), Jackson Mauricio Lopes Costa (Universidade Federal do Maranhão), João Batista Furtado Vieira (Fundação Nacional de Saúde), José Wellington de Oliveira Lima (Fundação Nacional de Saúde) e Reinaldo Dietze (Universidade Federal do Espírito Santo). Em fevereiro de 2001, as modificações propostas foram apresentadas para os representantes das secretarias estaduais de saúde e das coordenações regionais da Fundação Nacional de Saúde, para implementação. O programa brasileiro, iniciado há mais de 40 anos, é composto pela integração de três medidas de saúde pública: a distribuição gratuita do tratamento específico, o controle de reservatórios domésticos e o controle de vetores. A medicação distribuída nas unidades públicas de saúde onde se trata LV são compostos de antimônio pentavalente, com dose recomendada de 20mg/kg/dia por no mínimo 20 dias. O controle de reservatórios tem sido feito através do diagnóstico sorológico de todos os cães domésticos onde existe transmissão de Leishmania chagasi para seres humanos. Para isto, foi estruturada uma rede de testes de imunofluorescência, utilizando-se eluato de papel de filtro; todos os cães com resultado reagente têm sido sacrificados. Finalmente, o controle do vetor, essencialmente para o flebótomo Lutzomyia longipalpis, é aplicado eventualmente com o uso de inseticidas, por After two decades of efforts to control visceral leishmaniasis (VL) in Brazil, the nation’s number of cases have had a distinct increase, and invaded cities where VL met AIDS 27. The recent proposition of the Ministry of Health to evaluate the programs of control of endemic diseases and the recognition of the poor performance of the Brazilian program for VL, led to the calling of a committee of advisers. They were asked to analyze the present program and to suggest changes for the control of the disease in the country. Some meetings took place in the year 2,000, the last in the 4 th of December. The following advisers attended this last meeting: the Counselor of the Ministerio da Saúde e Technician of the Fundação Nacional de Saeude: Almério de Castro Gomes (Universidade de São Paulo), Carlos Henrique Nery Costa ( Universidade Federal do Piauí), Jackson Mauricio Lopes Costa (Universidade Federal do Maranhão), João Batista Furtado Vieira (Fundação Nacional de Saúde), José Wellington de Oliveira Lima (Fundação Nacional de Saúde) e Reinaldo Dietze (Universidade Federal do Espírito Santo). In February of 2001, the proposed changes were presented to the regional offices of Fundação Nacional de Saúde and to the state health offices, for implementation.

Discovery of markers of exposure specific to bites of Lutzomyia longipalpis, the vector of Leishmania infantum chagasi in Latin America.

Background Sand flies deliver Leishmania parasites to a host alongside salivary molecules that affect infection outcomes. Though some proteins are immunogenic and have potential as markers of vector exposure, their identity and vector specificity remain elusive. Methodology/Principal Findings We screened human, dog, and fox sera from endemic areas of visceral leishmaniasis to identify potential markers of specific exposure to saliva of Lutzomyia longipalpis. Human and dog sera were further tested against additional sand fly species. Recombinant proteins of nine transcripts encoding secreted salivary molecules of Lu. longipalpis were produced, purified, and tested for antigenicity and specificity. Use of recombinant proteins corresponding to immunogenic molecules in Lu. longipalpis saliva identified LJM17 and LJM11 as potential markers of exposure. LJM17 was recognized by human, dog, and fox sera; LJM11 by humans and dogs. Notably, LJM17 and LJM11 were specifically recognized by humans exposed to Lu. longipalpis but not by individuals exposed to Lu. intermedia. Conclusions/Significance Salivary recombinant proteins are of value as markers of vector exposure. In humans, LJM17 and LJM11 emerged as potential markers of specific exposure to Lu. longipalpis, the vector of Leishmania infantum chagasi in Latin America. In dogs, LJM17, LJM11, LJL13, LJL23, and LJL143 emerged as potential markers of sand fly exposure. Testing these recombinant proteins in large scale studies will validate their usefulness as specific markers of Lu. longipalpis exposure in humans and of sand fly exposure in dogs.

How effective is dog culling in controlling zoonotic visceral leishmaniasis? a critical evaluation of the science, politics and ethics behind this public health policy

INTRODUCTION Zoonotic kala-azar, a lethal disease caused by protozoa of the genus Leishmania is considered out of control in parts of the world, particularly in Brazil, where transmission has spread to cities throughout most of the territory and mortality presents an increasing trend. Although a highly debatable measure, the Brazilian government regularly culls seropositive dogs to control the disease. Since control is failing, critical analysis concerning the actions focused on the canine reservoir was conducted. METHODS In a review of the literature, a historical perspective focusing mainly on comparisons between the successful Chinese and Soviet strategies and the Brazilian approach is presented. In addition, analyses of the principal studies regarding the role of dogs as risk factors to humans and of the main intervention studies regarding the efficacy of the dog killing strategy were undertaken. Brazilian political reaction to a recently published systematic review that concluded that the dog culling program lacked efficiency and its effect on public policy were also reviewed. RESULTS No firm evidence of the risk conferred by the presence of dogs to humans was verified; on the contrary, a lack of scientific support for the policy of killing dogs was confirmed. A bias for distorting scientific data towards maintaining the policy of culling animals was observed. CONCLUSIONS Since there is no evidence that dog culling diminishes visceral leishmaniasis transmission, it should be abandoned as a control measure. Ethical considerations have been raised regarding distorting scientific results and the killing of animals despite minimal or absent scientific evidence.

Characterization and speculations on the urbanization of visceral leishmaniasis in Brazil

The available hypotheses or explanations for the urbanization of American visceral leishmaniasis are insufficient. An alternative hypothesis is that changes in the ecology and biology of the vector, Lutzomyia longipalpis, might explain all the new urban epidemiological features of the disease. To tackle the knowledge gaps in this process, certain key research areas need to be prioritized: the role of dogs in expanding transmission in cities, community trials to evaluate new insecticides, and research on the ecological and molecular determinants of Leishmania chagasi transmission. Investment of public funds should focus on the development of a human vaccine, since such a vaccine now appears to be within reach. Even small effects from a vaccine could substantially reduce the impact of the disease, which in the last quarter century has challenged and defeated both the scientific community and the public health field around the world.

Vaccines for the leishmaniases: proposals for a research agenda.

The International Symposium on Leishmaniasis Vaccines, held in Olinda, Brazil, on March 9–11, 2009, congregated international experts who conduct research on vaccines against the leishmaniases. The questions that were raised during that meeting and the ensuing discussions are compiled in this report and may assist in guiding a research agenda. A group to further discussion on issues raised in this policy platform has been set up at http://groups.google.com/group/leishvaccines-l.

Prognostic Factors for Death from Visceral Leishmaniasis in Teresina, Brazil

Abstract.Background: A possible strategy to reduce fatality rates of visceral leishmaniasis is to identify prognostic factors that can be easily assessed and used as an aid to clinical decision-making. Patients and Methods: A case-control study was developed in Teresina, Brazil, in which cases were patients who died during treatment (n = 12) and controls (n = 78) comprised a random sample of patients who were alive when treatment was finished. Results: Variables significantly associated with death were severe anemia, fever for more than 60 days, diarrhea and jaundice. The prognostic system had a sensitivity of 85.7% and a specificity of 92.5%. Conclusion: The prognostic model developed in this study had satisfactory performance and might be useful in developing countries, since it is simple and inexpensive. However, it is still preliminary and needs to be improved and validated using larger and more recent samples.

The urban spread of visceral leishmaniasis: clues from spatial analysis.

Background. The pattern of spread of visceral leishmaniasis in Brazilian cities is poorly understood. Methods. We used geographic information systems and spatial statistics to evaluate the distribution of 1061 cases of visceral leishmaniasis in Teresina, Brazil, in 1993 through 1996. Results. A locally weighted (LOESS) regression model, which was fit as a smoothed function of spatial coordinates, demonstrated large-scale variation, with high incidence rates in peripheral neighborhoods that bordered forest land and pastures. Moran’s I indicated small-scale variation and clustering up to 300 m, roughly the flight range of the sand fly vector. Conclusions. Spatial analytical techniques can identify high-risk areas for targeting control interventions.

Genotypes of the Mannan-Binding Lectin Gene and Susceptibility to Visceral Leishmaniasis and Clinical Complications

BACKGROUND Visceral leishmaniasis (VL) is almost always lethal if not treated, but most infections with the causative agents are clinically silent. Mannan-binding lectin (MBL), an opsonin, is a candidate molecule for modifying progression to VL because it may enhance infection with intracellular pathogens. Mutations in the MBL2 gene decrease levels of MBL and may protect against development of VL. This case-control study examines genotypes of MBL2 and levels of MBL in individuals presenting with different outcomes of infection with Leishmania chagasi. METHODS Genotypes for MBL2 and levels of serum MBL were determined in uninfected control subjects (n=76) and in individuals presenting with asymptomatic infection (n=90) or VL (n=69). RESULTS Genotypes resulting in high levels of MBL were more frequent (odds ratio [OR], 2.5 [95% confidence interval [CI], 1.3-5.0]; P=.006) among individuals with VL than among those with asymptomatic infections and were even more frequent (OR, 3.97 [95% CI, 1.10-14.38]; P=.043) among cases of VL presenting with clinical complications than among those with uneventful courses. Serum levels of MBL were higher (P=.011) in individuals with VL than in asymptomatic infections . CONCLUSIONS Genotypes of the MBL2 gene predict the risk for developing VL and clinical complications in infections with L. chagasi.

Factors associated with the incidence of urban visceral leishmaniasis: an ecological study in Teresina, Piauí State, Brazil

The objective of this study was to identify socioeconomic and environmental factors associated with the incidence of visceral leishmaniasis in the city of Teresina, Piauí State, Brazil. This was an ecological study based on 1,744 cases reported from 1991 to 2000, and the citys neighborhoods served as the unit of analysis. Mean annual incidence rates were related to socioeconomic and demographic indicators and a vegetation index derived from remote sensing images by means of spatial multiple linear regression models. The neighborhoods with the highest incidence rates were mostly located in the citys peripheral areas. Multivariate analysis identified an interaction between population growth and the vegetation index, so that areas with high population growth and abundant vegetation showed the highest incidence rates. The percentage of households with piped water was inversely associated with visceral leishmaniasis incidence. Spatial distribution of visceral leishmaniasis in Teresina during the 1990s was heterogeneous, and incidence of the disease was associated with the peripheral neighborhoods with the heaviest vegetation cover, subject to rapid occupation and lack of adequate sanitation infrastructure.