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Poverty is intrinsically related to the incidence of Neglected Tropical Diseases (NTDs). The main countries that have the lowest human development indices (HDI) and the highest burdens of NTDs are located in tropical and subtropical regions of the world. Among these countries is Brazil, which is ranked 70th in HDI. Nine out of the ten NTDs established by the World Health Organization (WHO) are present in Brazil. Leishmaniasis, tuberculosis, dengue fever and leprosy are present over almost the entire Brazilian territory. More than 90% of malaria cases occur in the Northern region of the country, and lymphatic filariasis and onchocerciasis occur in outbreaks in a particular region. The North and Northeast regions of Brazil have the lowest HDIs and the highest rates of NTDs. These diseases are considered neglected because there is not important investment in projects for the development of new drugs and vaccines and existing programs to control these diseases are not sufficient. Another problem related to NTDs is co-infection with HIV, which favors the occurrence of severe clinical manifestations and therapeutic failure. In this article, we describe the status of the main NTDs currently occurring in Brazil and relate them to the HDI and poverty.

Visceral leishmaniasis (VL) is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania) infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin American network for coinfections of Leishmania and HIV to improve the consistency of research on the current situation of VL-HIV coinfections. Such a network would improve the collection of vital data and samples for better understanding of the clinical manifestations and immunopathogenic aspects of VL in immunosuppressed patients. Ultimately, a concerted effort would improve trials for new diagnostic methodologies and therapeutics, which could accelerate the implementation of more specific and effective diagnosis as well as public policies for treatments to reduce the impact of VL-HIV coinfections on the Latin American population.

Visceral leishmaniasis (VL) is caused by Leishmania donovani and Leishmania infantum. The burden of VL is concentrated in tropical and subtropical areas; however, HIV infection has spread VL over a hyperendemic area. Several outcomes are observed as a result of VL–HIV coinfection. Impacts are observed in immunopathogenesis, clinical manifestation, diagnosis, and therapeutic response. Concerning clinical manifestation, typical and unusual manifestation has been observed during active VL in HIV-infected patient, as well as alteration in immunoresponse, inducing greater immunosuppression by low CD4 T-lymphocyte count or even by induction of immunoactivation, with cell senescence. Serological diagnosis of VL in the HIV-infected is poor, due to low humoral response, characterized by antibody production, so parasitological methods are more recommended. Another important and even more challenging point is the definition of the best therapeutic regimen for VL in HIV-coinfected patients, because in this population there is greater failure and consequently higher mortality. The challenge of better understanding immunopathogenesis in order to obtain more effective therapies is one of the crucial points to be developed. The combination of drugs and the use of secondary prophylaxis associated with highly active antiretroviral therapy may be the best tool for treatment of HIV coinfection. Some derivatives from natural sources have action against Leishmania; however, studies have been limited to in vitro evaluation, without clinical trials.

Leishmaniasis is a disease caused by protozoa of the genus Leishmania, and visceral leishmaniasis is a form in which the inner organs are affected. Since knowledge about immunity in experimental visceral leishmaniasis is poor, we present here a review on immunity and immunosuppression in experimental visceral leishmaniasis in mouse and hamster models. We show the complexity of the mechanisms involved and differences when compared with the cutaneous form of leishmaniasis. Resistance in visceral leishmaniasis involves both CD4 + and CD8 + T cells, and interleukin (IL)-2, interferon (IFN)-γ, and IL-12, the latter in a mechanism independent of IFN-γ and linked to transforming growth factor (TGF)-ß production. Susceptibility involves IL-10 but not IL-4, and B cells. In immune animals, upon reinfection, the elements involved in resistance are different, i.e., CD8 + T cells and IL-2. Since one of the immunopathological consequences of active visceral leishmaniasis in humans is suppression of T-cell responses, many studies have been conducted using experimental models. Immunosuppression is mainly Leishmania antigen specific, and T cells, Th2 cells and adherent antigen-presenting cells have been shown to be involved. Interactions of the co-stimulatory molecule family B7-CTLA-4 leading to increased level of TGF-ß as well as apoptosis of CD4 + T cells and inhibition of macrophage apoptosis by Leishmania infection are other components participating in immunosuppression. A better understanding of this complex immune response and the mechanisms of immunosuppression in experimental visceral leishmaniasis will contribute to the study of human disease and to vaccine development.

Immune reconstitution inflammatory syndromes (IRISs) have been reported in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (AIDS) since the introduction of highly active antiretroviral therapy (HAART). This syndrome is characterized by clinical manifestations of opportunistic infections when signs of immune reconstitution are observed during therapy. We report on leishmaniasis, suggestive of HAART-induced IRIS, in 2 patients with AIDS. After beginning HAART, 1 patient presented with disseminated, tegumentary lesions, whereas the other patient's preexisting lesions worsened and became more extensive; however, at the same time, their CD4(+) T cell counts were recovering and their virus loads were decreasing significantly. The lesions healed with anti-Leishmania therapy.

Clinical manifestations of tegumentary leishmaniasis in HIV-infected patients are diverse. Our data emphasize possible unusual manifestations of this disease in HIV-infected patients, particularly in severely immunosuppressed cases (< 200 CD4+ cells mm(-3)).