Epidemiological, clinical and laboratory aspects of human visceral leishmaniasis (HVL) associated with human immunodeficiency virus (HIV) coinfection: a systematic review.

Coinfection with human visceral leishmaniasis (HVL) and human immunodeficiency virus (HIV) has become an emerging public health problem in several parts of the world, with high morbidity and mortality rates. A systematic review was carried out in the literature available in PubMed, Scielo and Lilacs related to HVL associated with HIV coinfection, seeking to analyze epidemiological, clinical and laboratory aspects. Of the 265 articles found, 15 articles were included in the qualitative analysis, which referred to the results of HVL treatment in patients coinfected with HIV. In the published articles between 2007 and 2015, 1171 cases of HVL/HIV coinfection were identified, 86% males, average age 34 years, liposomal amphotericin B was the most commonly used drug, cure rates 68 and 20% relapses and 19% deaths, five different countries, bone marrow was used in 10/15 manuscripts. HVL/HIV coinfection is a major challenge for public health, mainly due to the difficulty in establishing an accurate diagnosis, low response to treatment with high relapse rates and evolution to death. In addition, these two pathogens act concomitantly for the depletion of the immune system, contributing to worsening the clinical picture of these diseases, which requires effective surveillance and epidemiological control measures.

Hormone levels are associated with clinical markers and cytokine levels in human localized cutaneous leishmaniasis.

Leishmaniasis is a serious health problem in several parts of the world, and localized cutaneous leishmaniasis (LCL) is the most frequent presentation of the tegumentary form of this disease cluster. Clinical presentations of leishmaniasis are influenced by both parasite and host factors, with emphasis on the host immune response. Alterations in plasma hormone levels have been described in many infections, and changes in hormone levels could be related to an imbalanced cytokine profile. In the present work, we evaluated a group of patients with LCL to determine changes in plasma hormone levels (cortisol, DHEA-S, estradiol, prolactin and testosterone) and their association with clinical markers of disease (lesion size, dose used to reach cure and time to cure) and with cytokines produced by PBMC stimulated by SLA (IFN-γ, IL-10 and TNF-α). Individuals with LCL exhibited lower plasma levels of DHEA-S, prolactin and testosterone compared with sex-matched controls, whereas levels of cortisol and estradiol were similar between patients and controls. Plasma levels of cortisol, estradiol or prolactin positively correlated with at least one clinical parameter. Cortisol and prolactin levels exhibited a negative correlation with levels of IFN-γ, whereas no correlation was observed with IL-10 or TNF-α levels. A decrease in DHEA-S levels was observed in male LCL patients when compared to male healthy controls. No other differences between the sexes were observed. Our results indicate a role for neuroendocrine regulation that restricts Th1 responses in human LCL. It is possible that, although impairing parasite killing, such neuroimmunomodulation may contribute to limiting tissue damage.

Immune and inflammatory responses to Leishmania amazonensis isolated from different clinical forms of human leishmaniasis in CBA mice.

Leishmania amazonensis causes different diseases depending on the host and parasitic virulence factors. In this study, CBA mice were infected with L. amazonensis isolates from patients with localized (Ba125), diffuse cutaneous (Ba276) or visceral leishmaniasis (Ba109). Mice infected with Ba125 and Ba276 progressed rapidly and lesions displayed an infiltrate rich in parasitized macrophages and were necrotic and ulcerated. Ba109 induced smaller lesions and a mixed inflammatory infiltrate without necrosis or ulceration. Ba109 induced an insidious disease with lower parasite load in CBA mice, similar to human disease. Levels of IFN-γ, IL-4 and IL-10 did not differ among the groups. Because all groups were unable to control the infection, expression of IL-4 associated with low production of IFN-γ in the early phase of infection may account for susceptibility, but others factors may contribute to the differences observed in inflammatory responses and infection progression. Evaluation of some parasitic virulence factors revealed that Ba276 exhibits higher ecto-ADPase and 5'-nucleotidase activities compared to the Ba109 and Ba125 strains. Both Ba276 and Ba125 had higher arginase activity in comparison to Ba109. Finally, these data suggest that the differences in enzyme activities among parasites can account for differences in host inflammatory responses and infection progression.

Isolation of Fonsecaea pedrosoi from the shell of the babassu coconut (Orbignya phalerata Martius) in the Amazon region of Maranhão Brazil.

Fonsecaea pedrosoi, a dematiaceous fungus and the main causative agent of chromoblastomycosis, has been isolated in worldwide from different natural sources in regions where the disease is endemic. In the Amazon region of Maranhão, Brazil, where the disease is prevalent, the breaking of the babassu coconut (Orbignya phalerata Martius) represents an important agricultural activity. In order to determine the presence of this fungus on this plant and on other natural substrates, material was collected in the Fortaleza Village Municipality of Pinheiro, Maranhão, in April and September 2002. A total of 68 samples, including 18 (26.5%) obtained from the shell of the babassu coconut, were analyzed. Samples were cultured using a standard method. Isolates were identified based on macromorphological aspects of the colonies on Sabouraud dextrose agar and based on the micromorphology of the conidia after growth on potato dextrose agar. Exophiala sp. was the most prevalent fungus isolated from the different natural substrates analyzed, while Cladophialophora sp. was only isolated from decomposing wood. Fonsecaea pedrosoi was isolated from one sample of babassu coconut shell suggesting that this coconut represents an important source of infection of chromoblastomycosis during extraction of the plant product in this region.

[Space expansion of the American visceral leishmaniasis in São Luis, Maranhão, Brazil]. / Expansão espacial da leishmaniose visceral americana em São Luis, Maranhão, Brasil.

The space occupation and the expansion of American visceral leishmaniasis (AVL) were described in the municipality of São Luis, Maranhão, Northeast Brazil. AVL medical notes from the Fundação Nacional de Saúde as well as official documents about the space occupation were analyzed from September 1982 to December 1996. AVL cases were more likely to occur in recently settled suburbs and tended to follow the same spatial pattern observed for land occupations secondary to migratory fluxes.

[Profile of leprosy patients in a hiperendemic area of Amazonian Maranhão, Brazil]. / Perfil dos pacientes com hanseníase em área hiperendêmica da Amazinia do Maranhão, Brasil.

An epidemiological cross-sectional study of 207 patients with leprosy disease, was undertaken between August 1998 to november 2000, aiming at evaluating the socioeconomic, demographic and ambiental profiles of the patients as well as physical incapacity due to the disease. The study was performed in the municipality of Buriticupu-Maranh o state, a hiperendemic leprosy area in the Amazonian Maranh o. The level of incapacity was assessed from parameters established by the Brazilian Health Minister. The clinical evaluation and the results of the physical tests were registered in a standardized form. It was observed a predominance of married people (45,9%), with low level of education (56%), being lend workers (40,1%), with familiar income to the minimum wage (76,3%), aged from 14 to 44 years (63,3%), males (60,9%) and brown (67,6%); 44% living in mud huts, 82,6% deposited their excrements in cesspits and 63,8% do not treat the drinking water, 58% utilized well-water and 51,7% do not use treated water for ingestion. The most affected segments of the body were the feet (62,3%), eyes (51,2%) end hands (7,2%), being the higher percentage of physical incapacitaties found among the patients bearing the borderline form of the disease (93%) mainly hands and feet, and in the virchowian form greatest frequency of eyes incapacities. It is concluded that the hyperendemicity associated with the precarious socioeconomic conditions and with a high level of physical incapacities may be involved with the living quality of the patients.

[Assessment of a leprosy control program in a hyperendemic county in the State of Maranhão, Brazil, 1991-1995]. / Avaliação do programa de controle da hanseníase em um município hiperendêmico do Estado do Maranhão, Brasil, 1991-1995.

This is a descriptive study to assess the leprosy control program in the municipality of Buriticupu in Maranhão State, Brazil. The records of 214 patients with different forms of leprosy were studied. Patients were treated at a health center of the Federal University in Maranhão located in the above-mentioned municipality. The study population was comprised of 110 cases with paucibacillary leprosy (PB) and 104 with multibacillary leprosy (MB). The patients were registered between January 1991 and December 1995. Data on the form of the disease, number of contacts registered, examined, and assessed, degree of disability at the beginning and end of treatment, and the register's status were collected on a form designed specifically for this purpose. Analysis of results was based on operational guidelines developed by the Ministry of Health. There was a slight predominance of the PB form. Observation of patients with physical disabilities at the beginning and end of treatment was low, as were levels of successful treatment and examined contacts. There was a high dropout level. The program was considered "low-level performance" for all indicators used in the study.

[Eco-epidemiology of cutaneous leishmaniasis in Buriticupu, Amazon region of Maranhão State, Brazil, 1996-1998]. / Ecoepidemiologia da leishmaniose tegumentar no Município de Buriticupu, Amazônia do Maranhão, Brasil, 1996 a 1998.

This study presents the distribution of leishmaniasis in the town of Buriticupu, Maranhão, Brazil, by month, season, occupation, gender, and age from 1996 to 1998. These data were compared with those on sand flies obtained by other authors during the same period. The disease affected all age groups, in the following order: 0-5 years (4.1%), 6-10 (7.1%), 11-15 (13.6%), 16-21 (20.8%), 22-30 (21.1%), and > 30 (33.3%). The disease predominantly affected males (70.1%) and agricultural workers (52.5%), followed by students (17.7%), and domestic workers (16.0%). Like the sand fly vector, the disease was distributed throughout the year, but the greatest concentration of cases was recorded in the dry season (58.5%), while sand flies presented bimodal peaks in the first two years and occurred more frequently in the rainy season in 1998. The disease continues to present the same characteristics as in the past, but there was a proportional increase in cases among children and females, suggesting transmission in the anthropic environment.

Review of the current treatments for leishmaniases.

Leishmaniases are vector-borne zoonotic diseases that are prevalent in tropical and subtropical areas in the world, with two million new cases occurring yearly. Visceral and tegumentary forms of leishmaniasis are known. The latter form may present as localized cutaneous or mucosal forms, disseminated, diffuse forms, or leishmaniasis recidiva cutis. Visceral leishmaniasis is caused by parasites of the species Leishmania (Leishmania) donovani and L. (L.) infantum, and tegumentary leishmaniasis is caused by 15 other species, with distinct distributions in the Old and New World. The varied clinical manifestations, the multitude of Leishmania species, and the increasing incidence of HIV coinfection make the diagnosis and treatment of leishmaniases complex. Since there are no solid data relating clinical manifestations, treatment outcomes and Leishmania species the decision regarding the best therapeutic option is almost entirely based on clinical manifestations. Because most of the literature is focused on leishmaniasis in the Old World, in this review we present data on the treatment of New World leishmaniasis in more detail. Ranked therapeutic options, clinical trials, and also observations, even with a restricted number of subjects, on treatment outcome of visceral and different forms of tegumentary leishmaniasis, are presented. Treatment for leishmaniasis in HIV-coinfected patients is addressed as well. Some of these data strongly suggest that the differences in the outcome of the treatment are related to the Leishmania species. Therefore, although it is not possible at most points of care to identify the species causing the infection - a process that requires a well equipped laboratory - the infecting species should be identified whenever possible. More recent approaches, such as the use of immunomodulators and immunotherapy, and the lines for development of new candidate drugs are mentioned.

[Bacterial infection in cutaneous leishmaniasis: bacterial pattern and sensitivity to antibiotics]. / Infecção bacteriana na leishmaniose cutânea: padrão bacteriano e sensibilidade a antibióticos.

The bacterial flora from leishmanial ulcers was studied. The aerobic species Staphylococcus aureus and Pseudomonas aeruginosa were found most frequently. Evaluation of the sensitivity of these species to antibiotics showed that 100% of these isolates of Staphylococcus aureus were sensitive to vancomycin, amikacin and chloramphenicol, while 100% of the isolates of Pseudomonas aeruginosa were sensitive to amikacin, gentamicin and tobramycin. These species were generally resistant to penicillins and tetracycline.

Immune and inflammatory responses to Leishmania amazonensis isolated from different clinical forms of human leishmaniasis in CBA mice

Leishmania amazonensis causes different diseases depending on the host and parasitic virulence factors. In this study, CBA mice were infected with L. amazonensis isolates from patients with localized (Ba125), diffuse cutaneous (Ba276) or visceral leishmaniasis (Ba109). Mice infected with Ba125 and Ba276 progressed rapidly and lesions displayed an infiltrate rich in parasitized macrophages and were necrotic and ulcerated. Ba109 induced smaller lesions and a mixed inflammatory infiltrate without necrosis or ulceration. Ba109 induced an insidious disease with lower parasite load in CBA mice, similar to human disease. Levels of IFN-γ, IL-4 and IL-10 did not differ among the groups. Because all groups were unable to control the infection, expression of IL-4 associated with low production of IFN-γ in the early phase of infection may account for susceptibility, but others factors may contribute to the differences observed in inflammatory responses and infection progression. Evaluation of some parasitic virulence factors revealed that Ba276 exhibits higher ecto-ADPase and 5'-nucleotidase activities compared to the Ba109 and Ba125 strains. Both Ba276 and Ba125 had higher arginase activity in comparison to Ba109. Finally, these data suggest that the differences in enzyme activities among parasites can account for differences in host inflammatory responses and infection progression.

Subclinical form of the American visceral leishmaniasis.

The subclinical form of visceral leishmaniasis (VL) shows nonspecific clinical manifestations, with difficulties being frequently met in its clinical characterization and diagnostic confirmation. Thus, the objective of the present study was to define the clinical-laboratory profile of this clinical form. A cohort study was conducted in the state of Maranhão, Brazil, from January/1998 to December/2000, with monthly follow-up of 784 children aged 0-5 years. Based on the clinical-laboratory parameters reported in the literature, four categories were established, with the children being classified (according to their clinical-evolutive behavior) as asymptomatic (N = 144), as having the subclinical form (N = 33) or the acute form (N = 12) or as subjects "without VL" (N = 595). Multiple discriminant analysis demonstrated that the combination of fever, hepatomegaly, hyperglobulinemia, and increased blood sedimentation rate (BSR) can predict the subclinical form of VL as long as it is not associated with splenomegaly or leukopenia. Subjects with the subclinical form did not show prolonged or intermittent evolution or progression to the acute form of VL. Subclinical cases have a profile differing from the remaining clinical forms of VL, being best characterized by the combination of fever, hepatomegaly, hyperglobulinemia, and increased BSR.

Mimetismo apoptótico como possível mecanismo imunopatogênico da Leishmaniose Cutânea Difusa (LCD) / ApoptoticC mimicry as a possible immunopatogenic mechanism of Diffuse Cutaneous Leishmaniasis (DCL)

A Leishmaniose Cutânea Difusa (LCD) é uma manifestação clínica rara das leishmanioses, caracterizada pela presença de inúmeros macrófagos intensamente parasitados. Tem sido sugerido que a LCD resulta da ausência de resposta imune celular a antígenos de Leishmania, levando ao crescimento descontrolado do parasita. No Brasil, a LCD é quase que exclusivamente causada pela Leishmania (Leishmania) amazonensis. Nessa revisão discutiremos o papel da morte celular programada por apoptose como possível mecanismo imunopatogênico na infecção por L. amazonensis. Semelhante ao que ocorre durante o reconhecimento e fagocitose de células apoptóticas, formas amastigotas de L. amazonensis expõem PS em sua superfície, em um mecanismo chamado "Mimetismo Apoptótico" que resulta na desativação do macrófago e possibilita o estabelecimento e manutenção da infecção. Nesse contexto, o estudo da exposição de PS nos isolados de L. amazonensis de pacientes com LCD pode contribuir na elucidação de mecanismos supressores nessa patologia