Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-γ, TNF-α and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-α, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-γ was lower in the VL patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.

Neurological involvement in visceral leishmaniasis: case report

Visceral leishmaniasis is a severe and potentially fatal vector-borne disease. The most typical symptoms are fever, hepatosplenomegaly, weight loss, bleeding and bacterial infections. Neurological changes are rarely reported. This paper describes a child who presented with neurological signs as the first symptoms of leishmaniasis; tone was diminished and tremors in the extremities were observed. A diagnosis of visceral leishmaniasis was confirmed by parasite detection in the bone marrow. Symptoms were reversed by specific treatment. The nature of a possible mechanism of neurological involvement in visceral leishmaniasis remains unexplained.

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

Splenectomy in a patient with treatment-resistant visceral leishmaniasis: a case report

Visceral leishmaniasis (VL), also known as Kala-azar, is a systemic infection caused by a protozoan (Leishmania) and, in its classic form, is a serious illness associated with malnutrition, anemia, hepatosplenomegaly, infectious processes and coagulopathies. The effect of splenectomy in patients with visceral leishmaniasis is not well defined; however, it is known that the spleen is the largest reservoir of infected cells belonging to the reticulo endothelial system. Therefore, the surgical procedure is an option for the debulking of parasites, providing a cure for refractory VL and minimizing the complications of hypersplenism.

Hemophagocytic lymphohistiocytosis associated with H1N1 virus infection and visceral leishmaniasis in a 4.5-month-old infant

We present a case of a 4.5-month-old boy from Turkey with hemophagocytic lymphohistiocytosis (HLH) associated with H1N1 virus and Leishmania spp. coinfection. Because visceral leishmaniasis can mimic hematologic disorders like HLH, it is important to rule out this clinical condition before starting immunosuppressive therapy. In our case, treatment with liposomal amphotericin B resulted in a dramatic resolution of clinical and laboratory abnormalities.

Profile and geographic distribution of reported cases of visceral leishmaniasis in Campo Grande, State of Mato Grosso do Sul, Brazil, from 2002 to 2009

INTRODUCTION: This study sought to describe the profile and geographic distribution of reported cases of visceral leishmaniasis (VL) in the City of Campo Grande, State of Mato Grosso do Sul (MS), Brazil, from 2002 to 2009. METHODS: Human data were collected from the Brazilian National Information System for Notifiable Diseases. Canine cases and entomological data were obtained from the Information Service for Canine Visceral Leishmaniasis Control/Campo Grande, MS. RESULTS: A total of 951 records from 2002 to 2009 were investigated. The number of reported cases of VL in males was significantly higher (p < 0.0001) than that in females. The higher frequency observed among males was associated with age (p < 0.0001), which increased in individuals aged 40 years and older. The overall fatality rate was 7.4%. Entomological surveys conducted in 2006, 2007, and 2009 showed the insect vector Lutzomyia longipalpis to be present in all urban regions of the county. CONCLUSIONS: VL cases in humans and dogs, as well as in vectors, occurs in all urban regions of Campo Grande. Despite not observing tendencies of increase or reduction in the incidence of the disease due to aging, the major incidence in men is higher in those aged 40 years or above.

Triatomines in dwellings and outbuildings in an endemic area of Chagas disease in northeastern Brazil

INTRODUCTION: The present study identified the triatomines collected in intra and peri-domestic environments, observed the occurrence of Trypanosoma cruzi infection in triatomines and correlated this information with housing conditions and the fauna associated with the rural areas of the City of Itabaianinha, located in the State of Sergipe, Brazil. METHODS: Quarterly visits were conducted between March 2009 and March 2010, and the homes to be visited for the active search of insects were determined by random selection. In each housing unit, the insects were collected by a manual search with a metal clip and flashlight to inspect openings and cavities, with a collection time of one hour/home/individual. The Pirisa® dislodge chemical was used to force the insects to leave their ecotopes. Analysis of the intestinal contents of triatomines was performed in the laboratory to establish the presence of Trypanosomatidae. RESULTS: Of the 103 dwellings surveyed, 17.5% were infested with Panstrongylus megistus. The village of Mutuca exhibited the highest infestation rate (38.1%). All the villages with relevant infestation rates were situated in the northern area of the city. The highest percentage of vector infection was found in the village of Água Boa (56.5%). The rural dwellings were found to be primarily brick or wooden house with or without roughcast or plastered walls, and the outbuilding most frequently associated with triatomines was the chicken run. CONCLUSIONS: These results emphasise the need for broader vector control and surveillance and for educational campaigns in the context of the Chagas Disease Control Program.

Involvement and interactions of different immune cells and their cytokines in human visceral leishmaniasis

Visceral leishmaniasis (VL) or kala-azar, a disseminated infection of the lymphoreticular system of the body, is marked by severe defect in immune system of the host. Successful cure of VL depends on the immune status of the host in combination with the effects of the antileishmanial drugs. The rationale approach towards eradication of this disease would be to potentiate the immune functioning of the host in addition to parasite killing. This review deals with different aspects of adaptive and innate immune responses and explores their role in protection or pathogenesis of VL. IL-10 has emerged as the principal cytokine responsible for disease pathogenesis, although evidences regarding its source during active VL remain inconclusive. On the other hand, IFNγ, under the influence of IL-12, is mostly correlated with healing of the disease. Chemokines are important in mounting cell-mediated immune response as they can prevent parasite invasion in association with cytokines. Different types of T cells like CD4, CD8 and NK T cells also contribute to the immunology of this disease. In spite of conflicting reports, the role of regulatory T cells in VL pathogenesis is important. Recently discovered Th17 subset and its different members have been reported to perform diverse functions in the course of VL and leishmaniasis as a whole. Innate immune responses, depending on the cell types, are essential in early parasite detection and subsequent development of an efficient NK cell response. Immunotherapy targeting IL-10 could be looked upon as an interesting option for the treatment of VL.

Serologic assessment of yellow fever immunity in the rural population of a yellow fever-endemic area in Central Brazil

IntroductionThe yellow fever epidemic that occurred in 1972/73 in Central Brazil surprised the majority of the population unprotected. A clinical-epidemiological survey conducted at that time in the rural area of 19 municipalities found that the highest (13.8%) number of disease cases were present in the municipality of Luziânia, State of Goiás.MethodsThirty-eight years later, a new seroepidemiological survey was conducted with the aim of assessing the degree of immune protection of the rural population of Luziânia, following the continuous attempts of public health services to obtain vaccination coverage in the region. A total of 383 volunteers, aged between 5 and 89 years and with predominant rural labor activities (75.5%), were interviewed. The presence of antibodies against the yellow fever was also investigated in these individuals, by using plaque reduction neutralization test, and correlated to information regarding residency, occupation, epidemiological data and immunity against the yellow fever virus.ResultsWe found a high (97.6%) frequency of protective titers (>1:10) of neutralizing antibodies against the yellow fever virus; the frequency of titers of 1:640 or higher was 23.2%, indicating wide immune protection against the disease in the study population. The presence of protective immunity was correlated to increasing age.ConclusionsThis study reinforces the importance of surveys to address the immune state of a population at risk for yellow fever infection and to the surveillance of actions to control the disease in endemic areas.

Biochemical and nutritional evaluation of patients with visceral leishmaniasis before and after treatment with leishmanicidal drugs

Introduction Visceral leishmaniasis (VL) is caused by the intracellular protozoan Leishmania donovani complex. VL may be asymptomatic or progressive and is characterized by fever, anemia, weight loss and the enlargement of the spleen and liver. The nutritional status of the patients with VL is a major determinant of the progression, severity and mortality of the disease, as it affects the clinical progression of the disease. Changes in lipoproteins and plasma proteins may have major impacts in the host during infection. Thus, our goal was evaluate the serum total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, glucose, albumin, globulin and total protein levels, as well as the body composition, of VL patients before and after treatment. Methods Nutritional evaluation was performed using the bioelectrical impedance analysis (BIA) to assess body composition. Biochemical data on the serum total cholesterol, HDL, LDL, triglycerides, glucose, albumin, globulin and total protein were collected from the medical charts of the patients. Results BIA indicated that both pre-treatment and post-treatment patients exhibited decreased phase angles compared to the controls, which is indicative of disease. Prior to treatment, the patients exhibited lower levels of total body water compared to the controls. Regarding the biochemical evaluation, patients with active VL exhibited lower levels of total cholesterol, HDL, LDL and albumin and higher triglyceride levels compared to patients after treatment and the controls. Treatment increased the levels of albumin and lipoproteins and decreased the triglyceride levels. Conclusions Our results suggest that patients with active VL present biochemical and nutritional changes that are reversed by treatment.

Severe visceral leishmaniasis in children: the relationship between cytokine patterns and clinical features

Introduction The relationship between severe clinical manifestations of visceral leishmaniasis (VL) and immune response profiles has not yet been clarified, despite numerous studies on the subject. This study aimed to investigate the relationship between cytokine profiles and the presence of immunological markers associated with clinical manifestations and, particularly, signs of severity, as defined in a protocol drafted by the Ministry of Health (Brazil). Methods We conducted a prospective, descriptive study between May 2008 and December 2009. This study was based on an assessment of all pediatric patients with VL who were observed in a reference hospital in Maranhão. Results Among 27 children, 55.5% presented with more than one sign of severity or warning sign. Patients without signs of severity or warning signs and patients with only one warning sign had the highest interferon-gamma (IFN-γ) levels, although their interleukin 10 (IL-10) levels were also elevated. In contrast, patients with the features of severe disease had the lowest IFN-γ levels. Three patients who presented with more than two signs of severe disease died; these patients had undetectable interleukin 2 (IL-2) and IFN-γ levels and low IL-10 levels, which varied between 0 and 36.8pg/mL. Conclusions Our results showed that disease severity was associated with low IFN-γ levels and elevated IL-10 levels. However, further studies with larger samples are needed to better characterize the relationship between disease severity and cytokine levels, with the aim of identifying immunological markers of active-disease severity.

Freshwater gastropods of the Baixada Maranhense Microregion, an endemic area for schistosomiasis in the State of Maranhão, Brazil: I - qualitative study

Introduction: The Baixada Maranhense Microregion currently has the highest prevalence of schistosomiasis in the State of Maranhão, likely because this parasitosis is characterized as an occupational disease, and increased contact with water increases the risk of infection by Schistosoma mansoni. This paper reports the results of the first comprehensive freshwater malacological survey performed in the Baixada Maranhense Microregion. Methods: Freshwater mollusks were collected from the twenty-one municipalities of the Baixada Maranhense Microregion and from Bacurituba and Cajapió and were evaluated for infection by trematodes. Results: A total of 9,129 mollusks were collected (sixteen species), which included the first records of six species in the State of Maranhão: Gundlachia radiata, G. ticaga, Hebetancylus moricandi, Plesiophysa guadeloupensis, Pomacea bridgesii diffusa and Omalonyx sp. Biomphalaria glabrata was found in five municipalities, whereas B. straminea was found in nine. Biomphalaria glabrata and B. straminea were observed in syntopy in Pinheiro and São Bento. Of the 990 specimens of B. glabrata and the 2,109 specimens of B. straminea that were exposed to and/or analyzed for the presence of larval trematodes, only a single specimen of B. glabrata (0.1%) from São Bento shed S. mansoni. Other larval trematodes were first observed in mollusks from the State of Maranhão. Conclusions: These results indicate that the study area is epidemiologically important due to the presence of two natural vectors of schistosomiasis and the active transmission of schistosomiasis, which was confirmed in the infected specimen that was collected in this study.

Evaluation of parasitological examination, kDNA polymerase chain reaction and rK39-based immunochromatography for the diagnosis of visceral leishmaniasis in seropositive dogs from the screening-culling program in Brazil

Introduction Dogs play a primary role in the zoonotic cycle of visceral leishmaniasis (VL). Therefore, the accurate diagnosis of infected dogs, primarily asymptomatic dogs, is crucial to the efficiency of VL control programs. Methods We investigated the agreement of four diagnostic tests for canine visceral leishmaniasis (CVL): parasite detection, either after myeloculture or by direct microscopic examination of tissue imprints; kinetoplast-deoxyribonucleic acid-polymerase chain reaction (kDNA-PCR); and an immunochromatographic test (ICT). An enzyme-linked immunosorbent assay (ELISA) and an indirect immunofluorescence test (IFAT), both of which were adopted as part of the screening-culling program in Brazil, were used as reference tests. Our sample set consisted of 44 seropositive dogs, 25 of which were clinically asymptomatic and 19 were symptomatic for CVL according to ELISA-IFAT. Results The highest and lowest test co-positivities were observed for ICT (77.3%) and myeloculture (58.1%), respectively. When analyzed together, the overall percentage of co-positive tests was significantly higher for the symptomatic group compared to the asymptomatic group. However, only ICT was significantly different based on the results of a separate analysis per test for each group of dogs. The majority (93.8%) of animals exhibited at least one positive test result, with an average of 2.66 positive tests per dog. Half of the symptomatic dogs tested positive for all four tests administered. Conclusions The variability between test results reinforces the need for more efficient and reliable methods to accurately diagnose canine VL, particularly in asymptomatic animals.

High similarity of Trypanosoma cruzikDNA genetic profiles detected by LSSP-PCR within family groups in an endemic area of Chagas disease in Brazil

IntroductionDetermining the genetic similarities among Trypanosoma cruzi populations isolated from different hosts and vectors is very important to clarify the epidemiology of Chagas disease.MethodsAn epidemiological study was conducted in a Brazilian endemic area for Chagas disease, including 76 chronic chagasic individuals (96.1% with an indeterminate form; 46.1% with positive hemoculture).ResultsT. cruzi I (TcI) was isolated from one child and TcII was found in the remaining (97.1%) subjects. Low-stringency single-specific-primer-polymerase chain reaction (LSSP-PCR) showed high heterogeneity among TcII populations (46% of shared bands); however, high similarities (80-100%) among pairs of mothers/children, siblings, or cousins were detected.ConclusionsLSSP-PCR showed potential for identifying similar parasite populations among individuals with close kinship in epidemiological studies of Chagas disease.

Outbreak of canine visceral leishmaniasis in Barra Mansa, State of Rio de Janeiro

Introduction In Brazil, visceral leishmaniasis (VL) has spread to various regions. This study reports canine cases of VL in Barra Mansa, where human VL cases were recently reported. Methods Using the human index case, a canine survey was performed by dual-path platform immunochromatography and enzyme-linked immunosorbent assay. Seropositive animals were euthanized. Cultures were collected to detect Leishmania parasites. Results Serological tests detected 141 canine VL cases, and Leishmania chagasi were isolated from 82.2% animals. Conclusions Leishmania chagasi is in circulation in Barra Mansa. This study broadens information on the parasite's distribution in the State of Rio de Janeiro.