Aluízio Prata

Clinical and epidemiological aspects of Chagas disease

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. During the past decades, after urban migrations, Chagas disease became frequent in cities and a health problem in non-endemic countries, where it can be transmitted vertically and by blood transfusion or organ transplantation. Microepidemics of acute Chagas disease have been reported, probably due to oral transmission. Heart involvement is the major feature of the disease because of its characteristics, frequency, and consequences, and is also the source of most controversies. The indeterminate clinical form, despite its good prognosis on at least a medium-term basis (5-10 years), has acquired increasing importance due to the controversial meaning of the abnormality of some tests and the myocardial focal lesions found in many patients. Simultaneous evaluation of the parasympathetic and of the sympathetic system in the heart has been done by spectral analysis of heart rate. The physiopathological and clinical significance of denervation in Chagas disease is still incompletely understood. There are major divergences of opinion on specific treatment during the chronic phase because of the doubts about cure rates. Changes of Chagas disease prevalence in many countries have been certified by the Pan American Health Organization, and are ascribed to large-scale vector-control programmes with modern pyrethroid insecticides and to improvement in lifestyle.

Problems and perspectives for Chagas disease control: in search of a realistic analysis

Chagas disease was an important medical and social problem in almost all of Latin America throughout the twentieth century. It has been combated over a broad swath of this continent over recent decades, with very satisfactory results in terms of vector and transfusional transmission. Today, a surveillance stage still remains to be consolidated, in parallel with appropriate care required for some millions of infected individuals who are today living in endemic and non-endemic areas. Contradictorily, the good results attained have generated excessive optimism and even disregard among health authorities, in relation to this disease and its control. The loss of visibility and priority may be a logical consequence, particularly in Latin American healthcare systems that are still disorganized and overburdened due to insufficiencies of financial and human resources. Consolidation of the victories against Chagas disease is attainable but depends on political will and continual attention from the most consequential protagonists in this struggle, especially the Latin American scientific community.

Mixed inflammatory/regulatory cytokine profile marked by simultaneous raise of interferon-gamma and interleukin-10 and low frequency of tumour necrosis factor-alpha(+) monocytes are hallmarks of active human visceral Leishmaniasis due to Leishmania chagasi infection.

Considering the complexity of the immunological events triggered during active visceral Leishmaniasis (VL), the relevance of the segregation of the immune response during human VL into type 1 and type 2 still remains unclear. For this purpose, in individuals living in risk areas for VL, we have evaluated especially asymptomatic individuals and patients with active VL, the plasmatic levels of cytokines and reactive nitrogen species under ex vivo conditions. In addition, we have also performed an analysis of intracellular cytokine patterns of circulating leucocytes after short‐term culture, particularly in the absence of antigenic‐specific stimulation, in order to reflect dynamic events of immune response in vivo during Leishmania chagasi infection. Although asymptomatic individuals and non‐infected subjects presented a similar immunological profile, an outstanding inflammatory/regulatory profile, based on higher plasmatic levels of cytokines such as interleukin (IL)‐8, interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α, IL‐6 and IL‐10, was associated with clinical status observed in active VL. In this context, we hypothesize that IL‐10, through its ability to inhibit anti‐leishmanial macrophage activation, associated with the lower frequency of TNF‐α+ monocytes and ordinary levels of nitrite and nitrate are the major mechanisms associated with disease onset.

Report of the Second Satellite Symposium on Ultrasound in Schistosomiasis

A group of experts on schistosomiasis and ultrasonography discussed the experiences and results obtained with the Niamey-Belo Horizonte Protocol on Ultrasonography in Schistosomiasis. A series of recommendations about qualitative and quantitative data obtained by ultrasound in studies performed in Africa and Brazil are presented. Immunological, genetic and epidemiological studies must rely on ultrasound for the identification of patients with periportal thickening/fibrosis.

Influência da parasitemia na evolução da doença de Chagas crônica

During 13 years, 190 individuals with chagasic infection were submitted to clinical and parasitological examinations to investigate the relationship between parasitemia and the evolution of chronic chagasic infection. Fifty-six patients with positive xenodiagnosis and 134 with negative exams were compared from 1988 to 91, it was found that 22 (39.3%) and 50 (37.3%), respectively, presented disease progression. The parasitemia was stratified into high, medium and low and the relation with the disease evolution showed that 5 (62.5%), 10 (41.7%) and 57 (36.1%), respectively, presented progressive disease, though without a statistically significant difference (p>0.05). When 20 patients with persistent parasitemia in 1976/91, were compared with 59 with negative xenodiagnosis, a progressive evolution was observed in 6 (30%) and 17 (28.8%), respectively. Comparing six patients with high parasitemia and 59 with negative exams, it was verified that 3 (50%) and 17 (28.8%), respectively, showed progressive disease, but this was not statistically significant, (p>0.05). Mean age with high, medium and low parasitemia were 39.6, 45.3 and 41.5 years, respectively, (p>0.05). Mean age in patients showing progressive, unaltered and regressive evolution was 46.4, 39.8 and 32.6 years, respectively, with a statistically significant difference between progressive and regressive evolution (p<0.05). It is suggested that high parasitemia did not have an influence on the evolution of the chronic infection.

Th1/Th2 immune responses are associated with active cutaneous leishmaniasis and clinical cure is associated with strong interferon-γ production

In leishmaniasis, Th1-related cytokines production seems to be crucial for host control of parasite burden and clinical cure. Visceral and diffuse cutaneous leishmaniasis are characterized by negative skin test for parasite antigens and failure to produce Th1 cytokines, whereas tegumentary leishmaniasis is characterized by positive skin test and the ability of peripheral blood mononuclear cells (PBMCs) to produce Th1 cytokines. In this study, specific antibody plasma levels and cytokine production in PBMC culture supernatants were evaluated by enzyme-linked immunoabsorbent assay in patients with active or cured cutaneous leishmanial lesions and in subjects without disease history living in the same endemic area. Higher tumor necrosis factor-alpha, interferon (IFN)-gamma, interleukin (IL)-12, IL-4, and IL-10 levels were observed in patients with active lesions, whereas cured subjects produced only IFN-gamma at elevated levels. Analysis of specific antibody isotypes correlate with cellular immune response observed in vitro, as the production of IgG1 and IgG3 was higher in patients with active lesions. Our results suggest the presence of a mixed Th1/Th2 response during active disease and that clinical cure is associated with a sustained Th1 response characterized by elevated IFN-gamma levels and down-modulation of IL-4 and IL-10 production.

Phlebotomine sand flies in Porteirinha, an area of American visceral leishmaniasis transmission in the State of Minas Gerais, Brazil

A study of the phlebotomine sand fly fauna was carried out in an endemic area of American visceral leishmaniasis (AVL) in the municipality of Porteirinha, in the Brazilian state of Minas Gerais. Captures were performed with CDC light traps in 7 districts, 5 days per month, during 2 consecutive years (January 2000 to December 2001). A total of 3240 sand flies were captured and identified. Sixteen species were found, among which 15 belonged to the genus Lutzomyia and one to the genus Brumptomyia. Lutzomyia longipalpis, a proven vector of AVL, was the predominant species (71.85%) throughout the time period. The interference of climatic factors (temperature, humidity, and rainfall) over the populational dynamics of the sand flies was determined. Statistical analysis of the data showed a significant correlation among the number of phlebotomine sand flies collected, rainfall, and humidity, whereas the effect of temperature was negligible, in that particular region. The amount of collected phlebotomine, the number of human cases, and the prevalence of canine AVL in the districts of Porteirinha are discussed.

Aspectos da ecologia e do comportamento de flebotomíneos em área endêmica de leishmaniose visceral, Minas Gerais

Studies on the behavioral and feeding habits of some species of phlebotominae sand flies have contributed to the comprehension of the epidemiology of leishmaniasis. In the present work, systematic captures were performed monthly in the municipality of Porteirinha (MG) using 28 light traps (CDC) from January to December 2002. Fourteen different species of phlebotomine were captured in a total of 1,408 specimens. The highest percentage of individuals (53.3%) was collected in the peridomicile against 46.7% in the intradomicile. Lutzomyia longipalpis was the predominant species in that region. The blood feeding of 38 females of this species from the field was analyzed by precipitin reaction. The results indicated that Lutzomyia longipalpis is an opportunist (65.1%) species that feeds on a wide variety of vertebrates in nature.

Regressão da hepatosplenomegalia pelo tratamento específico da esquistossomose

Twenty three patients with a less than six year history of the hepatosplenic form of schistosomiasis were treated with oxamniquine. They remained in the endemic area, were reinfected and re-examined after 2-4 years. Improvement was noted in 78,3% of the patients. The recovery varied from complete reversion of the hepatosplenomegaly (26%) to a reduction of the splenomegaly with or without persistent hepatic nodular lesions. Response to the treatment was not influenced by the number of S. mansoni eggs in the feces nor by repetitions of the treatment. In schistosomiasis with portal hypertension, at least in theabsenceofdigestive hemorrhages, specific treatment must preceed any recommended surgery.

Immune Response in Human Visceral Leishmaniasis: Analysis of the Correlation Between Innate Immunity Cytokine Profile and Disease Outcome

We investigated the cytokine profile of cells of the innate immune response and its association with active (ACT), asymptomatic (AS) and cured (CUR) human visceral leishmaniasis (VL), as well as noninfected (NI) subjects. The frequency of cytokine‐producing cells was determined after short‐term in vitro incubation of whole peripheral blood samples with soluble Leishmania antigen (SLA). Our data demonstrated a predominant type 2 cytokine profile in NI and ACT. In NI, we observed an increase of IL‐4+ neutrophils, IL‐10+ eosinophils besides a decrease of tumour necrosis factor (TNF)‐α+ eosinophils/monocytes. Yet in ACT, we observed an increase of IL‐4+ neutrophils and natural killer (NK) cells and IL‐10+ monocytes, a reduced frequency of IL‐12+ and IFN‐γ+ eosinophils and lower levels of TNF‐α+ and IL‐12+ monocytes. AS presented a mixed profile, characterized by an increase of IFN‐γ+ neutrophils/eosinophils and NK cells, of IL‐12+ eosinophils/monocytes, as well as increase of IL‐4+ neutrophils and NK cells and IL‐10+ eosinophils/monocytes. In contrast, CUR was characterized by a type 1 response with an increase of IFN‐γ+ neutrophils/eosinophils and NK cells, associated with an increase in IL‐12+ monocytes. In conclusion, we show a correlation between innate immune cytokine patterns and clinical status of VL, suggesting that these cells, in addition to other factors, may contribute to the cytokine microenvironment in which Leishmania‐specific T cells are primed and to disease outcome.