Studies on control of visceral leishmaniasis: impact of dog control on canine and human visceral leishmaniasis in Jacobina, Bahia, Brazil.

To assess the effect of removing leishmania-infected dogs on the incidence of visceral leishmaniasis, a controlled intervention study was performed in northeast Brazil. The attempted elimination of seropositive dogs resulted in an initial significant decrease in the annual incidence of seroconversion among dogs from 36% to 6% over the first two years. In the following two years, the incidence increased to 11% and 14%, respectively. In a control area in which dogs were surveyed but seropositive dogs were not removed, the cumulative incidence did not vary significantly from year to year, ranging from 16% to 27%. In the intervention area, the prevalence of dog seropositivity decreased from 36% before the intervention to 10% and remained stable. These findings suggest that attempting to remove seropositive dogs is insufficient as a measure for eradicating visceral leishmaniasis in dogs. However, the force of transmission of infection among dogs can be reduced by such programs. Also, when the number of human cases before and after the start of the intervention was calculated, a significant decrease in incidence of disease in the intervention area was observed among children less than 15 years of age (P < 0.01). The results of this intervention study suggest that the elimination of the majority of seropositive dogs may affect the cumulative incidence of seroconversion in dogs temporarily and may also diminish the incidence of human cases of visceral leishmaniasis.

Detection by Western blot of four antigens characterizing acute clinical leishmaniasis due to Leishmania infantum.

Western blot analysis of sera from 32 patients with acute clinical leishmaniasis due to Leishmania infantum showed the simultaneous presence of antibodies against 4 antigens with molecular masses of 18, 21, 23, 31 kDa. The simultaneous presence of these 4 antigens was specific to the clinical disease and it was not detected in 47 sera from asymptomatic individuals living in the leishmaniasis endemic area of Alpes-Maritimes (southern France) or in 37 sera from patients with other protozoan infections.

Human T-cell activation by 14- and 18-kilodalton nuclear proteins of Leishmania infantum.

Leishmanial antigens which stimulate T lymphocytes from primed individuals may be candidates for a vaccine. We recently found a significant concordance between the humoral response specific for two proteins from Leishmania infantum promastigotes, p14 and p18, and a positive leishmanin delayed-type hypersensitivity reaction, testifying to the occurrence of cell-mediated immunity. In this communication, we describe a partial characterization of these antigens and an in vitro analysis of their capacity to activate primed human T cells. We showed, by immunofluorescent staining and through analysis of subcellular fractions by Western immunoblotting, that in stationary-phase promastigotes, p14 and p18 were located only in the parasite nuclei; in the middle of the log phase, a transitory and only weak expression outside the nucleus was detected. We then showed that p14 and p18 antigens shared a common epitope(s). Finally, we analyzed the in vitro proliferation and interleukin-2 production induced by leishmanial proteins in human peripheral blood mononuclear cells from sensitized subjects. We showed that in some individuals who have been exposed to L. infantum the specific response to the whole lysate was mostly due to the nuclear antigens. We demonstrated directly the capacity of nitrocellulose-bound p14 and p18 to activate in vitro all of the tested primed peripheral blood mononuclear cells, which contrasted with a lack of stimulatory activity of other membrane-bound leishmanial proteins. Taken together, our results suggest that an antigenic determinant(s) dominant for some individuals might exist on both antigens.

rK39: a cloned antigen of Leishmania chagasi that predicts active visceral leishmaniasis.

The diagnosis of visceral leishmaniasis (VL), a serious and often fatal parasitic disease caused by members of the Leishmania donovani complex, remains problematic. Current methods rely on clinical criteria, parasite identification in aspirate material, and serology. The latter methods use crude antigen preparations lacking in specificity. A previously described cloned antigen, rK39, of Leishmania specific for all members of the L. donovani complex (L. chagasi, L. donovani, L. infantum) was very useful in the serodiagnosis by ELISA of both human and canine VL. The present study demonstrated that rK39 seroreactivity correlated with active disease. The sera from early or self-healing infected subjects reacted with leishmanial lysate and were generally nonreactive with rK39. These data demonstrate the utility of rK39 in the serodiagnosis of VL and as an indicator of active disease.

Spread and diversity of human populations in Bahia, Brazil.

PIP: Data from surnames and racial subgroups were obtained in 60 localities to reconstruct the history of population spread and mixing over the state of Bahia, Brazil. Using the historically significant location of Cachoeira and Sao Felix as central points, the sampled localities were distributed along 7 main paved roads. 20% of the elementary school children were selected, but only the surnames of 12,872 boys were used in the analysis. The following parameters were estimated for each of the localities: black phenotype index (BPI), which is the proportion of 3 racial classifications determined by gene frequency analysis; black cultural index (BCI) determined by the frequency of devotional surnames; and indian cultural index (ICI) determined by the frequency of animal-plant surnames; and the isolated frequency of the surname Santos. The results of regression analysis indicate a negative association between BPI and BCI and the distance from Cachoeira-Sao Felix. Although not significant, ICI increases slightly with increased distance from Cachoeira-Sao Felix. The isolated frequency of the surname Santos is associated with the BCI but does not decrease significantly with distance from Cachoeira-Sao Felix. Construction of a map characterizing each of the 60 localities by its most representative racial admixture confirms the analysis and reveals the spread of blacks toward 4 cardinal points. A review of the historical background of the state explains the migration of blacks as related to the needs for slave labor during the development of gold mining and cocoa and sugar cultivation. The higher concentrations of indian admixtures farther from Cachoeira-Sao Felix reflects their retreat to survive the incoming foreign settlers. Given the strong link between the observed diversity in the population and major historical events, it is suggested that historical reconstruction of a population be an initial step before undertaking sampling for gene frequency analysis.^ieng