Predictors of relapse of visceral leishmaniasis in inner São Paulo State, Brazil

Abstract

Objectives: Visceral leishmaniasis (VL) is a public health threat for several tropical countries, including Brazil. Therapy failures and relapses aggravate VL morbidity and mortality. Our study aimed at identifying predictors of relapse and thus contributes to directing therapeutic options and patient followup. Methods: A nonconcurrent cohort of 571 subjects who completed successful therapy for VL in the city of Bauru, São Paulo State, Brazil, was followed for 24 months in order to identify the incidence and predictors of relapse. Extensive review of medical charts and laboratory files was conducted. Univariate and multivariable Cox regression models were used to identify predictors for the outcome of interest. A hierarchical strategy was used for variable selection in multivariable models. Results: Relapses occurred in 6.8% of treated subjects, after a median of 6 months (interquartile range, 4-9). In a comprehensive multivariable model, relapse was associated with: HIV-coinfection (hazard ratio [HR], 7.47; 95% confidence interval [CI], 2.58-21.55); the presence of lower limb edema (HR, 6.06; 95%CI, 1.38-26.77) and low platelet count upon admission (HR for platelet count  1000, 0.99; 95%CI, 0.98-0.99) ; and secondary pneumonia (HR, 5.49; 95%CI, 1.49-20.18). On the other hand, therapy with Liposomal Amphotericin (as opposed to Antimoniate) was not independently associated with relapse (HR, 5.97; 95% CI, 0.63-56.29). Conclusion: Besides reinforcing the impact of HIV coinfection on the outcome of VL, our study points to clinical and laboratory findings that characterize patients who were more likely to relapse. Those groups should be more closely followed, and possibly could benefit from novel therapeutic options.

High Levels of anti-Leishmania IgG3 and Low CD4+ T Cells Count were Associated with Relapses in Visceral Leishmaniasis

“…Splenomegaly at study enrollment was observed in both groups, being a usual manifestation of VL [9]. Splenomegaly and thrombocytopenia have already been identi ed as markers of VL relapses [28,[32][33]. NR-VL patients showed signi cant platelet elevation after treatment, different from observed for R-VL group.…”

“…There are many studies carried out in India [33], Sudan [32], Georgia [34] and Brazil [28] addressing retrospectively non-HIV infected patients presenting a VL relapsing course, but divergent ndings in terms of clinical and laboratorial aspects associated with relapses were found. In the present study, the patients' symptoms were quite similar in the active phase, and it was not possible to identify signi cant differences between R-and NR-VL groups.…”

“…In the literature, the vast majority of studies are related to therapeutic failure reports [26]. There are few VL relapses reports and those which have it, present a great variability in the incidence of relapses according to the population and regions studied [27][28][29][30]. In a Spanish cohort, VL relapse rate was 12% [27] while in Sudan, the clinical follow-up during an epidemic in Babar showed 5.7% of relapses, most of patients concentrated in few families [31].…”

“…In Georgia, a pediatric cohort showed that children younger than one-year-old had a higher chance of relapse as the ones who were late diagnosed [34]. More recently, a Brazilian study showed that in addition to HIV infection, thrombocytopenia, lower limb edema and secondary pneumonia were factors independently associated with relapse [28]. VL relapsing patients should not achieve an effector immune response able to maintain the remission of the disease.…”

Hematological consequences of malaria in mice previously treated for visceral leishmaniasis

“…In contrast to the wealth of data on coinfection, the question of whether previous history of VL impacts on subsequent episodes of malaria has not been documented. Similarly, risk factors for VL recurrence have been identified including persistent splenomegaly, poor hematological response and VL/HIV coinfection [14][15][16][17] . In regions where malaria is common, exposure of previously-treated VL patients to Plasmodium may occur early after discharge, but whether these risk factors for VL recurrence are also risk factors for malaria or other secondary infections is currently unknown.…”