Hierarchical spatiotemporal modeling of human visceral leishmaniasis in Rio Grande do Norte, Brazil.

Visceral leishmaniasis (VL) is a neglected tropical disease that is globally distributed and has the potential to cause very serious illness. Prior literature highlights the emergence and spread of VL is influenced by multiple factors, such as socioeconomic status, sanitation levels or animal and human reservoirs. The study aimed to retrospectively investigate the presence and infectiousness of VL in Rio Grande do Norte (RN), Brazil between 2007 and 2020. We applied a hierarchical Bayesian approach to estimate municipality-specific relative risk of VL across space and time. The results show evidence that lower socioeconomic status is connected to higher municipality-specific VL risk. Overall, estimates reveal spatially heterogeneous VL risks in RN, with a high probability that VL risk for municipalities within the West Potiguar mesoregion are more than double the expected VL risk. Additionally, given the data available, results indicate there is a high probability of increasing VL risk in the municipalities of Natal, Patu and Pau dos Ferros. These findings demonstrate opportunities for municipality-specific public health policy interventions and warrant future research on identifying epidemiological drivers in at-risk regions.

Bayesian compartmental model for an infectious disease with dynamic states of infection.

Population-level proportions of individuals that fall at different points in the spectrum [of disease severity], from asymptomatic infection to severe disease, are often difficult to observe, but estimating these quantities can provide information about the nature and severity of the disease in a particular population. Logistic and multinomial regression techniques are often applied to infectious disease modeling of large populations and are suited to identifying variables associated with a particular disease or disease state. However, they are less appropriate for estimating infection state prevalence over time because they do not naturally accommodate known disease dynamics like duration of time an individual is infectious, heterogeneity in the risk of acquiring infection, and patterns of seasonality. We propose a Bayesian compartmental model to estimate latent infection state prevalence over time that easily incorporates known disease dynamics. We demonstrate how and why a stochastic compartmental model is a better approach for determining infection state proportions than multinomial regression is by using a novel method for estimating Bayes factors for models with high-dimensional parameter spaces. We provide an example using visceral leishmaniasis in Brazil and present an empirically-adjusted reproductive number for the infection.

Epidemiological and Experimental Evidence for Sex-Dependent Differences in the Outcome of Leishmania infantum Infection.

Leishmania infantum causes visceral leishmaniasis (VL) in Brazil. We previously observed that VL is more common in males than females living in endemic neighborhoods, despite similar exposure. Using a larger sample, we document that VL is more common in males than females, but only after puberty. BALB/c and C57BL/6 mouse models confirmed that there is a biological basis for male susceptibility to symptomatic VL, showing higher parasite burdens in males than females. Female C57BL/6 mice generated more antigen-induced cytokines associated with curative responses (interferon-γ, interleukin [IL]-1ß). Males expressed higher levels of IL-10 and tumor necrosis factor, which are linked to exacerbated disease. Different parasite lines entered or survived at a higher rate in macrophages of male- than female-origin. These results suggest that males are inherently more susceptible to L. infantum than females and that mice are a valid model to study this sex-dependent difference.

Changing epidemiology of visceral leishmaniasis in northeastern Brazil: a 25-year follow-up of an urban outbreak.

Background: Visceral leishmaniasis (VL) continues to be a deadly parasitic disease in Brazil but the epidemiology has changed. The objective of this study was to assess the evolution of urban VL in the city of Natal, Brazil, over the past 25 y. Methods: A retrospective study of human VL was performed, considering reported cases over the past 25 y in Natal. Analyses considered the spatial distribution of VL cases, human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) co-infection, Leishmania infantum infection in dogs, density of the insect vector (Lutzomyia longipalpis) and socio-economic factors. Results: Paralleling migration of the population, VL cases changed from mostly rural to predominantly urban regions. The incidence of human VL was highest during the initial years (1990-1994) of our study. Human VL was positively associated with a high density of L. longipalpis, a high prevalence of canine L. infantum infection and HIV/AIDS co-infection. The average age at diagnosis increased over prior years and males were more frequently affected. The overall fatality rate was 6%. Socio-economic variables indicative of poverty were associated with a greater incidence of VL and clusters of VL. Conclusion: VL has become endemic in Natal. The disease is associated with poverty and male gender. Surprisingly, there has been an increase in the age at diagnosis.

Leishmania infantum chagasi in northeastern Brazil: asymptomatic infection at the urban perimeter.

Visceral leishmaniasis (VL) is endemic in large cities in Brazil, including Natal. We determined the prevalence of asymptomatic human infection with Leishmania infantum chagasi and associated environmental risks around Natal. Infection was detected by Leishmania skin test (LST) and anti-leishmanial antibodies in humans and anti-leishmanial antibodies in dogs. Amongst 345 humans, 24.6% were seropositive, and 38.6% were LST-positive. Prevalence of positive serology was similar in both sexes and across all ages. However, positive LST responses increased with age, suggesting that LST is long-lasting and cumulative. Multinomial logistic analysis showed that LST response varied with location (P = 0.007) and that males were more frequently LST-positive (P = 0.027). Indicators of lower socioeconomic status associated significantly with human infection. Furthermore, there was geographic coincidence of seropositive humans and dogs (r = 0.7926, P = 0.011). These data suggest that dog and human L. i. chagasi infection are intimately interrelated in environmental conditions associated with low income.