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Does deforestation drive visceral leishmaniasis transmission? A causal analysis.

ABSTRACT: Vector-borne diseases (VBDs) are important contributors to the global disease burden and are a key factor in perpetuating economic inequality. Although environmental changes are often cited as drivers of VBDs, the link between deforestation and VBD occurrence remains unclear. Here, we examined this relationship in detail using the spread of visceral leishmaniasis (VL) in São Paulo state (Brazil) as the case study. We used a two-step approach to estimate the causal effects (overall, direct, and indirect) of deforestation on the occurrence of the VL vector, canine visceral leishmaniasis (CVL), and human visceral leishmaniasis (HVL). We first estimated the parameters via a double Metropolis-Hastings algorithm and then estimated the causal effects through a Gibbs sampler. We observed that the odds of vector, CVL, and HVL occurrence were 2.63-, 2.07-, and 3.18-fold higher, respectively, in deforested compared with forested municipalities. We also identified a significant influence of the presence of vector, CVL, and HVL in one municipality on disease occurrence in previously naive neighbouring municipalities. Lastly, we found that a hypothetical reduction in deforestation prevalence from 50 to 0% across the state would reduce vector, CVL, and HVL occurrence by 11%, 6.67%, and 29.87%, respectively. Our results suggest that implementing an eco-friendly development strategy that considers trade-offs between agriculture, urbanization, and conservation could be an effective mechanism of controlling VL.

SUBMITTER: Santos CVBD

PROVIDER: S-EPMC8385339 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Does deforestation drive visceral leishmaniasis transmission? A causal analysis.

Santos Cleber Vinicius Brito Dos CVBD Sevá Anaiá da Paixão ADP Werneck Guilherme Loureiro GL

Proceedings. Biological sciences 20210825 1957

Vector-borne diseases (VBDs) are important contributors to the global disease burden and are a key factor in perpetuating economic inequality. Although environmental changes are often cited as drivers of VBDs, the link between deforestation and VBD occurrence remains unclear. Here, we examined this relationship in detail using the spread of visceral leishmaniasis (VL) in São Paulo state (Brazil) as the case study. We used a two-step approach to estimate the causal effects (overall, direct, and i ...[more]

PMID: 34428972

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Project description:BackgroundLeishmaniasis are a group of diseases caused by more than 20 species of the protozoan that are transmitted through the bite of female sand fly. The disease is endemic to 98 countries of the world. It affects most commonly the poorest of the poor and mainly males. Several research has been conducted to propose disease control strategies. Effective medical care, vector control, environmental hygiene, and personal protection are the mainstays of the current preventative and control methods. The mathematical models for the transmission dynamics of the disease studied so far did not consider the sex-biased burden of the disease into consideration.MethodologyUnlike the previous VL works, this study introduces a new deterministic sex-structured model for understanding the transmission dynamics of visceral leishmaniasis. Basic properties of the model including basic reproduction number ([Formula: see text]), and conditions for the existence of backward bifurcation of the model are explored. Baseline parameter values were estimated after the model was fitted to Ethiopia's VL data. Sensitivity analysis of the model was performed to identify the parameters that significantly impact the disease threshold. Numerical simulations were performed using baseline parameter values, and scenario analysis is performed by changing some of these parameters as appropriate.ConclusionThe analysis of the model shows that there is a possibility for a backward bifurcation for [Formula: see text], which means bringing [Formula: see text] to less than unity may not be enough to eradicate the disease. Our numerical result shows that the implementation of disease-preventive strategies, as well as effectively treating the affected ones can significantly reduce the disease prevalence if applied for more proportion of the male population. Furthermore, the implementation of vector management strategies also can considerably reduce the total prevalence of the disease. However, it is demonstrated that putting more effort in treating affected reservoir animals may not have any significant effect on the overall prevalence of the disease as compared to other possible mechanisms. The numerical simulation infers that a maximum of 60% of extra preventative measures targeted to only male population considerably reduces the total prevalence of VL by 80%. It is also possible to decrease the total prevalence of VL by 69.51% when up to 50% additional infected males receive treatment with full efficacy. Moreover, applying a maximum of 15% additional effort to reduce the number of vectors, decreases the total VL prevalence by 57.71%. Therefore, in order to reduce the disease burden of visceral leishmaniasis, public health officials and concerned stakeholders need to give more emphasis to the proportion of male humans in their intervention strategies.

Project description:IntroductionTo sustain the achievement of kala-azar elimination program (KEP), early detection and treatment of the visceral leishmaniasis (VL) cases and associated modalities such as treatment failure (TF), relapse VL (RVL), and Post-kala-azar dermal leishmaniasis (PKDL) is the cornerstone. A predictive biomarker for VL development and related complications could also play a crucial role in curtailing disease incidence and transmission. Investigations to find a biomarker with prospective capabilities are, however, scarce. Using samples and known clinical outcomes generated within two previous longitudinal cohort studies, we aimed to determine if fluctuations in serum anti-rK39 antibody levels could provide such predictive value.Materials and methodsSerum samples collected at four different time points (Baseline, 12, 18, and 24 months) from 16 patients who had developed VL within the monitoring period and 15 of their asymptomatic healthy controls counterparts were investigated. To investigate potential prediction of VL related complications, serum samples of 32 PKDL, 10 RVL, 07 TF, and 38 cured VL from a single dose AmBisome trial were analyzed. Of this second panel, all patients were monitored for 5 years and sera were collected at four time points (Baseline then 1, 6, and 12 months after treatment). The level of anti-rK39 antibodies in archived samples was measured by a semi-quantitative ELISA.ResultsThe mean antibody level was significantly higher in VL patients compared to their asymptomatic healthy counterparts at each time point. Likewise, we observed a trend toward elevations in antibody levels for PKDL, RVL, TF relative to the reducing levels observed in cured VL. Receiver operating characteristic (ROC) analysis found a promising predictive power of rK39 antibody levels to reveal progression from asymptomatic Leishmania donovani infection stage to VL, defined as 87.5% sensitive and 95% specific. Following treatment, rk39 antibody notably showed 100% sensitivity and 95% specificity in predicting TF.ConclusionOur data indicate that the relative quantity of serum anti-rK39 antibody has promise within either a predictive or prognostic algorithm for VL and VL-related modalities. These could enable VL control programs to implement more effective measures to eliminate the disease. Further research is, however, imperative to standardize the rK39 antibody ELISA between sites prior to broader use.

Project description:BackgroundVisceral leishmaniasis in Brazil is caused by the protozoan Leishmania (Leishmania) chagasi and it is transmitted by sandfly of the genus Lutzomyia. Dogs are an important domestic reservoir, and control of the transmission of visceral leishmaniasis (VL) to humans includes the elimination of infected dogs. However, though dogs are considered to be an important element in the transmission cycle of Leishmania, the identification of infected dogs representing an immediate risk for transmission has not been properly evaluated. Since it is not possible to treat infected dogs, they are sacrificed when a diagnosis of VL is established, a measure that is difficult to accomplish in highly endemic areas. In such areas, parameters that allow for easy identification of reservoirs that represents an immediate risk for transmission is of great importance for the control of VL transmission. In this study we aimed to identify clinical parameters, reinforced by pathological parameters that characterize dogs with potential to transmit the parasite to the vector.ResultsThe major clinical manifestations of visceral leishmaniasis in dogs from an endemic area were onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. The transmission potential of these dogs was assessed by xenodiagnosis using Lutzomyia longipalpis. Six of nine symptomatic dogs were infective to Lutzomyia longipalpis while none of the five asymptomatic dogs were infective to the sandfly. Leishmania amastigotes were present in the skin of all clinically symptomatic dogs, but absent in asymptomatic dogs. Higher parasite loads were observed in the ear and ungueal region, and lower in abdomen. The inflammatory infiltrate was more intense in the ears and ungueal regions of both symptomatic and asymptomatic dogs. In clinically affected dogs in which few or none Leishmania amastigotes were observed, the inflammatory infiltrate was constituted mainly of lymphocytes and macrophages. When many parasites were present, the infiltrate was also comprised of lymphocytes and macrophages, as well as a larger quantity of polymorphonuclear neutrophils (PMNs).ConclusionDogs that represent an immediate risk for transmission of Leishmania in endemic areas present clinical manifestations that include onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. Lymphadenopathy in particular was a positive clinical hallmark since it was closely related to the positive xenodiagnosis.

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Does deforestation drive visceral leishmaniasis transmission? A causal analysis.

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Does deforestation drive visceral leishmaniasis transmission? A causal analysis.

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