Risk analysis and prediction of visceral leishmaniasis dispersion in São Paulo State, Brazil

<div><p>Visceral leishmaniasis (VL) is an important neglected disease caused by a protozoan parasite, and represents a serious public health problem in many parts of the world. It is zoonotic in Europe and Latin America, where infected dogs constitute the main domestic reservoir for the parasite and play a key role in VL transmission to humans. In Brazil this disease is caused by the protozoan <i>Leishmania infantum chagasi</i>, and is transmitted by the sand fly <i>Lutzomyia longipalpis</i>. Despite programs aimed at eliminating infection sources, the disease continues to spread throughout the Country. VL in São Paulo State, Brazil, first appeared in the northwestern region, spreading in a southeasterly direction over time. We integrate data on the VL vector, infected dogs and infected human dispersion from 1999 to 2013 through an innovative spatial temporal Bayesian model in conjunction with geographic information system. This model is used to infer the drivers of the invasion process and predict the future progression of VL through the State. We found that vector dispersion was influenced by vector presence in nearby municipalities at the previous time step, proximity to the Bolívia-Brazil gas pipeline, and high temperatures (i.e., annual average between 20 and 23°C). Key factors affecting infected dog dispersion included proximity to the Marechal Rondon Highway, high temperatures, and presence of the competent vector within the same municipality. Finally, vector presence, presence of infected dogs, and rainfall (approx. 270 to 540mm/year) drove the dispersion of human VL cases. Surprisingly, economic factors exhibited no noticeable influence on disease dispersion. Based on these drivers and stochastic simulations, we identified which municipalities are most likely to be invaded by vectors and infected hosts in the future. Prioritizing prevention and control strategies within the identified municipalities may help halt the spread of VL while reducing monitoring costs. Our results contribute important knowledge to public and animal health policy planning, and suggest that prevention and control strategies should focus on vector control and on blocking contact between vectors and hosts in the priority areas identified to be at risk.</p></div

Parameter estimates for VL vector (<i>Lu</i>. <i>longipalpis</i>), VL infected dogs and VL infected humans.

<p>Parameter estimates for VL vector (<i>Lu</i>. <i>longipalpis</i>), VL infected dogs and VL infected humans.</p

Actual (2013) and predicted (2016, 2018, 2020) spatial distribution of municipalities with presence of visceral leishmaniasis vector (<i>Lu</i>. <i>longipalpis</i> sand fly), infected dogs and infected humans in São Paulo State, Brazil.

<p>The probability of “invasion” was calculated using the posterior distribution of the parameters (described in the section “Covariates”) from the Bayesian model and forward simulations, as described in the section “Predictions”.</p

Spatial distribution of the top 20 municipalities in terms of 2020 invasion probability for vectors, infected dogs, and infected humans.

<p>Numbers assigned to municipalities are described in the <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005353#pntd.0005353.s008" target="_blank">S1 Table</a>, as superscripts.</p

Predicted probability of invasion by vectors and human cases in São Paulo State municipalities by 2015 (y-axis) for invaded and not-invaded municipalities in 2015 (x-axis).

<p>Boxes represent the 25% and 75% percentiles, with the central horizontal line representing the median, while whiskers extend to the minimum and maximum values.</p

Brazil and São Paulo State.

<p>Brazil and São Paulo State.</p

Global sensitivity analysis and its p-values of “Daily biting rates” and “vectors per host” parameters.

<p>“Daily bites of vector on hosts” rate (<b>a</b>_h, <b>a</b>_d, <b>a</b>_c, <b>a</b>_r and <b>a</b>_l) and “vectors per host” rate (<b>ρ</b>_h, <b>ρ</b>_d, <b>ρ</b>_c, <b>ρ</b>_r and <b>ρ</b>_l), following the sequence of hosts: human, dog, cat, rabbits and hares.</p

Efficacies of prevention and control measures applied during an outbreak in Southwest Madrid, Spain

<div><p>Leishmaniasis is a vector-borne disease of worldwide distribution, currently present in 98 countries. Since late 2010, an unusual increase of human visceral and cutaneous leishmaniasis cases has been observed in the south-western Madrid region, totaling more than 600 cases until 2015. Some hosts, such as human, domestic dog and cat, rabbit (<i>Oryctolagus cuniculus</i>), and hare (<i>Lepus granatensis</i>), were found infected by the parasite of this disease in the area. Hares were described as the most important reservoir due to their higher prevalence, capacity to infect the vector, and presence of the same strains as in humans. Various measures were adopted to prevent and control the disease, and since 2013 there was a slight decline in the human sickness. We used a mathematical model to evaluate the efficacy of each measure in reducing the number of infected hosts. We identified in the present model that culling both hares and rabbits, without immediate reposition of the animals, was the best measure adopted, decreasing the proportion of all infected hosts. Particularly, culling hares was more efficacious than culling rabbits to reduce the proportion of infected individuals of all hosts. Likewise, lowering vector contact with hares highly influenced the reduction of the proportion of infected hosts. The reduction of the vector density per host in the park decreased the leishmaniasis incidence of hosts in the park and the urban areas. On the other hand, the reduction of the vector density per host of the urban area (humans, dogs and cats) decreased only their affected population, albeit at a higher proportion. The use of insecticide-impregnated collar and vaccination in dogs affected only the infected dogs’ population. The parameters related to the vector contact with dog, cat or human do not present a high impact on the other hosts infected by <i>Leishmania</i>. In conclusion, the efficacy of each control strategy was determined, in order to direct future actions in this and in other similar outbreaks. The present mathematical model was able to reproduce the leishmaniasis dynamics in the Madrid outbreak, providing theoretical support based on successful experiences, such as the reduction of human cases in Southwest Madrid, Spain.</p></div

Haematological variables (mean ± SD) evaluated in infected (INF) and non-infected (NI) hamsters following the 14% and 3% protein diets.

<p>The comparison of the groups showed at least one significant difference among the averages of MCV (p<0.0001), MCH (p = 0.001), RDW (p<0.0001), leukocytes (p = 0.008), lymphocytes (p = 0.013), CD4 (p = 0.05), I-E^k+ (p = 0.029), monocytes (p = 0.002) and granulocytes (p = 0.005). Statistically significant differences are indicated by (A) for 3%INF vs. 14%INF; (B) for 3%INF vs. 3%NI; (C) for 14%INF vs. 14%NI; and (D) for 3%NI vs. 14%NI. Letters with * indicate p<0.05; letters with ** indicate p<0.01; letters with *** indicate p<0.001. Abbreviations: PLT- platelets, MCV- mean corpuscular volume, MCH- mean corpuscular haemoglobin, RDW- red blood cell distribution width.</p

Human prevalences according the variations of the parameters “daily biting rate in humans” (a_h) and “vector density per human” (ρ_h).

<p>A) a_h fixed at 1.8249 and <b>ρ</b>_h varied from 0.03 to 0.0003; B) a_h fixed at 0.18249 and <b>ρ</b>_h varied from 0.03 to 0.0003; and C) a_h fixed in 18.249 and <b>ρ</b>_h varied from 0.03 to 0.0003.</p