Factors associated with visceral leishmaniasis in the americas: a systematic review and meta-analysis

Abstract

Background: Still today, more than 30 years after the beginning of the process of visceral leishmaniasis' urbanization, there is little knowledge about the risk factors for its occurrence, despite their relevance to the control and understanding of disease dynamics. The present study is the first systematic review with meta-analysis about factors associated with Leishmania infantum infection in humans in the Americas.

Methods and findings: After searching different databases, consultations to the reference lists of articles and to experts in the field, 51 studies were reviewed. Theoretical discussions or meta-analysis of p-values or of effect sizes were used to pool information about each variable. The Q test and the I(2) statistic were used to assess heterogeneities among the studies. Male sex was associated with visceral leishmaniasis in studies which used the leishmanin skin test for diagnosis and in those where the outcome was the clinical disease; the opposite occurred when serological diagnosis was applied. Younger individuals were less frequently infected than adults, but were more prone to illness. Although with different levels of evidence and of heterogeneity, the presence of dogs at home, higher dog seropositivity in nearby areas, lower socioeconomic status and highly vegetated areas were associated with L. infantum infection. This was not noticed for the presence of chickens in the house and with nutritional status. Susceptibilities to bias and limitations in the analysis and in the description of results were often identified in the studies analyzed.

Conclusions: Results showed the existence of consistent patterns for some of the factors analyzed and should be taken into account in developing more effective and well-targeted control measures. Studies must be conducted in new areas of the continent, with improved methodological quality and prioritizing the investigation of the patterns identified and their causes, as well as variables for which knowledge is poor.

Figure 1. Flowchart showing the selection of studies analyzed in this review.

Figure 2. Forest plot for the variable gender: studies divided into subgroups according method for measuring the outcome.

CS-Cross-sectional; *Serological result from study with two tests; #Result in adults; (2) Second study from the same publication; LST- Leishmania skin test; Squares represent the weight of each study; Lozenges represent the summary measure of each subgroup; Reference: Females, OR = 1.

Figure 3. Forest plot for the variable age: studies divided into subgroups according to the method for measuring the outcome.

CS-Cross-sectional; *Serological result from study with two tests; #Result in adults; LST- Leishmania skin test; Squares represent the weight of each study; Lozenges represent the summary measure of each subgroup; Reference: Being Over 10 y.o.a., OR = 1.

Figure 4. Forest plot: malnutrition.

CS-Cross-sectional; *Serological result from study with two tests; (2) According to a study from the same publication; LST-Leishmania skin test; Squares represent the weight of each study; Lozenges represent the summary measure. Reference: Lack of Malnutrition, OR = 1.

Figure 5. Forest plot for the presence of dogs in the household: studies divided into subgroups according to type of study.

CS-Cross-sectional; *Serological result from study with two tests; (2) According to a study from the same publication; LST-Leishmania skin test; Squares represent the weight of each study; Lozenges represent the summary measure; Reference: Not Owning Dogs, OR = 1.

Figure 6. Forest plot with ecological studies that correlated cases in dogs and in humans in a given analyzed land unit.

*Terms used in the primary study (for details, see table S1).

Figure 7. Forest plot for the presence of chickens, birds or chicken coops in the household.

CS-Cross-sectional; *Serological result from study with two tests; (2) According to a study from the same publication; LST-Leishmania skin test; Squares represent the weight of each study; Lozenges represent the summary measure; Reference: Not Owning Birds, OR = 1.

Figure 8. Forest plot: prior cases in relatives or neighbors.

CS-Cross-sectional; *Serological result from study with two tests; (2) According to a study from the same publication; LST-Leishmania skin test; #Neighborhood results for studies that also studied relatives; Squares represent the weight of each study; Lozenges represent the summary measure of each subgroup; Reference: Lack of Cases Among Relatives/Neighbors, OR = 1.

Figure 9. Funnel plot for the variables employed in the detection of publications bias in the review.

a-gender; b-age; c-presence of dogs in the household; d-presence of chickens or birds in the household; Dots refer to studies imputed by the Trim and Fill method. Open diamonds represent the original estimate of the Odds ratios while solid diamonds represent Odds rations recomputed by the statistic of Durval and Tweedie's Trim and Fill.