Premature deaths by visceral leishmaniasis in Brazil investigated through a cohort study: A challenging opportunity?

Abstract

BackgroundVisceral Leishmaniasis (VL) is the most severe form of leishmaniasis because it can lead to death. In the Americas, 96% of cases are in Brazil, and despite efforts, the fatality rate has increased in the past years. We analyzed deaths associated to VL in Brazil and investigated the factors that could influence on the timeliness of fatal outcome with emphasis on time (tStoD).MethodologyThe registered deaths by VL were sourced from the Brazilian National Notification System from 2007–2014. Through a retrospective cohort study, univariate and multivariable Cox proportional hazards model analysis were performed and investigated the factors that could influence the time (tStoD). These factors were analyzed through survival models.ResultsOut of the 1,589 reported deaths, the median for onset of the symptoms and the case notification date (tStoN) is 25 days (10–61), and for date of case notification and death (tNotD) is 9 days (4–17). The time (tStoN) to event investigation for HIV non-infected individuals was 1.4 (1.16–1.68) greater than the HIV positive group. At the same time peri-urban and urban area were 0.83 (0.47–1.44) and 1.33 (1.16–1.52), respectively. The explorations revealed apparent differences between the time to event investigation (both for tStoN and tNotD) and the age at the onset of the symptoms. According to the tStoN the rate of notification is 1.73 times greater in patients under 5 years old at the onset of the clinical symptoms compared to older patients.ConclusionVL patients under 5 years old were diagnosed earlier and had shorter survival. It could mean that in younger population, although properly diagnosed, the fatality pattern might be related to the severity of the disease. Main host characteristics were evaluated, and age and co-infections seem to have an impact in the disease progression.

Parasite genotype is a major predictor of mortality from visceral leishmaniasis

“…Strain-specific differences that affect male and female disease severity may be the cause of the higher occurrence of infections in males. 15 The majority of the other traits were affected primarily by SNP/indel variations, rather than CNVs. Approximately a third of clinical traits ( n =5) are affected by independent heritability components, while the majority of traits ( n =11) are complex, with multiple types of genotypic variation contributing to host phenotype.…”

“…Disease outcomes are known to be associated with patient age, sex, comorbidities, 4 adverse effects of treatment, and co-infections such as HIV. 15 Genome-scale association studies (GWAS) have shown to human genotypes influence VL disease severity in East Africa, Brazil and the Indian subcontinent, 16 including a strong influence from the HLA-DR-DQ region within the major histocompatibility complex. 17 However, apart from studies of drug-resistance, 10,18 the influence of natural parasite genetic variation on disease severity has not been investigated using genome-scale methods.…”

Parasite Genotype Is a Major Predictor of Mortality from Visceral Leishmaniasis

“…Sex was also strongly associated with SNP/indel variation (0.60 ± 0.27; 95% confidence interval, 0.33 to 0.87), indicating that parasite genotype influences the susceptibility of males and females to VL differentially. Strain-specific differences that affect male and female disease severity may be the cause of the higher occurrence of infections in males ( 15 ). The majority of the other traits were affected primarily by SNP/indel variations, rather than CNVs.…”

“…Hence, understanding the factors that lead to severe disease and mortality is a priority for leishmaniasis research. Disease outcomes are known to be associated with patient age, sex, comorbidities ( 4 ), adverse effects of treatment, and coinfections such as HIV ( 15 ). Genome-wide association studies (GWAS) have shown to human genotypes influence VL disease severity in East Africa, Brazil, and the Indian subcontinent ( 16 ), including a strong influence from the HLA-DR-DQ region within the major histocompatibility complex ( 17 ).…”

Inequalities of visceral leishmaniasis case-fatality in Brazil: A multilevel modeling considering space, time, individual and contextual factors

“…The higher case-fatality among HIV co-infected VL patients is in turn well demonstrated in Brazil and in other countries where the two infections are endemic. Recently, Elkhoury and colleagues [ 45 ] have demonstrated that time of symptoms up to VL reporting for HIV infected individuals was longer than for non-HIV infected patients, which could be explained by the existence of numerous opportunistic conditions with clinical manifestations similar to VL, and HIV itself. The other case-fatality marker found was low schooling, a condition previously linked to VL mortality.…”