Al Rashed, Ali Mohsen; (2025) Uncovering an Infectious Cause of Mesoamerican Nephropathy. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Mesoamerican Nephropathy (MeN) is a leading cause of death among young male agriculture workers in Central America. The cause is unknown, but recent studies raise the possibility of a role of an infectious organism in disease aetiology. Therefore, the aim of this study was to characterise potential infectious pathogens in the population at risk of MeN. Two main approaches were undertaken with analyses of biosamples and data from an existing community-based follow-up study conducted in northwest Nicaragua. The first was a set of hypothesis-driven approaches using targeted molecular and serological methods to determine the prevalence of known pathogens. Overall IgG prevalence of Chikungunya, Zika, Hantavirus and Leptospira were 45.3%, 59.4%, 4.0%, and 10.4%, respectively. Leptospira seropositivity/seroconversion was associated with onset of kidney dysfunction and established MeN. Leptospira is a common zoonotic disease known to cause acute kidney injury. Chronic carriage of Leptospira is well-described in several animal species, but it remains unclear whether this occurs in humans. Therefore, DNA from urine was tested using an optimised nested-PCR technique which showed that 12/77 (15.6%) individuals were asymptomatic urinary carriers. The second set of analyses aimed to identify known or poorly characterised pathogens using unbiased metagenomic sequencing of dried blood spots taken by participants at documented time of fever. In total, sequences from 36 viral families were detected in the cohort which included seven viral human-pathogenic species. These included sequences identified as Lymphocytic choriomeningitis mammarenavirus (LCMV). Follow-up serology testing of the cohort showed that 3.4% of the cohort were LCMV IgG seropositive. These studies did not detect a single pathogen that could account for MeN in this population, but the infectious hypothesis has not been disproved. Ways to improve the sensitivity of future analyses are suggested.

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