# Molecular Epidemiology of Isoniazid-resistant M tuberculosis in Port-au-Prince, Haiti

## TL;DR

This study finds that isoniazid-resistant tuberculosis is common in Haiti, especially among adolescents, and spreads in community settings.

## Contribution

The study identifies community-based transmission of isoniazid-resistant TB in Haiti using genomic data and highlights higher resistance in younger patients.

## Key findings

- 7.7% of tuberculosis cases in Haiti were isoniazid-resistant.
- Adolescents under 20 years old had a higher risk of isoniazid-resistant TB.
- Genomic analysis revealed 5 clusters of isoniazid-resistant TB cases, likely transmitted in community settings.

## Abstract

Isoniazid-resistant, rifampin-susceptible tuberculosis (Hr-TB) is associated with poor treatment outcomes and higher rates of acquisition of further drug resistance during treatment. Due to a lack of widespread diagnostics, Hr-TB is frequently undetected and its epidemiology is incompletely understood.

We studied the molecular epidemiology of Hr-TB among all patients diagnosed with culture-positive pulmonary tuberculosis between January 1 and June 30, 2017, at an urban referral tuberculosis clinic in Port-au-Prince, Haiti. Demographic and clinical data were extracted from the electronic medical record. Archived diagnostic Mycobacterium tuberculosis isolates were tested for genotypic and phenotypic isoniazid resistance using the Genotype MTBDRplus assay (Hain, Nehren, Germany) and culture-based testing, respectively. All isoniazid-resistant isolates and a randomly selected subset of isoniazid-susceptible isolates underwent whole-genome sequencing to confirm the presence of mutations associated with isoniazid resistance, to validate use of Genotype MTBDRplus in this population, and to identify potential transmission links between isoniazid-resistant isolates.

Among 845 patients with culture-positive pulmonary tuberculosis in Haiti, 65 (7.7%) had Hr-TB based on the Genotype MTBDRplus molecular assay. Age < 20 years was significantly associated with Hr-TB (odds ratio, 2.39; 95% confidence interval, 1.14, 4.70; P = .015). Thirteen (20%) isoniazid-resistant isolates were found in 5 putative transmission clusters based on a single nucleotide polymorphism distance of ≤ 5. No patients in these transmission clusters were members of the same household. Adolescents are at higher risk for Hr-TB. Strains of isoniazid-resistant M tuberculosis are actively circulating in Haiti and transmission is likely occurring in community settings.

The overall proportion of tuberculosis in Haiti that is isoniazid resistant is 7.7%; a higher proportion of resistance in younger cases suggests a rise in the fraction of incident tuberculosis that is resistant. Genomic analyses suggest transmission of isoniazid-resistant Mycobacterium tuberculosis in community settings.