Characterization of the Proportion of Clustered Tuberculosis Cases in Guatemala: Insights from a Molecular Epidemiology Study, 2010-2014.

There is little information about the amount of recent tuberculosis transmission in low-income settings. Genetic clustering can help identify ongoing transmission events. A retrospective observational study was performed on Mycobacterium tuberculosis isolates from persons living with HIV (PLHIV) and HIV-seronegative participants who submitted samples to a referral tuberculosis laboratory in Guatemala City, Guatemala from 2010 to 2014. Genotyping results were classified according to the international spoligotyping database, SITVIT2. Spoligotype patterns were categorized as clustered or nonclustered depending on their genotype. The proportion of clustering and the index of recent transmission index (RTIn-1) were estimated. In the RTIn-1 method, clustered cases represent recent transmission, whereas nonclustered cases represent reactivation of older tuberculosis infections. As a secondary aim, the potential risk factors associated with clustering in isolates from the subset of participants living with HIV were explored. From 2010 to 2014, a total of 479 study participants were confirmed as culture-positive tuberculosis cases. Among the 400 available isolates, 71 spoligotype patterns were identified. Overall, the most frequent spoligotyping families were Latin American-Mediterranean (LAM) (39%), followed by T (22%) and Haarlem (14%). Out of the 400 isolates, 365 were grouped in 36 clusters (range of cluster size: 2-92). Thus, the proportion of clustering was 91% and the RTIn-1 was 82%. Among PLHIV, pulmonary tuberculosis was associated with clustering (OR = 4.3, 95% CI 1.0-17.7). Our findings suggest high levels of ongoing transmission of M. tuberculosis in Guatemala as revealed by the high proportion of isolates falling into genomic clusters.

Annotated Genome Sequences of 16 Lineage 4 Mycobacterium tuberculosis Strains from Guatemala.

Whole-genome sequencing has resulted in new insights into the phylogeography of Mycobacterium tuberculosis However, only limited genomic data are available from M. tuberculosis strains in Guatemala. Here we report 16 complete genomes of clinical strains belonging to the Euro-American lineage 4, the most common lineage found in Guatemala and Central America.

Whole genome sequencing identifies circulating Beijing-lineage Mycobacterium tuberculosis strains in Guatemala and an associated urban outbreak.

Limited data are available regarding the molecular epidemiology of Mycobacterium tuberculosis (Mtb) strains circulating in Guatemala. Beijing-lineage Mtb strains have gained prevalence worldwide and are associated with increased virulence and drug resistance, but there have been only a few cases reported in Central America. Here we report the first whole genome sequencing of Central American Beijing-lineage strains of Mtb. We find that multiple Beijing-lineage strains, derived from independent founding events, are currently circulating in Guatemala, but overall still represent a relatively small proportion of disease burden. Finally, we identify a specific Beijing-lineage outbreak centered on a poor neighborhood in Guatemala City.

Evaluación de resistencia genotípica del VIH-1 en pacientes con fallo virológico de Guatemala / Evaluation of genotypic resistance of HIV-1 in patients with virologic failure Guatemala

La resistencia a la terapia antirretroviral (TARV) es un factor determinante para el fallo virológico en pacientes con VIH. El objetivo de este estudio fue identificar los patrones genotípicos de resistencia en pacientes con fallo virológico. Fueron incluidos pacientes de las diferentes unidades de atención integral de VIH en Guatemala, de quienes se sospechaba resistencia y que necesitaban cambios en la TARV por fallo virológico, se requirió haber evaluado la adherencia y una carga viral ≥1,000 copias/ml. La información clínica y demográfica fue recolectada a través de la forma de solicitud. El análisis de resistencia se realizó a través de la metodología TRUGENE® HIV-1. La muestra se restringió a 25 pacientes por motivos de accesibilidad. El 68% de las muestras analizadas presentaron resistencia; por familia de ARV la resistencia fue de 88.2% para ITINN, 70.5% para ITIAN y 17.6% para IP. Se identificaron 79 mutaciones entre el grupo de estudio, el 46.8% de fueron asociadas a ITINN, 76.6% a ITIAN y 26.6% a IP. Para ITIAN las mutaciones más frecuentes fueron la M184V 43%, M184I 14% y K219E 10%; el 23.8% fueron mutaciones TAMs. Para ITINN fueron la V179D 16%, K103N 14%, G190A 14% y Y181C 14%. Para los IP la mutación más frecuente fue la M36I con 29%. La resistencia identificada en este grupo, fue menor a lo reportado en otros países latinoamericanos; sin embargo es similar a lo reportado por OMS en países con bajo o medio ingreso económico.

ARV drug resistance is one of the leading causes of virologic failure among HIV patients on HAART. Theobjective of this study was to determine genotypic resistance profiles among HIV patients on virologic failure. Patients from one HIV clinic in Guatemala on whom ARV drug resistance was suspected and needed a change in their ARV regimen due to virologic failure were included. In order to perform the genotype, the patient had to demonstrate good adherence to therapy and a confirmed viral load ≥1,000 copies/ml. Demographics andclinical data were collected through the resistance-testing questionnaire. The TRUGENE® HIV-1 methodology was used for resistance analysis. The patient sample was restricted to 25 patients due to accessibility, 68% presented resistance to at least one ARV drug. By ARV class, 88.2% presented resistance to NNRTIs, 70.5% to NRTIs and 17.6% to IPs. We found 79 mutations among the samples analyzed. Of the mutations found, 46.8% were associated with NNRTI resistance, 76.6% to NRTI resistance and the remainder 26.6% to PI resistance. The most frequent NRTI associated mutations were M184V 43%, M184I 14% and K219E 10%; 23.8% were TAM. The NNRTI associated mutations were V179D 16%, K103N 14%, G190A 14% and Y181C 14%. For the PI the most frequent mutation was M36I with 29%. The resistance found in this study was lower to that reported in other Latin American studies, however, it is similar to what is reported by WHO in low and middle income countries.