Screening of inmates transferred to Spain reveals a Peruvian prison as a reservoir of persistent Mycobacterium tuberculosis MDR strains and mixed infections

Abstract

It is relevant to evaluate MDR-tuberculosis in prisons and its impact on the global epidemiology of this disease. However, systematic molecular epidemiology programs in prisons are lacking. A health-screening program performed on arrival for inmates transferred from Peruvian prisons to Spain led to the diagnosis of five MDR-TB cases from one of the biggest prisons in Latin America. They grouped into two MIRU-VNTR-clusters (Callao-1 and Callao-2), suggesting a reservoir of two prevalent MDR strains. A high-rate of overexposure was deduced because one of the five cases was coinfected by a pansusceptible strain. Callao-1 strain was also identified in 2018 in a community case in Spain who had been in the same Peruvian prison in 2002-5. A strain-specific-PCR tailored from WGS data was implemented in Peru, allowing the confirmation that these strains were currently responsible for the majority of the MDR cases in that prison, including a new mixed infection.

Figure 1

MIRU-VNTR analysis and resistance profile of inmates transferred from El Callao prison to Spain. The two clusters, Callao-1 and Callao-2, are indicated by dashed line rectangles. The MIRU-types for the two strains (MDR and S) coinfecting the patient PrC2 are included.

Figure 2

Network of relationships obtained from the WGS analysis of the Callao-1 cluster. Each black dot corresponds to a SNP (details of the SNPs are depicted on the Supplementary Table S1). MV: median vectors. Each box corresponds to a patient. When two or more cases share identical sequences (0 SNPs between them), they are surrounded by a line. Arrows indicate targeted SNPs for the ASO-PCR design.

Figure 3

Design and evaluation of the Callao-1 strain–specific PCR. (A) In silico amplification patterns expected. (B) Amplification patterns obtained when applying Callao-1 ASO-PCR to a selection of representatives of the cluster and a random selection of non–Callao-1 strains. The arrow indicates the pattern obtained for a mixed sample (patient PrC2, who presented coinfection with a Callao-1 present branch strain and a non–Callao-1 strain). (C) Amplification patterns obtained when applying Callao-1 ASO-PCR to the 11 MDR-TB cases obtained from El Callao prison (years 2016-17). Panels B and C include two parts of the same gel cropped (indicated by a space between them) to eliminate non-informative lanes.

Figure 4

Network of relationships obtained from the WGS analysis of the new isolates, captured by strain-specific PCR (stripped boxes), included in the prison present branch of Callao-1 cluster. The present prison branch corresponds to the one depicted in Fig. 3.