XDR-TB acquired via transmission, not treatment failure

27 February 2015

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The large majority of cases of extensively drug-resistant tuberculosis (XDR-TB) in Kwa-Zulu Natal, South Africa, were acquired via person-to-person, and not as a result of treatment failure, as originally believed. These results were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle this week, and demonstrate the need to focus attention on infection control and prevention in the region.

A person is defined as having multi-drug resistant TB (MDR-TB) when they are resistant to two or more ‘first-line’ antibiotic drugs, whilst XDR-TB is defined when a person is resistant to three or more of the six available ‘second-line’ antibiotics. Both are serious, however when a person has XDR-TB, it is extremely expensive and hard to formulate an effective treatment regime for them. Many people with XDR-TB will die before they even realise they have the extremely resistant strain.

In a bid to understand the patterns of transmission, 377 patients with XDR-TB, and diagnosed between 2011-2014, were enrolled in the study. They were reviewed based on their demographics, geography, previous HIV and TB history, potential exposures, healthcare engagement and treatment history to determine how they may have acquired their resistance. The mycobacterial isolates of the patients underwent a genotyping and targeted sequencing of nine genes known to be resistant to treatment. In instances where they found clusters of the same genotypic resistance, whole genome sequencing was conducted for further information about any patterns of transmission.

The study found that only 21 percent of the patients had had any antibiotics for MDR-TB in the past, meaning that 79 percent of XDR-TB infections are attributed to transmission, and not treatment failure. Delving further, the researchers found that 47 percent of all XDR-TB infections in the sample came from one specific cluster, and 87% of the participants had an isolate belonging to one of 16 clusters. Only 13 percent of the isolates were unique.

From 2006, Kwa-Zulu Natal has been the epicentre of an increased number of cases of XDR-TB. Lead researcher, N. Sarita Shah, stated: “South Africa has among the highest burden of drug-resistant TB worldwide and has seen a fivefold increase in the number of XDR-TB cases occurring each year. Prevention of XDR-TB is essential to reduce morbidity and mortality of this disease.”

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