Africa-Press – Botswana. Botswana may be facing a fresh multi drug resistant catastrophe after it emerged that “a tool (GeneXpert MTB/RIF) widely used for diagnosing tuberculosis has limitations for detecting rifampin resistance in certain variants.” Rifampin is a medication used to prevent and treat tuberculosis and other bacterial infections. In a paper published recently in the United State Government’s state-owned Centres for Disease Control and Prevention, researchers reported a “transmission of a pre–extensively drug-resistant variant in Botswana that went undetected by GeneXpert.”
The researchers noted that: “The public health impact of misdiagnosis emphasizes the need for comprehensive molecular testing to identify resistance and guide treatment.” “We report a case of a multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strain in Botswana with a rifampin resistance–conferring mutation…not detected by Xpert MTB/RIF.” The researchers found that the “Genomic epidemiology suggested that the infection was part of a transmission chain spanning more than five years.” According to the paper, the patient was a 44-year-old man who, in August 2021, sought treatment at a public health clinic in Botswana for cough, fever, and night sweats.
“The case-patient reported no previous TB history. He had also newly tested positive for HIV at the time of TB diagnosis and had a CD4+ T-cell count of 117 cells/mm3, reflective of advanced HIV-associated immunosuppression,” the report says. The report says the case-patient completed the 6-month rifampin and concurrently started antiretroviral therapy. His TB signs and symptoms resolved; sputum smear tests became negative, and by February 2022, treatment was successfully completed. But the report says in October 2022, the researchers’ analysis found that “the patient carried a lineage 4.3.3 MTBC strain with some mutation, causing rifampin resistance not detected by the tool widely used to diagnose TB…” The researchers indicated that a public health investigation conducted in November 2022 found that the case-patient remained asymptomatic “but was culture positive for MTBC on Mycobacteria growth indicator tube…”
According to the report: “Drug susceptibility testing indicated resistance to medications for treatment of TB…” The researchers tested five members of the patient’s household with Xpert MTB/RIF and identified no additional TB cases. But in in January 2023, “the case-patient developed TB symptoms and was placed on an individualized pre–XDR TB treatment…” The researchers stated: “We are conducting additional investigations to explore the extent of the outbreak of undetected MTBC strains.” The researchers found that: “This case demonstrates the clinical and public health utility of whole-genome sequencing for detecting TB drug resistance missed by conventional molecular tests.”
Of note, the researchers said: “Failing to detect the patient’s pre–XDR TB resulted in ineffective initial treatment and potentially over a year of infectious TB. Early… TB detection could have led to effective initial treatment and reduced the risk of onward transmission,” the researchers said. The researchers also concluded that their “study highlights the utility of WGS for identifying TB outbreaks and informing public health actions in high–TB burden countries.” They observed that “that approach supports the World Health Organization’s recent strategic guidelines for rapidly communicating results from targeted next-generation sequencing combined with conventional tests to inform TB treatment decisions.”
The researchers indicated that: “Although Botswana has had remarkable success in improving HIV management, persons not adequately reached by the HIV care system remain at elevated risk of developing TB, including drug-resistant forms.” The authors of the study further stated that “Additional efforts are needed to ensure that high-quality HIV and TB care are delivered to underserved communities.”
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