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New TB detection technology speeds up case finding

A new mobile TB detecting clinic using the latest technology has accelerated case finding by two weeks and stands to hugely curb the spread of one of SA’s biggest killer diseases, writes Chris Bateman for MedicalBrief.

Designed and piloted by Professor Keertan Dedha, the principal investigator based at the University of Cape Town (UCT) and the London School of Hygiene and Tropical Medicine, the study is regarded as one of the most significant developments in the recent history of the disease in SA.

The replicable study, conducted in the resource-poor and deprived districts of Mitchell’s Plain and Klipfontein in Cape Town, found that the time to treatment initiation was far more rapid with the DNA-based diagnostic than with the more traditional smear microscopy.

Called Gene Xpert Edge, the new technology has a median ‘time to treatment initiation’ of just seven days versus over three weeks with the more traditional smear microscopy. Smear microscopy, (involving looking for bugs under a microscope at a local community health centre), remains the relatively treacle-slow standard of care in such low-income settings country wide. The more expensive and advanced DNA-based diagnostics were until recently reserved for more difficult to diagnose cases.

However, with sufficient political will and funding, such mobile clinics will be able to reach into the furthest corners of rural South Africa, and even more importantly, reduce the spread of the deadly Extensively Drug Resistant TB (XDRTB), first detected by vocation-driven mission doctors at Tugela Ferry in KwaZulu-Natal in February 2005.

Dheda said evidence around the optimum strategy to find TB patients in the community remained ‘sparse and controversial,” adding that “this study fills an important gap.”

The current global public health strategy for TB mostly involves passive case finding, i.e. the patient self-presents to healthcare facilities when symptomatic, which has a fundamental drawback – considerable TB transmission occurs prior to diagnosis.

Dheda said the XACT model used ‘active case finding’, which referred to moving diagnostics out of healthcare facilities and into the community to ‘actively’ find patients needing treatment.”

Dheda said the “punchline’ was that the DNA-based diagnostic (Xpert Edge) picked up ‘almost all’ the probably infectious cases, often called ‘super spreaders’, associated with disease transmission and amplification of the epidemic.

“It’s traditionally thought that smear microscopy identifies patients likely to be highly infectious, but our study used more innovative tools, including cough aerosol sampling, which quantifies the number of infectious and viable bugs in respirable particles that penetrate deeply into the lung, to identify the most infectious patients.”

Rapid treatment initiation remained the most effective way of rendering patients non-infectious. Thus, the XACT case finding strategy could be linked to new advances in TB treatment characterised by shortening of treatment regimens for both drug-sensitive and resistant TB, Dheda emphasised.

The latest development comes within months of the roll-out of the national TB recovery treatment plan that reduces the DR-TB treatment regimen from nine (and sometimes 18 months), to six months by adding a highly effective new WHO-approved drug called Pretomanid, manufactured by Viatris in India. According to Dr Norbert Ndjeka, chief director for TB Control and Management, Viatris was due to deliver pretomanid to all provinces early this year. The national Department of Health was helping revise DR-TB guidelines.

Ndjeka said “more than 95% of our adult drug resistant cohort will get this (pretomanid) in combination with bedaquiline, linezolid and moxifloxacin. It’s not yet indicated for children under 15, but we’re hoping something will become available for them as the global research continues and gets WHO approval.”

A startling statistic is that 4m people with TB (two in every five cases) remain undetected or undiagnosed. Such patients predominantly reside in peri-urban informal settlements and shanty towns in TB endemic countries. This problem has worsened after Covid-19, making the implementation of active case finding even more important.

Nature Medicine – Comparison of two diagnostic intervention packages for community-based active case finding for tuberculosis: an open-label randomized controlled trial

Study details

Comparison of two diagnostic intervention packages for community-based active case finding for tuberculosis: an open-label randomized controlled trial
Aliasgar Esmail, Philippa Randall, Suzette Oelofse, Michele Tomasicchio, Anil Pooran, Richard Meldau, Edson Makambwa, Lynelle Mottay, Shameem Jaumdally, Gregory Calligaro, Stuart Meier, Marianna de Kock, Tawanda Gumbo, Robin Mark Warren & Keertan Dheda
Nature Medicine (2023)Cite this article

Abstract

Two in every five patients with active tuberculosis (TB) remain undiagnosed or unreported. Therefore community-based, active case-finding strategies require urgent implementation. However, whether point-of-care (POC), portable battery-operated, molecular diagnostic tools deployed at a community level, compared with conventionally used POC smear microscopy, can shorten time-to-treatment initiation, thus potentially curtailing transmission, remains unclear. To clarify this issue, we performed an open-label, randomized controlled trial in periurban informal settlements of Cape Town, South Africa, where we TB symptom screened 5,274 individuals using a community-based scalable mobile clinic. Some 584 individuals with HIV infection or symptoms of TB underwent targeted diagnostic screening and were randomized (1:1) to same-day smear microscopy (n = 296) or on-site DNA-based molecular diagnosis (n = 288; GeneXpert). The primary aim was to compare time to TB treatment initiation between the arms. Secondary aims included feasibility and detection of probably infectious people. Of participants who underwent targeted screening, 9.9% (58 of 584) had culture-confirmed TB. Time-to-treatment initiation occurred significantly earlier in the Xpert versus the smear-microscopy arm (8 versus 41 d, P = 0.002). However, overall, Xpert detected only 52% of individuals with culture-positive TB. Notably, Xpert detected almost all of the probably infectious patients compared with smear microscopy (94.1% versus 23.5%, P = <0.001). Xpert was associated with a shorter median time to treatment of probably infectious patients (7 versus 24 d, P = 0.02) and a greater proportion of infectious patients were on treatment at 60 d compared with the probably noninfectious patients (76.5% versus 38.2%, P < 0.01). Overall, a greater proportion of POC Xpert-positive participants were on treatment at 60 d compared with all culture-positive participants (100% versus 46.5%, P < 0.01). These findings challenge the traditional paradigm of a passive case-finding, public health strategy and argues for the implementation of portable DNA-based diagnosis with linkage to care as a community-oriented, transmission-interruption strategy. The study was registered with the South African National Clinical Trials Registry (application ID 4367; DOH-27-0317-5367) and ClinicalTrials.gov (NCT03168945).

 

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