Targeted screening improves TB diagnosis in people with HIV in South Africa

Dr Limakatso Lebina (bottom row) presenting to CROI 2021.
Dr Limakatso Lebina (bottom row) presenting to CROI 2021.

Screening everyone with HIV and others at high risk of tuberculosis for active TB increased diagnosis rates by 17% compared to testing people who had potential symptoms of TB such as cough and fever, Dr Limakatso Lebina of the University of Witwatersrand reported to the 2021 virtual Conference on Retroviruses and Opportunistic Infections this week.

TB is under-diagnosed in people with HIV in sub-Saharan Africa, where it remains the biggest killer of people with HIV. Around 150,000 cases of TB are missed each year in South Africa – almost half the entire burden – and these people die or transmit TB to others before their illness is detected.

TB screening in most resource-limited settings relies on asking people if they have experienced a cough lasting more than two weeks, fever, night sweats, or weight loss. This symptom screen performs poorly in identifying TB cases in people on antiretroviral treatment, where it misses around half of all cases, and very badly in pregnant women with HIV, where it misses 70% of TB cases.


confirmatory test

A second test, to show that the result of a previous test was correct. Because the diagnosis of HIV infection is so important, a second (confirmatory) test, is done. The confirmatory test should be of a different type than the first test.

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

active TB

Active disease caused by Mycobacterium tuberculosis, as evidenced by a confirmatory culture, or, in the absence of culture, suggestive clinical symptoms.


In a bacteria culture test, a sample of urine, blood, sputum or another substance is taken from the patient. The cells are put in a specific environment in a laboratory to encourage cell growth and to allow the specific type of bacteria to be identified. Culture can be used to identify the TB bacteria, but is a more complex, slow and expensive method than others.


A unit of heredity, that determines a specific feature of the shape of a living organism. This genetic element is a sequence of DNA (or RNA, for viruses), located in a very specific place (locus) of a chromosome.

The TB symptom screen was developed in the late 2000s when laboratory tests were out of reach in most resource-limited settings. Over the past 15 years international donors and governments in southern Africa have invested in the Gene Xpert diagnostic platform. The Xpert Ultra MTB/RIF test uses affordable, rapid nucleic acid testing to test for TB and identify drug resistance. Using Xpert Ultra MTB/RIF testing as the primary test for TB, rather than as a confirmatory test after screening, and screening everyone at high risk of TB, has the potential to improve rates of diagnosis.

The Targeted Universal Testing for TB  (TUTT) study was designed to investigate whether screening everyone with HIV, anyone with a history of TB in the past two years and anyone who reported close contact with a TB case in the past year would increase TB diagnoses by 25%. Preliminary findings from the study, presented at the 2020 Union World Conference on Lung Health, showed that approximately half the TB cases diagnosed using Xpert Ultra MTB/RIF were in people without TB symptoms.

The study was carried out in primary healthcare clinics in KwaZulu-Natal, Western Cape and Gauteng provinces. Thirty clinics were randomised to carry out symptom testing for TB. Thirty were randomised to carry out targeted screening, plus testing of people who did not have a risk factor but had symptoms. People with risk factors were tested using Xpert Ultra MTB/RIF and liquid culture, while people with symptoms in both study arms were tested using Xpert Ultra MTB/RIF.

The study enrolled 32,000 patients in the intervention clinics, 71% living with HIV. Participants were predominantly female (62%) and 28% had TB symptoms. Forty-one per cent had a contact with TB and 5% had been diagnosed with TB in the past two years.

Of those tested, 6% were positive for TB. Rates were 5% among people with HIV, 7.5% among TB contacts and 12.2% among prior TB cases. People with a prior history of TB were twice as likely as those without to test positive, whereas people with HIV were 40% less likely to test positive than HIV-negative people.

Targeted testing revealed that the burden of undiagnosed TB was higher in people with HIV not on antiretroviral treatment, who accounted for 70% of TB cases among people with HIV. They were three times more likely to be diagnosed with TB than people with HIV on antiretroviral treatment.

The investigators calculated that TB diagnoses increased by 17% in intervention clinics compared to the standard-of-care clinics in the follow-up period. In the standard-of-care clinics, TB diagnoses fell by 8% compared with the prior period. These differences were statistically significant.

Cost-effectiveness analysis of targeted TB testing will be reported at a future scientific conference.


Lebina L et al. A cluster randomized trial of targeted universal testing for TB in clinics. Conference on Retroviruses and Opportunistic Infections, abstract 234, 2021.

Download the abstract eBook from the conference website.