CROI: TB rates skyrocketing in Western Cape township — most infectious cases associated with HIV coinfection

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Infectious smear-positive (tuberculosis) TB is most commonly found in people with HIV coinfection, which is likely to be responsible for the skyrocketing rates of TB in South Africa according to a survey of TB and HIV prevalence in a peri-urban township south of Cape Town. There was also a high number of smear-negative TB cases, but it was more likely to be found among HIV-negative individuals.

“In this community with high HIV prevalence, both smear-positive and smear-negative TB is increasing,” said Dr Linda-Gail Bekker of the Desmond Tutu HIV Centre at the University of Cape Town. She presented the study investigating HIV’s association with TB in the township at the Thirteenth Conference on Retroviruses and Opportunistic Infections in Denver. This presentation can be viewed or listened to online .

The study

To better understand the associations between age, sex, HIV prevalence with TB in the township, Dr Bekker and colleagues conducted a cross-sectional survey. The study involved a random selection of 8% of adults aged over 14 years.

At each clinic visit, participants were given an oral HIV test, questioned about TB symptoms and risk factors, and early morning sputum and nebulised sputum samples were collected (a nebuliser is a inhaler-type device that, with a small amount of saline, can induce a cough more likely to produce sputum which may contain evidence of TB). Sputum samples were sent to a reference laboratory for culturing (a process that takes several weeks to diagnose TB) and AFB microscopy (a more rapid process that looks for evidence of TB in a stained sputum sample or ‘smear’ under a microscope).

Glossary

smear

A specimen of tissue or other material taken from part of the body and smeared onto a microscope slide for examination. A Pap smear is a specimen of material scraped from the cervix (neck of the uterus) examined for precancerous changes.

sputum

Material coughed up from the lungs, which can be examined to help with diagnosis and management of respiratory diseases.

culture

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.

opportunistic infection (OI)

An infection that occurs more frequently or is more severe in people with weakened immune systems, such as people with low CD4 counts, than in people with healthy immune systems. Opportunistic infections common in people with advanced HIV disease include Pneumocystis jiroveci pneumonia; Kaposi sarcoma; cryptosporidiosis; histoplasmosis; other parasitic, viral, and fungal infections; and some types of cancer. 

drug interaction

A risky combination of drugs, when drug A interferes with the functioning of drug B. Blood levels of the drug may be lowered or raised, potentially interfering with effectiveness or making side-effects worse. Also known as a drug-drug interaction.

A few categories of TB were examined in the study. ‘Prevalent TB’ was defined as cases that had already been diagnosed and were receiving TB therapy. Newly-diagnosed TB cases were defined as “smear positive” if one or two specimens were AFB positive and culture positive, or “smear negative” if specimens were negative under microscopy but culture positive.

TB in Africa and in the township

“The World Health Organization control strategy based on DOTS (directly observed therapy) is failing to control the African TB epidemic,” said Dr Bekker, “and this is thought probably to be as a result of the HIV epidemic.”

In many African countries annual TB notification rates have increased fourfold since 1999, and last year, the TB epidemic was declared a regional emergency

Some of the highest TB rates have been observed in the peri-urban townships of South Africa but little is known about the interaction of the two infections at the community level.

Dr Bekker focused on one such community in the Western Cape, which she described as a well-demarcated township with an estimated population of 13,711, and an HIV prevalence of 23%. In 2005, the township had a TB notification rate of over 2,000 per 100,000 and 62% of the cases were HIV coinfected. (Most of these diagnoses were of smear-positive TB, which is both simpler to diagnose and more easily transmitted.)

Data from the national TB programme in 2004, show that about 70% of the population with TB completed their treatment (64% of people with HIV). A higher percentage of people with HIV died (8%) or had to interrupt TB treatment (8%) than among than total population (5% and 4% respectively).

Looking at the last ten years, TB has increased in all age groups; but the greatest increase in incidence has been among those aged between 20 and 40 years, the age at which most HIV infection occurs. This effect has become even more pronounced over the past couple of years.

Results

A total of 1457 subjects were selected for the study, but only 959 could be located and 197 declined to participate — which could suggest a fear of stigma from having their HIV or TB diagnosed. In the end, 762 individuals participated in the survey.

A total of 174 people (23%) were HIV-infected. The burden of HIV was greatest in young women (close to 40% of women between the ages of 20-29 were HIV-positive).

A total of 37 individuals had TB (4.8% of the total population): eleven with prevalent TB, six with smear-positive TB and 20 with smear-negative TB. The majority of those with prevalent and smear-positive TB were HIV-positive (70% and 83% respectively), but one of the study’s most surprising findings was that the majority of those with smear-negative TB were HIV-negative (65%).

By looking at the prevalence in the survey and comparing how many people were already on TB treatment at the start of the study, the team could assess how good the local TB programme was at identifying TB and getting people on treatment. They found that the best case finding was in HIV-negative cases with smear-positive TB, about 67% of whom had already been diagnosed and placed on treatment. For people with HIV, only 36% of those with smear-positive TB and 19% with smear-negative TB were on treatment. However, this was better than the case finding of smear-negative TB in HIV-negative people — as only about 5% of those cases had been identified and put on treatment.

The team also calculated the mean number of days in the community between developing smear-positive TB or smear- negative TB and receiving TB treatment. Again, the HIV-negative smear-positive group received the best treatment, starting TB treatment within a mean of 87 days. For the people with HIV the mean wait for TB treatment is 240 days for smear-positive TB, and 479 days for smear-negative TB. But for the people without HIV and smear-negative TB, the mean number of days before TB treatment is 3414 days.

One possible explanation for this is that in the overall population, there was no correlation between any individual symptom or combined symptom score against laboratory confirmed disease (not even the classic coughing for more than 21 days). Smear-negative TB without symptoms is less likely to be detected in people without TB than in people with TB who may have other symptoms which lead them to seek clinical evaluation.

Conclusion

“Case finding needs to be improved, particularly among the smear-positives,” concluded Dr Bekker. “In addition, the importance of this group of HIV-negative people with TB needs to be further elucidated.”

In the question and answer session, she said that they had plans to look into the group further. She said that they referred these patients to the local TB clinic but only five had actually gone in for treatment. “We need to see the natural history in these patients. Do they move on to smear positivity?” She said that symptoms don’t seem to be a problem, but feared that they may serve as a reservoir for infection which could be enhanced by the highly susceptible HIV population.

References

Bekker L-G et al. Prevalence of HIV and undiagnosed tuberculosis in a peri-urban community in South Africa. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 69, 2006.