Tuberculosis

Mass Screening, Prevention Did Not Improve TB Control in South African Trial

Widespread screening for tuberculosis, treatment of people with active disease, and providing everyone with preventive isoniazid did not significantly improve tuberculosis (TB) control in a study of workers in South African gold mines, researchers reported in the January 23, 2014, New England Journal of Medicine.

Alison Grant and fellow investigators with the Thibela TB Study Teamevaluated an intervention intended to interrupt tuberculosis transmission among South African miners. In this large study of nearly 79,000 miners, 8 groups were screened for TB; if diagnosed with active disease, they were referred for treatment, and if not they were offered prophylactic isoniazid for 9 months. 7 control groups did not receive this intervention. In the intervention clusters, 66% underwent screening, 87% started taking isoniazid, and 35%-79% (depending on cluster) continued isoniazid for at least 6 months.

The researchers found that the intervention did not significantly reduce active TB cases during the 12 months after it ended, with incidence rates of 3.02 and 2.95 per 100 person-years in the intervention and control groups, respectively. Prophylactic Isoniazid did reduce incidence of active TB during therapy (1.10 vs 2.91 per 100 person-years, respectively), but the protective effect was rapidly lost after stopping the drug.

Below is an edited excerpt from a press release issued by the London School of Hygiene and Tropical Medicine describing the research and its findings.

Major South African Trial Did Not Improve Tuberculosis Control in Gold Mines

January 23, 2014 -- A major trial aiming to cut the rate of tuberculosis (TB) among South Africa’s gold miners did not reduce the number of cases or deaths from the disease, according to a study published in the New England Journal of Medicine.

Researchers from the London School of Hygiene and Tropical Medicine say that the results demonstrate the scale of the TB problem in South African gold mines, and highlight the need for a "combination prevention" approach to improve TB control.

The TB epidemic in South Africa’s gold mines worsened with the advent of the HIV epidemic in the 1990s. In 2008, around 3% of miners started TB treatment each year.

The Thibela TB study of 78,744 miners in 15 gold mines from 2006 to 2011 looked at the effectiveness of screening and treating active TB, and providing preventive therapy to the entire workforce with the aim of interrupting TB transmission.

27,126 miners in eight gold mines were screened for TB. Miners found to have active TB disease were given TB treatment, and all other miners were offered a nine-month course of isoniazid preventive therapy (a low-cost medication that prevents latent tuberculosis infection from progressing to clinically apparent disease). In the other seven mines, the mine TB control programs continued their usual practice, which included access to free TB diagnosis and treatment services, and active screening for TB at least once a year, with isoniazid preventive therapy included as part of HIV care.

Although isoniazid preventative therapy was found to be safe and effective in preventing TB among people who took it, the effect wore off very rapidly once the treatment stopped. 12 months after the end of the intervention, researchers did not find any difference in the number of cases of TB between the workers in the mines where mass TB screening and preventive therapy was offered, compared to mines continuing standard practice. 

Lead London School of Hygiene and Tropical Medicine investigator Alison Grant, Professor of International Health, said: "HIV, exposure to silica dust in the mines and close working and living conditions predispose South African gold miners to TB. As conventional control methods were not working, we investigated a radical approach to TB control. Our study shows that isoniazid preventive therapy works while people take it, but, in this setting, the effect was not enough to improve overall TB control. The findings highlight the scale of the problem of TB in these mines."

"Our data suggests that to control TB in South African gold mines, we need a 'combination prevention' approach with better tests to find TB, prompt treatment for those found to have active TB, increased coverage of HIV treatment and effective TB preventive therapy regimens. Continuous isoniazid preventative therapy should be considered for miners at highest risk of TB infection, such as those with HIV."

Thibela TB means "Prevent TB" in Sotho, a predominant language among South African gold miners. The study was conducted by the London School of Hygiene and Tropical Medicine in partnership with the Aurum Institute, and was funded by the Bill and Melinda Gates Foundation, with additional funding from the South African Mine Health and Safety Council, the Foundation for Innovative New Diagnostics, Switzerland, the National Institutes of Health/National Institutes of Allergy and Infectious Diseases, the UK National Institute for Health Research and the UK Medical Research Council. Sanofi-Aventis donated isoniazid for the study.

1/28/14

References

GJ Churchyard, KL Fielding, JJ Lewis, AD Grant, et al. (Thibela TB Study Team). A Trial of Mass Isoniazid Preventive Therapy for Tuberculosis Control. New England Journal of Medicine370(4):301-310. January 23, 2014.

EJ Rubin. Troubles with Tuberculosis Prevention. New England Journal of Medicine370(4):375-376. January 23, 2014.

Other Source

London School of Hygiene and Tropical Medicine. Major South African Trial Did Not Improve Tuberculosis Control in Gold Mines. Press release. January 23, 2104.