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TB Notes 2, 2003


Update on BOTUSA Project Research

Botswana is located in southern Africa and has a population of approximately 1.7 million. It has one of the lowest population densities in the world, at 2.3 per square kilometer. It has a typically young population base (43% are younger than 15 years old), mostly settled in the urban settings. It is considered a success story in Africa in terms of education (79% adult literacy rate), respect for human rights, civilian control of a professional military, economic growth, low level of corruption, and public health infrastructure. Yet, 47% of the population lives below internationally established poverty levels.

TB is a major health problem in Botswana. The Botswana National Tuberculosis Control Program (BNTP) was established in 1975 with technical assistance from the World Health Organization (WHO). The establishment of this program initiated a decline in TB cases that was further enhanced by the introduction of short-course chemotherapy administered as directly observed therapy (DOT) countrywide in 1986. However, since 1989, Botswana has experienced a three-fold increase in TB incidence from 202/100,000 to 620/100,000 in 2001. This increase has largely been attributed to the country’s increasing HIV epidemic; in 2002, 35% of women attending prenatal clinics were HIV infected, an estimated 330,000 persons were living with HIV, and there were 24,000 AIDS deaths.

In 1995, the BOTUSA Project was established as a collaborative effort between the Botswana Ministry of Health (BMOH) and CDC to conduct TB/HIV research, provide epidemiologic program support, and build laboratory infrastructure. In 1998, the BOTUSA Project joined with the Global AIDS Program (GAP) for HIV/AIDS program support. BOTUSA conducts a range of basic, social science, epidemiologic, clinical, and operations research for contributions to Botswana TB control and international TB/HIV knowledge.

Since 1999, Dr. Elizabeth Talbot has been Associate Director for TB/HIV research at the BOTUSA Project. Under her leadership, the BOTUSA TB/HIV research team has conducted studies addressing several topics vital to controlling TB in settings with epidemic HIV. These include studies on 1)TB in congregate settings, 2) evaluation of TB control activities, 3) TB treatment interruption, and 4) new TB diagnostics.

TB in congregate settings
At the request of the BMOH, BOTUSA conducted TB prevalence surveys and needs assessments and made screening/TB control recommendations at the country’s largest prisons and at the refugee camp in Dukwe, Botswana.

Prison survey
Prisoners and guards were screened with a short questionnaire, and anyone with a cough of more than 2 weeks’ duration was asked to produce three sputum specimens for smear and culture. Persons found to have TB were administered a more extensive questionnaire and voluntary HIV testing and counseling was offered to them.

Of 1461 prisoners and guards at the prisons, 1,290 (88%) were screened. Forty-seven persons with TB were found among prisoners and guards; 22 of these were newly diagnosed cases identified by the screening alone. Risk factors for having TB in this population included a cough greater than 2 weeks, incarceration for more than 1 year, being in the first offenders prison, and having a prior history of TB in prison. DNA fingerprinting of isolates has identified several clusters suggesting TB transmission is occurring in the prisons. As a result, it was recommended that the prisons begin screening all incoming prisoners for active TB to prevent further transmission within this setting.

Refugee survey
A similar survey is underway now at Dukwe, a large refugee settlement in northeast Botswana, housing refugees from several other African countries including Angola, Zimbabwe, the Democratic Republic of the Congo (DRC), and Rwanda. Currently over 1,000 refugees have completed screening and several TB cases have been identified. These results will help the BNTP determine a policy for TB control in the camp.

Evaluation of TB control activities
From September to November 2002, the first in a series of annual TB skin test surveys was conducted in primary schoolchildren throughout the country. These surveys are being conducted to assess the burden of TB in the country, determine if the increasing TB case rate is increasing TB transmission at the community level, and evaluate TB control activities.

This survey was conducted in 56 schools and included more than 3,200 children across the country. The prevalence of TB infection (defined as greater than 15-mm induration) was measured as 6.8%, and the annual risk of infection (ARI) was 0.71%. This is a sharp increase since the last survey, conducted in 1989, which measured a prevalence of 0.75% and an ARI of 0.1%. The continued series of surveys will allow the BNTP to monitor future trends in TB infection and to evaluate TB/HIV control initiatives just beginning in Botswana (i.e., antiretroviral therapy and isoniazid preventive therapy).

TB treatment interruption
In 1998 in Botswana, 10% of those who started TB treatment did not complete it. BOTUSA staff conducted a case-control study to investigate risk factors for defaulting from TB treatment and to assess knowledge, attitudes, and beliefs about antiretroviral therapy (ART). Cases (treatment interrupters) and controls (treatment completers) were identified from the national electronic TB registry.

Of the 266 cases identified from the database, 170 (56%) were incorrectly classified. Many had actually died while on treatment, completed treatment, or transferred during treatment After reclassification, 63 cases and 173 controls were found and interviewed. In this population, being male, drinking alcohol, having a chaotic lifestyle, and having a deficit of TB knowledge were risk factors for treatment interruption.

Also, it was found that 75% of respondents overall would take an HIV test to see if they were eligible for ART, 89% would be willing to take ART if they qualified, 70% would even take directly administered ART (DAART), and 78% of the cases stated that they would have completed their TB treatment if ART had been offered to them at the end of TB treatment. Therefore, it seems that DAART would be highly acceptable and may be an incentive for HIV testing and TB treatment completion.

New TB diagnostics
Smear microscopy is the TB diagnostic tool used in most developing countries. It is inexpensive, but requires a microscope and has low sensitivity for detecting cases. There is a need for inexpensive, highly sensitive TB diagnostic tests to be available to high-burden countries. The objective of this study was to fieldtest commercially available serodiagnostic TB tests and a new immunochromatographic strip (ICS) serodiagnostic test for TB diagnosis in an HIV-positive population, using culture as the gold standard.

Data were collected on 444 consecutively enrolled inpatient TB suspects; 91% of these persons were found to be HIV positive and 32% had confirmed TB. In 23 (5%) of these patients, mycobacterial blood culture was the sole source of TB diagnosis. The sensitivities of the five serodiagnostic tests ranged from 0% to 37%, specificities from 62% to 99%, and positive predictive values from 0% to 50%. This study shows that TB is prevalent in the inpatient population, that HIV coinfection is common, and that blood cultures may be a useful adjunct for TB diagnosis in this population. Unfortunately, all five tests lacked sufficient sensitivity as a sole test for diagnosing TB. These tests will be further assessed in a pediatric population in an upcoming BOTUSA study.

Future plans
The BOTUSA TB/HIV research group is about to launch a large clinical trial comparing 6 months of isoniazid preventive therapy (IPT) to lifetime IPT (defined as 3 years) in a large HIV-positive cohort. This study will be very important in guiding TB preventive therapy for HIV-positive persons in the international community.

Unfortunately, after 2 1/2 years of exemplary leadership at BOTUSA, Elizabeth Talbot has left Botswana. She and her family are returning to the United States, stopping en route for a 3-month temporary duty assignment in Switzerland, where she is assisting WHO in developing guidelines for Global Fund–recipient countries for preventing drug resistance for TB, HIV, and malaria. Elizabeth will be sorely missed at BOTUSA by her collaborators and colleagues, and especially by the TB/HIV research staff. However, she will continue to collaborate on the IPT trial and other new studies just getting underway. The BOTUSA staff wish her well in her future endeavors and look forward to having her come back to Botswana to consult on research projects and to visit old friends.

—Submitted by Tracy Agerton, RN, MPH
Div of TB Elimination



Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
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