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TB Notes Newsletter

No. 3, 2005


BOTUSA’s Legacy During the First Decade: A Personal Reminiscence and Perspective on Tuberculosis
Presented by Kenneth G. Castro, MD

BOTUSA’s 10th anniversary was commemorated with a conference on TB and AIDS programs and research in Gaborone, Botswana, on March 1, 2005. Following are Dr. Castro’s remarks at the conference.

It is hard to believe that more than 10 years have elapsed since CDC staff members Drs. Kevin DeCock, Robin Huebner, and Nancy Binkin, and Mr. Harry Stern participated in the Botswana Program review organized by then Botswana’s Permanent Secretary of Health Dr. Eddie Maganu. Thus began the collaboration between CDC and the Botswana Ministry of Health.

That TB Program review raised awareness of how, in spite of excellent achievements by Botswana, gains in TB control were being eroded in association with growing numbers of persons infected with HIV, the etiologic agent of AIDS.

In 1993 I joined CDC’s Division of Tuberculosis Elimination (DTBE) following several years of epidemiologic work with CDC’s Division of HIV/AIDS, where I had gained an appreciation of the extraordinary benefits of field work, as demonstrated by Projet SIDA in Kinshasa, Zaire (now the Democratic Republic of Congo) and Projet Retro-CI in Abidjan, Ivory Coast. I was therefore eager to promote the establishment of similar field sites by DTBE to focus on collaborative research projects in TB prevention and control. Subsequent discussions explored the feasibility of initiating a collaborative venture between CDC’s DTBE and the Botswana Ministry of Health to investigate risk factors associated with HIV and Mycobacterium tuberculosis coinfection. Soon it became evident that both CDC and Botswana’s Ministry of Health (MOH) were facing a unique opportunity for CDC and MOH to engage in epidemiologic projects of mutual interest, aimed at improving our understanding and providing the scientific basis for public health policies to reduce the suffering caused by the intersection of TB and HIV.

Dr. Robin Huebner, who years earlier had served as a Peace Corps volunteer in Botswana’s TB control program and worked with Dr. Maganu, became the first CDC DTBE assignee to live in Botswana and initiate the collaboration. To reflect the partnership between Botswana and the United States of America, the project was named BOTUSA.  From its earliest stages, all the research agenda was jointly set by CDC staff (Drs. Huebner, Binkin, Castro) and Dr. Maganu from MOH, with input from Dr. Themba Moeti, Dr. Howard Moffat at Princess Marina Hospital, Dr. Nick Hone at Nyangabgwe Hospital in Francistown, and Dr. Rumisha as well as Mr. B.S. Koosimile of the Botswana TB Control Program. Epidemic Intelligence Service (EIS) Officer Dr. Shahin Lockman and Medical Officer Dr. Jordan Tappero implemented the first series of operational research projects. Activities continued to grow, and Dr. Huebner was later succeeded by Dr. Tom Kenyon and Ms. Ethleen Lloyd. During Dr. Kenyon’s tenure as CDC assignee to BOTUSA, the US government initiated the LIFE (Leadership and Investment in Fighting an Epidemic) Initiative, and CDC’s Global AIDS Program (GAP) came to be. As GAP started a series of field sites throughout Africa, BOTUSA’s oversight was transferred from DTBE to GAP – only after several soul-searching and reassuring conversations with Dr. Eugene McCray. Dr. Elizabeth Talbot was selected by DTBE and assigned to BOTUSA to ensure the continuation of high-priority, TB-specific collaborative research activities within the context of GAP. Over time, Dr. Kenyon was succeeded by present BOTUSA CDC Director Dr. Peter Kilmarx, and Dr. Taraz Samandari followed Dr. Talbot. The collective work of these individuals, along with that of local key medical officers, research nurses, medical students, EIS Officers, outreach and district workers, and TB patients in Botswana have yielded a magnificent body of work relevant to the prevention and control of TB in a country also being ravaged by HIV.

BOTUSA’s 10-year history and immense contributions to public health are extensive, reflective of consistently high productivity.  Because of space limitations, I will limit myself to brief descriptions of ten selected projects.

  1. The electronic TB register (ETR) project and surveillance strengthening were some of the first areas of collaboration. The ETR has facilitated more rigorous and comprehensive TB case recording and reporting than was previously possible in Botswana. Patient-based data are recorded and reported at the district level and then transmitted centrally. It has also facilitated a number of operational research projects focused on addressing TB program issues. As a result of Botswana’s experience with use of the electronic TB register, seven other sub-Saharan African countries (including South Africa and Tanzania) decided to adopt ETR and have been using it very successfully.
  2. Autopsy studies of adults and children who died with HIV infection in the mid/late 1990s suggested that the spectrum of HIV-associated opportunistic pathogens would not be adequately covered with cotrimoxazole preventive therapy (CPT). These data enabled Botswana to develop a data-based policy that does not rely on CPT, unlike other countries pressured to adopt this intervention on the basis of findings demonstrating a beneficial effect of CPT in Ivory Coast and Malawi.
  3. Operational research identified alcohol consumption as a strong risk factor for HIV among TB patients, thus drawing attention to the need to address this risk during HIV prevention messages in Botswana.
  4. In trying to explain relatively high rates of defaults observed among HIV-infected persons with TB, research showed a large misclassification bias occurs in labeling TB cases as defaulters; many “defaults” are actually deaths. This provided a compelling argument to offer antiretroviral (ARV) treatment for HIV-infected TB patients.
  5. A 3-year annual rate of tuberculosis infection (ARTI) study demonstrated how a novel sampling technique reduced the necessary sample size to obtain an accurate estimate of ARTI. This study was carried out against the backdrop of ARV program implementation and expansion, and will be integrated over the longer term in general program activities (to be performed every 3–5 years). This activity provides a key tool for measuring the potential effect of ARVs on TB transmission.
  6. Serodiagnostic tests for TB have been field-tested among adults and children in Botswana. The evaluated tests did not pan out as viable; however, we learned that 15% of all microbiologically confirmed adult TB cases were detected through blood culture alone. Most developing countries rely solely on acid-fast sputum smear microscopy as the basis for diagnosing TB. These BOTUSA data strongly suggest that TB is being underdiagnosed in settings of high-background HIV infection, such as Botswana, and suggest that improvements in laboratory capacity are required to enhance the ability to diagnose TB in persons with HIV.
  7. A novel strategy of performing rapid HIV testing on TB patient sputum specimens was validated through BOTUSA, and showed that Oraquick® used in this manner had about 94% sensitivity, and provided important population-based HIV prevalence data among persons with TB. Simultaneously, it was acknowledged that the sensitivity was insufficient for relying on this test as the basis of an individual’s HIV diagnosis. As part of the 2002 anti-TB drug resistance survey, HIV testing was anonymously performed on approximately 2000 TB patients included in the survey. This strategy resulted in the first representative, population-based data of HIV prevalence among TB patients in Botswana (and in sub-Saharan Africa); 60% of TB patients were infected with HIV—somewhat lower than the 70%–80% previously reported in hospital-based surveys. This strategy is being used more widely now in a number of settings following the example of Botswana.
  8. Results from the BOTUSA 2002 anti-TB drug resistance survey confirm increasing trends in anti-TB drug resistance in Botswana—the only sub-Saharan country with trend data—including any drug resistance, isoniazid, and streptomycin among new patients. Changes in multidrug-resistant TB are not statistically significant, but suggest a worrisome trend among new patients, from 0.2% in 1996 to 0.5% in 1999, and to 0.8% in 2002. In the past, Botswana has not relied on fixed-drug combination (FDC) tablets for treatment of patients with TB. These data have provided an impetus for Botswana to introduce FDCs for TB patient care as an effort to limit selective drug treatment interruptions and thus control further emergence of drug resistance.
  9. An isoniazid preventive therapy (IPT) program was successfully piloted by MOH and BOTUSA in 2000–2001; approximately 1000 attendees to a voluntary counseling and testing (VCT) clinic who were identified as HIV infected were screened, and approximately 600 ultimately initiated IPT. Completion was 70%—better than the rates observed in other WHO-supported ProTEST pilot projects.  This pilot IPT project also served to demonstrate that a symptom screen was nearly as sensitive as performing a chest radiograph to rule out active TB. This information was published in The Lancet. Furthermore, the results of the IPT pilot project provided the basis for the MOH decision to proceed with implementation of IPT in 2002. As such, thousands of persons have been screened and started on IPT, now being delivered through the general clinic network. Close monitoring and evaluation of the program as it continues to expand will be essential to ascertain that patients are being screened appropriately to rule out the presence of active TB and thus prevent the unintended use of inappropriate isoniazid monotherapy in persons requiring multidrug regimens for active TB. To facilitate better monitoring and evaluation capacity, BOTUSA is assisting MOH with the development of an electronic recording and reporting data system and will assist with another national anti-TB drug resistance survey in 2005 to closely monitor isoniazid resistance trends.
  10. A critical trial for Botswana and the international community was just launched in November 2004 comparing 6-month IPT to life-long (3 years). Botswana currently follows the UNAIDS recommendation of 6-month duration of IPT, but is keen to learn if longer duration in a setting where patients are likely re-exposed to persons with active TB will result in measurable improvements in protecting highly vulnerable HIV-infected persons against TB.

As we celebrate the achievements of the past decade, it is most appropriate to assess the present situation objectively and identify future challenges to TB prevention and control. Botswana is acknowledged to represent one of the countries with the highest incidence and notification rates of TB worldwide. Paradoxically, in the 1980s Botswana had implemented solid TB control measures, only to be soon undermined by the epidemic of HIV, and possibly by incipient complacency in TB control. Despite the country’s historically strong record of TB control, resource commitments for the TB program have diminished over time as the government has had to grapple with the HIV epidemic. For example, the number of TB-specific district-level coordinators has been greatly reduced such that now only a few districts have staff fully dedicated to TB control. The human-resource deficit is costing the TB program greatly, leading to the inability to sustain the previous high quality of services. Without the ability to make certain that all persons with active TB receive their treatment until cured, interruptions in therapy and suboptimal regimens are probably contributing to the growing burden of drug resistance. Future challenges to BOTUSA include the need to help with the necessary training, education, and building of capacity to deliver high-quality public health services aimed at reducing the suffering and premature deaths associated with the coepidemics of TB and HIV.

It is my sincere hope that the next decade of collaboration in BOTUSA continues to provide relevant research findings for sound policies coupled with local capacity building to make a difference in the lives of those afflicted with TB and HIV.

I am grateful to Dr. Peter Kilmarx, CDC GAP, BOTUSA Director, for his leadership and for the invitation to share this perspective on the occasion of the tenth anniversary of the BOTUSA Collaboration, to Drs. Charles Wells and Lisa Nelson, CDC DTBE, International Research and Programs Branch, for much of the information described above and for their insightful comments, to Dr. Taraz Samandari for his outstanding work in Botswana, to President Festus Mogae for his enlightened leadership and commitment to the well-being of his country, to all those mentioned above and others who I have inadvertently omitted for their key roles in making BOTUSA a reality, and to the very fine people of Botswana who have helped BOTUSA become a “value-added” contribution for the benefit of so many others. Pula!


Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division of Tuberculosis Elimination -

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