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TB Notes 2, 2003
UPDATE FROM THE INTERNATIONAL ACTIVITY OFFICE
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
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 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
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.
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
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.
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