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Intensified tuberculosis case finding among people living with the human immunodeficiency virus in a hospital clinic in Ethiopia

Authors:
  • ICAP, Columbia University Program in Ethiopia

Abstract

Intensified tuberculosis case finding (ICF) is used in people living with the human immunodeficiency virus (PLHIV) to reduce the burden of tuberculosis (TB). We conducted a retrospective study in 300 PLHIV attending an HIV care clinic in Ethiopia to assess ICF performance during a 12-month period. Between 80% and 95% of patients were screened for TB at enrolment and at each 3-month follow-up visit. Thirty-four (11%) patients were diagnosed with TB, of whom 27 (79%) were identified in the first 6 months. This study assessed serial ICF in routine settings, showing that TB screening had its largest diagnostic yield in the first 6 months.
INT J TUBERC LUNG DIS 15(3):411–413
© 2011 The Union NOTES FROM THE FIELD
[A version in French of this article is available from the Editorial Of ce in Paris and from the Union website www.theunion.org]
Intensifi ed tuberculosis case fi nding among people
living with the human immunodefi ciency virus in
a hospital clinic in Ethiopia
D. Assefa,* Z. Melaku,* T. Gadissa,* A. Negash,* S. G. Hinderaker,†‡ A. D. Harries†§
*
International Centre for AIDS Care and Treatment Programme, Columbia University, Addis Ababa, Ethiopia;
International Union Against Tuberculosis and Lung Disease, Paris, France;
Centre for International Health, University
of Bergen, Bergen, Norway; §
London School of Hygiene & Tropical Medicine, London, UK
Correspondence to: Dawit Assefa, International Centre for AIDS Care and Treatment Programme, Columbia University,
PO Box 165/1110, Addis Ababa, Ethiopia. Tel: (+251) 911 228 246. Fax: (+251) 1 1 115 545 454. e-mail: davassefa@
yahoo.com
Article submitted 22 March 2010. Final version accepted 5 August 2010.
Intensi ed tuberculosis case  nding (ICF) is used in
people living with the human immunode ciency virus
(PLHIV) to reduce the burden of tuberculosis (TB). We
conducted a retrospective study in 300 PLHIV attending
an HIV care clinic in Ethiopia to assess ICF performance
during a 12-month period. Between 80% and 95% of
patients were screened for TB at enrolment and at each
3-month follow-up visit. Thirty-four (11%) patients were
diagnosed with TB, of whom 27 (79%) were identi ed
in the  rst 6 months. This study assessed serial ICF in
routine settings, showing that TB screening had its larg-
est diagnostic yield in the  rst 6 months.
KEY WORDS: Intensi ed case  nding; PLHIV; Ethiopia
INTENSIFIED TUBERCULOSIS case  nding (ICF),
combined with infection control and isoniazid pre-
ventive therapy, aims to reduce the tuberculosis (TB)
burden in persons living with the human immuno-
de ciency virus (PLHIV).1 ICF should lead to early
diagnosis and treatment of TB, improve individual
outcomes and reduce transmission of infection. A sys-
tematic review of ICF found that 8–10% of PLHIV
attending antiretroviral treatment (ART) clinics and
voluntary counselling and testing services can be di-
agnosed with TB.2 A study among newly enrolled
PLHIV in Ethiopia showed similar results.3
The World Health Organization’s (WHO’s) ‘Three
Is’ strategy recommends repeated ICF in PLHIV.4,5
However, no empirical data are available on the use of
serial screening. There is a call for studies to establish
the optimum TB screening interval and TB diagnostic
yield during serial ICF.2 We therefore conducted a
study in an HIV care clinic in Ethiopia to assess rou-
tine TB screening activities in PLHIV. We speci cally
determined 1) whether ICF occurred at enrolment and
during follow-up visits, and 2) the diagnostic yield of
TB in those who were actively screened.
METHODS
A retrospective cross-sectional medical record review
of ICF in PLHIV was carried out in Dil Chora Refer-
ral Hospital, one of 36 public hospitals supported by
the International Centre for AIDS Care and Treat-
ment Program-Ethiopia (ICAP-E) in Eastern Ethio-
pia. A comprehensive care and treatment package for
PLHIV is provided mainly by nurses in the HIV clin-
ics, and includes provision of ART, treatment and
prevention of opportunistic infections, ICF and eval-
uation of TB suspects, and referral of diagnosed pa-
tients for TB treatment. Patients are reviewed at the
HIV clinic every 3 months or more frequently, de-
pending on their clinical condition.
All PLHIV should be screened for TB at enrolment
and at every follow-up visit with a symptom-based
questionnaire asking about cough >2 weeks, fever
>2 weeks, night sweats >2 weeks, weight loss 3 kg
in the last month and history of TB contact. Any pa-
tient with a cough >2 weeks or an af rmative response
to two other questions is considered a TB suspect. Pul-
monary TB (PTB) suspects are evaluated by sputum
smear examination and, if negative, by chest radiog-
raphy and response to antibiotics. Extra-pulmonary
TB suspects are investigated according to type of clin-
ical presentation, e.g.,  ne-needle aspiration of en-
larged lymph nodes. Those with a diagnosis of TB are
transferred to the TB clinic for registration and start
of anti-tuberculosis treatment. Results of screening
and TB diagnosis are recorded in patient medical  les
stored in the medical records department.
All PLHIV aged >15 years who were newly en-
rolled in HIV care and treatment at the Dil Chora
Hospital from September 2007 to August 2008 were
included in the study. Patients already diagnosed with
SUMMARY
412 The International Journal of Tuberculosis and Lung Disease
TB prior to enrolment at the HIV clinic (n = 90) were
excluded. Data were collected from patient medical
les between November and December 2009 using a
structured form, and were cross-checked with pre-
ART, ART and TB registers. Outcome variables in-
cluded demographic, clinical and laboratory char-
acteristics, whether TB screening was carried out at
enrolment and during follow-up visits and numbers
diagnosed with TB at 3-monthly intervals.
Data were double entered and analysed using Epi-
Data software (EpiData Association, Odense, Den-
mark). The study was approved by the Ethics Advisory
Group of the International Union Against Tubercu-
losis and Lung Disease and the local Dire Dawa
health of ce.
RESULTS
There were 300 PLHIV (187 female, median age
33 years) enrolled for HIV care, with a baseline me-
dian CD4 cell count of 161 cells/μl (range 4–830).
Cotrimoxazole preventive therapy was started in 275
(92%) patients, and 260 (87%) started ART between
enrolment and the end of the study period. The num-
ber of PLHIV seen and the number and proportion
screened for TB at each of the time periods are shown
in Table 1. The number of PLHIV attending follow-
up visits progressively decreased over 12 months. A
very high proportion of patients was screened for TB
at enrolment, but this signi cantly decreased at the
3-month visit to 80% (P < 0.001), only to increase
again at subsequent visits.
A total of 34 (11%) patients were diagnosed with
TB: 5 (15%) with smear-positive PTB, 18 (53%)
with smear-negative PTB, and 6 (17%) with extra-
pulmonary TB (EPTB); for 5 (15%) patients the type
of TB was not recorded. The diagnosis of TB at enrol-
ment and at subsequent 3-month intervals, along with
CD4 counts and ART status, is shown in Table 2.
Twenty-seven (79%) patients were diagnosed with TB
in the  rst 6 months of ICF, with the proportion de-
clining signi cantly thereafter.
DISCUSSION
The study shows that a high proportion of PLHIV at-
tending an HIV clinic was screened for TB, with pro-
portions varying at enrolment and subsequent follow-
up visits. Over 10% of patients were diagnosed with
TB; the majority were identi ed in the  rst 6 months
of follow-up. Most of those diagnosed with TB had
smear-negative disease, either PTB or EPTB, raising
important questions about the type of laboratory ca-
pacity needed for optimal TB screening.
The strengths of this study were that all patients
enrolled at the HIV clinic at Dil Chora Hospital over a
12-month period were included, and the study report
adhered to STROBE (strengthening the reporting of
observational studies in epidemiology) guidelines.6
However, the study has several limitations. This was
not a countrywide study, the medical  les had informa-
tion missing, including type of TB, the reasons for pa-
tients progressively failing to attend the clinic during
the 12 months were not recorded, and the majority of
TB diagnoses were not con rmed microbiologically.
There are still many unanswered questions. Pro-
spective, more sophisticated studies would provide
better, comprehensive information about the timing
Table 1 TB screening of PLHIV at enrolment and at 3-month follow-up visits, September 2007–August 2008, Dil Chora Hospital,
Dire Dawa, Ethiopia*
Enrolment
n (%)
3-month
follow-up
n (%)
6-month
follow-up
n (%)
9-month
follow-up
n (%)
12-month
follow-up
n (%)
PLHIV attending the HIV clinic at enrolment
and at scheduled 3-month intervals 300 253 237 217 211
Patients actively screened for TB at enrolment
and at each scheduled 3-month visit 284 (95) 202 (80) 208 (88) 200 (92) 195 (92)
*
There were 1218 patient visits in the 12 months; screening for TB took place for 1089: 147 were screened for TB at all fi ve clinic visits, 36 at four clinic visits,
37 at three clinic visits, 25 at two clinic visits and 49 were screened only once.
TB = tuberculosis; PLHIV = persons living with the human immunodefi ciency virus.
Table 2 Diagnosis of TB and type of TB at enrolment and at 3-month intervals, September
2007–August 2008, Dil Chora Hospital, Dire Dawa, Ethiopia
Enrolment 3 months 6 months 9 months 12 months
Patients diagnosed with TB* 4 13 10 2 5
Type of TB
Smear-positive PTB
Smear-negative PTB
EPTB
Not recorded
0
4
0
0
1
4
4
4
3
6
1
0
0
2
0
0
1
2
1
1
*
28 (82%) patients who were diagnosed with TB had a CD4 count < 350 cells/μl at the time of diagnosis, and
22 (65%) had already been started on antiretroviral treatment before TB was diagnosed.
TB = tuberculosis; PTB = pulmonary tuberculosis; EPTB = extra-pulmonary tuberculosis.
TB screening in an HIV clinic 413
of screening and the optimal laboratory investiga-
tions needed for diagnosis. We also do not know why
more patients were diagnosed with TB during the
rst 6 months, although, with many having low CD4
counts, this is likely to be due to prevalent TB (undi-
agnosed disease manifesting during early months of
ART and the unmasking of TB due to immune re-
constitution in ammatory syndrome).7,8 Incident TB
cases would be more likely to be diagnosed beyond
6 months. Despite these problems, this is one of the
rst studies to assess serial ICF in the routine setting,
and suggests that TB screening has the largest diag-
nostic yield in the  rst 6 months.
Acknowledgement
This research was supported through an operational research
course, that was jointly developed and run by the Centre for Oper-
ational Research, International Union Against Tuberculosis and
Lung Disease, and the Operational Research Unit, Médecins Sans
Frontières, Brussels.
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TB screening in an HIV clinic i
Un dépistage intensi é de la tuberculose (ICF) est utilisé
chez les sujets infectés par le virus de l’immunodé cience
humaine (PLHIV) a n de réduire le fardeau de la tuber-
culose (TB). Nous avons mené une étude rétrospective
chez 300 PLHIV fréquentant un dispensaire de soins
pour VIH en Ethiopie a n d’évaluer les performances en
matière d’ICF au cours d’une période de 12 mois. Entre
80% et 95% des patients ont été dépistés pour la TB
lors de leur entrée ainsi qu’à chaque visite de suivi
tous les 3 mois. Le diagnostic de TB a été porté chez
34 patients (11%), parmi lesquels 27 (79%) ont été
identi és au cours des 6 premiers mois. Cette étude a
évalué l’ICF en série dans des contextes de routine et dé-
montré que le rendement du dépistage de la TB est le
plus élevé au cours des 6 premiers mois.
RÉSUMÉ
En las personas con infección por el virus de la inmuno-
de ciencia humana (PLHIV) se aplica la estrategia de
búsqueda intensi cada de casos con el  n de disminuir
la carga de morbilidad por tuberculosis (TB). Se llevó a
cabo un estudio retrospectivo de 300 PLHIV que acu-
dieron a un consultorio por atención en Etiopía, cuyo
objeto fue evaluar el rendimiento de la búsqueda intensi-
cada de casos durante un período de 12 meses. Se prac-
ticó la detección sistemática de la TB en entre 80% y
95% de los pacientes en el momento de su inscripción
en la atención de la infección por el VIH y en cada con-
sulta trimestral de seguimiento. Se estableció el dia-
gnóstico de TB en 34 pacientes (11%) y en 27 de ellos
(79%) durante los primeros 6 meses. La evaluación de
la búsqueda intensi cada de casos en este ámbito reveló
que la detección de la TB ofrece el mayor rendimiento
durante los primeros 6 meses.
RESUMEN
... This observation was in agreement with the evidence of declining TB incidence after enrolment and HAART initiation reported in cohorts of HIV-infected persons in sub Saharan Africa (29) and Ethiopia (34). The peak TB incidence shortly after enrollment may have several explanations. ...
... A study done in Arba Minch Hospital, Ethiopia showed that TB incidences were 3.7 and 11.1 per 100 PY in the ART and Pre ART groups, respectively (33). Other recent Evidences in literatures (19,22,34), revealed that HAART reduce the risk of TB as it was also found in our study. ...
... In this study, the overall incidence of TB was 9.12 per 100 person years (PY). The incidence was similar to rates reported in other studies done in Ethiopia and many other Sub-Saharan African countries with reported incidences ranging from 5.4 to 11 per 100 PY. 12 www.mchandaids.org | © 2020 Global Health and Education Projects, Inc. ...
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Intensified case finding is the regular screening for evidence of tuberculosis in people infected with HIV, at high risk of HIV, or living in congregate settings. We systematically reviewed studies of intensified case finding published between January, 1994, and April, 2009. In 78 eligible studies, the number of people with tuberculosis detected during intensified case finding varied substantially between countries and target groups of patients. Median prevalence of newly diagnosed tuberculosis was 0.7% in population-based surveys, 2.2% in contact-tracing studies, 2.3% in mines, 2.3% in programmes preventing mother-to-child transmission of HIV, 2.5% in prisons, 8.2% in medical and antiretroviral treatment clinics, and 8.5% in voluntary counselling and testing services. Metaregression analysis of studies that included only people with HIV showed that for each increment in national prevalence of tuberculosis of 100 cases per 100 000 population, intensified case finding identified an additional one case per 100 screened individuals (p=0.03). Microbiological sputum examination of all individuals without prior selection by symptom screening yielded an additional four cases per 100 individuals screened (p=0.05). Data on the use of serial screening, treatment outcomes in actively identified cases of tuberculosis, and cost-effectiveness, however, were lacking. Concerted action is needed to develop intensified case finding as an important method for control of tuberculosis.
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Ein Großteil der biomedizinischen Forschung ist beobachtend, und die Qualität der veröffentlichten Berichte über diese Forschung ist oft unzureichend. Dies behindert die Beurteilung der Stärken und Schwächen einer Studie und ihrer Übertragbarkeit. Die Strengthening the Reporting of Observational Studies in Epidemiology (STROBE-) Initiative hat Empfehlungen entwickelt, was in einem akkuraten und vollständigen Bericht einer Beobachtungsstudie enthalten sein sollte. Die Empfehlungen wurden von uns so definiert, dass sie 3 Hauptstudientypen abdecken: Kohorten-, Fallkontroll- und Querschnittsstudien. Im September 2004 veranstalteten wir einen zweitägigen Workshop mit Methodikern, Forschern und Herausgebern wissenschaftlicher Zeitschriften, um eine Checkliste zu entwerfen. Anschließend wurde der Entwurf bei mehreren Treffen der Koordinierungsgruppe und nach E-Mail-Diskussionen mit der erweiterten STROBE-Gruppe revidiert und dabei empirische Evidenz und methodologische Aspekte berücksichtigt. Das Ergebnis des Workshops und des anschließenden iterativen Prozesses aus Beratung und Revision war eine Checkliste von 22 Punkten (STROBE-Statement), die sich auf die Bereiche Titel, Abstract, Einleitung, Methoden, Ergebnisse und Diskussion eines Artikels beziehen. 18 der Punkte sind relevant für alle 3 Studiendesigns, während 4 der Punkte spezifisch für Kohorten-, Fallkontroll- und Querschnittsstudien sind. Ein ausführlicher Begleitartikel (Explanation and Elaboration) wurde separat veröffentlicht und ist auf den Webseiten von PLoS Medicine, Annals of Internal Medicine und Epidemiology frei zugänglich. Wir hoffen, dass das STROBE-Statement dazu beitragen kann, dass Beobachtungsstudien besser berichtet werden.
Article
To evaluate commonly available screening tests for pulmonary tuberculosis (TB), using sputum bacteriology as a gold standard, in HIV-infected persons attending an urban voluntary counseling and testing clinic in Addis Ababa, Ethiopia. Prospective enrollment of HIV-infected persons, all of whom underwent TB screening, regardless of symptoms, with: (1) symptom screening and physical examination, (2) 3 sputum specimens for smear microscopy, and (3) chest radiograph. One sputum was also sent for concentrated smear microscopy and mycobacterial culture. Chest radiographs were reviewed by 2 independent radiologists. A confirmed TB diagnosis was defined as 1 positive sputum smear and/or 1 positive sputum culture. We enrolled 438 HIV-infected persons: 265 (61%) females, median age 34 years (range: 18-65), median CD4 cell count 181 cells per cubic millimeter (range: 2-1185). Overall, 32 (7%) persons were diagnosed with TB, of whom 5 (16%) were asymptomatic but culture-confirmed TB cases. Screening for cough >2 weeks would have detected only 12 (38%) confirmed TB cases; screening for cough or fever, of any duration, would have detected 24 (75%) cases, with specificity of 64%. Negative predictive value of screening for these 2 symptoms was 97%. Simulation of the current Ethiopian national guidelines had a sensitivity of 63% and specificity of 83% for diagnosing TB disease among study patients. Traditional symptom screening is insufficient for detecting TB disease among HIV-infected persons but may serve to exclude TB disease. More sensitive, rapid, and low-cost diagnostic tests are needed to meet the demand of resource-limited settings.
Article
This paper describes the incidence of immune reconstitution syndrome (IRS) from the developing world and implications for clinicians. Eleven of 144 HIV and tuberculosis (TB)-coinfected individuals followed for 72 person-years developed IRS within 6 months of initiating generic highly active antiretroviral therapy (HAART). All of the IRS patients were male, with a median age of 29 years; median CD4 at HAART initiation was 123 cells/mm3, and 6-month median CD4 rise was 124 cells/mm3. There was no statistical difference in CD4 rise or CD4 count and duration of TB treatment at HAART initiation between those who did and those who did not develop IRS (P = 0.8380). The median time to development of clinical IRS was 42 days (range 10-89 days). The incidence of IRS in this cohort is 15.2 cases per 100 patient-years. With increased coprevalence of opportunistic infections, especially TB, and increasing access to antiretroviral therapy in the developing world, clinicians in these countries must be able to identify IRS and relieve symptoms without compromising clinical care.
Article
There is little systematic information regarding the immune reconstitution inflammatory syndrome (IRIS). To determine the incidence, risk factors, and long-term outcome of IRIS in HIV-infected patients receiving highly active antiretroviral therapy (HAART) who were coinfected with one of three common opportunistic pathogens. A retrospective cohort identified through a city-wide prospective surveillance program. A retrospective chart review was performed for 180 HIV-infected patients who received HAART and were coinfected with Mycobacterium tuberculosis, Mycobacterium avium complex, or Cryptococcus neoformans between 1997 and 2000. Medical records were reviewed for baseline demographics, receipt and type of HAART, response to antiretroviral therapy, development of IRIS, and long-term outcome. In this cohort, 31.7% of patients who received HAART developed IRIS. Patients with IRIS were more likely to have initiated HAART nearer to the time of diagnosis of their opportunistic infection (P < 0.001), to have been antiretroviral naive at time of diagnosis of their opportunistic infection (P < 0.001), and to have a more rapid initial fall in HIV-1 RNA level in response to HAART (P < 0.001). IRIS is common among HIV-infected persons coinfected with M. tuberculosis, M. avium complex, or C. neoformans. Antiretroviral drug-naive patients who start HAART in close proximity to the diagnosis of an opportunistic infection and have a rapid decline in HIV-1 RNA level should be monitored for development of this disorder.