Poor performance of a novel serological test for diagnosis of pulmonary tuberculosis in Bangui, Central African Republic.
ABSTRACT We assessed the performance of a serological test for tuberculosis (SDHO Laboratories Inc., Canada) in our setting. Among 68 of 99 suspected pulmonary tuberculosis patients who were scored as having tuberculosis on the basis of Mycobacterium tuberculosis-positive culture, the sensitivity of the serological test was lower than that of sputum smear microscopic examination (20.6% versus 80.9%, respectively; P < 0.000001).
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ABSTRACT: A sentinel serosurveillance study was conducted in Central African Republic to estimate the prevalence of HIV seropositivity in the general adult population in each province so that the public health authorities can target HIV prevention programmes to the priority areas. Blood samples were collected from women attending 48 antenatal clinics in urban and rural areas of the Central African Republic. These samples were tested for HIV antibodies in an anonymous and unlinked manner using strategy II recommended by WHO. The data were extrapolated to all women of reproductive age in Central African Republic by use of a parity-based adjustment involving the application of correction factors to the observed prevalence rates. A total of 9,305 pregnant women were recruited from November 2001 to October 2002. HIV seroprevalence was high in all age groups (12% in the less than 20 year age group to 17% in the 25-29 year age group). The median prevalence of HIV in antenatal clinics was similar for rural areas, for Bangui and for other urban areas (16.5, 15.0, and 12.5% respectively). Adjustment for parity and fertility pattern increased the prevalence of HIV in all antenatal clinics except in Bangui. This first national study of HIV prevalence in Central African Republic revealed that the HIV epidemic is continuing to spread in both urban and rural areas. Thus, efforts to reduce transmission should be made in every part of the country.Journal of Medical Virology 04/2004; 72(3):358-62. · 2.37 Impact Factor
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ABSTRACT: Rapid diagnostic tests for tuberculosis (TB) are needed to facilitate early treatment of TB and prevention of Mycobacterium tuberculosis transmission. The ICT Tuberculosis test is a rapid, card-based immunochromatographic test for detection of antibodies directed against M. tuberculosis antigens. The objective of the study was to evaluate the performance of the ICT Tuberculosis test for the diagnosis of active pulmonary TB (PTB) with whole blood, plasma, and serum from patients suspected of having PTB and from asymptomatic controls in a setting with a high prevalence of PTB. Seventy patients suspected of having PTB (and who were later confirmed to have or not to have PTB by use of M. tuberculosis culture as the "gold standard") and 42 controls were studied. Twenty-one controls were neither vaccinated with Mycobacterium bovis bacillus Calmette-Guérin (BCG) nor tuberculin skin test (TST) positive (group A controls), and 21 controls were TST positive and/or had previously been vaccinated with BCG (group B controls). Study subjects were drawn from one hospital and one primary health care unit in Rio de Janeiro City, Brazil. One version of the test (ICT-1) was evaluated by using whole blood, plasma, and serum samples. Sera obtained for this study were frozen and later tested with a manufacturer-modified version of the test (ICT-2). Among the patients suspected of having PTB, the sensitivities of the ICT-1 with whole blood, serum, and plasma were 83, 65, and 70%, respectively, and the specificities were 46, 67, and 56%, respectively. Among the group A controls, the specificities of ICT-1 with the three specimen types were 95, 100, and 95%, respectively. Among the group B controls, the specificities of ICT-1 with the three specimen types were 71, 86, and 86%, respectively. Among the patients suspected of having PTB, the sensitivity of ICT-2 was 70% and the specificity was 65%. Among the group A controls, the specificity of ICT-2 was 95%, and among the group B controls, the specificity of ICT-2 was 81%. With a 29% observed prevalence of PTB among patients suspected of having PTB, the positive predictive values of the ICT tests ranged from 39 to 50% and the negative predictive values ranged from 82 to 87%. The ICT Tuberculosis tests were not sufficiently predictive to warrant their widespread use as routine diagnostic tests for PTB in this setting. However, further evaluation of these tests in specific epidemiologic settings may be warranted.Journal of Clinical Microbiology 07/2002; 40(6):1989-93. · 4.07 Impact Factor
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ABSTRACT: With the development of the acquired immunodeficiency syndrome (AIDS) epidemic, the isolation of mycobacteria from blood has become a common problem for clinical laboratories. In this study two methods were used for the recovery of mycobacteria from blood specimens obtained from AIDS patients: (1) direct inoculation of a biphasic medium, and (2) a non-commercial lysis-centrifugation method. A total of 3 consecutive blood samples were taken at 15-minute intervals from each of 50 AIDS patients with clinical suspicion of disseminated mycobacterial disease. Mycobacterium growth was noted in 70/138 blood specimens from 30 (60%) patients. These cultures yielded Mycobacterium tuberculosis in 19 (63%) and Mycobacterium avium complex organisms in 11 (37%) patients. Cultures using the lysis-centrifugation method were positive in 54% of the patients while cultures using biphasic medium were positive in 44% (P > 0.05). The positivity for M. avium complex was higher with lysis-centrifugation (91%) than with biphasic medium (45.4%) (P < 0.05). However, the positivities for M. tuberculosis with the lysis-centrifugation method (89.5%) and direct inoculation in biphasic medium (100%) were similar (P > 0.05). The use of a non-commercial lysis-centrifugation technique is inexpensive, reliable, and can be an alternative method for the diagnosis of mycobacteraemia in developing countries.Bulletin of the World Health Organisation 02/1997; 75(4):361-6. · 5.25 Impact Factor
CLINICAL AND VACCINE IMMUNOLOGY, June 2006, p. 702–703
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Vol. 13, No. 6
Poor Performance of a Novel Serological Test for Diagnosis of
Pulmonary Tuberculosis in Bangui, Central African Republic
Eric Kassa-Kelembho,1† Edith Kassa,1Germain Zandanga,1Yves-Brillant Service,2
Albert Ignaleamoko,3and Antoine Talarmin1*
Institut Pasteur de Bangui,1Department of Medicine, Ho ˆpital Communautaire,2and Chest Clinic,
National Teaching Hospital,3Bangui, Central African Republic
Received 28 June 2005/Returned for modification 19 September 2005/Accepted 22 March 2006
We assessed the performance of a serological test for tuberculosis (SDHO Laboratories Inc., Canada) in our
setting. Among 68 of 99 suspected pulmonary tuberculosis patients who were scored as having tuberculosis on
the basis of Mycobacterium tuberculosis-positive culture, the sensitivity of the serological test was lower than
that of sputum smear microscopic examination (20.6% versus 80.9%, respectively; P < 0.000001).
Tuberculosis (TB) remains a major health problem, with an
estimated 8 million new cases and 2 million deaths due to this
disease every year worldwide (4). Microscopic examination of
sputum smears is still the only rapid, technically simple, and
inexpensive test available for the routine diagnosis of TB in
most developing countries. However, its sensitivity for pulmo-
nary tuberculosis (PTB), even in good centers, is only about 60
to 70% with reference to sputum culture. Various antibody-
based serological tests have been developed. Unfortunately,
most do not perform sufficiently well to be used as routine field
diagnostic tests (6, 9, 11, 12). Here, we assessed the diagnostic
performance of the SDHO MTB test (SDHO Laboratories
Inc., Canada), a novel and commercially available serological
test for the detection of PTB, in the Central African Republic,
which is a setting with high prevalences of both TB (13) and
human immunodeficiency virus (HIV) infection (1, 7).
Study participants were recruited from the Department of
Medicine at Bangui Community Hospital and from the Chest
Clinic at National Teaching Hospital in Bangui, Central Afri-
can Republic, between 12 July and 1 September 2004. Eligible
participants were suspected PTB cases, defined as patients who
had a history of cough lasting ?3 weeks and who were iden-
tified by a physician as needing an evaluation for TB. Giving of
informed consent, age of ?18 years, and either sex were con-
sidered inclusion criteria for the study. All consecutive sus-
pected PTB patients who fulfilled the inclusion criteria were
enrolled and underwent an evaluation that is considered rou-
tine for suspected PTB in the Central African Republic. This
consisted of providing three sputum specimens for acid-fast
bacillus smearing within 48 h of enrollment. In addition, these
same sputum specimens and blood samples were processed for
mycobacterial culture (3, 5). Blood samples were also used for
HIV testing as described elsewhere (8).
The SDHO MTB test (SDHO Laboratories Inc., Canada)
utilizes the principle of immunochromatography and is a unique
two-site immunoassay on a membrane. As the test sample flows
through the membrane assembly of the device, a colored recom-
binant TB antigen-colloidal gold conjugate complexes with anti-
TB antibodies in the sample. This complex moves through the
membrane to the test region, where it is immobilized by the
recombinant TB antigen coating of the membrane, leading to
formation of a colored band which confirms a positive test result.
The absence of this colored band in the test region indicates a
negative test result. The unreacted conjugate and unbound com-
plex, if any, move further on the membrane along with rabbit
immunoglobulin G (IgG) in the colloidal gold conjugate and are
subsequently immobilized by goat anti-rabbit antibodies on the
membrane at the control region, forming a pink band. This con-
trol band serves to validate the test results. In our laboratory, the
test was performed with 50 microliters of blood serum specimens
as soon as possible on the day of collection. The results were
interpreted after 15 min of migration, according to the instruc-
tions of the manufacturer.
Patients were confirmed as having PTB disease on the
basis of positive sputum and/or blood culture for Mycobac-
terium tuberculosis. Sensitivity, specificity, and positive and
negative predictive values were assessed for microscopic
examination and for the serological test. Chi-square and
Yates corrected P values were used for comparisons of per-
formance between these two methods.
A total of 99 suspected PTB patients were included for
evaluation during the study period. The median age was 31
years (range, 18 to 72 years), with 53 men and 46 women.
Among 98 patients who accepted the HIV serology test, 55
(56.1%) were HIV positive. M. tuberculosis was isolated from
31 (56.4%) of the HIV-positive patients and from 37 (86.0%)
of the HIV-negative patients (P ? 0.002). The patient who
refused HIV testing was culture negative for M. tuberculosis.
The sensitivity of sputum smear examination was much lower
among HIV-positive PTB patients (21 of 31; 67.7%) than
among HIV-negative PTB patients (34 of 37; 91.9%) (P ?
0.01). A similar tendency was observed for the SDHO MTB
test; the sensitivity was 16.1% (5 of 31) among HIV-positive
PTB patients and 32.4% (12 of 37) among HIV-negative PTB
patients. However, this difference was not statistically signifi-
cant (P ? 0.12). The overall sensitivity of the SDHO MTB test
was only 20.6% (17 of 68), which is much lower than that of
* Corresponding author. Present address: Institut Pasteur de Mada-
gascar, BP 1274, Antananarivo 101, Madagascar. Phone: (261 20) 22
412 72. Fax: (261 20) 22 415 34. E-mail: firstname.lastname@example.org.
sputum smear examination (80.9%; 55 of 68). The specificities
of sputum smear examination (100.0%) and the SDHO MTB
test (90.3%) were similar (Table 1).
This preliminary study indicates that the SDHO MTB test
performed poorly compared to sputum smear examination in the
detection of PTB. Similarly poor performance has previously
been reported for other serological tests to identify PTB patients;
in particular, sensitivity is poor to moderate (16% to 57%) for
seven serological tests, including two immunochromatographic
tests (ICT Tuberculosis and RAPID TEST TB) and five enzyme-
linked immunosorbent assays (TUBERCULOSIS IgA enzyme
immunoassay, PATHOZYME-TB complex, PATHOZYME-
MYCO IgG, PATHOZYME-MYCO IgA, and PATHOZYME-
MYCO IgM) (10). The same conclusion was also drawn more
recently after evaluation in Botswana of a new prototype immu-
nochromatographic strip and five commercially available serodi-
agnostic TB tests with a predominantly HIV-infected population
of hospitalized patients with cough (12).
The sensitivity of sputum smear examination was much
lower among HIV-positive patients than among HIV-negative
patients. This is consistent with previous reports (9), and al-
though the reasons are unclear, it could be due in part to the
degree of cellular immunocompromise. The likelihood of a
positive sputum smear is lower, because inflammation in the
lung decreased with the severity of cellular immunocompro-
mise associated with HIV. The same trend was observed with
the SDHO MTB test, and this is not surprising because sero-
logical tests are not very sensitive in HIV patients (2). How-
ever, these results should not preclude further experiments
using other commercial serological tests with large groups of
TB- and HIV-positive patients to address the observation of
Despite an acceptable specificity, this novel serological test
lacks the sensitivity required to replace the sputum smear
microscopy method in our population. Further improvements
are needed before this test could be useful in our setting.
We are grateful to A. Bere, F. Yango, and T. B. Nambea-Koisset for
their technical assistance with mycobacteriology laboratory techniques
and to SDHO Laboratories Inc., Canada, for providing us with the
serological test kits.
We are grateful to the French Association Raoul Follereau for
This article is dedicated to the memory of our friend and colleague,
Eric Kassa-Kelembho, who died on a mission against tuberculosis. His
death is a loss to both us and the Central African Republic.
1. Breton, G., Y. B. Service, E. Kassa-Kelembho, C. D. Mbolidi, and P. Minssart.
2002. Tuberculose et VIH a ` Bangui, Re ´publique Centrafricaine: forte pre ´v-
alence et difficulte ´s de prise en charge. Med. Trop. 62:623–626.
2. Chan, E. D., L. Heifets, and M. D. Iseman. 2000. Immunologic diagnosis of
tuberculosis: a review. Tuber. Lung. Dis. 80:131–140.
3. David, H., V. Levy-Fre ´bault, and M. F. Thorel. 1989. Me ´thodes de labora-
toire de mycobacte ´riologie clinique, p. 87. Institut Pasteur Press, Paris,
4. Dye, C., S. Scheele, P. Dolin, V. Pathania, M. C. Raviglione, et al. 1999.
Consensus statement. Global burden of tuberculosis: estimated incidence,
prevalence, and mortality by country. JAMA 282:677–686.
5. Fandinho, F. C., B. Grinsztejn, V. G. Veloso, M. C. Lourenco, E. Werneck-
Barroso, E. Joao, S. A. Nogueira, and L. S. Fonseca. 1997. Diagnosis of
disseminated mycobacterial infection: testing a simple and inexpensive
method for use in developing countries. Bull. W. H. O. 75:361–366.
6. Gounder, C., F. C. De Queiroz Mello, M. B. Conde, W. R. Bishai, A. L.
Kritski, R. E. Chaisson, and S. E. Dorman. 2002. Field evaluation of a rapid
immunochromatographic test for tuberculosis. J. Clin. Microbiol. 40:1989–
7. Matsika-Claquin, M. D., M. Massanga, D. Menard, J. Mazi-Nzapako, J. P.
Tenegbia, M. J. Mandeng, J. Willybiro-Sacko, A. Fontanet, and A. Talarmin.
2004. HIV epidemic in Central African Republic: high prevalence rates in
both rural and urban areas. J. Med. Virol. 72:358–362.
8. Menard, D., E. E. Mavolomade, M. J. Mandeng, and A. Talarmin. 2003.
Advantages of an alternative strategy based on consecutive HIV serological
tests for detection of HIV antibodies in Central African Republic. J. Virol.
9. Perkins, M. D., M. B. Conde, M. Martins, and A. L. Kritski. 2003. Serologic
diagnosis of tuberculosis using a simple commercial multiantigen assay.
10. Pottumarthy, S., V. C. Wells, and A. J. Morris. 2000. A comparison of seven
tests for serological diagnosis of tuberculosis. J. Clin. Microbiol. 38:2227–
11. Rasolofo, V., T. Rasolonavalona, H. Ramarokoto, and S. Chanteau. 2000.
Predictive values of the ICT Tuberculosis test for the routine diagnosis of
tuberculosis in Madagascar. Int. J. Tuberc. Lung. Dis. 4:184–185.
12. Talbot, E. A., D. C. Hay Burgess, N. M. Hone, M. F. Iademarco, M. J.
Mwasekaga, H. J. Moffat, T. L. Moeti, R. A. Mwansa, P. Letsatsi, N. T.
Gokhale, T. A. Kenyon, and C. D. Wells. 2004. Tuberculosis serodiagnosis in
a predominantly HIV-infected population of hospitalized patients with
cough, Botswana, 2002. Clin. Infect. Dis. 39:e1–e7.
13. World Health Organization. 2004. Global tuberculosis control: surveillance,
planning, financing. WHO report WHO/HTM/TB/2004.331. World Health
Organization, Geneva, Switzerland.
TABLE 1. Performances of microscopy examination and the SDHO MTB test with culture-confirmed PTB patients and non-PTB
patients in Bangui, Central African Republic
No. of samples % (95% confidence interval)
aNS, not significant.
bND, not determined.
VOL. 13, 2006NOTES 703