You are on page 1of 7

See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/250308417

Extrapulmonary tuberculosis and HIV coinfection in patients treated for


tuberculosis at the Douala General Hospital in Cameroon

Article  in  Annals of Tropical Medicine and Public Health · January 2013


DOI: 10.4103/1755-6783.115207

CITATIONS READS

14 194

6 authors, including:

Henry Namme Luma Marie Doualla


Hôpital Général de Douala HOPITAL GENERAL DOUALA
193 PUBLICATIONS   1,258 CITATIONS    75 PUBLICATIONS   273 CITATIONS   

SEE PROFILE SEE PROFILE

Bertrand Hugo Mbatchou Ngahane Elvis Temfack


Hôpital Général de Douala Hôpital Général de Douala
103 PUBLICATIONS   297 CITATIONS    51 PUBLICATIONS   522 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

ISAAC Polokwane collaborating centre, South Africa View project

ANRS 12 367 MOTYCCIC study View project

All content following this page was uploaded by Elvis Temfack on 03 June 2014.

The user has requested enhancement of the downloaded file.


Extrapulmonary tuberculosis and HIV coinfection in patients treated
ORIGINAL ARTICLE

for tuberculosis at the Douala General Hospital in Cameroon


Luma Henry Namme1, Doualla Marie-Solange2, Mbatchou Ngahane Hugo Bertrand3, Temfack Elvis4,
Joko Henry Achu5, Kuaban Christopher6
Department of Internal Medicine, Douala General Hospital, Departments of 1Infectious Diseases, 1,2,6Internal Medicine, Faculty of
1-5

Medicine and Biomedical Sciences, University of Yaoundé, 3Department of Medicine, Faculty of Medicine and Pharmaceutical Sciences,
University of Douala, 6Department of Internal Medicine, Jamot Hospital, Yaoundé, Cameroon

ABSTRACT
Context: Human immunodeficiency virus (HIV) infection and resulting immune depression are associated
with increase proportions of extrapulmonary tuberculosis (EPTB). The prevalence of EPTB varies across
studies between 15 and 50% and depends on the region, ethnic group studied, and HIV coinfection rates. In
Cameroon, no studies have been done so far to evaluate the magnitude of this form of tuberculosis (TB), the
various sites involved, and their association with HIV infection. Aims: To determine the prevalence of EPTB,
the various organ sites affected and their association with HIV infection in a population of patients treated
for TB. Settings and Design: We did cross-sectional analysis of the data from the TB register of the Douala
General Hospital, a tertiary health institution situated in Douala, Cameroon. All cases of TB diagnosed between
1stJuly 2007 and 30thJune 2011 were included. Results: Of total of 749 patients recorded for anti-TB treatment,
the overall prevalence of HIV was 41.5% (95% confidence interval [CI]38-45.1). The prevalence of EPTB was
42.9% (321). HIV infection was present in 33.6% of patients with EPTB. The most affected sites of disease
were bones and joints (29.6%), lymph nodes (17.8%), the pleura (15%), peritoneum (14.3%), and the central
nervous system and meninges (9%). Neuromeningeal TB however, less common was most strongly associated
with HIV infection, odd ratio (OR)2.3 (95% CI 1.1-5.0, p < 0.05). Conclusions: The proportion of EPTB among
TB patients treated in the Douala General Hospital is relatively high with bone and joints being the most
affected sites. HIV infection is most strongly associated with neuromeningeal forms.

Key words: Bone and joints tuberculosis, extrapulmonary tuberculosis, human immunodeficiency virus
coinfection, neuromeningeal tuberculosis

Introduction active TB in 2009 at 9.4 million cases and a prevalence


of 14 million cases.[1] About 11-13% of these incident
Tuberculosis (TB), which is one of the three largest cases were among HIV-infected persons.[1] This is
single-agent cause of infectious diseases[1] (along with because HIV-associated immune depression increases
malaria and human immunodeficiency virus [HIV]), the risk of active TB from about 5% in a lifetime to
is a global public health problem due to its high 10% per year.[2] Although this risk depends on the
morbidity and mortality. At present, it is estimated that degree of immune depression, prevailing socioeconomic
at least one third of the human population is infected conditions, and risk of TB exposure, high burden of
by Mycobacteriumtuberculosis.[1] The World Health HIV in Sub-Saharan Africa[3] accounts for4of 5HIV-
Organisation (WHO) estimated a global incidence of associated TB in the world[1] with rates of up to 30%
per year among those with low CD4 counts.[4] Although
Access this article online TB is acquired by inhalation of contaminated droplets,
Quick Response Code: Website: it can produce disease in any organ system other than
www.atmph.org
the lungs, which is usually the initial site of infection.
With this increase awareness on the burden of TB, there
DOI:
has been an increase in the number of reported cases
10.4103/1755-6783.115207 of extrapulmonary tuberculosis (EPTB), and depending
on the region, ethnic group, and HIV coinfection rates,
the prevalence of EPTB is between 15 and 50%.[5] This

Correspondence to:
Dr. Luma Henry Namme, Department of Internal Medicine, P. O. Box 4856, Douala, Cameroon. E-mail: hnluma@yahoo.com

100
100 Annals of Tropical Medicine and Public Health | Jan-Feb 2013 | Vol 6 | Issue 1
Namme, et al.: Extrapulmonary tuberculosis and HIV in Douala

increase in the proportion of cases of EPTB may reflect pieces of tissue obtained by biopsy. Patients with
either an improved ability for detection or an increased PTB associated or not with extrapulmonary sites are
survival of immune suppressed people and the likelihood considered pulmonary cases and recorded as such. No
of TB reactivation at various sites. Compared withHIV- mycobacterial cultures are done in this hospital due to
uninfected person in whom EPTB accounts for about logistic reasons.
20% of TB, HIV-infected persons are more prone to
EPTB in whom it accounts for 53-62% of TB cases.[6] In the Douala General Hospital also, all patients
The term EPTB, which encompasses all forms of TB diagnosed with TB are offered voluntary counseling
other than pulmonary TB (PTB), has a broad spectrum and testing (VCT) for HIV in accordance with the
of clinical manifestations, hence a real diagnostic National AIDS Control Programme in Cameroon.[11]
challenge.[7] The diagnosis whose confirmation HIV antibodies are detected using a third-generation
reposes on obtaining material for culture is much enzyme-linked immunosorbent assay (ELISA) test
more difficult[5] and technically more demanding than BIOREX® (Biorex Diagnostics Limited, Antrim, United
for PTB. In Cameroon, where the prevalence of HIV Kingdom). If the test is positive, a second sample is
is estimated at 5.3% of the adult population,[3] annual collected for a second ELISA which if positive, a
incidence of TB is estimated at 177 per 100,000 people third test Genie® III HIV-1/HIV-2 Assay (Bio-Rad
per year.[1] Although estimated HIV–TB coinfection Diagnostics, Marnes La Coquette, France) is done
rates approach 50%,[8,9] there is no published data on which distinguishes HIV 1 from HIV 2. When the three
the association between HIV and EPTB whose diagnosis tests are positive, the patient is considered positive
is still very uncommon among many physicians. To for HIV. In case of a discordant result, a confirmation
bridge this information gap, we decided to determine test is carried out by the Western blot technique (New
the prevalence of EPTB, the various organ sites affected, LAV blot, Diagnostics, Pasteur, Marnes La Coquette,
and their association with HIV infection in a group France). The results of this test are also recorded in the
of patients receiving anti-TB treatment at the Douala TB register.
General Hospital.
Methods
Subjects and Methods
All patients consecutively diagnosed with TB at the
Douala General Hospital from July 1, 2007 to June 30,
Study setting
2011, were studied. The diagnosis for each patient was
The study was undertaken at the Douala General
obtained through a thorough review of the TB register
Hospital, a tertiary health facility in Douala, the
and the consultation register of the internal medicine
economic capital city of Cameroon. In this hospital,
unit. Information on age, sex, HIV serostatus, and
all patients diagnosed with TB are registered in
form of TB (pulmonary or extrapulmonary) and if
a TB register before commencement of therapy.
extrapulmonary, organ or structure affected, was
The diagnosis of TB is based on the guidelines of
extracted for each patient and recorded in a pre-prepared
the National Tuberculosis Control Programme.[10]
data collection form. Information on CD4 count of
Smear-positive PTB is diagnosed on the basis of a
HIV-positive patients was not included in the analysis
suggestive clinical history and the presence of acid-
because it was not available in the records used.
fast bacilli (AFB) on at least one of the three smears
prepared from three sputum samples submitted on
three consecutive days for microscopic examination Data analysis
after staining by Ziehl–Neelsen’s technique. The Data analysis was done using STATA11.2 statistical
diagnosis of smear-negative PTB is retained for a software (Stata Corporation, College Station, Texas).
patient with clinical signs and symptoms suggestive We expressed our results as proportions of total
of the disease despite the negativity of the first series populations and used the Pearson Chi-square test to
of sputum examinations, no improvement after a 10- compare proportions. For univariate analysis, we used
day course of nonspecific antibiotic therapy, persistent Mantel–Haenszel method and reported results as odd
negative results of a new series of two sputum smear ratio (OR) together with their 95% confidence intervals
examinations, no evident course of the disease, and (CI). A two-tailed P-value with cut-off of significance of
a chest X-ray image suggestive of PTB. The diagnosis less than 0.05 was used.
of EPTB lies for the most part on the clinical decision
based on suggestive clinical signs and evidence of a Results
predominantly lymphocytic exudate as in the case of
peritoneal TB with ascites or granulomatous lesions on During the study period, a total of 749 patients were
histopathological examination of lymph nodes or other recorded for anti-TB treatment of whom 53.8% (402)
Annals of Tropical Medicine and Public Health | Jan-Feb 2013 | Vol 6 | Issue 1 101
Namme, et al.: Extrapulmonary tuberculosis and HIV in Douala

were men. The overall prevalence of HIV in this no statistically significant difference between men and
population was 41.5% (95% CI38-45.1) and was similar women (OR 1.2, 95%CI 0.7-1.9, P = 0.5). However,
in both sexes: OR 1.2 (95%CI0.7-1.9, P > 0.05). Of patients with PTB were more likely to be HIV
the total population, 42.9% (321) were diagnosed with seropositive than those with EPTB, OR 1.8 (95% CI
1.3-2.4, P = 0.001). There was no association between
EPTB [Table 1]. Their mean age was 37.8±15.6 years.
age, TB diagnostic circumstances, and HIV-positive
serostatus (OR 1.1 and 0.9, respectively, P > 0.05).
The prevalence of HIV among these patients with The most common extrapulmonary site of TB lesions
EPTB was 33.6% (95% CI 28.5-38.8) [Table 1], with was bones and joints in 29.6% (95) of patients [Table 2,
Figure 1], and the least common was neuromeningeal
Table 1: Prevalence of EPTB (n) in patients on TB TB in 9% (29) of patients [Table 2]. Other sites that
treatment (N) stratified by sociodemographic included TB of the skin, bladder, and genitals were
characteristics and HIV serostatus found in 14.3% (46) of patients.
N n EPTB (%) 95% confidence
interval (CI) Bone and joint TB, although the most prevalent, had
Age group the lowest prevalence of HIV [Figure 1]. Although
<15 64 19 29.7 18.4-41.0 pleural and peritoneal TB were associated with HIV,
15-24 93 38 40.9 30.8-50.9 neuromeningeal TB had the highest prevalence of
25-34 185 85 45.9 38.7-53.2 HIV, and compared with all other EPTB sites, it was
35-44 182 70 38.5 31.4-45.6 strongly associated with HIV-positive serostatus, OR
45-54 137 67 48.9 40.5-57.3 2.3 (95% CI 1.1-5.0, P = 0.03). Most (44.8%) of those
55-64 58 28 48.3 35.3-61.3 with neuromeningeal TB were between the age group
>65 30 14 46.7 28.5-64.9 of 25and 34 years [Table 2]. After adjusting for age,
Sex neuromeningeal TB still remained strongly associated
Male 402 163 40.5 35.7-45.4 with HIV-positive serostatus (adjusted OR 2.7, 95%CI
Female 347 158 45.5 40.3-50.8
1.1-6.5, P = 0.02)
Diagnostic circumstance
In ward 210 78 37.1 30.6-43.7
Discussion
Out patient 531 239 45.0 40.8-49.3
Screening 8 4 50 12.9-87.1
HIV serostatus
Our study which was aimed at determining the
HIV positive 438 108 33.6 28.5-38.8
prevalence of EPTB, the various organ sites involved,
HIV negative 311 213 66.4 61.2-71.5 and their association with HIV in patients registered
Total 749 321 42.9 39.3-46.4 for anti-TB treatment in the General Hospital Douala
EPTB: Extrapulmonary tuberculosis, TB: Tuberculosis, HIV: Human immunodeficiency
was done by a cross-sectional analysis. We chose
virus this study design because it was the most suitable

Table 2: Site of tuberculosis lesions with respect to age group, sex, and HIV serostatus
Total EPTB Sitesof TB lesions, n(%)
Bones and joints Lymph nodes Pleural Peritoneal Neuromeningeal Other EPTB
Age group
<15 19 10 (10.5) 4 (7.0) 2 (4.2) 0(0) 2 (6.9) 1 (2.2)
15-24 38 13 (13.7) 4 (7.0) 8 (16.7) 5 (10.9) 3 (10.3) 5 (10.9)
25-34 85 18 (18.9) 20 (35.1) 9 (18.8) 14 (30.4) 13 (44.8) 12 (26.1)
35-44 70 14 (14.7) 13 (22.8) 13 (27.1) 15 (32.6) 4 (13.8) 10 (21.7)
45-54 67 24 (25.3) 8 (14.0) 15 (31.3) 8 (17.4) 3 (10.3) 9 (19.6)
55-64 28 11 (11.6) 5 (8.8) 0(0) 3 (6.5) 3 (10.3) 6 (13.0)
>65 14 5 (5.3) 3 (5.3) 1 (2.1) 1 (2.2) 1 (3.4) 3 (6.5)
Sex
Male 163 50 (52.6) 23 (40.4) 27 (56.3) 23(50) 13 (44.8) 27 (58.7)
Female 158 45 (47.4) 34 (59.6) 21 (43.7) 23(50) 16 (55.2) 21 (41.3)
HIV status
Positive 108 19(20) 16 (28.1) 20 (41.7) 19 (41.3) 15 (51.7) 19 (41.3)
Negative 213 76(80) 41 (71.9) 28 (58.3) 27 (58.7) 14 (48.3) 27 (58.7)
Total 321 95(29.6) 57(17.8) 48(15.0) 46(14.3) 29(9.0) 46(14.3)
EPTB: Extrapulmonary tuberculosis, TB: Tuberculosis, HIV: Human immunodeficiency virus

102
102 Annals of Tropical Medicine and Public Health | Jan-Feb 2013 | Vol 6 | Issue 1
Namme, et al.: Extrapulmonary tuberculosis and HIV in Douala

HIV prevalence in our study was 33.6% in patients with


EPTB, and even higher among patients with PTB. Even
so, this high coinfection rate could be explained by the
fact that Cameroon is situated in a region with a high
burden of both infections compared with other regions
like the United States of America.[5,16,23] However, our
finding of higher HIV prevalence among PTB patients
might be because in our institution, patients with both
PTB and EPTB are registered as having PTB. Given
evidence shows that EPTB is more associated with
HIV,[24] and the EPTB–HIV co-infected patients registered
as having PTB might have contributed to this high PTB–
HIV coinfection rate that we found. Either way, HIV and
Figure 1: Prevalence of extrapulmonary tuberculosis according to the TB coinfection rates are high in Cameroon.
organ sites affected and their association with HIV

Neuromeningeal TB was the least common in our study


means of attaining our objectives using this registered with a prevalence of 9%. This finding is lower than that of
information. a recent American study which reported a prevalence of
neuromeningeal TB of 22% among patients with EPTB.[25]
A prevalence of EPTB of 42.9% in our study is quite We also found that neuromeningeal TB compared with
high compared with a recent finding of EPTB of 17% other TB sites was strongly associated with HIV infection.
in Yaoundé the capital city of Cameroon.[12] This This finding is in line with what leeds and collaborators
difference might be due to the fact that the study in found where they showed that HIV infection especially
Yaoundé was carried out in the chest unit of a reference with a low CD4 count of <100 cells/ml was a factor
hospital, and the patients with EPTB could have been associated with severe forms of EPTB among which
those with associated PTB. Our finding is, however, neuromeningeal and disseminated.[25] Given that we did
similar to what was found in Nepal in 2008[13] and not include CD4 cell count in our analysis, we cannot
in India in 2006,[14] which are settings with similar predict whether this association in our population
TB burden like ours. Relatively lower prevalence of increases with severity of immune depression.
20-25% was found in Iran and in many areas of the
United States,[5,15,16] which are areas with lower TB There were certain limitations to our study. First, being
burden. However, in some areas with low TB burden, a hospital-based study in an institution with many
the prevalence among African and Asian immigrants specialties which are not available in other hospitals
was similar to ours[17] and therefore might be reflecting in the same town, there was some selection bias of
the burden of EPTB in the country of origin of these our study population and our finding might not really
immigrants. Furthermore, in our study, this prevalence reflect the reality of EPTB in Cameroon. Second,
could as well be an underestimation as patients with being an observational study from hospital registers,
both PTB and EPTB were all recorded in the TB register analysis was limited only to the variables available in
as PTB. these registers. That notwithstanding, we have shown
that the prevalence of EPTB among patients on TB
We found bones and joints to be the most common
treatment is high with bones and joints being the most
site affected. This was very different from what has
affected sites. Central nervous system and meningeal
been reported in many different studies where lymph
TB were strongly associated with HIV infection. Our
node involvement was the most common site of
study therefore gives some perspective of EPTB and HIV
infection.[17-22] This finding simply reflects the reality
coinfection in Cameroon thereby setting a platform for
of our study setting which happens to harbor the largest
more studies. Furthermore, our findings might help
rheumatology, neurology, and orthopedic reference units
reinforce the need for integrated management of HIV
of the subregion where most patients with joint and bone
and TB in Cameroon, which is mandatory for the global
diseases are referred including those with TB-related
fight against TB.
causes. Also in Douala, there is a big TB diagnostic and
treatment center with chest physicians who provide a
cheaper service. This may therefore lead to a selection
References
bias. Nevertheless, lymph node and pleural involvements 1. World Health Organisation. Global tuberculosis control2011,.Avail-
were the next main sites of infection in our study, similar able from: http://www.who.int/tb/publications/global_report/2011/
to other studies.[17,18] gtbr11_full.pdf. [Last accessed 2012 May 02].

Annals of Tropical Medicine and Public Health | Jan-Feb 2013 | Vol 6 | Issue 1 103
Namme, et al.: Extrapulmonary tuberculosis and HIV in Douala
2. Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, challenges and the next steps in tuberculosis control. Indian J Med
et al. The growing burden of tuberculosis: Global trends and interac- Res 2006;123:702-6.
tions with the HIV epidemic. Arch Intern Med 2003;163:1009-21. 15. Horne DJ, Hubbard R, Narita M, Exarchos A, Park DR, Goss CH.
3. UNAIDS. UNAIDS Report on the global AIDS epidemic,2010.Available Factors associated with mortality in patients with tuberculosis. BMC
from: http://www.unaids.org/globalreport/documents/20101123_Glo- Infect Dis 2010;10:258.
balReport_full_en.pdf. Last accessed 2012 May 02]. 16. Peto HM, Pratt RH, Harrington TA, LoBue PA, Armstrong LR. Epidemi-
4. Holmes CB, Wood R, Badri M, Zilber S, Wang B, Maartens G, et al. ology of extrapulmonary tuberculosis in the United States, 1993-2006.
CD4 decline and incidence of opportunistic infections in Cape Town, Clin Infect Dis 2009;49:1350-7.
South Africa: Implications for prophylaxis and treatment. J Acquir 17. teBeek LA, van der Werf MJ, Richter C, Borgdorff MW. Extrapulmonary
Immune Defic Syndr 2006;42:464-9. tuberculosis by nationality, The Netherlands, 1993-2001.Emerg Infect
5. Gonzalez OY, Adams G, Teeter LD, Bui TT, Musser JM, Graviss EA. Dis 2006;12:1375-82.
Extra-pulmonary manifestations in a large metropolitan area with a 18. Khazaei HA, Rezaei N, Bagheri GR, Dankoub MA, Shahryari K, Tahai
low incidence of tuberculosis. Int J Tuberc Lung Dis 2003;7:1178-85. A, et al. Epidemiology of tuberculosis in the Southeastern Iran. Eur J
6. Raviglione MC, Narain JP, Kochi A. HIV-associated tuberculosis in Epidemiol 2005;20:879-83.
developing countries: Clinical features, diagnosis, and treatment. Bull 19. Gopi PG, Subramani R, Santha T, Chandrasekaran V, Kolappan C,
World Health Organ 1992;70:515-26. Selvakumar N, et al. Estimation of burden of tuberculosis in India for
7. Al-Freihi HM, Al-Mohaya SA, Ibrahim EM, Al-Idrissi HY, Baris I. the year 2000. Indian J Med Res 2005;122:243-8.
Extrapulmonary tuberculosis: Diverse manifestations and diagnosis 20. Kempainen R, Nelson K, Williams DN, Hedemark L. Mycobacterium
challenge. East Afr Med J 1987;64:295-301. tuberculosis disease in Somali immigrants in Minnesota. Chest
8. Sume GE, Etogo D, Kabore S, Gnigninanjouena O, Epome SS, Metch- 2001;119:176-80.
endje JN. Seroprevalence of human immunodeficiency virus infection 21. Wiwatworapan T, Anantasetagoon T. Extra-pulmonary tuberculosis
among tuberculosis patients in the Nylon district hospital tuberculosis at a regional hospital in Thailand. Southeast Asian J Trop Med Public
treatment centre. East Afr Med J 2008;85:529-36. Health 2008;39:521-5.
9. PefuraYone EW, Kuaban C, Simo L. Tuberculous pleural effusion in 22. Al-Otaibi F, El Hazmi MM. Extra-pulmonary tuberculosis in Saudi
Yaounde, Cameroon: The influence of HIV infection. Rev Mal Respir Arabia. Indian J Pathol Microbiol 2010;53:227-31.
2011;28:1138-45. 23. Kipp AM, Stout JE, Hamilton CD, Van Rie A. Extrapulmonary tuber-
10. Cameroon national tuberculosis strategic plan 2010-2014,2011. culosis, human immunodeficiency virus, and foreign birth in North
Available from: http://dev.cdnss.dros-minsante-cameroun.org/ Carolina, 1993 - 2006. BMC Public Health 2008;8:107.
sites/dev.cdnss.dros-minsante-cameroun.org/files/biblio/2011/ 24. Onorato IM, McCray E. Prevalence of human immunodeficiency virus
nationaltuberculosisstrategicplan2010.pdf. [Last accessed 2012 infection among patients attending tuberculosis clinics in the United
Jun 24]. States. J Infect Dis 1992;165:87-92.
11. Cameroon National Strategic plan for the fight against HIV/AIDS and 25. Leeds IL, Magee MJ, Kurbatova EV, del Rio C, Blumberg HM, Leonard
STIs,2011. Available from: http://www.circb.com/doc/PSN%202011- MK, et al. Site of extrapulmonary tuberculosis is associated with HIV
2015.pdf. [Last accessed 2012 Jun 24]. infection. Clin Infect Dis 2012;55:75-81.
12. PefuraYone EW, Kengne AP, Kuaban C. Incidence, time and deter-
minants of tuberculosis treatment default in Yaounde, Cameroon:
A retrospective hospital register-based cohort study. BMJ Open
2011;1:e000289. Cite this article as: Namme LH, Marie-Solange D, Hugo Bertrand MN,
13. Sreeramareddy CT, Panduru KV, Verma SC, Joshi HS, Bates Elvis T, Achu JH, Christopher K. Extrapulmonary tuberculosis and HIV
MN.Comparison of pulmonary and extrapulmonary tuberculosis in coinfection in patients treated for tuberculosis at the Douala General
Nepal- a hospital-based retrospective study. BMC Infect Dis 2008;8:8. Hospital in Cameroon. Ann Trop Med Public Health 2013;6:100-4.
14. Tahir M, Sharma SK, Rohrberg DS, Gupta D, Singh UB, Sinha
Source of Support: None, Conflict of Interest: None declared.
PK. DOTS at a tertiary care center in northern India: Successes,

104
104 Annals of Tropical Medicine and Public Health | Jan-Feb 2013 | Vol 6 | Issue 1

View publication stats

You might also like