Prevalence of extrapulmonary tuberculosis among people living with HIV/AIDS in sub-Saharan Africa: a systemic review and meta-analysis

Figures & data

Figure 1 Study flow.

Notes: The number of studies and the sample size contributed by 12 countries from SSA that had included studies were as follows: ten studies with 2,837 people with HIV/AIDS were from Ethiopia,^18–27 four each were from Nigeria (2,042)^28–31 and South Africa (13,929),^32–35 and three were from Cameroon (2,246).^11,36,37 Two each were from Uganda (245)^38,39 and Zambia (471),^40,41 one each was from Tanzania (175),⁴² Benin (521),⁴³ Burkina Faso (112),⁴⁴ Malawi (5,561),⁴⁵ Kenya (846),⁴⁶ and Gabon (205)⁴⁷ (Table 1).
Abbreviations: EPTB, extrapulmonary TB; TB, tuberculosis.

Table 1 Characteristics of the studies included in the systemic review in SSA, 2017

Study	Country	Population characteristics	Setting	EPTB investigation	Study types	Date	Sample size or total included (HIV/AIDS)	Event
Ade et al^Citation43	Benin	All EPTB and new PTB patients with or without HIV and all age groups	Hospital	As per national program	Retrospective cohort	January to December 2011	521	72
Adejumo et al^Citation30	Nigeria	All TB patients with or without HIV and all age groups	UBTH	Diagnosed as per Nigerian national program	Retrospective review of treatment cards of patients	January 1, 2014, to December 31, 2014	72	10
Affusim et al^Citation29	Nigeria	All HIV-positive TB patients, >18 years	Teaching hospital	As per national program	Cross-sectional	January to April 2007	330	21
Agbor et al^Citation11	Cameroon	All HIV/TB patients and inpatients, aged ≥15 years	Hospital	As per national program	Cross-sectional	January 1, 2006, to June 30, 2013	335	119
Alemie and Gebreselassie^Citation18	Ethiopia	All TB patients with or without HIV and all age groups	Private health institution	As per national program	Cross-sectional	In the year 2008/2009	159	52
Amare^Citation19	Ethiopia	All children with TB aged <15 years with or without HIV	Private, public (primary, secondary, tertiary)	As per national TB program, for histological and radiological performance	Retrospective cohort	January 1, 2012, to December 31, 2013	133	49
Gebreegziabher et al^Citation20	Ethiopia	All TB patients with or without HIV and all age groups	30 public health facilities	As per national guidelines	Retrospective cohort study	July 2007 and June 2012	753	249
Daniel et al^Citation28	Nigeria	All TB patients with or without HIV and all age groups	Hospital	Culture and/or sputum smear, rapid test for HIV	Retrospective review	January 1, 1991, to December 31, 1991	320	23
Deribew et al^Citation21	Ethiopia	All adult ≥15-year TB patients with or without HIV	Health centers	TB lymphadenitis was diagnosed based on clinical parameters and cytological examination	Cross-sectional	February 2009 to March 2009	81	10
Esmael et al^Citation22	Ethiopia	All TB patients with or without HIV and all age groups	Referral hospital	AFB, chest radiographs, and for EPTB, pathological examination	Retrospective record review	June 2008 to August 2013	321	51
Feldacker et al^Citation45	Malawi	All TB patients with or without HIV and all age groups	TB/HIV integrated clinic	Bacteriological or histopathological, opt-out HIV testing	Retrospective cohort	January 2008 to December 2010	5,561	1,117
Gupta et al^Citation32	South Africa	All TB patients with or without HIV and all age groups	Electronic TB registry	ICD-10 classification used for EPTB, serology for HIV	Retrospective analysis	2009	13,237	2,328
Hailu et al^Citation23	Ethiopia	All children with TB aged <15 years with or without HIV	Health centers	Clinical history, chest X-ray, HIV testing, and histopathology	Retrospective study	January 2007 to December 2011	346	103
Hoffmann et al^Citation33	South Africa	All adult >18-year HIV-positive patients with liver TB	Hospital	Clinical, laboratory, and radiography	Retrospective study	2001–2009	108	28
Iliyasu and Babashani^Citation31	Nigeria	All HIV-positive patients with or without TB and all age groups	Teaching hospital	Biopsy of tissue specimen, TB culture	Retrospective review of charts	January 2006 to December 2006	138	50
Kamenju and Said^Citation42	Tanzania	All TB patients with or without HIV and all age groups	Hospital	Smear, radiological tests, culture, biopsy, or a combination	Retrospective cross-sectional analyses	August 2008 to July 2009	175	19
Malkin et al^Citation44	Burkina Faso	All TB patients with or without HIV and all age groups	TB center	Smear, radiological tests, culture, biopsy, or a combination	Cohort study	October 1988 to March 1992	112	22
Mekonnen et al^Citation24	Ethiopia	All TB patients with or without HIV and all age groups	Hospital and private clinic	Clinical history with X-ray, ultrasound, and/or pathological techniques	Retrospective study	January 2011 to December 2014	236	78
Muttai et al^Citation46	Kenya	Adult ≥15-year TB patients diagnosed with HIV+	Hospitals and health centers	Not reported	Retrospective chart review	October 2006 to April 2008	846	145
Namme et al^Citation36	Cameroon	All TB patients with or without HIV and all age groups	Hospital	Smear, radiological tests, biopsy, or combination	Cross-sectional	July 1, 2007, to June 30, 2011	438	108
Njozing et al^Citation37	Cameroon	All TB patients with or without HIV and all age groups	TB/HIV treatment center	Clinical and/or radiological, biopsies and laboratory examination of aspirates from affected areas	Retrospective cohort	January 2006 to December 2007	1,473	206
Ocama et al^Citation38	Uganda	All HIV-positive patients who suspected for liver disease	Teaching hospital	Stool analysis, ultrasound-guided liver biopsies	Cross-sectional	May 2004 to March 2005	77	7
Nglazi et al^Citation34	South Africa	All TB patients with or without HIV aged ≥15 years	Hospital	As per national guidelines	Retrospective cohort study	October 2009 and June 2011	472	159
Siddiqi et al^Citation40	Zambia	All HIV-positive patients with a CNS infection requiring a LP	Teaching hospital	Receiving an LP microscopy, culture, Gram stain, and India ink testing on CSF	Cross-sectional study	October 1, 2010 to May 31, 2012	331	48
Skogmar et al^Citation25	Ethiopia	All TB patients with or without HIV and ≥18 years old	Hospitals and health centers	As per national program	Cross-sectional study	September 2010 to March 2012	307	91
Tarekegne et al^Citation26	Ethiopia	All TB patients with or without HIV and all age groups	Hospital	Pathological examination and/or clinical symptoms	Retrospective study	September 2009 to August 2012	404	58
Wobudeya et al^Citation39	Uganda	All children with TB aged <15 years with or without HIV	Five districts	As per national program and WHO	Retrospective cross-sectional study	January 1, 2009, to December 31, 2010	168	24
Yassin et al^Citation27	Ethiopia	All TB patients with or without HIV and all age groups	District hospital	Sputum microscopy, X-ray facilities	Prospective cohort	Not reported	97	10
Sinkala et al^Citation41	Zambia	All abdominal TB and HIV positive	University Teaching Hospital, Lusaka, Zambia	Culture and/or granulomatous on histopathological examination microscopy	Cross-sectional study	September 2005 until May 2006	140	22
Stolp et al^Citation47	Gabon	All TB with or without HIV and all age groups	Albert Schweitzer Hospital, Lambarene, Gabon	Neelsen-stained sputum smear or on clinical grounds, HIV test	Retrospective study	January 2007 to December 2012	205	40
van der Plas et al^Citation35	South Africa	Adults (>18 years), hospitalized HIV and PTB or EPTB patients, not on ART	BCH, Cape town	Smear or culture, WHO guidelines, smear negative or EPTB in HIV-1-infected people	Prospective observational cohort	April 29, 2009, until February 28, 2011	112	20

Abbreviations: AFB, acid-fast bacilli; ART, antiretroviral therapy; BCH, Brooklyn Chest Hospital; CNS, central nervous system; CSF, cerebrospinal fluid; extrapulmonary TB; LP, lumbar puncture; PTB, pulmonary TB; SSA, sub-Saharan Africa; TB, tuberculosis; UBTH, University of Benin Teaching Hospital.

Table 2 Critical appraisal results of studies of EPTB among PLWHA by using JBI prevalence critical appraisal checklist, SSA, 2017

Study	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8	Q9	Q10	Total
											Y	N	U
Ade et al^Citation43	Y	Y	Y	Y	Y	Y	Y	Y	N	Y	9	1	0
Adejumo et al^Citation30	N	N	U	Y	Y	Y	Y	Y	N	N	5	4	1
Affusim et al^Citation29	Y	Y	Y	Y	Y	Y	Y	Y	Y	U	9	0	1
Agbor et al^Citation11	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	10	0	0
Alemie and Gebreselassie^Citation18	U	Y	N	U	Y	Y	U	Y	Y	Y	6	2	2
Amare^Citation19	Y	Y	Y	Y	Y	N	N	Y	Y	Y	8	2	0
Gebreegziabher et al^Citation20	Y	Y	Y	Y	U	Y	Y	Y	Y	Y	9	0	1
Daniel et al^Citation28	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	10	0	0
Deribew et al^Citation21	Y	N	Y	Y	Y	Y	Y	Y	Y	Y	9	1	0
Esmael et al^Citation22	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	10	0	0
Feldacker et al^Citation45	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	10	0	0
Gupta et al^Citation32	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	10	0	0
Hailu et al^Citation23	Y	U	Y	Y	Y	Y	Y	Y	Y	Y	9	0	1
Hoffmann et al^Citation33	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	10	0	0
Iliyasu and Babashani^Citation31	Y	Y	Y	Y	Y	Y	Y	Y	N	Y	9	1	0
Kamenju and Said^Citation42	Y	Y	N	Y	Y	Y	Y	Y	U	Y	8	1	1
Malkin et al^Citation44	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	10	0	0
Mekonnen et al^Citation24	Y	U	U	Y	Y	Y	Y	Y	U	Y	7	0	3
Muttai et al^Citation46	Y	Y	U	Y	Y	Y	Y	Y	Y	Y	9	0	1
Namme et al^Citation36	Y	N	U	Y	Y	Y	Y	Y	Y	Y	8	1	1
Njozing et al^Citation37	Y	Y	Y	Y	Y	N	N	Y	Y	Y	8	2	0
Ocama et al^Citation38	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	10	0	0
Nglazi et al^Citation34	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	10	0	0
Siddiqi et al^Citation40	Y	Y	U	Y	Y	Y	Y	Y	Y	Y	9	0	1
Skogmar et al^Citation25	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	10	0	0
Tarekegne et al^Citation26	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	10	0	0
Wobudeya et al^Citation39	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	10	0	0
Yassin et al^Citation27	Y	Y	U	Y	Y	Y	Y	Y	Y	Y	9	0	1
Sinkala et al^Citation41	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	10	0	0
Stolp et al^Citation47	Y	Y	Y	Y	Y	Y	Y	Y	U	Y	9	0	1
van der Plas et al^Citation35	Y	Y	U	Y	Y	Y	Y	Y	Y	Y	9	0	0

Abbreviations: EPTB, extrapulmonary tuberculosis; JBI, Joanna Briggs Institute; N, number; PLWHA, people living with HIV/AIDS; Q, question; SSA, sub-Saharan Africa; U, unclear; Y, yes.

Figure 2 Forest plot including all available relevant studies on EPTB among PLWHA in SSA, 2017.

Abbreviations: df, degrees of freedom; EPTB, extrapulmonary tuberculosis; PLWHA, people living with HIV/AIDS; SE, standard error; SSA, sub-Saharan Africa.

Table 3 Heterogeneity assessment summary by using sensitivity and subgroup analyses, SSA, 2017

Subgroup analysis (PICO)	Number of studies	Prevalence of EPTB (95% CI), random-effects model	Heterogeneity
			τ^2	I^2 (%)	P-value (Q)
Overall	31	20% (17, 22)	0	94	<0.00001
Sensitivity analysis by removing one large study	30	20% (17, 23)	0.01	94	<0.00001
Clinical heterogeneity by age groups Children <15 years Adults >15 or >18 years All age groups	3 7 21	17% (3, 31) 23% (14, 32) 18% (16, 19)	0.01 0.01 0	97 97 86	<0.00001 <0.00001 <0.00001
Clinical heterogeneity by EPTB types Different EPTB TB of lymph node TB of hepatic or TB of abdomen	27 2 2	22% (19, 25) 14% (12, 16) One each, not estimated	0.01 0	97 0	<0.00001 0.65
Methodological heterogeneity by study design Cross-sectional Retrospective record review Retrospective cohort Prospective cohort	9 14 5 2	20% (13, 27) 19% (16, 22) 23% (17, 29) 16% (11, 20)	0.01 0 0 0	96 91 97 36	<0.00001 <0.00001 <0.00001 0.21
By subregion of SSA Eastern SSA Southern SSA Western SSA Central SSA	16 4 10 1	20% (16, 23) 21% (15, 26) 19% (13, 24) Not estimated	0 0 0.01	92 92 96	<0.00001 <0.00001 <0.00001
By countries of SSA having ≥ two studies Ethiopia Nigeria Cameroon South Africa Uganda Zambia Others	10 4 3 4 2 2 6	23% (17, 29) 15% (7, 24) 25% (12, 37) 17% (14, 20) 12% (7, 17) 15% (12, 18) 17% (14, 20)	0.01 0.01 0.01 0 0 0 0	93 94 97 84 35 0 84	<0.00001 <0.00001 <0.00001 0.0003 0.21 0.74 <0.0001
Study time variation 1990–2000 2001–2010 2011–2017	1 3 27	Not estimated 19% (3, 34) 20% (18, 23)	0.02 0	94 94	<0.00001 <0.00001

Abbreviations: EPTB, extrapulmonary tuberculosis; PICO, people, intervention, comparison, outcomes; SSA, sub-Saharan Africa; TB, tuberculosis.

Figure 3 Scatter plot showing the effect of publication year on point estimate of prevalence of EPTB among PLWHA, SSA, 2017.

Abbreviations: EPTB, extrapulmonary tuberculosis; PLWHA, people living with HIV/AIDS; SSA, sub-Saharan Africa.

Figure 4 Funnel plot for SE by point estimate (A) for included studies (B) and input studies that shown similar pooled estimate.

Abbreviation: SE, standard error.

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