Prevalence of opportunistic bacterial infections (tuberculosis and pneumonia) among people with HIV in Ethiopia: Systematic review and meta-analysis

Aleka Aemiro; Abayeneh Girma; Getachew Alamnie; Demsew Beletew; Amere Genet

doi:10.1371/journal.pone.0315599

. 2025 Oct 21;20(10):e0315599. doi: 10.1371/journal.pone.0315599

Prevalence of opportunistic bacterial infections (tuberculosis and pneumonia) among people with HIV in Ethiopia: Systematic review and meta-analysis

Aleka Aemiro ¹, Abayeneh Girma ^1,^*, Getachew Alamnie ¹, Demsew Beletew ², Amere Genet ¹

Editor: Miquel Vall-llosera Camps³

PMCID: PMC12539741 PMID: 41118391

Abstract

Background

Individuals with weakened immune systems, such as those living with Human Immunodeficiency Virus (HIV), are more vulnerable to opportunistic bacterial infections, which include tuberculosis and pneumonia. This systematic review and meta-analysis looked at the pooled prevalence of opportunistic bacterial infections among people living with HIV in different regions of Ethiopia.

Methods

By looking through open online databases, articles written in English were considered. Joanna Briggs Institute’s critical appraisal tool for prevalence study was used to check the quality of each article. Inverse variance (I²), sensitivity analysis, funnel plot, and Egger’s regression tests were used to check heterogeneity and publication bias. Because of a high heterogeneity, a random-effects model was used to estimate the pooled prevalence of opportunistic bacterial infections among people living with HIV.

Results

About 18.06% (1824/9651) with (95% CI: 14.09–22.02) of the pooled population had opportunistic tuberculosis from 20 studies included, while from 16 included studies, the pneumonia infection was 11.64% (1040/8095/) with (95% CI: 8.45–14.83).

Conclusion

The prevalence of tuberculosis and pneumonia among people living with HIV in Ethiopia is high. Therefore, policymakers and health planners should put a great deal of emphasis on the implementation of relevant prevention and control measures.

Registration

The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the registration number “CRD42024587645”, on September 17, 2024.

Introduction

Opportunistic infections (OIs) are caused by microorganisms, such as bacteria, fungi, parasites and viruses that typically do not cause disease in healthy people but can become pathogenic when the host's immune system is weakened [1]. Over 80% of AIDS (Acquired immunodeficiency syndrome)-related deaths are caused by OIs, which are intestinal parasites and bacteria that more easily infect immunocompromised patients [2]. In 2023, there were 39.9 million people living with HIV globally, and 630,000 deaths from HIV-related causes [3], including 1.4 million children (under the age of 15) [4]. A similar year report also states that OI was the main cause of nearly 76,000 million child deaths from HIV-related causes [5].

Children living with HIV and newborns who have been exposed to it are more likely to suffer from bacterial respiratory tract infections than HIV-uninfected children [6]. Tuberculosis (TB) and pneumonia are the most frequent causes of hospital admissions among all HIV-related OIs for children living with HIV on antiretroviral therapy (ART) in Europe, East China, and other low- and middle-income countries [7]. In 2017, an estimated 6.3 million fatalities were reported worldwide , with children between the ages of 5 and 14 accounting for one million of those deaths [8]. In 2022, TB was the second-leading cause of death from an infectious disease worldwide, with COVID-19 being the first. Additionally, while 10.6 million people fell ill with TB in 2022, 7.5 million were newly diagnosed [9]. In children worldwide, pneumonia is the most common cause of sickness and death [10].

In Ethiopia, pneumonia is a major health threat to children under five, where it is a leading cause of death, accounting for about 18% of all deaths in this age group [11]. Reports from a 2020 meta-analysis of 12 studies indicate the pooled prevalence of pneumonia among children under five in Ethiopia was 20.68% [12]. Globally, Ethiopia ranks sixth among the top 15 countries in terms of morbidity and mortality from pneumonia [13] and the burden is high with pneumonia/HIV patients. Regarding TB, in 2022, around 151,000 people in Ethiopia were diagnosed for TB, leading to over 19,000 deaths each year due to the illness. Moreover, Ethiopia is one of the 30 countries with a high TB and TB/HIV burden; with an estimated annual TB incidence of 126/100,000 persons and a death rate of 12 per 100,000 people, according to the 2023 Global TB Report [9].

Previously, Woldegeorgis and colleagues [14] conducted a systematic review and meta-analysis regarding the prevalence and determinants of OIs among HIV-infected adults receiving ART in Ethiopia. However, the prevalence of opportunistic bacterial infections, particularly tuberculosis and pneumonia, among people of all age groups living with HIV in the country is not collected, well organised, and documented as a systematic review and meta-analysis. Therefore, the objective of this systematic review and meta-analysis is to estimate the overall prevalence of opportunistic bacterial infections among people living with HIV from available research conducted in different regions of Ethiopia. The findings of this work will be used by the concerned stakeholders to reduce the prevalence of opportunistic bacterial infections and design evidence-based interventions.

Methods

Design and protocol registration

This systematic review and meta-analysis was designed to estimate the country pooled prevalence of opportunistic bacterial infections among people with HIV in Ethiopia. The result was reported following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-2020 guideline [15] (see S1 Table). The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42024587645.

Search strategy

Electronic databases such as, ScienceDirect, PubMed, and the Cochrane Library were used in a comprehensive search (S2 Table). Core search terms and phrases such as “Prevalence,” “epidemiology,” “magnitude,” “opportunistic infections,” “opportunistic bacterial infections,” “people with HIV,” and “Ethiopia” were used to search articles. The work was limited to studies with clearly stated sample sizes, numbers of positive cases, and study locations. The study was conducted between September 06/2024 and December 1/2024 and the study’s objective was to determine the prevalence of opportunistic bacterial infections among people with HIV in Ethiopia.

Eligibility criteria of the studies

The articles collected through the searches were evaluated for inclusion in the meta-analysis based on the following criteria: (i) only prospective and retrospective studies on opportunistic bacterial infections, (ii) reports published only in English, (iii) studies that reported prevalence (iv), studies conducted in Ethiopia (v) and articles published between 2013 and 2023. Excluded from this review were studies with no full-text access, publications that were duplicated or expanded upon from an original study, articles with insufficient information, research results derived from subjective opinions, articles reported outside the parameters of the outcome of interest, case reports, unpublished data, qualitative investigation design, abstracts, conference presentations and previous systematic reviews.

Study selection process

Articles found through the electronic database search were entered into an EndNote X9 reference program, where duplicate studies were removed. Two authors (AA and AG) independently screened the titles and abstracts obtained from the search according to the inclusion criteria. To assess if multiple authors’ systematic reviews of the same topic are similar, inter-rater agreement (IRA) is calculated using Cohen’s kappa, often with the Cochrane Handbook as a guide for methods and interpretation of agreement [16]. The screened articles were then reviewed for a full-text assessment by two independent authors (GA and DB), to ensure that only eligible studies are included in the final review and to minimize bias. Predefined eligibility criteria were used to determine which records were irrelevant and which should be included in the review. If additional information was needed to answer eligibility questions, other authors were involved. Disagreements were resolved through discussion. In addition, reasons for excluding articles were recorded at each stage.

Data extraction

Two authors (AA and AG) independently abstracted the relevant data using a standardized Microsoft excel 2016 spreadsheet. The data extraction process includes the following details: The first author’s name, the year of publication, the regions of the country, the study design, the sample size, the number of positive cases, and the prevalence of opportunistic bacterial infections. If the study was conducted over an extended period of time in a single field, the most recent year falling within the designated range was used.

Quality assessment of individual studies

The articles that meet the eligibility criteria and are sufficiently valid for our research question underwent full-text appraisal. The Joanna Briggs Institute (JBI) critical checklist for prevalence studies was used for quality appraisal using 9 criteria [17]. For each question, a score was assigned (no for ‘not reported or not appropriate’ and yes ‘for reported’); the scores were summarized across the items to achieve a total score of 0–9, for prevalence studies. The studies were then classified as low (≤ 2), medium (3–4), and high (≥ 5) quality based on the points awarded. Studies with a final quality score of 50% or higher were considered for inclusion in the systematic review and meta-analysis (S1 and S2 Tables).

Data analysis

Because of a high heterogeneity, a random-effects model was used to determine the pooled effect sizes. To uncover sources of heterogeneity, we conduct a sensitivity analysis (the impact of each individual studies on the pooled effect size) and subgroup analysis based on the study’s region, sample size, and year of publication. The inverse variance (I²) statistics were used to assess the magnitude of heterogeneity of the included articles. The I² test was used to assess the heterogeneity across studies with interpretations assigned to I² values: 0% (no heterogeneity), 0–25% (low heterogeneity), 25–50% (medium heterogeneity), and >75% (high heterogeneity) [18]. The risks of publication bias for studies have been examined using funnel plot symmetry and the Egger’s test. During Egger’s test, p-values less than 0.05 were an indication of a significant presence of publication bias [19]. This meta-analysis was conducted using Stata version 14 software (StataCorp LLC 4905 Lakeway Drive College Station, Texas 77845−4512, USA) with “metan” command.

Results

A total of 276 articles were retrieved on the prevalence of OIs among people living with HIV in Ethiopia. One hundred twenty five of these articles were excluded due to duplicates. Of the remaining 141 articles, 114 were excluded based on specific criteria included in the inclusion criteria and data extraction protocol. Of the remaining 27 articles, 7 articles were further removed due to lack number of positive cases. Therefore, 20 of the studies met the eligibility criteria and were included in the final systematic review and meta-analysis (Fig 1).

Characteristics of the eligible studies

Table 1 represents the features of the studies that were subjected to this meta-analysis, concerning the pooled prevalence of TB among people living with HIV. The meta-analysis had twenty (20) studies that matched the eligibility criteria. All studies were cross-sectional carried out between 2013 and 2023. Regarding the study year, seven, eight and five studies were conducted between 2013 and 2018, 2019 and 2021, and 2022 and 2023, respectively. Based on the criteria, Addis Ababa (2 articles), Amhara (9 articles), Oromia (4 articles), SNNPR (4 articles), and Tigray (1 article) were involved. The prevalence of opportunistic TB infections among people living with HIV ranged from 7.1% to 43.5% (Table 1).

Table 1. Characteristics of included studies to calculate the pooled prevalence of TB among people living with HIV.

Author	Publication year	Region	Study design	Sample size	Case	Prevalence (%)
Damtie et al.	2013 [20]	Amhara	Cross-sectional	360	35	9.72
Moges & Kassa	2014 [21]	Amhara	Cross-sectional	423	41	9.7
Mitku et al.	2015 [22]	Oromia	Cross-sectional	358	76	21.23
Alemayehu et al.	2017 [23]	SNNPR	Cross-sectional	362	70	19.4
Deribe & Estifanos	2018 [24]	A/Ababa	Cross-sectional	315	137	43.5
Solomon et al.	2018 [25]	SNNPR	Cross-sectional	744	133	18.0
Urgessa et al.	2018 [26]	Oromia	Cross-sectional	418	55	13.2
Dereje et al.	2019 [27]	A/Ababa	Cross-sectional	384	38	9.8
Melkamu et al.	2020 [28]	Amhara	Cross-sectional	408	122	29.8
Fite & Aga	2020 [29]	Oromia	Cross-sectional	497	78	15.7
Wachamo & Bonja	2020 [30]	SNNPR	Cross-sectional	420	48	11.6
Weldearegawi et al.	2020 [31]	Tigray	Cross-sectional	400	38	9.5
Tegegne et al.	2020 [32]	Amhara	Cross-sectional	354	75	21.1
Chanie et al.	2021 [33]	Amhara	Cross-sectional	349	25	7.1
Dembelu & Wosenelh	2021 [34]	SNNPR	Cross-sectional	450	94	21.0
Kebede et al.	2022 [35]	Amhara	Cross-sectional	405	111	27.5
Mequanente et al.	2022 [36]	Amhara	Cross-sectional	389	41	10.6
Birmeka	2023 [37]	Oromia	Cross-sectional	1448	408	28.2
Dagnaw et al.	2023 [38]	Amhara	Cross-sectional	715	78	10.9
Mekonnen et al.	2023 [39]	Amhara	Cross-sectional	452	121	26.7

Open in a new tab

Table 2 lists the features of the studies that were subjected to a meta-analysis, concerning the pooled prevalence of pneumonia among people living with HIV. The meta-analysis of pneumonia prevalence includes sixteen (16) studies that matched the eligibility criteria. All studies were cross-sectional carried out between 2013 and 2023. Three, seven, and six investigations on the prevalence of pneumonia were conducted between 2013 and 2015, 2018 and 2020, and 2021 and 2023, respectively. Addis Ababa (2 studies), Amhara (7 articles), Oromia (4 articles), and SNNPR (3 articles) regions were taken into consideration in this meta-analysis of pneumonia prevalence. Table 2 shows that among studies that were eligible, the prevalence of opportunistic pneumonia infections varied from 1% to 29.8%.

Table 2. Characteristics of included studies to calculate the pooled prevalence of pneumonia among people living with HIV.

Author	Publication year	Region	Study design	Sample size	Case	Prevalence (%)
Damtie et al.	2013 [20]	Amhara	Cross-sectional	360	5	1.38
Moges & Kassa	2014 [21]	Amhara	Cross-sectional	423	25	5.9
Mitku et al.	2015 [22]	Oromia	Cross-sectional	358	10	2.8
Deribe & Estifanos	2018 [24]	A/Ababa	Cross-sectional	315	38	12.1
Solomon et al.	2018 [25]	SNNPR	Cross-sectional	744	121	16.3
Urgessa et al.	2018 [26]	Oromia	Cross-sectional	418	42	10.1
Dereje et al.	2019 [27]	A/Ababa	Cross-sectional	384	4	1.0
Melkamu et al.	2020 [28]	Amhara	Cross-sectional	408	122	29.8
Fite & Aga	2020 [29]	Oromia	Cross-sectional	497	29	5.8
Wachamo & Bonja	2020 [30]	SNNPR	Cross-sectional	420	90	21.5
Dembelu& Wosenelh	2021 [34]	SNNPR	Cross-sectional	450	45	10.0
Chanie et al.	2021 [33]	Amhara	Cross-sectional	349	13	3.7
Tegegne et al.	2022 [32]	Amhara	Cross-sectional	354	53	14.9
Birmeka	2023 [37]	Oromia	Cross-sectional	1448	166	11.5
Dagnaw et al.	2023 [38]	Amhara	Cross-sectional	715	149	20.8
Mekonnen et al.	2023 [39]	Amhara	Cross-sectional	452	128	28.3

Open in a new tab

Pooled prevalence of opportunistic bacterial infections

The pooled prevalence of tuberculosis and pneumonia infection among people living with HIV in Ethiopia was estimated using a random-effects model because of the high heterogeneity among studies. The pooled prevalence of tuberculosis infection among people living with HIV in Ethiopia was 18.06% (95% CI: 14.09 − 22.02) with observed heterogeneity (I² = 95.9, p < 0.001) (Fig 2) and pneumonia infection was 11.64% (95% CI: 8.45 − 14.83) with observed heterogeneity (I² = 95.5, p < 0.001) (Fig 3).

Sub-group analysis of tuberculosis among people living with HIV

Subgroup analysis was performed using sample size, study region, and year of publication. When we compare the pooled prevalence of tuberculosis, the prevalence is higher in studies with a sample size of 384 and below (18.79%; 95% CI: 9.02, 28.56) than in studies with a sample size greater than 384 (17.57%; 95% CI: 13.71, 21.42) (Table 3).

Table 3. Subgroup analysis of the magnitude of tuberculosis among people with HIV in Ethiopia.

Variables	Characteristics	Included studies	Sample size	Prevalence (95% CI)	I², p–value
Sample size	≤384	7	2482	18.79 (95% CI: 9.02, 28.56)	97.8, p < 0.001
Sample size	>384	13	7169	17.57 (95% CI: 13.71, 21.42)	93.5, p < 0.001
Region	Oromia	4	2721	19.32 (95% CI: 13.29, 25.36)	86.5, p < 0.001
	SNNPR	4	1976	17.52 (95% CI: 13.4, 21.63)	72.1, p < 0.013
	Amhara	9	3855	16.68 (95% CI: 11.50, 21.87)	95.2, p < 0.001
	Tigray	1	400	9.5 (95% CI: 6.9, 12.1)	0.0,______
	Addis Ababa	2	699	26.63 (95% CI: −6.40, 59.65)	99.5, p < 0.001
Publication Year	2013–2018	7	2980	19.23(95% CI: 10.13, 28.34)	97.4, p < 0.001
	2019–2021	8	3262	15.22 (95% CI: 10.83, 19.61)	90.9, p < 0.001
	2022-2023	5	3409	20.57 (95% CI: 12.35, 28.80)	96.7, p < 0.001
	Overall	20	9651	18.06 (95% CI: 14.09, 22.02)	95.9, p < 0.001

Open in a new tab

SNNPR, Southern Nations, Nationalities and People’s Region

The Addis Ababa area of Ethiopia had the greatest pooled prevalence of tuberculosis infections among people living with HIV, reported at 26.63% (95% CI: −6.40 − 59.65), while Tigray had the lowest prevalence, recorded at 9.5% (95% CI: 6.9–12.1) (Table 3).

The greatest recorded pooled prevalence of tuberculosis during the research period was 20.57% (95% CI: 12.35–28.80) between 2022 and 2023, followed by 19.23%; 95% CI: 10.13 − 28.34) between 2013 and 2018, and the lowest was between 2019 and 2021 (15.22%; 95% CI: 10.83 − 19.61) (Table 3), with high heterogeneity in all groups.

Sub-group analysis of pneumonia among people living with HIV

Subgroup analysis was performed using sample size, study region, and year of publication. The pooled prevalence of pneumonia is lower in studies with a sample size of 384 and below (5.58%; 95% CI: 2.24, 8.92) compared with those with a sample size greater than 384 (15.53%; 95% CI: 10.97, 20.09) (Table 4), with high heterogeneity in both groups.

Table 4. Subgroup analysis of the magnitude of pneumonia among people with HIV in Ethiopia.

Variables	Characteristics	Included studies	Sample size	Prevalence (95% CI)	I², P–value
Sample size	≤384	6	2120	5.58 (95% CI: 2.24, 8.92)	93.2, P < 0.001
Sample size	>384	10	5975	15.53 (95% CI: 10.97, 20.09)	94.1, P < 0.001
Region	Oromia	4	2721	7.30 (95% CI: 3.57, 11.03)	89.5, P < 0.001
	SNNPR	3	1614	15.65 (95% CI: 9.31–21.99)	82.0, P = 0.004
	Amhara	7	3061	14.46 (95% CI: 8.00, 20.92)	96.9, P < 0.001
	Addis Ababa	2	699	6.47 (95% CI: −4.41, 17.35)	97.5, P < 0.001
Publication Year	2013-2015	5	1141	3.31 (95% CI: 0.82, 5.8)	82.8, P < 0.003
	2018-2020	8	3186	13.4 (95%CI: 7.44, 19.36)	96.6, P < 0.001
	2021-2023	5	3768	14.50 (95% CI: 8.13, 20.88)	93.9, P < 0.001
	*Overall*	16	8095	11.64 (95% CI: 8.45, 14.83)	95.5, P < 0.001

Open in a new tab

SNNPR, Southern Nations, Nationalities and People’s Region

Regarding study regions, Addis Ababa had the lowest prevalence of pneumonia infections at 6.47% (95% CI: −4.41 − 17.35), the SNNPR region of Ethiopia had the highest pooled prevalence among people living with HIV, at 15.65% (95% CI: 9.31 − 21.99) (Table 4), with high heterogeneity in both groups.

The highest pooled prevalence of pneumonia among people with HIV was recorded during the 2021–2023 study period at 14.50% (95% CI: 8.13 − 20.88). This was followed by the 2018–2020 period at 13.4% (95%CI: 7.44 − 19.36), and the lowest prevalence was recorded between 2013 and 2015 at 3.31% (95% CI: 0.82 − 5.8) (Table 4). High heterogeneity was observed in all groups.

Quality assessment and publication bias

Information on the quality assessment of individual studies is presented in S1 and S2 Tables. Briefly, 100% of the included studies were of high quality (low risk of bias). The asymmetry of the funnel plot indicated the existence of publication bias among the included studies (Figs 4–5). Similarly, the Egger test (Figs 6–7) revealed statistically significant publication bias (P = 0.001). Because of a high level of heterogeneity in the included studies, a sensitivity analysis was performed by removing single study one at a time to assess the impact of each study on the pooled effect size. During the sensitivity analysis, studies not included in Figs 8–9 had relatively determinant effects on the overall magnitude of tuberculosis and pneumonia among people living with HIV in Ethiopia.

Discussion

This systematic review and meta-analysis aimed to study the pooled prevalence of opportunistic bacterial infections among people living with HIV in Ethiopia. Tuberculosis (TB) is the most prevalent and dangerous opportunistic disease among people living with HIV, serving as the clinical manifestation of AIDS in more than half of cases in developing countries. TB was declared a worldwide emergency in 1993. More recently, the Director General of the WHO proclaimed AIDS to be an emergency as well. Pneumonia, which is an inflammation of the lung parenchymal structure caused by aspiration, inhalation, or hematogenous-spread pathogens, is also one of the most common opportunistic infections, particularly in children living with HIV.

The overall national prevalence of tuberculosis infection was 18.06%. The result is almost in accordance with the result of another meta-analysis done in Ethiopia [14]. The finding is also in agreement with results from India, which reported a TB/HIV co-infection rate of 17% [40]; South Africa (17.3%) [41]; Nigeria (16.8%) [42,43]; and Rwanda (20%) [44]. Whereas, a higher prevalence has been reported in Iran (38.2%) [45], Nepal (27.3%), and Nigeria (22.7%) [46,47]. On the other hand, the pooled prevalence was lower than a study conducted in Tanzania (8.3%) [48], Mozambique (10.1%) [49], another study from Tanzania (7.9%) [50], USA (11.5%) [51] and China (7.2%) [52]. This difference might be due to variations in sample size, study design, and diagnosis method. Moreover, the discrepancy could stem from differences in geographical areas of study participants, high exposure to infectious agents, social-economic status, drug resistance, immunity, and nutrition. All these factors may affect the magnitude of tuberculosis, as well as the community’s awareness to seek healthcare for TB and HIV.

The overall national prevalence of pneumonia infection was 11.64%. The pooled prevalence found in this current review is in line with a previous report conducted in Ethiopia, which found a pooled prevalence of 12.50% [14]. Pneumonia prevalence in patients was 31.2% [45]. However, our finding is lower than those reported in several other African nations, including Uganda (25.6%) [53], Nigeria (31.6%) [54], Sudan (65%) [55], Kenya (74%) [56] and a previous systematic review and meta-analysis conducted in Iran 31.2% [45]. Conversely, our finding is higher than results from Vietnam (5%) [57], India (5%) [58], Mali (6.7%) [59], South Africa (0.5%) [60] and Malawi (1.0%) [61]. Variations among studies could arise from varied settings, environmental-related factors, household facilities, and the sociodemographic characteristics of mothers or caregivers.

The highest prevalence of tuberculosis among people living with HIV in Ethiopia was reported from Addis Ababa (26.63%). The finding of this result is comparable to studies conducted in the Jimma zone (28.1%) [62], Afar (26.4%) [63] and Shashamene (24.9%) [64]. In addition, it is consistent with the study done in Nigeria (24.5%) [65] and Albania (27.4%) [66]. In contrast, the pooled prevalence in this review for the Tigray region is accounting 9.5%. The variations in different regions might be due to the environmental, socioeconomic, and educational status of study participants.

The highest pooled prevalence of pneumonia is reported from SNNPR region (15.65%). The result is lower than the findings from Goncha Siso Enesie (24.3%), Sheka zone (23.8%) [67], Gondar (26.3%) [68], and Uganda (25.6%) [53]. Nevertheless, the lowest prevalence of pneumonia infections was observed in Addis Ababa (6.47%), which is in harmony with studies conducted in Uganda (6.9%) [69] and Kenya (6.9%) [70]. The difference in prevalence of pneumonia across different regions of Ethiopia could be due to variations in socio-demographic factors (such as race/ethnicity and immigration status), geographical inequality, seasonal variation, socioeconomic differences, and environmental change.

The highest pooled prevalence of tuberculosis was recorded between 2022 and 2023 at 20.57%, followed by 2013 and 2018 at 19.23%, whereas the lowest prevalence was recorded between 2019 and 2021 at 15.22%. Regarding pneumonia, the highest pooled prevalence was recorded between 2021 and 2023 at 14.50%, followed by the year between 2018 and 2020 at 13.4% and the lowest prevalence was recorded between 2013 and 2015 at 3.31%.The data from the pneumonia review suggests that the pooled prevalence has generally increased from 2013 to 2023. This increase in infection rates at the current time could be due to people giving less attention to these bacterial opportunistic infections.

Strengths and limitations

A key strength of this systematic review and meta-analysis is that it is the first to determine the pooled prevalence estimates of opportunistic bacterial infections among people living with HIV in Ethiopia. However, this study may have certain drawbacks. Specifically, a small number of eligible papers were collected from the included regions, and no published data was available from the Afar, Gambela, Somali, and Benishangul-Gumuz regions. This exclusion may affect the overall national prevalence estimates of opportunistic bacterial infections in Ethiopia.

Conclusions and recommendations

The pooled prevalence of tuberculosis and pneumonia among people living with HIV in Ethiopia is high, with an increasing trend observed from 2013 to 2023. This rising prevalence, regardless of its underlying cause, has the potential to negatively impact the health and well-being of people living with HIV. Consequently, policymakers and health planners should place a great deal of emphasis on implementing relevant prevention and control measures. Furthermore, extensive research is needed in this population across different regions of the country to fully understand the nature, dynamics, and risk factors associated with TB and pneumonia among people living with HIV.

Supporting information

S1 Table. PRISMA 2020 Checklist.

The checklists/protocols following during writing this systematic review and meta-analysis.

(DOCX)

pone.0315599.s001.docx^{(16.8KB, docx)}

S2 Table. Search Strategy.

Comprehensive search strategy for common opportunistic bacterial infections among people living with HIV in Ethiopia.

(DOCX)

pone.0315599.s002.docx^{(13.9KB, docx)}

S3 Table. Quality appraisal result of included studies.

The quality of included studies was evaluated using the Joanna Briggs Institute (JBI) quality appraisal checklist for prevalence studies.

(DOCX)

pone.0315599.s003.docx^{(27.2KB, docx)}

Abbreviations:

AOR: Adjusted Odds Ratio
CI: Confidence Interval
GRADE: Grading of Recommendations Assessment, Development and Evaluation
OIs: Opportunistic infections
PLHIV: People Living with Human Immunodeficiency Virus
PRISMA: Preferred Reporting Items for Systematic reviews and Meta-Analyses
SNNPR: Southern Nations, Nationalities and People’s Region
SSA: Sub-Saharan Africa.

Data Availability

All relevant data are included in the paper and its Supporting information files.

Funding Statement

The author(s) received no specific funding for this work.

References

1.Riccardi N, Rotulo GA, Castagnola E. Definition of Opportunistic Infections in Immunocompromised Children on the Basis of Etiologies and Clinical Features: A Summary for Practical Purposes. Curr Pediatr Rev. 2019;15(4):197–206. doi: 10.2174/1573396315666190617151745 [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Yates T, Lantagne D, Mintz E, Quick R. The impact of water, sanitation, and hygiene interventions on the health and well-being of people living with HIV: a systematic review. J Acquir Immune Defic Syndr. 2015;68 Suppl 3:S318–30. doi: 10.1097/QAI.0000000000000487 [DOI] [PubMed] [Google Scholar]
3.WHO. HIV/AIDS Epidemiology. 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/hiv-aids#:~:text=Transmission%20is%20ongoing%20in%20all,1.3%20million%20people%20acquired%20HIV. Accessed June 24, 2024.
4.Global H. AIDS statistics—2018 fact sheet. Geneva: UNAIDS. 2019. https://www.avert.org/professionals/hiv-around-world/sub-saharan-africa/overview [Google Scholar]
5.Global H. AIDS statistics–2018 fact sheet. Geneva: Joint United Nations Programme on HIV. AIDS. 2018. [Google Scholar]
6.Jeena PM. Respiratory Diseases Amongst HIV Infected Children. HIV Infection in Children and Adolescents. Springer International Publishing. 2020:55–72. doi: 10.1007/978-3-030-35433-6_6 [DOI] [Google Scholar]
7.Kiya GT, Mekonnen Z, Melaku T, Tegene E, Gudina EK, Cools P, et al. Prevalence and mortality rate of sepsis among adults admitted to hospitals in sub-Saharan Africa: a systematic review and meta-analysis. J Hosp Infect. 2024;144:1–13. doi: 10.1016/j.jhin.2023.11.012 [DOI] [PubMed] [Google Scholar]
8.Macpherson L, Ogero M, Akech S, Aluvaala J, Gathara D, Irimu G, et al. Risk factors for death among children aged 5-14 years hospitalised with pneumonia: a retrospective cohort study in Kenya. BMJ Glob Health. 2019;4(5):e001715. doi: 10.1136/bmjgh-2019-001715 [DOI] [PMC free article] [PubMed] [Google Scholar]
9.World Health Organization. Meeting report of the WHO expert consultation on the definition of extensively drug-resistant tuberculosis. World Health Organization. 2021. https://iris.who.int/bitstream/handle/10665/338776/9789240018662-eng.pdf [Google Scholar]
10.Pandey A, Galvani AP. The burden of childhood pneumonia in India and prospects for control. Lancet Child Adolesc Health. 2020;4(9):643–5. doi: 10.1016/S2352-4642(20)30238-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
11.UNICEF. UNICEF Ethiopia: Annual Report 2019. NY, USA: Unicef. 2019. https://www.unicef.org/ethiopia/media/2481/file/Annual%20Report%202019.pdf [Google Scholar]
12.Alamneh YM, Adane F. Magnitude and Predictors of Pneumonia among Under-Five Children in Ethiopia: A Systematic Review and Meta-Analysis. J Environ Public Health. 2020;2020:1606783. doi: 10.1155/2020/1606783 [DOI] [PMC free article] [PubMed] [Google Scholar]
13.Hailemariam S, Gebeyehu Y, Loha E, Johansson KA, Lindtjørn B. Inadequate management of pneumonia among children in South Ethiopia: findings from descriptive study. BMC Health Serv Res. 2019;19(1):426. doi: 10.1186/s12913-019-4242-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
14.Woldegeorgis BZ, Zekarias Z, Adem BG, Obsa MS, Kerbo AA. Prevalence and determinants of opportunistic infections among HIV-infected adults receiving antiretroviral therapy in Ethiopia: A systematic review and meta-analysis. Front Med (Lausanne). 2023;10:1087086. doi: 10.3389/fmed.2023.1087086 [DOI] [PMC free article] [PubMed] [Google Scholar]
15.Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71 [DOI] [PMC free article] [PubMed] [Google Scholar]
16.Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019;10(10):ED000142. doi: 10.1002/14651858.ED000142 [DOI] [PMC free article] [PubMed] [Google Scholar]
17.Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Systematic reviews of prevalence and incidence. Joanna Briggs Institute. 2017. [Google Scholar]
18.Borenstein M. Heterogeneity in meta-analysis. The Handbook of Research Synthesis and Meta-Analysis. Russell Sage Foundation. 2019:453–68. doi: 10.7758/9781610448864.23 [DOI] [Google Scholar]
19.Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34. doi: 10.1136/bmj.315.7109.629 [DOI] [PMC free article] [PubMed] [Google Scholar]
20.Damtie D, Yismaw G, Woldeyohannes D, Anagaw B. Common opportunistic infections and their CD4 cell correlates among HIV-infected patients attending at antiretroviral therapy clinic of Gondar University Hospital, Northwest Ethiopia. BMC Res Notes. 2013;6:534. doi: 10.1186/1756-0500-6-534 [DOI] [PMC free article] [PubMed] [Google Scholar]
21.Moges NA. Prevalence of Opportunistic Infections and Associated Factors among HIV Positive Patients taking Anti-Retroviral Therapy in DebreMarkos Referral Hospital, Northwest Ethiopia. J AIDS Clin Res. 2014;05(05). doi: 10.4172/2155-6113.1000301 [DOI] [Google Scholar]
22.Mitiku H, Weldegebreal F, Teklemariam Z. Magnitude of opportunistic infections and associated factors in HIV-infected adults on antiretroviral therapy in eastern Ethiopia. HIV AIDS (Auckl). 2015;7:137–44. doi: 10.2147/HIV.S79545 [DOI] [PMC free article] [PubMed] [Google Scholar]
23.Alemayehu M, Yisehak Y, Alaro W, Alemayehu B. Opportunistic Infections among HIV/AIDS Patients taking Anti-Retroviral Therapy at Tertiary Care Hospital in Wolaita Zone, Southern Ethiopia. J AIDS Clin Res. 2017;08(02). doi: 10.4172/2155-6113.1000665 [DOI] [Google Scholar]
24.Addisu D. Magnitude and Determinants of Opportunistic Infections Among Hiv/Aids Patients in Sphmmc, Addis Ababa, Ethiopia: Retrospective Study. JOJPH. 2018;4(1). doi: 10.19080/jojph.2018.04.555627 [DOI] [Google Scholar]
25.Solomon FB, Angore BN, Koyra HC, Tufa EG, Berheto TM, Admasu M. Spectrum of opportunistic infections and associated factors among people living with HIV/AIDS in the era of highly active anti-retroviral treatment in Dawro Zone hospital: a retrospective study. BMC Res Notes. 2018;11(1):604. doi: 10.1186/s13104-018-3707-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
26.Urgessa F, Ararsa A, Ataro Z. Prevalence and Associated Risk Factors of Opportunistic Infections among Anti-Retro Viral Treatment Naive HIV/AIDS Infected Patients. J AIDS Clin Res. 2018;09(03). doi: 10.4172/2155-6113.1000763 [DOI] [Google Scholar]
27.Dereje N, Moges K, Nigatu Y, Holland R. Prevalence And Predictors Of Opportunistic Infections Among HIV Positive Adults On Antiretroviral Therapy (On-ART) Versus Pre-ART In Addis Ababa, Ethiopia: A Comparative Cross-Sectional Study. HIV AIDS (Auckl). 2019;11:229–37. doi: 10.2147/HIV.S218213 [DOI] [PMC free article] [PubMed] [Google Scholar]
28.Melkamu MW, Gebeyehu MT, Afenigus AD, Hibstie YT, Temesgen B, Petrucka P, et al. Incidence of common opportunistic infections among HIV-infected children on ART at Debre Markos referral hospital, Northwest Ethiopia: a retrospective cohort study. BMC Infect Dis. 2020;20(1):50. doi: 10.1186/s12879-020-4772-y [DOI] [PMC free article] [PubMed] [Google Scholar]
29.Fite MB, Aga DJ. Spectrum of Opportunistic Disease and Associated Factors among Patients Attending ART Clinic, Nekemte Specialized Hospital, Western Ethiopia. Cold Spring Harbor Laboratory. 2020. doi: 10.1101/2020.10.06.327668 [DOI] [Google Scholar]
30.Wachamo D, Bonja F. Magnitude of Opportunistic Infections and Associated Factors Among HIV-Positive Adults on ART at Selected Public Hospitals in Sidama National Regional State, Southern Ethiopia. HIV AIDS (Auckl). 2020;12:479–87. doi: 10.2147/HIV.S265274 [DOI] [PMC free article] [PubMed] [Google Scholar]
31.Weldearegawi TZ, Gerensea H, Berihu H, Gidey G, Welearegay MZ. The magnitude of opportunistic infections and associated factors in HIV-infected adults on antiretroviral therapy in southern zone Tigray, Ethiopia: a cross-sectional study. Pan Afr Med J. 2020;35:126. doi: 10.11604/pamj.2020.35.126.17839 [DOI] [PMC free article] [PubMed] [Google Scholar]
32.Dagnaw Tegegne K, Cherie N, Tadesse F, Tilahun L, Kassaw MW, Biset G. Incidence and Predictors of Opportunistic Infections Among Adult HIV Infected Patients on Anti-Retroviral Therapy at Dessie Comprehensive Specialized Hospital, Ethiopia: A Retrospective Follow-Up Study. HIV AIDS (Auckl). 2022;14:195–206. doi: 10.2147/HIV.S346182 [DOI] [PMC free article] [PubMed] [Google Scholar]
33.Chanie ES, Bayih WA, Birhan BM, Belay DM, Asmare G, Tiruneh T, et al. Incidence of advanced opportunistic infection and its predictors among HIV infected children at Debre Tabor referral Hospital and University of Gondar Compressive specialized hospitals, Northwest Ethiopia, 2020: A multicenter retrospective follow-up study. Heliyon. 2021;7(4):e06745. doi: 10.1016/j.heliyon.2021.e06745 [DOI] [PMC free article] [PubMed] [Google Scholar]
34.Dembelu M, Kote M, Gilano G, Mohammed T. Incidence and predictors of reoccurrence of opportunistic infection among adult HIV/AIDS patients attending ART clinic at public health facilities in Arba Minch town, southern Ethiopia: A retrospective cohort study. PLoS One. 2021;16(12):e0261454. doi: 10.1371/journal.pone.0261454 [DOI] [PMC free article] [PubMed] [Google Scholar]
35.Kebede N, Ambaye T, Bazie GW. Opportunistic infections and associated factors among HIV-infected adults on antiretroviral therapy attending health facilities in North Wollo, Ethiopia. Journal of Infectious Diseases. 2023. [Google Scholar]
36.Mequanente DA, Srinivasan P, Mallika G, Ansari PMT, Wale M. Incidence of Opportunistic Infections among HIV-infected Children on ART at Gondar University Specialized Hospital, Ethiopia. IJST. 2022;15(34):1675–82. doi: 10.17485/ijst/v15i34.1073 [DOI] [Google Scholar]
37.Birmeka M. Distribution pattern and prevalence of opportunistic infections and their possible reciprocal effects among HIV patients, Burayu health centers, Ethiopia. J Infect Dev Ctries. 2023;17(7):1022–9. doi: 10.3855/jidc.15105 [DOI] [PubMed] [Google Scholar]
38.Dagnaw M, Fekadu H, Gebre Egziabher A, Yesfue T, Indracanti M, Tebeje A. Incidence of opportunistic infections and its predictors among HIV/AIDS patients on antiretroviral therapy in Gondar University Comprehensive and Specialized Hospital, Ethiopia. HIV Res Clin Pract. 2023;24(1):2187013. doi: 10.1080/25787489.2023.2187013 [DOI] [PubMed] [Google Scholar]
39.Mekonnen GB, Birhane BM, Engdaw MT, Kindie W, Ayele AD, Wondim A. Predictors of a high incidence of opportunistic infections among HIV-infected children receiving antiretroviral therapy at Amhara regional state comprehensive specialized hospitals, Ethiopia: A multicenter institution-based retrospective follow-up study. Front Pediatr. 2023;11:1107321. doi: 10.3389/fped.2023.1107321 [DOI] [PMC free article] [PubMed] [Google Scholar]
40.Padyana M, Bhat RV, Dinesha M, Nawaz A. HIV-Tuberculosis: A Study of Chest X-Ray Patterns in Relation to CD4 Count. N Am J Med Sci. 2012;4(5):221–5. doi: 10.4103/1947-2714.95904 [DOI] [PMC free article] [PubMed] [Google Scholar]
41.Lawn SD, Nicol MP. Xpert® MTB/RIF assay: development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance. Future Microbiol. 2011;6(9):1067–82. doi: 10.2217/fmb.11.84 [DOI] [PMC free article] [PubMed] [Google Scholar]
42.Azuonwu O, Putheti R, Amadi F, Obire O. Prevalence of Tuberculosis in HIV infected patients. J Adv Pharm Educ Res. 2011;1:1–11. [Google Scholar]
43.Maori L. Prevalence of tuberculosis among HIV/AIDS patients attending Zambuk General Hospital. New York Science Journal. 2012;5:33–6. [Google Scholar]
44.Itanga I, Ndagijimana A, Simbi CMC, Ntaganira J. Opportunistic Infections and Associated Factors among HIV-Infected Adult Persons on Antiretroviral Therapy at Ruhengeri Referral Hospital, Rwanda: A cross-sectional study. Rwanda J Med Health Sci. 2022;5(3):323–31. doi: 10.4314/rjmhs.v5i3.7 [DOI] [PMC free article] [PubMed] [Google Scholar]
45.Khademi F, Yousefi-Avarvand A, Sahebkar A, Ghanbari F, Vaez H. Bacterial Co-infections in HIV/AIDS-positive Subjects: A Systematic Review and Meta-analysis. Folia Med (Plovdiv). 2018;60(3):339–50. doi: 10.2478/folmed-2018-0007 [DOI] [PubMed] [Google Scholar]
46.Yadav D, Jha N, Pokharel P, Niraula S, Bhattacharya S, Nagesh S. Study On The Prevalence Of Pulmonary Tuberculosis Among Hiv Positive Attending Hiv Clinics In Eastern Nepal. SAARC J Tuber Lung Dis HIV/AIDS. 1970;8(1):1–8. doi: 10.3126/saarctb.v8i1.5885 [DOI] [Google Scholar]
47.Amuta E, Tsaku I, Akyala I. A retrospective study on the epidemiological trend of human immunodeficiency virus (HIV) and pulmonary tuberculosis (PTB) co-infection in Nasarawa state, Nigeria. 2013.
48.Ngowi BJ, Mfinanga SG, Bruun JN, Morkve O. Pulmonary tuberculosis among people living with HIV/AIDS attending care and treatment in rural northern Tanzania. BMC Public Health. 2008;8:341. doi: 10.1186/1471-2458-8-341 [DOI] [PMC free article] [PubMed] [Google Scholar]
49.Floridia M, Ciccacci F, Andreotti M, Hassane A, Sidumo Z, Magid NA, et al. Tuberculosis Case Finding With Combined Rapid Point-of-Care Assays (Xpert MTB/RIF and Determine TB LAM) in HIV-Positive Individuals Starting Antiretroviral Therapy in Mozambique. Clin Infect Dis. 2017;65(11):1878–83. doi: 10.1093/cid/cix641 [DOI] [PubMed] [Google Scholar]
50.Liu E, Makubi A, Drain P, Spiegelman D, Sando D, Li N, et al. Tuberculosis incidence rate and risk factors among HIV-infected adults with access to antiretroviral therapy. AIDS. 2015;29(11):1391–9. doi: 10.1097/QAD.0000000000000705 [DOI] [PMC free article] [PubMed] [Google Scholar]
51.Kempker RR, Chkhartishvili N, Kinkladze I, Schechter MC, Harrington K, Rukhadze N, et al. High Yield of Active Tuberculosis Case Finding Among HIV-Infected Patients Using Xpert MTB/RIF Testing. Open Forum Infect Dis. 2019;6(6):ofz233. doi: 10.1093/ofid/ofz233 [DOI] [PMC free article] [PubMed] [Google Scholar]
52.Ji Y-J, Liang P-P, Shen J-Y, Sun J-J, Yang J-Y, Chen J, et al. Risk factors affecting the mortality of HIV-infected patients with pulmonary tuberculosis in the cART era: a retrospective cohort study in China. Infect Dis Poverty. 2018;7(1):25. doi: 10.1186/s40249-018-0405-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
53.Kiconco G, Turyasiima M, Ndamira A, Yamile OA, Egesa WI, Ndiwimana M, et al. Prevalence and associated factors of pneumonia among under-fives with acute respiratory symptoms: a cross sectional study at a Teaching Hospital in Bushenyi District, Western Uganda. Afr Health Sci. 2021;21(4):1701–10. doi: 10.4314/ahs.v21i4.25 [DOI] [PMC free article] [PubMed] [Google Scholar]
54.Ujunwa F, Ezeonu C. Risk Factors for Acute Respiratory Tract Infections in Under-five Children in Enugu Southeast Nigeria. Ann Med Health Sci Res. 2014;4(1):95–9. doi: 10.4103/2141-9248.126610 [DOI] [PMC free article] [PubMed] [Google Scholar]
55.Gritly SM, Elamin MO, Rahimtullah H, Ali AYH, Dhiblaw A, Mohamed EA. Risk factors of pneumonia among children under 5 years at a pediatric hospital in Sudan. International Journal of Medical Research & Health Sciences. 2018;7(4):60–8. [Google Scholar]
56.Wanjiku Ndungu E. Cross Sectional Survey of Care Seeking For Acute Respiratory Illness in Children Under 5 Years in Rural Kenya. AJP. 2018;4(3):69. doi: 10.11648/j.ajp.20180403.15 [DOI] [Google Scholar]
57.Louie JK, Chi NH, Thao LTT, Quang VM, Campbell J, Chau NVV, et al. Opportunistic infections in hospitalized HIV-infected adults in Ho Chi Minh City, Vietnam: a cross-sectional study. Int J STD AIDS. 2004;15(11):758–61. doi: 10.1258/0956462042395159 [DOI] [PubMed] [Google Scholar]
58.Rajagopalan N, Suchitra JB, Shet A, Khan ZK, Martin-Garcia J, Nonnemacher MR, et al. Mortality among HIV-Infected Patients in Resource Limited Settings: A Case Controlled Analysis of Inpatients at a Community Care Center. Am J Infect Dis. 2009;5(3):219–24. doi: 10.3844/ajidsp.2009.219.224 [DOI] [PMC free article] [PubMed] [Google Scholar]
59.Bénet T, Sylla M, Messaoudi M, Sánchez Picot V, Telles J-N, Diakite A-A, et al. Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study. PLoS One. 2015;10(12):e0145447. doi: 10.1371/journal.pone.0145447 [DOI] [PMC free article] [PubMed] [Google Scholar]
60.Corbett EL, Churchyard GJ, Charalambos S, Samb B, Moloi V, Clayton TC, et al. Morbidity and mortality in South African gold miners: impact of untreated disease due to human immunodeficiency virus. Clin Infect Dis. 2002;34(9):1251–8. doi: 10.1086/339540 [DOI] [PubMed] [Google Scholar]
61.van Oosterhout JJG, Laufer MK, Perez MA, Graham SM, Chimbiya N, Thesing PC, et al. Pneumocystis pneumonia in HIV-positive adults, Malawi. Emerg Infect Dis. 2007;13(2):325–8. doi: 10.3201/eid1302.060462 [DOI] [PMC free article] [PubMed] [Google Scholar]
62.Andualem Z, Adane T, Tigabu A, Yallew WW, Wami SD, Dagne H, et al. Pneumonia among Under-Five Children in Northwest Ethiopia: Prevalence and Predictors-A Community-Based Cross-Sectional Study. Int J Pediatr. 2020;2020:3464907. doi: 10.1155/2020/3464907 [DOI] [PMC free article] [PubMed] [Google Scholar]
63.Ahmed A, Mekonnen D, Kindie M. Incidence and predictors of tuberculosis among adult people living with HIV/AIDS in Afar public health facilities, Northeast Ethiopia. AIDS. 2015;1:3–10. [Google Scholar]
64.Ayeno HD. Prevalence and Factors Affecting the Development of Active-TB among HIV-Positive Patients at Shashemene Referral Hospital, Shashemene, West Arsi, Ethiopia. J Bioanal Biomed. 2018;10(4). doi: 10.4172/1948-593x.1000215 [DOI] [Google Scholar]
65.Akanbi MO, Achenbach C, Taiwo B, Idoko J, Ani A, Isa Y, et al. Evaluation of gene xpert for routine diagnosis of HIV-associated tuberculosis in Nigeria: A prospective cohort study. BMC Pulm Med. 2017;17(1):87. doi: 10.1186/s12890-017-0430-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
66.Gjergji M, Bushati J, Harxhi A, Hafizi H, Pipero P. Tuberculosis in HIV/AIDS patients. Adv Tech Clin Microbiol. 2017;1(3):16. [Google Scholar]
67.Tsegay T, Biyadgie W. Association of indoor air pollution and other risk factors with acute respiratory infections among children in Sheka Zone, South West Ethiopia. J Harmon Res Med Health Sci. 2018;5(1):1–9. doi: 10.30876/JOHR.5.1.2018.1-9 [DOI] [Google Scholar]
68.Mekuriaw AL, Hardeep R. Household fuel use and acute respiratory infections in children under five years of age in Gondar city of Ethiopia. J Environ Earth Sci. 2014;4(7):77–85. [Google Scholar]
69.Tuhebwe D, Tumushabe E, Leontsini E, Wanyenze RK. Pneumonia among children under five in Uganda: symptom recognition and actions taken by caretakers. Afr Health Sci. 2014;14(4):993–1000. doi: 10.4314/ahs.v14i4.31 [DOI] [PMC free article] [PubMed] [Google Scholar]
70.Hammitt LL, Kazungu S, Morpeth SC, Gibson DG, Mvera B, Brent AJ, et al. A preliminary study of pneumonia etiology among hospitalized children in Kenya. Clin Infect Dis. 2012;54 Suppl 2(Suppl 2):S190–9. doi: 10.1093/cid/cir1071 [DOI] [PMC free article] [PubMed] [Google Scholar]

PLoS One. doi: 10.1371/journal.pone.0315599.r001

Decision Letter 0

Mengistu Hailemariam Zenebe

14 Aug 2024

Please submit your revised manuscript by Sep 28 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Mengistu Hailemariam Zenebe, PhD

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. When completing the data availability statement of the submission form, you indicated that you will make your data available on acceptance. We strongly recommend all authors decide on a data sharing plan before acceptance, as the process can be lengthy and hold up publication timelines. Please note that, though access restrictions are acceptable now, your entire data will need to be made freely accessible if your manuscript is accepted for publication. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If you are unable to adhere to our open data policy, please kindly revise your statement to explain your reasoning and we will seek the editor's input on an exemption. Please be assured that, once you have provided your new statement, the assessment of your exemption will not hold up the peer review process.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Partly

Reviewer #2: No

**********

2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: No

**********

Reviewer #1: My comments and concerns are as follow:

Major

The focus of MS: Trends vs Systematic review & meta-analysis

The trends are not indicated properly.

What is the clear definition of pneumonia? Not clear and requires definition

If bacteriology confirmed pneumonia, the prevalence of predominant isolates should be reported.

How retrospective studies included in this study showed/confirmed the pneumonia?

Minor

Population: mainly focus on children, better to balance and align with objective of the study and title.

Is the study protocol registered in PRESPOROUS? If so, indicate the registration number

Language: better to use people/person first language. Thus, use ‘people with HIV’ than HIV positive patients.

I suggest the revisions of conclusion and recommendations according to the objective, title of the study and main findings

Good luck

Reviewer #2: COMMENTS

TITLE:

Prevalence and trends of opportunistic bacterial infections (Tuberculosis and pneumonia) among HIV positive patients in Ethiopia: Systematic review and meta-analysis

Comments: Since this study did not evaluate the trends of opportunistic infections (such as TB and pneumonia) among HIV-positive individuals, it would be inappropriate to include "trends of" in your title. Please remove "trend" from the title.

ABSTRACT

Conclusions: “This meta-analysis shows that the trend of tuberculosis infection is rising, then

falling, then rising again, while the trend of pneumonia infection among HIV-positive individuals

in Ethiopia is rising”.

Comments: If you’re certain that a trend analysis was conducted, please include the results in the abstract. However, I didn’t see this information in the results section.

Keywords: “ Ethiopia, meta-analysis, prevalence, pneumonia, tuberculosis, systemic review, and opportunistic infection”.

Comments: Better if you can make like

HIV(+)-people, opportunistic infections, tuberculosis, pneumonia, prevalence, systematic review, meta-analysis, Ethiopia

INTRODUCTION:

Comments: The introduction section does not adequately address Ethiopian studies on the prevalence of opportunistic infections, such as TB and pneumonia, among HIV-positive individuals in Ethiopia. Please revise the introduction to include this discussion.

AIDS

Comments: Please first provide the full definition of any term, followed by its abbreviation in parentheses, the first time it is mentioned in the document. After that, you may use the abbreviation consistently throughout the rest of the document.

“A 2019 report states that OI was the main cause of nearly 95,000 child deaths from

HIV-related causes [3].”

Comments: A 2019 global report…

“There were 310,000 OI-related fatalities among AIDS patients in the eastern and southern African regions, even though there is insufficient information about the OIs' recurrence rate in the continent [6].

Comment: please check the reference. "6. Teker AG. AIDS-related deaths in Turkey between 2009 and 2018. Epidemiology & Infection. 2021;149:e191."

“Globally, 9.9 million cases of tuberculosis and 214,000 HIV-positive deaths are expected in 2021, according to WHO estimates [9].”

Comments: Please review this sentence for accuracy, or consider using the most recent data.

“ Ethiopia is one of the 30 countries with a high TB and TB/HIV burden; with an estimated annual TB incidence of 140/100,000 persons and a death rate of 19 per 100,000 people, according to the 2020 Global TB Report [9]”.

Comments: Please refer to the updated WHO report on Ethiopia's TB burden, either the 2022 or 2023 edition.

METHODS

2. 1 Country profile

Comments: I believe the country profile information is not particularly relevant to this manuscript. Instead, it would be more appropriate for the authors to focus on the burden of HIV, TB, pneumonia, and other opportunistic infections in Ethiopia, and include related data that is pertinent to the manuscript.

If you believe the country profile is relevant to the manuscript, please revise it to include the most up-to-date information and provide appropriate citations or references.

2.2 Search strategy

….. ‘‘opportunistic bacterial infections in Ethiopia’’ ‘‘Prevalence of opportunistic bacterial

infections in HIV positive patients,’’ ‘‘Prevalence of opportunistic bacterial infections in Ethiopia,’’and ‘‘Magnitude of opportunistic bacterial infections among HIV positive patients in different regions of Ethiopia’’ were used to search journals.”

Comments: Please provide the search strategy you followed and the total number of articles captured in at least one database (e.g., PubMed) as a supplementary file. Ensure the information is formatted appropriately, either using "AND" or "OR" operators, or with commas, as needed.

……………..and study locations (conducted between September 14/2023 and December 1, 2023),

Comments: The above sentence is not clear, and needs revision

2.3 Inclusion and exclusion criteria of the studies

Comments: Please change with “eligibility criteria”

2.3.1 Inclusion criteria

Comments: This paragraph does not outline the inclusion criteria for potential papers in this systematic review and meta-analysis. Instead, it discusses the characteristics of the included studies. Please clearly state your inclusion criteria: specify which types of papers and necessary information were considered for inclusion, and detail which papers and types of information were deemed irrelevant or excluded.

2.3.2 Exclusion criteria

Comments: Please explicitly list all of your exclusion criteria.

What about papers that are only available as abstracts, conference presentations, or lack full-text access?

2.4. Study selection procedures

…. An EndNote X7 reference program,

Comments: Include the specifications for EndNote.

……inter-rater agreement was calculated after referring to the Cochrane Handbook of Systematic Reviews.

Comment: Cite the reference

2.7 Risk of publication bias

Comments: please remove this subheading and include the information (risk of publication bias into 2.8 Data analysis subheading section.

3. Results

Comments: include a subheading " Searching results"

“A total of 276 articles were retrieved on the prevalence and determinants of OIs among HIV positive patients were retrieved in Ethiopia”

Comments: Assessing the determinants of opportunistic infections among HIV-positive individuals is not the objective of your study. Please ensure that your focus remains on the actual objectives of your research.

“Of the remaining 27 articles, 7 articles were further removed for different purposes (lack of OR, CI and number of positive cases)”.

Comments: Why did you exclude articles that lacked OR and CI data, given that your primary outcome of interest is the prevalence of opportunistic infections (TB and pneumonia) among HIV-positive individuals? Since your study does not assess the determinants of these infections, it is unclear why these papers were excluded. Please revise this decision.

“Therefore, 20 of the studies met the eligibility criteria and were included in

the final systematic review and meta-analysis study (Figure 1)”.

Comments: Please revise the PRISMA flow chart as follows: Records after duplicates removed (n=151) → Records screened (n=151) → Full-text articles assessed for eligibility (n=27) → Studies included in the systematic review and meta-analysis (n=20).

3.1 Characteristics of the eligible studies

Comments: The paragraph requires significant editing and language revision.

Table 1: Prevalence of tuberculosis among HIV patients in Ethiopia

Comments: Characters-tics of included studies to calculate the pooled prevalence of TB among HIV(+)-individuals

Table 2: Prevalence of pneumonia among HIV patients in Ethiopia

Comments: Characteristics of included studies to calculate the pooled prevalence of pneumonia among HIV(+)-individuals

3.2 Pooled prevalence of opportunistic bacterial infections

Comments: Pooled prevalence of tuberculosis among HIV(+) individuals

4. Discussion

Comments:

The entire document requires thorough language editing, including improvements in sentence structure, grammar, and overall clarity. Careful attention should be given to revising the text to ensure it is well-constructed, grammatically correct, and easy to understand.

Your study presents a pooled or combined prevalence, which involves aggregating data from multiple sources to provide a more comprehensive and reliable estimate. Given the nature of this approach, it may not be appropriate or recommended to compare your findings with individual primary studies, as these studies typically offer a narrower scope and may not capture the broader trends that your meta-analysis addresses. Instead, it would be more suitable and meaningful to discuss your results in the context of other meta-analyses or national reports. These sources provide a wider perspective and are more comparable to your pooled data, allowing for a more accurate and robust discussion of your findings. By focusing on these broader sources, you can better validate your results and place them within the larger body of evidence.

5.1 Conclusions

“In terms of the prevalence of tuberculosis, the pattern is rising, falling, and rising.

However, pneumonia prevalence among HIV positive patients is increasing”.

Comments: You did not estimate the pooled prevalence of TB across different time intervals, so this statement is not accurate. Please ensure that your conclusions are precise and based directly on the findings of your study.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #1: No

Reviewer #2: Yes: Melese Abate Reta

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

Attachment

Submitted filename: Reviewed3062024.docx

pone.0315599.s004.docx^{(12.5KB, docx)}

Attachment

Submitted filename: Review report_Melese Abate Reta.docx

pone.0315599.s005.docx^{(18.4KB, docx)}

PLoS One. 2025 Oct 21;20(10):e0315599. doi: 10.1371/journal.pone.0315599.r002

Author response to Decision Letter 1

4 Oct 2024

Dear reviewers, we are grateful for your time and effort, and all your comments and suggestions are constructive and supportive, which increases the readability and overall quality of the paper. Below, we provide a point-by-point response explaining how we have addressed each of the reviewer's comments and suggestions. N.B., yellow and bright green, highlighted, are the answers for reviewers 1 and 2, respectively, and turquoise color for both reviewers. We hope that the revised manuscript will better fit the journal.

General Comments to the Author

Recommendation 1: Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: No

Answer 1: Dear reviewers, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion.

Recommendation 2: Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Answer 2: Dear reviewers, Thanks for your appreciation.

Recommendation 3: Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Answer 3: Dear reviewers, Thanks for your appreciation.

Recommendation 4: Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

Answer 4: Dear reviewer 2, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion.

Answer for Reviewer 1#

Major

Recommendation 1: The focus of MS: Trends vs Systematic review & meta-analysis. The trends are not indicated properly.

Answer 1: Dear reviewer, Thanks for your valuable recommendation, but the trend is not relevant and was removed.

Recommendation 2: What is the clear definition of pneumonia? Not clear and requires definition.

Answer 2: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the introduction?

Recommendation 3: If bacteriology confirmed pneumonia, the prevalence of predominant isolates should be reported.

Answer 3: Dear reviewer, Thanks for your valuable recommendation, but they are not mentioned in the primary studies.

Recommendation 4: How retrospective studies included in this study showed/confirmed the pneumonia?

Answer 4: Dear reviewer, Thanks for your valuable recommendation; but it was and editorial problem and now amended. Could you please go to the result?

Minor

Recommendation 30: Population: mainly focus on children, better to balance and align with objective of the study and title.

Answer 30: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the introduction?

Recommendation 31: Is the study protocol registered in PRESPOROUS? If so, indicate the registration number.

Answer 31: Dear reviewer, yes it is already registered and found in abstract methodology section.

Recommendation 32: Language: better to use people/person first language. Thus, use ‘people with HIV’ than HIV positive patients.

Answer 32: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the entire document of the manuscript?

Recommendation 33: I suggest the revisions of conclusion and recommendations according to the objective and title of the study and main findings.

Answer 33: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the conclusion and recommendation?

Answer for Reviewer 2#

Recommendation 1: Since this study did not evaluate the trends of opportunistic infections (such as TB and pneumonia) among HIV-positive individuals, it would be inappropriate to include "trends of" in your title. Please remove "trend" from the title.

Answer 1: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the title and other parts of the manuscript?

Recommendation 2: If you’re certain that a trend analysis was conducted, please include the results in the abstract. However, I didn’t see this information in the results section.

Answer 2: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the abstract?

Recommendation 3: Better if you can make the key words like, HIV (+)-people, opportunistic infections, tuberculosis, pneumonia, prevalence, systematic review, meta-analysis, Ethiopia

Answer 3: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the abstract?

Introduction:

Recommendation 4: The introduction section does not adequately address Ethiopian studies on the prevalence of opportunistic infections, such as TB and pneumonia, among HIV-positive individuals in Ethiopia. Please revise the introduction to include this discussion.

Answer 4: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the introduction?

Recommendation 5: Please first provide the full definition of any term, followed by its abbreviation in parentheses, the first time it is mentioned in the document. After that, you may use the abbreviation consistently throughout the rest of the document. “A 2019 report states that OI was the main cause of nearly 95,000 child deaths from HIV-related causes [3].”

Answer 5: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the introduction?

Recommendation 6: A 2019 global report… “There were 310,000 OI-related fatalities among AIDS patients in the eastern and southern African regions, even though there is insufficient information about the OIs' recurrence rate in the continent [6].

Answer 6: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the introduction?

Recommendation 7: please check the reference. "6. Teker AG. AIDS-related deaths in Turkey between 2009 and 2018. Epidemiology & Infection. 2021;149:e191." “Globally, 9.9 million cases of tuberculosis and 214,000 HIV-positive deaths are expected in 2021, according to WHO estimates [9].”

Answer 7: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the introduction?

Recommendation 8: Please review this sentence for accuracy, or consider using the most recent data. “Ethiopia is one of the 30 countries with a high TB and TB/HIV burden; with an estimated annual TB incidence of 140/100,000 persons and a death rate of 19 per 100,000 people, according to the 2020 Global TB Report [9]”.

Recommendation 9: Please refer to the updated WHO report on Ethiopia's TB burden, either the 2022 or 2023 edition

Answer 9: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the introduction?

Methods

Recommendation 10: Country profile: I believe the country profile information is not particularly relevant to this manuscript. Instead, it would be more appropriate for the authors to focus on the burden of HIV, TB, pneumonia, and other opportunistic infections in Ethiopia, and include related data that is pertinent to the manuscript. If you believe the country profile is relevant to the manuscript, please revise it to include the most up to-date information and provide appropriate citations or references.

Answer 10: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the methodology?

Recommendation 11: Please provide the search strategy you followed and the total number of articles captured in at least one database (e.g., PubMed) as a supplementary file. Ensure the information is formatted appropriately, either using "AND" or "OR" operators, or with commas, as needed.

Answer 11: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the methodology?

Recommendation 12: ……………..and study locations (conducted between September 14/2023 and December 1, 2023). The above sentence is not clear, and needs revision.

Answer 12: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the methodology?

Recommendation 13: Please change inclusion and exclusion criteria of the studies with “eligibility criteria”

Answer 13: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the methodology?

Recommendation 14: An Inclusion criterion, this paragraph does not outline the inclusion criteria for potential papers in this systematic review and meta-analysis. Instead, it discusses the characteristics of the included studies. Please clearly state your inclusion criteria: specify which types of papers and necessary information were considered for inclusion, and detail which papers and types of information were deemed irrelevant or excluded.

Answer 14: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the methodology?

Recommendation 15: Exclusion criteria, please explicitly list all of your exclusion criteria. What about papers that are only available as abstracts, conference presentations, or lack full-text access?

Answer 15: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the methodology?

Recommendation 16: Study selection procedures …. An EndNote X7 reference program, Include the specifications for EndNote. ……inter-rater agreement was calculated after referring to the Cochrane Handbook of Systematic Reviews. Cite the reference

Answer 16: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the methodology?

Recommendation 17: Risk of publication bias please removes this subheading and includes the information (risk of publication bias into 2.8 Data analysis subheading section.

Answer 17: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the methodology?

Results

Recommendation 18: include a subheading "Searching results" “A total of 276 articles were retrieved on the prevalence and determinants of OIs among HIV positive patients were retrieved in Ethiopia.

Answer 18: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the result?

Recommendation 19: Assessing the determinants of opportunistic infections among HIV-positive individuals is not the objective of your study. Please ensure that your focus remains on the actual objectives of your research. “Of the remaining 27 articles, 7 articles were further removed for different purposes (lack of OR, CI and number of positive cases)”.

Answer 19: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the result?

Recommendation 20: Why did you exclude articles that lacked OR and CI data, given that your primary outcome of interest is the prevalence of opportunistic infections (TB and pneumonia) among HIV- positive individuals? Since your study does not assess the determinants of these infections, it is unclear why these papers were excluded. Please revise this decision. “Therefore, 20 of the studies met the eligibility criteria and were included in the final systematic review and meta-analysis study (Figure 1)”.

Answer 20: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the result?

Recommendation 21: Please revise the PRISMA flow chart as follows: Records after duplicates removed (n=151) → Records screened (n=151) → Full-text articles assessed for eligibility (n=27) → Studies included in the systematic review and meta-analysis (n=20).

Answer 21: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the result?

Characteristics of the eligible studies

Recommendation 22: The paragraph requires significant editing and language revision

Answer 22: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the result?

Recommendation 23: Characteristics of included studies to calculate the pooled prevalence of TB among HIV (+) individuals on the prevalence of tuberculosis among HIV patients in Ethiopia

Answer 23: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the result?

Recommendation 24: Characteristics of included studies to calculate the pooled prevalence of pneumonia among HIV (+)-individuals on prevalence of pneumonia among HIV patients in Ethiopia

Answer 24: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the result?

Recommendation 25: Correct pooled prevalence of opportunistic bacterial infections to pooled prevalence of tuberculosis among HIV (+) individuals.

Answer 25: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the result?

Discussion

Recommendation 26: The entire document requires thorough language editing, including improvements in sentence structure, grammar, and overall clarity. Careful attention should be given to revising the text to ensure it is well-constructed, grammatically correct, and easy to understand. Your study presents a pooled or combined prevalence, which involves aggregating data from multiple sources to provide a more comprehensive and reliable estimate. Given the nature of this approach, it may not be appropriate or recommended to compare your findings with individual primary studies, as these studies typically offer a narrower scope and may not capture the broader trends that your meta-analysis addresses. Instead, it would be more suitable and meaningful to discuss your results in the context of other meta-analyses or national reports. These sources provide a wider perspective and are more comparable to your pooled data, allowing for a more accurate and robust discussion of your findings. By focusing on these broader sources, you can better validate your results and place them within the larger body of evidence.

Answer 26: Dear reviewer, Thanks for your valuable recommendation; we accepted it and corrected as per your suggestion. Could you please go to the Discussion?

Conclusions

Recomm

Attachment

Submitted filename: Response to Reviewers.docx

pone.0315599.s007.docx^{(21.4KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0315599.r003

Decision Letter 1

Mengistu Hailemariam Zenebe

14 Nov 2024

Dear Dr. Girma,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Dec 29 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Mengistu Hailemariam Zenebe, PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #2: Yes

Reviewer #3: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #2: Yes

Reviewer #3: No

**********

Reviewer #2: (No Response)

Reviewer #3: Firstly, I would like to thank the editor for inviting me to review this manuscript entitled prevalence of opportunistic bacterial infections (Tuberculosis and Pneumonia) among people living with HIV in Ethiopia: A systematic review and meta-analysis.

The authors’ relentless effort in conducting this interesting area of research is also appreciated. Knowing the burden of the problem can help plan strategies for responsible officials in the future. Saying this, I have some comments that need to be addressed before its consideration for publication.

At the very beginning, there is a study conducted previously with the same title and study area and even broader than the current study (prevalence and determinants of opportunistic infections among HIV-infected adults receiving ART in Ethiopia: A systematic review and meta-analysis). If so what is the main reason to conduct this study at the moment for fear of duplication effort?

Introduction

1. The introduction lacks chronological order; it would be better if the authors were encouraged to revise it as the following:

-Define the problem clearly, and report the burden of the problem from global to national or from developed to developing nations

-Explain the impacts/consequences of the problem if left unaddressed or untreated

-The possible risk factors of opportunistic infections in people with HIV (of course this is not your objective you can skip)

-Finally mention what has been done previously to tackle the problem and gaps your study is going to address. Here boldly show the justification of the current study.

2. Avoid citing wrong references. For instance, refer. 6

3. Focus on your objective only (pneumonia among non-RVI children is not objective so avoid it) and the introduction is mostly about pneumonia ignoring tuberculosis why?

Methods

1. In search strategy Google Scholar is not a database remove it.

2. Merge the inclusion and exclusion criteria into eligibility criteria and almost all articles from Ethiopia published in English. So this shouldn’t be a criteria remove it

3. Quality appraisal put cut off point of JBI for studies to be included or excluded

4. Data analysis: what is your base to conclude I2 25% is low and 75% high heterogeneity or p<0.05 significant publication bias? Put citations

Results

1. Bring the study selection procedure under the result subsection

2. This has publication so what did you do for that?

3. To identify the possible source of heterogeneity please consider meta-regression

4. When conducting subgroup analysis please try to merge smaller numbers into one as others (eg. Tigray region can be merged with Oromia or Amhara in the TB subgroup)

5. In the figures of sensitivity analysis (fig. 6) the estimates should be the same with pooled prevalence of TB and pneumonia.

Conclusion and recommendations

1. Try to conclude based on your study’s findings not based on your general knowledge.

2. In the recommendation section you mentioned that “Organize regular training sessions for healthcare workers to enhance their knowledge regarding opportunistic infections, diagnostic criteria, and treatment protocols specific to HIV-positive patients. Provide healthcare professionals with updated clinical guidelines, treatment algorithms, and educational resources that focus on the management of opportunistic infections in the context of HIV.” The question does your study reveal that the increment of opportunistic infection among people living with HIV is due to a lack of trained professionals or poor knowledge?

Generally, intense language editing is needed throughout the whole manuscript to make it clearer and easily understandable for readers. Please avoid using expressions like “HIV-positive” or “HIV patients” throughout the whole document they seem to be stigmatizing instead replace them with “people living with HIV” or “people with HIV”.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #2: Yes: Melese Abate Reta

Reviewer #3: No

**********

PLoS One. 2025 Oct 21;20(10):e0315599. doi: 10.1371/journal.pone.0315599.r004

Author response to Decision Letter 2

19 Nov 2024

Mengistu Hailemariam Zenebe, PhD

Academic Editor

PLOS ONE

November 19, 2024

Dear Dr. Mengistu Hailemariam Zenebe,

We are pleased to submit the revised draft of our manuscript, “Prevalence of opportunistic bacterial infections (tuberculosis and pneumonia) among people with HIV in Ethiopia: Systematic review and meta-analysis” (PONE-D-24-22113R1), to PLOS ONE. We appreciate the time and effort dedicated by the editorial staff and reviewers. The comments provided were valuable and helped us refine our paper. As such, we have made several revisions to the manuscript based on the suggestions given. Changes to the manuscript are yellow highlighted.

Below are our point-by-point responses to the reviewers’ comments.

Response to Reviewer 3

Thank you for your insightful comments and suggestions. Please find the answers to each of your questions below.

1. At the very beginning, there is a study conducted previously with the same title and study area and even broader than the current study (prevalence and determinants of opportunistic infections among HIV-infected adults receiving ART in Ethiopia: A systematic review and meta-analysis). If so what is the main reason to conduct this study at the moment for fear of duplication effort?

Response: Previously, Woldegeorgis and colleagues [14] conducted a systematic review and meta-analysis regarding the prevalence and determinants of opportunistic infections among HIV-infected adults receiving ART in Ethiopia. However, the prevalence of opportunistic bacterial infections, particularly tuberculosis and pneumonia, among people of all age groups living with HIV in the country is not collected, well organised, and documented as a systematic review and meta-analysis. Therefore, the objective of this systematic review and meta-analysis is to estimate the overall prevalence of opportunistic bacterial infections among people living with HIV from available research conducted in different regions of Ethiopia. The findings of this work will be used by the concerned stakeholders to reduce the prevalence of opportunistic bacterial infections and design evidence-based interventions (page 4, last paragraph).

2. Introduction

1. The introduction lacks chronological order; it would be better if the authors were encouraged to revise it as the following:

-Define the problem clearly, and report the burden of the problem from global to national or from developed to developing nations

-Explain the impacts/consequences of the problem if left unaddressed or untreated

-The possible risk factors of opportunistic infections in people with HIV (of course this is not your objective you can skip)

-Finally mention what has been done previously to tackle the problem and gaps your study is going to address. Here boldly show the justification of the current study.

2. Avoid citing wrong references. For instance, refer. 6

3. Focus on your objective only (pneumonia among non-RVI children is not objective so avoid it) and the introduction is mostly about pneumonia ignoring tuberculosis why?

Response: Thank you for your close reading of our paper. This is an important point, so we have amended as per your suggestions (pages 3 & 4).

3. Methods

1. In search strategy Google Scholar is not a database remove it.

2. Merge the inclusion and exclusion criteria into eligibility criteria and almost all articles from Ethiopia published in English. So this shouldn’t be a criteria remove it

3. Quality appraisal put cut off point of JBI for studies to be included or excluded

4. Data analysis: what is your base to conclude I2 25% is low and 75% high heterogeneity or p<0.05 significant publication bias? Put citations

Response: We agree with your suggestion and have modified accordingly (pages 5-8).

4. Results

1. Bring the study selection procedure under the result subsection

2. This has publication so what did you do for that?

3. To identify the possible source of heterogeneity please consider meta-regression

4. When conducting subgroup analysis please try to merge smaller numbers into one as others (eg. Tigray region can be merged with Oromia or Amhara in the TB subgroup)

5. In the figures of sensitivity analysis (fig. 6) the estimates should be the same with pooled prevalence of TB and pneumonia.

Response: Thank you for this observation our answer for all of your suggestions are found below. This is because (1) study selection process must be included in the method section as per “PRISMA-2020 checklist”. Please check the “Supplemental File 1”. The second (2) comment is not clear. (3) Dear reviewer, regarding identifying the possible source of heterogeneity using meta-regression is optional and our team chooses the figure representation rather than the meta-regression. (4) We did not do it because Tigray is one of the regions found in Ethiopia and merging with Oromia or Amhara region results falsified report or due to this study, stakeholders may not consider Tigray region particularly during reducing the prevalence of opportunistic bacterial infections and design evidence-based interventions. With regard to sensitivity analysis (5) As far as we know, a sensitivity analysis is carried out by removing each study one at a time in order to clarify the impact of each study on the pooled effect size. During the sensitivity analysis, studies not included in Figs 6a & b had relatively determinant effects on the overall magnitude of tuberculosis and pneumonia among people living with HIV in Ethiopia, so we removed them and this is scientifically valid way of reporting the sensitivity analysis. Dear reviewer, in this regard we recommended to see more information from different previously published works elsewhere or get in touch with statistician.

5. Conclusion and recommendations

1. Try to conclude based on your study’s findings not based on your general knowledge.

Response: We agree with your suggestion and have modified accordingly (pages 18 & 19).

6. Generally, intense language editing is needed throughout the whole manuscript to make it clearer and easily understandable for readers. Please avoid using expressions like “HIV-positive” or “HIV patients” throughout the whole document they seem to be stigmatizing instead replace them with “people living with HIV” or “people with HIV”.

Response: We agree with your suggestion and have modified accordingly (throughout the manuscript).

Sincerely,

Abayeneh Girma

Corresponding author

Attachment

Submitted filename: Response to Reviewer 3.docx

pone.0315599.s008.docx^{(16.4KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0315599.r005

Decision Letter 2

Vanessa Carels

18 Dec 2024

PONE-D-24-22113R2

Prevalence of opportunistic bacterial infections (tuberculosis and pneumonia) among people with HIV in Ethiopia: Systematic review and meta-analysis

PLOS ONE

Dear Dr. Girma,

Thank you for submitting your manuscript to PLOS ONE., and for responding to our recent requests regarding your submission. Unfortunately, in our final editorial checks of the documents that you supplied, we have concluded that your submission does not comply with our policies around data availability. We are therefore overturning the provisional editorial accept decision, and rejecting this manuscript.

PLOS journals require authors to make all data necessary to replicate their study’s findings publicly available without restriction at the time of publication (https://journals.plos.org/plosone/s/data-availability). In this case, the following underlying data were not provided as repeatedly requested:

A numbered table of all studies identified in the literature search, including those that were excluded from the analyses.

A table of all data extracted from the primary research sources for the systematic review and/or meta-analysis.

As a result of these concerns, we cannot consider the manuscript for publication. I am very sorry that this issue was identified at such a late stage.

Kind regards,

Vanessa Carels

Staff Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #2: Yes

Reviewer #3: Yes

**********

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #2: Yes: Melese Abate Reta

Reviewer #3: No

**********

- - - - -

For journal use only: PONEDEC3

PLoS One. 2025 Oct 21;20(10):e0315599. doi: 10.1371/journal.pone.0315599.r006

Author response to Decision Letter 3

28 Dec 2024

There is nothing to respond to from the decision letter since that was an acceptance letter.

Attachment

Submitted filename: Response_to_Reviewer_3_auresp_3.docx

pone.0315599.s009.docx^{(16.4KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0315599.r007

Decision Letter 3

Miquel Vall-llosera Camps

22 Sep 2025

Prevalence of opportunistic bacterial infections (tuberculosis and pneumonia) among people with HIV in Ethiopia: Systematic review and meta-analysis

PONE-D-24-22113R3

Dear Dr. Girma,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support .

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Miquel Vall-llosera Camps

Senior Staff Editor

PLOS One

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #3: Yes

**********

Reviewer #3: (No Response)

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #3: No

**********

PLoS One. doi: 10.1371/journal.pone.0315599.r008

Acceptance letter

Miquel Vall-llosera Camps

PONE-D-24-22113R3

PLOS ONE

Dear Dr. Girma,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

* All relevant supporting information is included in the manuscript submission,

* There are no issues that prevent the paper from being properly typeset

You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps.

Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing.

If we can help with anything else, please email us at customercare@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Miquel Vall-llosera Camps

Staff Editor

PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Table. PRISMA 2020 Checklist.

The checklists/protocols following during writing this systematic review and meta-analysis.

(DOCX)

pone.0315599.s001.docx^{(16.8KB, docx)}

S2 Table. Search Strategy.

Comprehensive search strategy for common opportunistic bacterial infections among people living with HIV in Ethiopia.

(DOCX)

pone.0315599.s002.docx^{(13.9KB, docx)}

S3 Table. Quality appraisal result of included studies.

The quality of included studies was evaluated using the Joanna Briggs Institute (JBI) quality appraisal checklist for prevalence studies.

(DOCX)

pone.0315599.s003.docx^{(27.2KB, docx)}

Attachment

Submitted filename: Reviewed3062024.docx

pone.0315599.s004.docx^{(12.5KB, docx)}

Attachment

Submitted filename: Review report_Melese Abate Reta.docx

pone.0315599.s005.docx^{(18.4KB, docx)}

Attachment

Submitted filename: Response to Reviewers.docx

pone.0315599.s007.docx^{(21.4KB, docx)}

Attachment

Submitted filename: Response to Reviewer 3.docx

pone.0315599.s008.docx^{(16.4KB, docx)}

Attachment

Submitted filename: Response_to_Reviewer_3_auresp_3.docx

pone.0315599.s009.docx^{(16.4KB, docx)}

Data Availability Statement

All relevant data are included in the paper and its Supporting information files.

[pone.0315599.ref001] 1.Riccardi N, Rotulo GA, Castagnola E. Definition of Opportunistic Infections in Immunocompromised Children on the Basis of Etiologies and Clinical Features: A Summary for Practical Purposes. Curr Pediatr Rev. 2019;15(4):197–206. doi: 10.2174/1573396315666190617151745 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref002] 2.Yates T, Lantagne D, Mintz E, Quick R. The impact of water, sanitation, and hygiene interventions on the health and well-being of people living with HIV: a systematic review. J Acquir Immune Defic Syndr. 2015;68 Suppl 3:S318–30. doi: 10.1097/QAI.0000000000000487 [DOI] [PubMed] [Google Scholar]

[pone.0315599.ref003] 3.WHO. HIV/AIDS Epidemiology. 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/hiv-aids#:~:text=Transmission%20is%20ongoing%20in%20all,1.3%20million%20people%20acquired%20HIV. Accessed June 24, 2024.

[pone.0315599.ref004] 4.Global H. AIDS statistics—2018 fact sheet. Geneva: UNAIDS. 2019. https://www.avert.org/professionals/hiv-around-world/sub-saharan-africa/overview [Google Scholar]

[pone.0315599.ref005] 5.Global H. AIDS statistics–2018 fact sheet. Geneva: Joint United Nations Programme on HIV. AIDS. 2018. [Google Scholar]

[pone.0315599.ref006] 6.Jeena PM. Respiratory Diseases Amongst HIV Infected Children. HIV Infection in Children and Adolescents. Springer International Publishing. 2020:55–72. doi: 10.1007/978-3-030-35433-6_6 [DOI] [Google Scholar]

[pone.0315599.ref007] 7.Kiya GT, Mekonnen Z, Melaku T, Tegene E, Gudina EK, Cools P, et al. Prevalence and mortality rate of sepsis among adults admitted to hospitals in sub-Saharan Africa: a systematic review and meta-analysis. J Hosp Infect. 2024;144:1–13. doi: 10.1016/j.jhin.2023.11.012 [DOI] [PubMed] [Google Scholar]

[pone.0315599.ref008] 8.Macpherson L, Ogero M, Akech S, Aluvaala J, Gathara D, Irimu G, et al. Risk factors for death among children aged 5-14 years hospitalised with pneumonia: a retrospective cohort study in Kenya. BMJ Glob Health. 2019;4(5):e001715. doi: 10.1136/bmjgh-2019-001715 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref009] 9.World Health Organization. Meeting report of the WHO expert consultation on the definition of extensively drug-resistant tuberculosis. World Health Organization. 2021. https://iris.who.int/bitstream/handle/10665/338776/9789240018662-eng.pdf [Google Scholar]

[pone.0315599.ref010] 10.Pandey A, Galvani AP. The burden of childhood pneumonia in India and prospects for control. Lancet Child Adolesc Health. 2020;4(9):643–5. doi: 10.1016/S2352-4642(20)30238-8 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref011] 11.UNICEF. UNICEF Ethiopia: Annual Report 2019. NY, USA: Unicef. 2019. https://www.unicef.org/ethiopia/media/2481/file/Annual%20Report%202019.pdf [Google Scholar]

[pone.0315599.ref012] 12.Alamneh YM, Adane F. Magnitude and Predictors of Pneumonia among Under-Five Children in Ethiopia: A Systematic Review and Meta-Analysis. J Environ Public Health. 2020;2020:1606783. doi: 10.1155/2020/1606783 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref013] 13.Hailemariam S, Gebeyehu Y, Loha E, Johansson KA, Lindtjørn B. Inadequate management of pneumonia among children in South Ethiopia: findings from descriptive study. BMC Health Serv Res. 2019;19(1):426. doi: 10.1186/s12913-019-4242-7 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref014] 14.Woldegeorgis BZ, Zekarias Z, Adem BG, Obsa MS, Kerbo AA. Prevalence and determinants of opportunistic infections among HIV-infected adults receiving antiretroviral therapy in Ethiopia: A systematic review and meta-analysis. Front Med (Lausanne). 2023;10:1087086. doi: 10.3389/fmed.2023.1087086 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref015] 15.Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref016] 16.Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019;10(10):ED000142. doi: 10.1002/14651858.ED000142 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref017] 17.Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Systematic reviews of prevalence and incidence. Joanna Briggs Institute. 2017. [Google Scholar]

[pone.0315599.ref018] 18.Borenstein M. Heterogeneity in meta-analysis. The Handbook of Research Synthesis and Meta-Analysis. Russell Sage Foundation. 2019:453–68. doi: 10.7758/9781610448864.23 [DOI] [Google Scholar]

[pone.0315599.ref019] 19.Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34. doi: 10.1136/bmj.315.7109.629 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref020] 20.Damtie D, Yismaw G, Woldeyohannes D, Anagaw B. Common opportunistic infections and their CD4 cell correlates among HIV-infected patients attending at antiretroviral therapy clinic of Gondar University Hospital, Northwest Ethiopia. BMC Res Notes. 2013;6:534. doi: 10.1186/1756-0500-6-534 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref021] 21.Moges NA. Prevalence of Opportunistic Infections and Associated Factors among HIV Positive Patients taking Anti-Retroviral Therapy in DebreMarkos Referral Hospital, Northwest Ethiopia. J AIDS Clin Res. 2014;05(05). doi: 10.4172/2155-6113.1000301 [DOI] [Google Scholar]

[pone.0315599.ref022] 22.Mitiku H, Weldegebreal F, Teklemariam Z. Magnitude of opportunistic infections and associated factors in HIV-infected adults on antiretroviral therapy in eastern Ethiopia. HIV AIDS (Auckl). 2015;7:137–44. doi: 10.2147/HIV.S79545 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref023] 23.Alemayehu M, Yisehak Y, Alaro W, Alemayehu B. Opportunistic Infections among HIV/AIDS Patients taking Anti-Retroviral Therapy at Tertiary Care Hospital in Wolaita Zone, Southern Ethiopia. J AIDS Clin Res. 2017;08(02). doi: 10.4172/2155-6113.1000665 [DOI] [Google Scholar]

[pone.0315599.ref024] 24.Addisu D. Magnitude and Determinants of Opportunistic Infections Among Hiv/Aids Patients in Sphmmc, Addis Ababa, Ethiopia: Retrospective Study. JOJPH. 2018;4(1). doi: 10.19080/jojph.2018.04.555627 [DOI] [Google Scholar]

[pone.0315599.ref025] 25.Solomon FB, Angore BN, Koyra HC, Tufa EG, Berheto TM, Admasu M. Spectrum of opportunistic infections and associated factors among people living with HIV/AIDS in the era of highly active anti-retroviral treatment in Dawro Zone hospital: a retrospective study. BMC Res Notes. 2018;11(1):604. doi: 10.1186/s13104-018-3707-9 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref026] 26.Urgessa F, Ararsa A, Ataro Z. Prevalence and Associated Risk Factors of Opportunistic Infections among Anti-Retro Viral Treatment Naive HIV/AIDS Infected Patients. J AIDS Clin Res. 2018;09(03). doi: 10.4172/2155-6113.1000763 [DOI] [Google Scholar]

[pone.0315599.ref027] 27.Dereje N, Moges K, Nigatu Y, Holland R. Prevalence And Predictors Of Opportunistic Infections Among HIV Positive Adults On Antiretroviral Therapy (On-ART) Versus Pre-ART In Addis Ababa, Ethiopia: A Comparative Cross-Sectional Study. HIV AIDS (Auckl). 2019;11:229–37. doi: 10.2147/HIV.S218213 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref028] 28.Melkamu MW, Gebeyehu MT, Afenigus AD, Hibstie YT, Temesgen B, Petrucka P, et al. Incidence of common opportunistic infections among HIV-infected children on ART at Debre Markos referral hospital, Northwest Ethiopia: a retrospective cohort study. BMC Infect Dis. 2020;20(1):50. doi: 10.1186/s12879-020-4772-y [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref029] 29.Fite MB, Aga DJ. Spectrum of Opportunistic Disease and Associated Factors among Patients Attending ART Clinic, Nekemte Specialized Hospital, Western Ethiopia. Cold Spring Harbor Laboratory. 2020. doi: 10.1101/2020.10.06.327668 [DOI] [Google Scholar]

[pone.0315599.ref030] 30.Wachamo D, Bonja F. Magnitude of Opportunistic Infections and Associated Factors Among HIV-Positive Adults on ART at Selected Public Hospitals in Sidama National Regional State, Southern Ethiopia. HIV AIDS (Auckl). 2020;12:479–87. doi: 10.2147/HIV.S265274 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref031] 31.Weldearegawi TZ, Gerensea H, Berihu H, Gidey G, Welearegay MZ. The magnitude of opportunistic infections and associated factors in HIV-infected adults on antiretroviral therapy in southern zone Tigray, Ethiopia: a cross-sectional study. Pan Afr Med J. 2020;35:126. doi: 10.11604/pamj.2020.35.126.17839 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref032] 32.Dagnaw Tegegne K, Cherie N, Tadesse F, Tilahun L, Kassaw MW, Biset G. Incidence and Predictors of Opportunistic Infections Among Adult HIV Infected Patients on Anti-Retroviral Therapy at Dessie Comprehensive Specialized Hospital, Ethiopia: A Retrospective Follow-Up Study. HIV AIDS (Auckl). 2022;14:195–206. doi: 10.2147/HIV.S346182 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref033] 33.Chanie ES, Bayih WA, Birhan BM, Belay DM, Asmare G, Tiruneh T, et al. Incidence of advanced opportunistic infection and its predictors among HIV infected children at Debre Tabor referral Hospital and University of Gondar Compressive specialized hospitals, Northwest Ethiopia, 2020: A multicenter retrospective follow-up study. Heliyon. 2021;7(4):e06745. doi: 10.1016/j.heliyon.2021.e06745 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref034] 34.Dembelu M, Kote M, Gilano G, Mohammed T. Incidence and predictors of reoccurrence of opportunistic infection among adult HIV/AIDS patients attending ART clinic at public health facilities in Arba Minch town, southern Ethiopia: A retrospective cohort study. PLoS One. 2021;16(12):e0261454. doi: 10.1371/journal.pone.0261454 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref035] 35.Kebede N, Ambaye T, Bazie GW. Opportunistic infections and associated factors among HIV-infected adults on antiretroviral therapy attending health facilities in North Wollo, Ethiopia. Journal of Infectious Diseases. 2023. [Google Scholar]

[pone.0315599.ref036] 36.Mequanente DA, Srinivasan P, Mallika G, Ansari PMT, Wale M. Incidence of Opportunistic Infections among HIV-infected Children on ART at Gondar University Specialized Hospital, Ethiopia. IJST. 2022;15(34):1675–82. doi: 10.17485/ijst/v15i34.1073 [DOI] [Google Scholar]

[pone.0315599.ref037] 37.Birmeka M. Distribution pattern and prevalence of opportunistic infections and their possible reciprocal effects among HIV patients, Burayu health centers, Ethiopia. J Infect Dev Ctries. 2023;17(7):1022–9. doi: 10.3855/jidc.15105 [DOI] [PubMed] [Google Scholar]

[pone.0315599.ref038] 38.Dagnaw M, Fekadu H, Gebre Egziabher A, Yesfue T, Indracanti M, Tebeje A. Incidence of opportunistic infections and its predictors among HIV/AIDS patients on antiretroviral therapy in Gondar University Comprehensive and Specialized Hospital, Ethiopia. HIV Res Clin Pract. 2023;24(1):2187013. doi: 10.1080/25787489.2023.2187013 [DOI] [PubMed] [Google Scholar]

[pone.0315599.ref039] 39.Mekonnen GB, Birhane BM, Engdaw MT, Kindie W, Ayele AD, Wondim A. Predictors of a high incidence of opportunistic infections among HIV-infected children receiving antiretroviral therapy at Amhara regional state comprehensive specialized hospitals, Ethiopia: A multicenter institution-based retrospective follow-up study. Front Pediatr. 2023;11:1107321. doi: 10.3389/fped.2023.1107321 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref040] 40.Padyana M, Bhat RV, Dinesha M, Nawaz A. HIV-Tuberculosis: A Study of Chest X-Ray Patterns in Relation to CD4 Count. N Am J Med Sci. 2012;4(5):221–5. doi: 10.4103/1947-2714.95904 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref041] 41.Lawn SD, Nicol MP. Xpert® MTB/RIF assay: development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance. Future Microbiol. 2011;6(9):1067–82. doi: 10.2217/fmb.11.84 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref042] 42.Azuonwu O, Putheti R, Amadi F, Obire O. Prevalence of Tuberculosis in HIV infected patients. J Adv Pharm Educ Res. 2011;1:1–11. [Google Scholar]

[pone.0315599.ref043] 43.Maori L. Prevalence of tuberculosis among HIV/AIDS patients attending Zambuk General Hospital. New York Science Journal. 2012;5:33–6. [Google Scholar]

[pone.0315599.ref044] 44.Itanga I, Ndagijimana A, Simbi CMC, Ntaganira J. Opportunistic Infections and Associated Factors among HIV-Infected Adult Persons on Antiretroviral Therapy at Ruhengeri Referral Hospital, Rwanda: A cross-sectional study. Rwanda J Med Health Sci. 2022;5(3):323–31. doi: 10.4314/rjmhs.v5i3.7 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref045] 45.Khademi F, Yousefi-Avarvand A, Sahebkar A, Ghanbari F, Vaez H. Bacterial Co-infections in HIV/AIDS-positive Subjects: A Systematic Review and Meta-analysis. Folia Med (Plovdiv). 2018;60(3):339–50. doi: 10.2478/folmed-2018-0007 [DOI] [PubMed] [Google Scholar]

[pone.0315599.ref046] 46.Yadav D, Jha N, Pokharel P, Niraula S, Bhattacharya S, Nagesh S. Study On The Prevalence Of Pulmonary Tuberculosis Among Hiv Positive Attending Hiv Clinics In Eastern Nepal. SAARC J Tuber Lung Dis HIV/AIDS. 1970;8(1):1–8. doi: 10.3126/saarctb.v8i1.5885 [DOI] [Google Scholar]

[pone.0315599.ref047] 47.Amuta E, Tsaku I, Akyala I. A retrospective study on the epidemiological trend of human immunodeficiency virus (HIV) and pulmonary tuberculosis (PTB) co-infection in Nasarawa state, Nigeria. 2013.

[pone.0315599.ref048] 48.Ngowi BJ, Mfinanga SG, Bruun JN, Morkve O. Pulmonary tuberculosis among people living with HIV/AIDS attending care and treatment in rural northern Tanzania. BMC Public Health. 2008;8:341. doi: 10.1186/1471-2458-8-341 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref049] 49.Floridia M, Ciccacci F, Andreotti M, Hassane A, Sidumo Z, Magid NA, et al. Tuberculosis Case Finding With Combined Rapid Point-of-Care Assays (Xpert MTB/RIF and Determine TB LAM) in HIV-Positive Individuals Starting Antiretroviral Therapy in Mozambique. Clin Infect Dis. 2017;65(11):1878–83. doi: 10.1093/cid/cix641 [DOI] [PubMed] [Google Scholar]

[pone.0315599.ref050] 50.Liu E, Makubi A, Drain P, Spiegelman D, Sando D, Li N, et al. Tuberculosis incidence rate and risk factors among HIV-infected adults with access to antiretroviral therapy. AIDS. 2015;29(11):1391–9. doi: 10.1097/QAD.0000000000000705 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref051] 51.Kempker RR, Chkhartishvili N, Kinkladze I, Schechter MC, Harrington K, Rukhadze N, et al. High Yield of Active Tuberculosis Case Finding Among HIV-Infected Patients Using Xpert MTB/RIF Testing. Open Forum Infect Dis. 2019;6(6):ofz233. doi: 10.1093/ofid/ofz233 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref052] 52.Ji Y-J, Liang P-P, Shen J-Y, Sun J-J, Yang J-Y, Chen J, et al. Risk factors affecting the mortality of HIV-infected patients with pulmonary tuberculosis in the cART era: a retrospective cohort study in China. Infect Dis Poverty. 2018;7(1):25. doi: 10.1186/s40249-018-0405-8 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref053] 53.Kiconco G, Turyasiima M, Ndamira A, Yamile OA, Egesa WI, Ndiwimana M, et al. Prevalence and associated factors of pneumonia among under-fives with acute respiratory symptoms: a cross sectional study at a Teaching Hospital in Bushenyi District, Western Uganda. Afr Health Sci. 2021;21(4):1701–10. doi: 10.4314/ahs.v21i4.25 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref054] 54.Ujunwa F, Ezeonu C. Risk Factors for Acute Respiratory Tract Infections in Under-five Children in Enugu Southeast Nigeria. Ann Med Health Sci Res. 2014;4(1):95–9. doi: 10.4103/2141-9248.126610 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref055] 55.Gritly SM, Elamin MO, Rahimtullah H, Ali AYH, Dhiblaw A, Mohamed EA. Risk factors of pneumonia among children under 5 years at a pediatric hospital in Sudan. International Journal of Medical Research & Health Sciences. 2018;7(4):60–8. [Google Scholar]

[pone.0315599.ref056] 56.Wanjiku Ndungu E. Cross Sectional Survey of Care Seeking For Acute Respiratory Illness in Children Under 5 Years in Rural Kenya. AJP. 2018;4(3):69. doi: 10.11648/j.ajp.20180403.15 [DOI] [Google Scholar]

[pone.0315599.ref057] 57.Louie JK, Chi NH, Thao LTT, Quang VM, Campbell J, Chau NVV, et al. Opportunistic infections in hospitalized HIV-infected adults in Ho Chi Minh City, Vietnam: a cross-sectional study. Int J STD AIDS. 2004;15(11):758–61. doi: 10.1258/0956462042395159 [DOI] [PubMed] [Google Scholar]

[pone.0315599.ref058] 58.Rajagopalan N, Suchitra JB, Shet A, Khan ZK, Martin-Garcia J, Nonnemacher MR, et al. Mortality among HIV-Infected Patients in Resource Limited Settings: A Case Controlled Analysis of Inpatients at a Community Care Center. Am J Infect Dis. 2009;5(3):219–24. doi: 10.3844/ajidsp.2009.219.224 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref059] 59.Bénet T, Sylla M, Messaoudi M, Sánchez Picot V, Telles J-N, Diakite A-A, et al. Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study. PLoS One. 2015;10(12):e0145447. doi: 10.1371/journal.pone.0145447 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref060] 60.Corbett EL, Churchyard GJ, Charalambos S, Samb B, Moloi V, Clayton TC, et al. Morbidity and mortality in South African gold miners: impact of untreated disease due to human immunodeficiency virus. Clin Infect Dis. 2002;34(9):1251–8. doi: 10.1086/339540 [DOI] [PubMed] [Google Scholar]

[pone.0315599.ref061] 61.van Oosterhout JJG, Laufer MK, Perez MA, Graham SM, Chimbiya N, Thesing PC, et al. Pneumocystis pneumonia in HIV-positive adults, Malawi. Emerg Infect Dis. 2007;13(2):325–8. doi: 10.3201/eid1302.060462 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref062] 62.Andualem Z, Adane T, Tigabu A, Yallew WW, Wami SD, Dagne H, et al. Pneumonia among Under-Five Children in Northwest Ethiopia: Prevalence and Predictors-A Community-Based Cross-Sectional Study. Int J Pediatr. 2020;2020:3464907. doi: 10.1155/2020/3464907 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref063] 63.Ahmed A, Mekonnen D, Kindie M. Incidence and predictors of tuberculosis among adult people living with HIV/AIDS in Afar public health facilities, Northeast Ethiopia. AIDS. 2015;1:3–10. [Google Scholar]

[pone.0315599.ref064] 64.Ayeno HD. Prevalence and Factors Affecting the Development of Active-TB among HIV-Positive Patients at Shashemene Referral Hospital, Shashemene, West Arsi, Ethiopia. J Bioanal Biomed. 2018;10(4). doi: 10.4172/1948-593x.1000215 [DOI] [Google Scholar]

[pone.0315599.ref065] 65.Akanbi MO, Achenbach C, Taiwo B, Idoko J, Ani A, Isa Y, et al. Evaluation of gene xpert for routine diagnosis of HIV-associated tuberculosis in Nigeria: A prospective cohort study. BMC Pulm Med. 2017;17(1):87. doi: 10.1186/s12890-017-0430-6 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref066] 66.Gjergji M, Bushati J, Harxhi A, Hafizi H, Pipero P. Tuberculosis in HIV/AIDS patients. Adv Tech Clin Microbiol. 2017;1(3):16. [Google Scholar]

[pone.0315599.ref067] 67.Tsegay T, Biyadgie W. Association of indoor air pollution and other risk factors with acute respiratory infections among children in Sheka Zone, South West Ethiopia. J Harmon Res Med Health Sci. 2018;5(1):1–9. doi: 10.30876/JOHR.5.1.2018.1-9 [DOI] [Google Scholar]

[pone.0315599.ref068] 68.Mekuriaw AL, Hardeep R. Household fuel use and acute respiratory infections in children under five years of age in Gondar city of Ethiopia. J Environ Earth Sci. 2014;4(7):77–85. [Google Scholar]

[pone.0315599.ref069] 69.Tuhebwe D, Tumushabe E, Leontsini E, Wanyenze RK. Pneumonia among children under five in Uganda: symptom recognition and actions taken by caretakers. Afr Health Sci. 2014;14(4):993–1000. doi: 10.4314/ahs.v14i4.31 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0315599.ref070] 70.Hammitt LL, Kazungu S, Morpeth SC, Gibson DG, Mvera B, Brent AJ, et al. A preliminary study of pneumonia etiology among hospitalized children in Kenya. Clin Infect Dis. 2012;54 Suppl 2(Suppl 2):S190–9. doi: 10.1093/cid/cir1071 [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

Prevalence of opportunistic bacterial infections (tuberculosis and pneumonia) among people with HIV in Ethiopia: Systematic review and meta-analysis

Aleka Aemiro

Abayeneh Girma

Getachew Alamnie

Demsew Beletew

Amere Genet

Roles

Abstract

Background

Methods

Results

Conclusion

Registration

Introduction

Methods

Design and protocol registration

Search strategy

Eligibility criteria of the studies

Study selection process

Data extraction

Quality assessment of individual studies

Data analysis

Results

Fig 1. Flow diagram summarizing the selection of eligible studies.

Characteristics of the eligible studies

Table 1. Characteristics of included studies to calculate the pooled prevalence of TB among people living with HIV.

Table 2. Characteristics of included studies to calculate the pooled prevalence of pneumonia among people living with HIV.

Pooled prevalence of opportunistic bacterial infections

Fig 2. Overall pooled prevalence of tuberculosis among HIV positive patients in Ethiopia.

Fig 3. Overall pooled prevalence of pneumonia among HIV positive patients in Ethiopia.

Sub-group analysis of tuberculosis among people living with HIV

Table 3. Subgroup analysis of the magnitude of tuberculosis among people with HIV in Ethiopia.

Sub-group analysis of pneumonia among people living with HIV

Table 4. Subgroup analysis of the magnitude of pneumonia among people with HIV in Ethiopia.

Quality assessment and publication bias

Fig 4. Funnel plot representing evidence of publication bias in tuberculosis studies among people living with HIV.

Fig 5. Funnel plot representing evidence of publication bias in pneumonia studies among people living with HIV.

Fig 6. Egger’s publication bias plot of in tuberculosis studies among people living with HIV.

Fig 7. Egger’s publication bias plot of in pneumonia studies among people living with HIV.

Fig 8. Sensitivity analysis result of the included studies that assessed the impact of each study on the overall magnitude of tuberculosis among people living with HIV.

Fig 9. Sensitivity analysis result of the included studies that assessed the impact of each study on the overall magnitude of pneumonia among people living with HIV.

Discussion

Strengths and limitations

Conclusions and recommendations

Supporting information

Abbreviations:

Data Availability

Funding Statement

References

Decision Letter 0

Mengistu Hailemariam Zenebe

Roles

Author response to Decision Letter 1

Decision Letter 1

Mengistu Hailemariam Zenebe

Roles

Author response to Decision Letter 2

Decision Letter 2

Vanessa Carels

Roles

Author response to Decision Letter 3

Decision Letter 3

Miquel Vall-llosera Camps

Roles

Acceptance letter

Miquel Vall-llosera Camps

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases