Magnitude of underweight, wasting and stunting among HIV positive children in East Africa: A systematic review and meta-analysis.

BACKGROUND: Malnutrition on the background of HIV (Human Immunodeficiency Virus) infection is a complex medical condition that carries significant morbidity and mortality for affected children, with greater mortality from SAM (Severe Acute Malnutrition) among HIV-positive children than their HIV-negative peers. HIV-induced immune impairment heightened risk of opportunistic infection and can worsen nutritional status of children. HIV infection often leads to nutritional deficiencies through decreased food intake, mal-absorption and increased utilization and excretion of nutrients, which in turn can hasten death.
OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the magnitude of underweight, wasting and stunting among HIV positive children in East Africa.
METHODS: The authors systematically reviewed and meta-analyzed studies that assessed the prevalence of underweight, wasting and stunting among HIV positive children in East Africa from PubMed, Cochrane Library, Google Scholar, and Gray Literatures using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. The last search date was December 30/2019. The data was extracted in excel sheet considering country, study design, year of publication, prevalence reported. Then the authors transformed the data to STATA 14 for analysis. Heterogeneity across the studies was assessed by the Q and the I2 test. A weighted inverse variance random-effects model was used to estimate the magnitude of underweight, wasting and stunting. The subgroup analysis was done by country, year of publication, and study design. To examine publication bias, a funnel plot and Egger's regression test were used.
RESULTS: For the analysis a total of 22 studies with 22074 patients were used. The pooled prevalence of under-weight, wasting, and stunting among HIV positive children in East Africa was found to be 41.63% (95%CI; 35.69-47.57; I2 = 98.7%; p<0.001), 24.65% (95%CI; 18.34-30.95; I2 = 99.2%; p<0.001), and 49.68% (95%CI; 42.59-56.77; I2 = 99.0%; p<0.001) respectively. The prevalence of under-weight among HIV positive children was found to be 49.67% in Ethiopia followed by 42.00 in Rwanda. It was high among cohort studies (44.87%). Based on the year of publication, the prevalence of under-weight among HIV positive children was found to be 40.88% from studies conducted from January 2008-December 2014, while it was 43.68% from studies conducted from 2015-2019. The prevalence of wasting among HIV positive children was found to be 29.7% in Tanzania followed by 24.94% in Ethiopia. Based on the study design, the prevalence of wasting among HIV positive children was found to be high in cohort studies (31.15%). The prevalence of stunting among HIV positive children was found to be 51.63% in Ethiopia, followed by 48.21% in Uganda.
CONCLUSIONS: The results presented above provide evidence of a higher prevalence of under nutrition among HIV positive children in East Africa. Despite the country level variations of child under nutrition in East Africa, still it is high in all aspects compared to the studies from other parts of Africa. It is recommended that further systematic review and meta-analysis need to be conducted on magnitude of malnutrition among HIV positive children in Sub-Saharan Africa as a whole.

Introduction

According to WHO malnutrition, in all its forms, includes under-nutrition (wasting, stunting, underweight), inadequate vitamins or minerals, overweight, obesity, and resulting diet-related non communicable diseases [1, 2]. The term under-nutrition is defined as the outcome of insufficient food intake (hunger) and repeated infectious disease; which includes being underweight for once age, too short for once age(stunted), dangerously thin(wasted) and deficient in vitamins and minerals (micronutrient malnutrition) [3]. Malnutrition on the background of HIV infection is a complex medical condition that carries significant morbidity and mortality for affected children, with greater mortality from SAM among HIV-positive children than their HIV-negative peers [4].

Nutritional and micronutrient deficiencies are common in HIV-infected persons and play a major and synergistic role in disease progression and in the retardation of growth and development of children. HIV/AIDS is most prevalent in sub-Saharan Africa, where it combines with other common conditions such as malnutrition and opportunistic infections to cause devastation effect among families, communities, and nations [5, 6].

Human Immune Virus and under nutrition interact in a vicious cycle; HIV-induced immune impairment heightened risk of opportunistic infection and can worsen nutritional status of children. HIV infection often leads to nutritional deficiencies through decreased food intake, mal-absorption and increased utilization and excretion of nutrients, which in turn can hasten death. Likewise, nutritional status modulates the immunological response to HIV infection, affecting the overall clinical outcome, since malnutrition is the primary cause of immunodeficiency [7-10].

Malnutrition is responsible for 11% of the total global disease burden and 35% of child deaths worldwide. In developing countries an estimated 19 million children are severely wasted [4, 11]. In some regions, notably sub-Saharan Africa, human immunodeficiency virus (HIV) infection poses an added challenge to the care of malnourished children. While the clinical context and interventions for many common causes of childhood mortality worldwide have been addressed over the last decade [12, 13], the management of malnutrition in children particularly in those infected with HIV remains poorly addressed [14].

In sub-Saharan Africa, the epidemiology of severe malnutrition has been increased in children requiring hospitalization composed of those who are HIV infected or HIV exposed with case-fatality rates reaches as high as 20–50% [15, 16]. Large percentages of HIV-positive children have an episode of severe malnutrition as their first AIDS-defining illness. Under nutrition is an important factor which might predict disease progression of HIV-infected individuals. It also results in higher risk of morbidity and mortality in both HIV-infected adults and children. Wasting and weight loss are common features of HIV infection, especially in resource-limited settings. It is known that children with HIV and severe malnutrition invariably have lower nutritional recovery and higher mortality rates than their HIV-negative counterparts [17, 18]. ART initiation in children can also cause metabolic disorders, and adverse effects on the nutritional status, especially in the first months of treatment, by causing complications, such as nausea and vomiting, or reduced bone mineral density [5, 19].

In East Africa, variety of previous studies have reported that the magnitude of under nutrition; accordingly the prevalence of under-weight, wasting and stunting was ranged from 19.4% to 77.1%, 7% to 77.1% and 13% to 71.8% respectively. This showed pronounced discrepancies among reports of under nutrition across different geographical settings and different time periods. Moreover, there is no regionally represented pooled data of under nutrition in East Africa. Therefore, this systematic review and meta-analysis was aimed to estimate the pooled prevalence of underweight, wasting and stunting in the East African context.

Methods

Review question

The review questions of this systematic review and meta-analysis were:

What is the pooled prevalence of under-weight, wasting and stunting among HIV positive children in East Africa context?

Study selection and screening

To exclude duplicate studies the retrieved studies were exported to Endnote version 8 reference managers. Before retrieval of full-text papers two investigators (BB and TG) independently screened the selected studies using article's title and abstracts. We used pre-specified inclusion criteria to further screen the full-text articles. Disagreements were resolved with third reviewer (GT) for the final decision on the selection of studies to be included in the analysis [20].

Inclusion and exclusion criteria

Those studies had reported the prevalence of at least one under-weight, wasting and stunting and published in English language from January 2008 to December 2019. Studies conducted with cross-sectional, and cohort study design was included. Studies conducted on marginalized groups/populations like children with any medical diseases, chronic diseases, or street mothers were excluded. Studies conducted on HIV/AIDS children in East Africa. The prevalence of under-weight, wasting, and stunting was considered when weight/ age, weight /height and height per age Z score <-2sd respectively within a specific population and multiply by 100 to be prevalence report.

Searching strategy

This review identified studies that provide data on the prevalence of under-weight, wasting, and stunting with the context of Eastern Africa. In the searching engine, mainly PubMed, Cochrane library, Google Scholar, and Gray Literatures were retrieved. The last search date was December 30/2019. The Authors searched using keywords that are the amalgamations of population, condition/outcome, and context. A snowball searching of the references of relevant papers for linked articles were also performed. Those search terms or phrases including were: “children”, “child”, “infant”, “under-nutrition”, “underweight”, “wasting”, stunting, HIV, AIDS and Eastern Africa. Using those key terms, the following search map was applied: (prevalence OR magnitude) AND (children [MeSH Terms] OR child OR infant) AND (under-nutrition [MeSH Terms] OR underweight OR wasting OR stunting) AND (HIV OR AIDS) AND Eastern Africa on PubMed database (S1 Table). Thus, the PubMed search combines #1 AND #2 AND #3 (S1 Table). These search terms were further paired with names of each East African country. On both Cochran Library, and Google scholar, a build in text search were used on the advanced search section of the sources. The search date was December 30/2019.

Quality assessment

The quality of the studies were appraised by three authors independently using the Joanna Briggs Institute (JBI) checklist [21]. The disagreement was resolved by the interference of a third reviewer. Studies were considered as high risk or poor quality, when it scored 3 and below [20-22] (S2 Table).

Data extraction

The authors developed data extraction form on the excel sheet in considering country, year of publication, study design and prevalence of underweight, wasting and stunting reported. The data extraction sheet was piloted using selecting four papers randomly the data extraction sheet was piloted and adjustment were made after the template were piloted. Using the extraction form two authors (BB and TG) extracted the data in collaboration. The third author (GT) independently assessed the accuracy of the data and discussions with a third reviewer were done when disagreements between reviewers occurred [20, 22].

Synthesis of results

The authors transformed the data to STATA 14 for analysis after it was extracted in excel sheet. Using a random effect meta-analysis model we pooled the overall prevalence estimates of underweight, wasting and stunting. Using Q statistic and the I2 statistics we assessed the heterogeneity of effect size. The I2statistic value of zero, 25, 50, and 75% indicates true homogeneity, low heterogeneity, moderate heterogeneity and high heterogeneity, respectively. Using study design, study country, and year of publication subgroup analysis was done by. Sensitivity analysis was done to assess the impact of a single study on the pooled estimate. Using funnel plot subjectively and objectively by Egger’s regression test publication bias was assessed [20].

Results

A total of 3094 studies were identified; 2050 from PubMed, 12 from Cochrane Library, 1010 from Google Scholar and 22 from other sources. After duplication removed, a total of 970 articles remained (2127 removed by duplication). Finally, 230 studies were screened for full-text review, and 22 articles with (n = 22074 patients) were selected for the analysis (Fig 1).

Fig 1

PRISMA–Adapted flow diagram showed the results of the search and reasons for exclusion [23, 24].

Characteristics of included studies

Twenty two studies were included in this systematic review and meta-analysis [18, 25–45]. Of them 12 studies were done in Ethiopia [18, 25–34, 37], 1 in Kenya [41], while 2 were in Uganda [38, 39], 1 in Rwanda [35], and 6 in Tanzania [36, 40, 42–45]. Based on the study design used 14 studies were done by cross-sectional study design [18, 26, 27, 30, 31, 33–35, 37, 38, 40, 41, 43, 45] and while other 8 studies were conducted by cohort study design [25, 27–29, 32, 36, 39, 42, 44]. 14/22(63.6%) were published between 2008 and 2014 and the remaining 8/22 (33.4%) were published between 2015 and 2019. The total number of participants in the included studies were ranges from 96 [32] to 5951 [38] (Table 1).

Table 1

Distribution of included studies on the prevalence underweight, wasting and stunting in East Africa, from January 2008-December 2019.

Author name	Publication Year	Country	Region	Study design	Sample size	Under weight	Wasting	Stunting	Cut of point	Reference
									Z-scor
1. Kedir et al	2014	Ethiopia	Adama/Et	Cohort	560	51.6			<-2sd	[25]
2. Mekonen et al	2014	Ethiopia	AA/ET	Cross sectional	255	47.5		71.3	<-2sd	[26]
3. Jeylan et al	2018	Ethiopia	Adama/ET	Cross sectional	412		21.8	13.4	<-2sd	[27]
4. Tekleab et al	2016	Ethiopia	AA/ET	Cohort	202	39.5	16.3	71.3	<-2sd	[28]
5. Yassin et al	2017	Ethiopia	Fiche/ET	Cohort	269				<3rd centile	[29]
6. Abdulkadir et al	2014	Ethiopia	Gonder/ET	Cross sectional	142		31.7	46.5	NR	[30]
7. Haileselassie et al	2019	Ethiopia	Harar/Et	Cross sectional	390		28.2	24.7	<-2sd	[31]
8. Teklemariam et al	2015	Ethiopia	Harar/ET	Cross sectional	108	51.6	31.5	49.1	<-2sd	[18]
9. Workneh et al	2009	Ethiopia	Jimma/ET	Cohort	96	77.1	47.5	63.5	<5th centile	[32]
10. Wondimu et al	2014	Ethiopia	Hawassa/Et	Cross sectional	455	41.2	21.4	60.5	<-2sd	[33]
11. Megabiaw et al	2012	Ethiopia	Gondar/ET	Cross sectional	301	41.7	5.8	65	<-2sd	[34]
12. Arpadi et al	2019	Rwanda	Rwanda	Cross sectional	374	42			<-2sd	[35]
13. Kamenju et al	2017	Tanzania	Tanzania	Cohort	2092	25.4	21.6	27.1	<-2sd	[36]
14. Sewale et al	2018	Ethiopia	Gojjam/Et	Cross sectional	372				<-2 sd	[37]
15. Nalwoga et al	2010	Uganda	Uganda	Cross sectional	5951	30	10	42	<-2 sd	[38]
16. Arinaitwe et al	2012	Uganda	Uganda	Cohort	358	39.7		71.8	<-2 sd m-s	[39]
17. Sunguya et al	2014	Tanzania	Tanzania	Cross sectional	748	40.6	30.2	60.8	≥-2sd	[40]
18. Herman et al	2102	Kenya	Kenya	Cross sectional	2275	19.4	7	28.6	<-2 sd	[41]
19. Mwiru et al	2015	Tanzania	Tanzania	Cohort	3144	53	33	56	<-2 sd	[42]
20. Sunguya et al	2011	Tanzania	Tanzania	Cross sectional	213	22.1	23.6	36.6	<-2sd	[43]
21. Mwiru et al	2014	Tanzania	Tanzania	Cohort	3144	30	40	52	<-2sd	[44]
22. Dundigalla et al	2015	Tanzania	Tanzania	Cross sectional	213	61	29.1	56.8	<-2sd	[45]

Meta-analysis

Underweight

Prevalence of under-weight among HIV positive children. Most of the studies (n = 17) have reported the prevalence of under-weight among HIV positive children. The prevalence of under-weight was ranged from 19.4% [41] to 77.1% [32]. The pooled prevalence of under-weight among HIV positive children in East Africa using random-effects model analysis was found to be 41.63% (95%CI; 35.69–47.57; I2 = 98.7%; p<0.001) (Fig 2).

Fig 2

Forest plot showing the pooled prevalence of under-weight among HIV positive children in East Africa, from January 2008-December 2019.

Subgroup analysis for the prevalence of under-weight among HIV positive children in Eastern Africa. Using country, study design, and year of publication as criteria subgroup analysis was done. Based on this, the prevalence of under-weight among HIV positive children was found to be 49.67% in Ethiopia, 42.00 in Rwanda, 38.59% in Tanzania, 34.52% in Uganda, and 19.4% in Kenya (Fig 3 and Table 2). The prevalence of under-weight among HIV positive children was found to be 39.33% in cross-sectional studies and 44.87% in cohort studies (Fig 4 and Table 2). It was found to be 40.88% from studies conducted from January 2008-December 2014, while it was 43.68% from studies conducted from 2015–2019 (Fig 5 and Table 2).

Fig 3

Forest plot showing the subgroup analysis of the prevalence of under-weight among HIV positive children by country in East Africa, from January 2008-December 2019.

Table 2

Summery of subgroup analysis of the prevalence of under-weight among HIV positive children in Eastern Africa by country, design and year of publication, from January 2008-December 2019.

Variables	Characteristics	Pooled prevalence, %(95% CI)	I2, (P-value)
By country	Ethiopia	49.67(42.06–57.27)	91.3%(<0.001)
	Rwanda	42.00(37.00–47.00)	-
	Tanzania	38.59(27.33–49.83)	99.2%(<0.001)
	Uganda	34.52(25.04–44.01)	92.5%(<0.001)
	Kenya	19.40(17.78–21.02)	-
By study design	Cross-sectional	39.33(32.54–46.12)	97.8% (<0.001)
	Cohort	44.87(33.97–55.77)	99.1%(<0.001)
By year of publication	2008–2014	40.88(33.58–48.17)	99.0% (<0.001)
	2015–2019	43.68(29.57–57.78)	97.5%(<0.001)

Fig 4

Forest plot showing the subgroup analysis of the prevalence of under-weight among HIV positive children by study design in East Africa, from January 2008-December 2019.

Fig 5

Forest plot showing the subgroup analysis of the prevalence of under-weight among HIV positive children by year of publication in East Africa, from January 2008-December 2019.

Sensitivity analysis for under-weight

To assess the influence of individual study on the pooled prevalence of under-weight in Eastern Africa we employed a sensitivity analysis. Accordingly the findings were not dependent on all included studies. The prevalence of under-weight varied between 39.55(33.67–45.43) [32] and 42.71(36.31–49.11) [36] after deletion of a single study (S1 Fig).

Publication bias

Subjectively the funnel plot indicated symmetrical distributions which indicate the absence of publication bias. The Egger’s regression test- also revealed the absence of publication bias; P-value was 0.064, (S2 Fig).

Wasting

Prevalence of wasting among HIV positive children in East Africa. Most of the studies (n = 16) have reported the prevalence of wasting among HIV positive children. The prevalence of wasting was ranged from 7% [41] to 77.1% [32]. The prevalence of wasting among HIV positive children in East Africa was found to be 24.65% (95%CI; 18.34–30.95; I2 = 99.2%; p<0.001) (Fig 6).

Fig 6

Forest plot shows the pooled prevalence of wasting among HIV positive children in East Africa, from January 2008-December 2019.

Subgroup analysis of the prevalence of wasting among HIV positive children in Eastern Africa. The subgroup analysis was by country, study design, and year of publication. Accordingly, the prevalence of wasting among HIV positive children was found to be 24.94% in Ethiopia, 29.7% in Tanzania, 10.0% in Uganda, and 7.0% in Kenya (Fig 7 and Table 3). The prevalence of wasting among HIV positive children was found to be 21.22% in cross-sectional studies and 31.15% in cohort studies (Fig 8 and Table 3). Based on the year of publication, the prevalence of wasting among HIV positive children was found to be 24.7% from studies conducted from January 2008-December 2014, while it was 24.02% from studies conducted from 2015–2019 (Fig 9 and Table 3).

Fig 7

Forest plot shows the pooled prevalence of wasting by country in East Africa, from January 2008-December 2019.

Table 3

Summery of subgroup analysis of the prevalence of wasting among HIV positive children in Eastern Africa by country, design and year of publication, from January 2008-December 2019.

Variables	Characteristics	Pooled prevalence, %(95% CI)	I2, (P-value)
By country	Ethiopia	24.94(16.83–33.05)	95.7%(<0.001)
	Tanzania	29.7(23.00–36.39)	97.8%(<0.001)
	Uganda	10.0(9.24–10.76)	-
	Kenya	7.0(5.95–8.95)	-
By study design	Cross-sectional	21.22(16.56–25.88)	97.6% (<0.001)
	Cohort	31.15(22.57–39.74)	98.5%(<0.001)
By year of publication	2008–2014	24.7(16.11–33.30)	99.5% (<0.001)
	2015–2019	24.02(20.35–27.70)	76.9%(<0.001)

Fig 8

Forest plot shows the pooled prevalence of wasting by year of publication in East Africa, from January 2008-December 2019.

Fig 9

Forest plot shows the pooled prevalence of wasting by study design in East Africa, from January 2008-December 2019.

Sensitivity analysis for wasting

To assess the influence of individual study on the pooled prevalence of wasting in Eastern Africa we employed a sensitivity analysis. Accordingly the findings were not dependent on all included studies. The prevalence of wasting varied between 23.29(16.85–29.74) [32] and 25.95(19.34–32.52) [34] after deletion of a single study (S3 Fig).

Subjectively the funnel plot indicated symmetrical distributions which indicate the absence of publication bias. The Egger’s regression test- also revealed the absence of publication bias; P-value was 0.068 (S4 Fig).

Stunting

Prevalence of stunting among HIV positive children. Most of the studies (n = 18) have reported the prevalence of stunting among HIV positive children. The prevalence of stunting was ranged from 13% [27] to 71.8% [39]. The pooled prevalence of stunting among HIV positive children in East Africa using a random-effects model analysis was found to be 49.68% (95%CI; 42.59–56.77; I2 = 99.0%; p<0.001) (Fig 10).

Fig 10

Forest plot shows the pooled prevalence of stunting in East Africa, from January 2008-December 2019.

Subgroup analysis of the prevalence of stunting among HIV positive children in Eastern Africa. Using country, study design, and year of publication as criteria subgroup analysis was done. Accordingly, the prevalence of stunting among HIV positive children was found to be 51.63% in Ethiopia, 38.59% in Tanzania, 48.21% in Uganda, and 28.60% in Kenya (Fig 11 and Table 4). Based on the study design, the prevalence of under-weight among HIV positive children was found to be 46.16% in cross-sectional studies and 56.73% in cohort studies (Fig 12 and Table 4). The prevalence of stunting among HIV positive children was found to be 54.44% from studies conducted from January 2008-December 2014, while it was 40.11% from studies conducted from 2015–2019 (Fig 13 and Table 4).

Fig 11

Forest plot shows the pooled prevalence of stunting by country in East Africa, from January 2008-December 2019.

Table 4

Summery of subgroup analysis of the prevalence of stunting among HIV positive children in Eastern Africa by country, design and year of publication, from January 2008-December 2019.

Variables	Characteristics	Pooled prevalence, %(95% CI)	I2, (P-value)
By country	Ethiopia	51.63(34.68–68.59)	98.9%(<0.001)
	Tanzania	48.21(36.52–59.91)	99.2%(<0.001)
	Uganda	56.81(27.61–86.02)	99.3%(<0.001)
	Kenya	28.60(26.74–30.46)	-
By study design	Cross-sectional	46.16(37.21–55.11)	98.8% (<0.001)
	Cohort	56.73(43.68–69.77)	99.3%(<0.001)
By year of publication	2008–2014	54.44(47.20–61.68)	98.8% (<0.001)
	2015–2019	40.11(25.93–54.30)	98.6%(<0.001)

Fig 12

Forest plot shows the pooled prevalence of stunting by year of publication in East Africa, from January 2008-December 2019.

Fig 13

Forest plot shows the pooled prevalence of stunting by study design in East Africa, from January 2008-December 2019.

Sensitivity analysis

To assess the influence of individual study on the pooled prevalence of stunting in Eastern Africa we employed a sensitivity analysis. Accordingly the findings were not dependent on all included studies. The prevalence of stunting varied between 48.3(41.27–55.44) [39] and 51.8(45.07–58.62) [27] after deletion of a single study (S5 Fig).

Subjectively the funnel plot indicated symmetrical distributions which indicate the absence of publication bias. The Egger’s regression test- also revealed the absence of publication bias; P-value was 0.068 (S6 Fig).

Discussion

Based on this systematic review and meta-analysis, it was found that the pooled prevalence of underweight in eastern Africa is 41%. This result is higher than the study conducted among HIV positive children, in Nigeria (12.1%), Cameroon (20.5%, 37.8%) and, and Burkina Faso (31%) [46-49] respectively. But this result is lower compared to large scale study conducted in southern Africa(47.3%) [50]. The discrepancy might be due to the difference in number of study participants across the studies.

The sub group analysis based on country revealed that, the pooled prevalence of under-weight among HIV positive children was found to be 49.67% in Ethiopia, followed by 42.00% in Rwanda. The result is higher compared to large scale DHS study in sub Saharan Africa, which accounts 31.2% in Ethiopia and 18.5% in Rwanda respectively [51], and EDHS 2109 mini report which accounts overall 21% [52]. Based on the study design, the pooled prevalence of under-weight among HIV positive children was 39.33% in cross-sectional studies and 44.87% in cohort studies respectively. This may be due to cohort studies apply strict follow-up trend of the patients; through this they can record more reliable reports of the patients overall character. The pooled prevalence of underweight on the studies conducted from (2015–2019) found to be increased (43.68%) compared to the studies conducted from January 2008-2014(40.88%). This indicates that underweight is still an alarming issue among HIV positive children’s in East Africa.

The pooled prevalence of wasting among HIV positive children in East Africa found to be 24.65% (95%CI; 18.34–30.95). This result is higher compared to the study conducted in central and West African countries (16%) [9], the study conducted by Pendal et al in Cameroon(18.4%) [49], and large scale study conducted in southern Africa(21.3%) [50]. The discrepancy might be due to the emphasis given by the government as well as stakeholders of the area regarding the effects of HIV/AIDS on child growth and development.

Regarding sub group analysis by country the prevalence of wasting is higher in Tanzania (29%) followed by Ethiopia (24.94%). This result is higher compared to the data reported by Ethiopian Demographic Health Survey (EDHS), 2019 mini report which accounted 7% of overall children wasted [52]. This shows that these two countries needs great emphasis to decrease the burden of acute under-nutrition due to HIV infection; and it is better to invite governmental and non-governmental organizations regarding nutritional support to HIV-infected children at ART initiation. The prevalence of wasting among HIV positive children in studies conducted by follow up were found to be higher compared to cross-sectional once.

The pooled prevalence of stunting among HIV positive children in East Africa found to be 49.68% (95%CI; 42.59–56.77). This result is higher compared to large scale study conducted on children with HIV positive in Central and West African (33%) HIV care programmes supported by the Growing up Programme in 2011 [9]. But this study is lower than the study conducted in southern Africa, which accounts (61.1%) of HIV positive children were chronically under nourished. This difference might be due to the action of non-governmental organizations on providing child nutrition compared to our study area.

The sub group analysis result based on country shows, greater than half (51.63%) of HIV positive children’s in Ethiopia found to be stunted followed by nearly half (48.21%) of HIV positive children’s in Uganda are under this scheme. This result is higher compared the data reported by mini EDHS, 2019 accounted (37%) [52], and large scale DHS study conducted in sub-Saharan countries, which accounted 26.2% in Ethiopia and 38.2% in Rwanda [51]. The inconsistency between results might be due to difference number and geographical area of study participants. This result calls the integration of nutritional support for HIV positive children and early initiation of ART to loosen the burden of chronic under nutrition in East African Countries.

The relationship between nutrition and HIV infection is very complex and is modified by factors such as nutritional status, including wasting or obesity, and micronutrient deficiencies along with HIV disease stage. Starting assessment, counseling, and education regarding nutrition shortly after HIV diagnosis is imperative. Good nutrition has been proven to increase resistance to infection and disease and improves energy. Severe malnutrition in HIV-infected persons is recognized as the “wasting syndrome,” defined by the Centers for Disease Control and Prevention (CDC) as a body weight loss equal to or greater than 10% with associated fatigue, fever, and diarrhea unexplained by another cause [53].

HIV positive children are the most vulnerable group for underweight, wasting and stunting among and need more medical and research attention [54].

Conclusion

The findings of this review results revealed a higher prevalence of under-nutrition among HIV positive children in East Africa. Despite the country level variations of child under-nutrition in East Africa, still it is high in all aspects compared to the studies from other parts of Africa. It is recommended that further systematic review and meta-analysis need to be conducted on magnitude of malnutrition among HIV positive children in Sub-Saharan Africa as a whole.

Strength and limitations

As strength the authors used a standardized JBI quality assessment checklist and the included studies were low risk of bias. Moreover, we employed subgroup analysis based on study country, study design, and year of publication and sensitivity analysis to identify the small study effect and the risk of heterogeneity. Nevertheless, there are a few limitations to consider in the present study. First, due to the cross-sectional design, the observed results cannot be interpreted as causal. Second, the self-reported measures of variables are subject to measurement, self-report, social desirability, and recall biases. Third, publication bias may occur because all grey literature may not be included and language bias; since all included studies are published in English only. Forth, since only HIV positive children were taken as a study subjects it is difficult to present the result comparing with HIV negative children.

Recommendations

Special attention and efforts to reduce the burden of under-nutrion in HIV positive children should be applied in East Africa. Health professionals working with HIV positive children should routinely screen and manage under nutrition (underweight, wasting and stunting). Policy makers should incorporate strategies regarding prevention, screening and management of under nutrition in management of HIV/AIDS. Parents of HIV positive children should improve their feeding practice so as to prevent under nutrition.

Hence, nutritional attention is needed for children living with HIV/AIDS and at the time of ART initiation. Future researchers should conduct comparative studies on nutritional status between HIV positive and negative children so that meta-analysis of those comparative studies is recommended by authors of this study.

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Search strategy used for one of the databases.

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Quality appraisal result of included studies in East Africa, from January 2000-December 2019.

Using Joanna Briggs Institute (JBI) quality appraisal checklist [16].

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Forest plot showing the sensitivity analysis of the prevalence of under-weight among HIV positive children in East Africa, from January 2008-December 2019.

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Publication bias of the prevalence of under-weight among HIV positive children in East Africa, from January 2008-December 2019.

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Sensitivity analysis of the pooled prevalence of wasting in East Africa, from January 2008-December 2019.

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Publication bias of the pooled prevalence of wasting in East Africa, from January 2008-December 2019.

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Sensitivity analysis for the pooled prevalence of stunting in East Africa, from January 2008-December 2019.

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Publication bias the pooled prevalence of stunting in East Africa, from January 2008-December 2019.

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29 Jul 2020

PONE-D-20-09693

Magnitude of underweight, wasting and stunting among HIV positive children in East Africa: a systematic review and meta-analysis

PLOS ONE

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2. We noticed you have some minor occurrence of overlapping text with the following previous publications, which needs to be addressed:

Rose AM, Hall CS, Martinez-Alier NAetiology and management of malnutrition in HIV-positive children Archives of Disease in Childhood 2014;99:546-551.

Eyasu Desta Menamo, 2014, Impact of Household Food Insecurity on Adherence to Antiretroviral Therapy (ART) among Urban PLHIV, Hamburg, Bedey Media GmbH, https://www.anchor-publishing.com/document/276651

Gabriel Anabwani, Peter Navario, Nutrition and HIV/AIDS in sub-Saharan Africa: An overview, Nutrition, Volume 21, Issue 1, 2005, Pages 96-99, ISSN 0899-9007, https://doi.org/10.1016/j.nut.2004.09.013. (http://www.sciencedirect.com/science/article/pii/S0899900704002254)

Byron, E., Gillespie, S., & Nangami, M. (2008). Integrating Nutrition Security with Treatment of People Living with HIV: Lessons from Kenya. Food and Nutrition Bulletin, 29(2), 87–97. https://doi.org/10.1177/156482650802900202

Trehan I, O'Hare BA, Phiri A, Heikens GT. Challenges in the Management of HIV-Infected Malnourished Children in Sub-Saharan Africa. AIDS Res Treat. 2012;2012:790786. doi:10.1155/2012/790786

Beletew, B., Mengesha, A., Wudu, M. et al. Prevalence of neonatal hypothermia and its associated factors in East Africa: a systematic review and meta-analysis. BMC Pediatr 20, 148 (2020). https://doi.org/10.1186/s12887-020-02024-w

The text that needs to be addressed involves the Background section.

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Reviewers' comments:

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Comments to the Author

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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: Yes

Reviewer #2: Partly

**********

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?

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Reviewer #1: Yes

Reviewer #2: No

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5. Review Comments to the Author

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Reviewer #1: Authors wrote a very interesting manuscript on an important issue. Congratulations.

Only some suggestions:

1.Introduction: well wrote

2. Methods: "The search date was December 30/2019" is in yellow please remove the color

3. Results, Figure and Tables: I appreciate a lot

4. Discussion and Conclusion: if you can improve your discussion with some items:

- the definition on Children at risk. underweight, wasting and stunting among HIV positive children are the most vulnerable group and need more medical and research attention

(Marotta C, Di Gennaro F, Pizzol D, et al. The At Risk Child Clinic (ARCC): 3 Years of Health Activities in Support of the Most Vulnerable Children in Beira, Mozambique. Int J Environ Res Public Health. 2018;15(7):1350").

- The central role of task shifting to sharing experience and best practice

(Marotta C, Giaquinto C, Di Gennaro F, et al. Pathways of care for HIV infected children in Beira, Mozambique: pre-post intervention study to assess impact of task shifting. BMC Public Health. 2018;18(1):703. Published 2018 Jun 7.)

Reviewer #2: The first time you use an abbreviation, please spell its and then use the abbreviation (i.e. SAM, HIV)

Abstract

method: who HIV condition is not mentioned?

Results: why in the abstract do you go in deep regarding the period (2008-2014/ 2015-2019) and no data on malnutrition on HIV negative patients are reported?

Background

About the definition of under-nutrition (as part of malnutrition) authors should refer to WHO definition that is not that reported

If the authors focused the review in East Africa, the background should be focused also in East and not in sub-Saharan Africa (especially considering that they are suggesting a further review on Sub-saharan)

the whole background is quite confused with a mix of epidemiological data and possible explanation of interaction between HIV and malnutrition: please reorganise.

Methods

The Review question “What is the pooled prevalence of under-weight, wasting and stunting in East Africa context?” has no reference on HIV

The search strategy again does not contain the HIV term

Results

- “A total of 3094 studies were identified; 2050 from PubMed, 12 from Cochrane Library, 1010 from Google Scholar and 22 from other 120 sources. After duplication removed, a total of 970 articles remained” Are authors saying that PubMed database had more than 1000 duplicates?

Discussion

authors should discuss the mutual relationship between HIV and nutrition

why authors divided studies before and after 2014? They should discuss their choice

Authors should provide data on nutrition status among HIV negative children in the same context

Author should provide limitations and strength of this study (those provided are not enough especially limitations)

which clinical, political and social implications have these results?

English editing required

**********

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Reviewer #1: Yes: Francesco Di Gennaro

Reviewer #2: No

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8 Aug 2020

Date: Jul 29 2020 08:52AM

To: "PLOS ONE" plosone@plos.org

From: "Biruk Beletew" birukkelemb@plos.com

Subject: Submitting Revision manuscript [PONE-D-20-09693]

Magnitude of underweight, wasting and stunting among HIV positive children in East Africa: a systematic review and meta-analysis

Claudia Marotta

Academic Editor

PLOS ONE

Dear Editor and Reviewers we appreciate the careful feedback on our manuscript. Since we have agreed with all points you raised we believe we have carefully amended the paper as per your point of view. We described these changes in detail by point by point response below.

Editor Comment: 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

Author response: we have amended the manuscript as per the PLOS ONE's style requirements using the PLOS ONE style templates as a guide.

Editor Comment: 2. We noticed you have some minor occurrence of overlapping text with the following previous publications, which needs to be addressed:

Rose AM, Hall CS, Martinez-Alier NAetiology and management of malnutrition in HIV-positive children Archives of Disease in Childhood 2014;99:546-551.

Eyasu Desta Menamo, 2014, Impact of Household Food Insecurity on Adherence to Antiretroviral Therapy (ART) among Urban PLHIV, Hamburg, Bedey Media GmbH, https://www.anchor-publishing.com/document/276651

Gabriel Anabwani, Peter Navario, Nutrition and HIV/AIDS in sub-Saharan Africa: An overview, Nutrition, Volume 21, Issue 1, 2005, Pages 96-99, ISSN 0899-9007, https://doi.org/10.1016/j.nut.2004.09.013. (http://www.sciencedirect.com/science/article/pii/S0899900704002254)

Byron, E., Gillespie, S., & Nangami, M. (2008). Integrating Nutrition Security with Treatment of People Living with HIV: Lessons from Kenya. Food and Nutrition Bulletin, 29(2), 87–97. https://doi.org/10.1177/156482650802900202

Trehan I, O'Hare BA, Phiri A, Heikens GT. Challenges in the Management of HIV-Infected Malnourished Children in Sub-Saharan Africa. AIDS Res Treat. 2012;2012:790786. doi:10.1155/2012/790786

Beletew, B., Mengesha, A., Wudu, M. et al. Prevalence of neonatal hypothermia and its associated factors in East Africa: a systematic review and meta-analysis. BMC Pediatr 20, 148 (2020). https://doi.org/10.1186/s12887-020-02024-w

The text that needs to be addressed involves the Background section.

In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed.

Author response: we have paraphrased the sentences which have textual overlaps. In addition we put sentences in quotation when we take others idea. Moreover, we cited those references we taken idea from.

Editor Comment: 3. Thank you for including your funding statement; "no". Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution.

Author response: The authors received no specific funding for this work

Editor Comment: 4. Thank you for including your competing interests statement; "no". Please complete your Competing Interests on the online submission form to state any Competing Interests. If you have no competing interests, please state "The authors have declared that no competing interests exist.", as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now

Author response: The authors have declared that no competing interests exist

Editor Comment: 5. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found.

Author response: All relevant data are within the paper and its Supporting information files

Editor Comment: Dear Authors, I appreciate your manuscript, but need major revisions.

Following reviewer suggestions you can improve your paper.

Author response: thank you again for your constructive comments and for your optimism

Response to Reviewers

To Reviewer 1 (Francesco Di Gennaro)

Reviewer comment 1: Authors wrote a very interesting manuscript on an important issue. Congratulations.

Only some suggestions:

Authors’ response: thank you again for your constructive comments and for your optimism

Reviewer comment 1.Introduction: well wrote

Reviewer comment 2. Methods: "The search date was December 30/2019" is in yellow please remove the color

Authors’ response: remove as recommended

Reviewer comment 3. Results, Figure and Tables: I appreciate a lot

Authors’ response: thank you very much

Reviewer comment 4. Discussion and Conclusion: if you can improve your discussion with some items:

- the definition on Children at risk. underweight, wasting and stunting among HIV positive children are the most vulnerable group and need more medical and research attention

(Marotta C, Di Gennaro F, Pizzol D, et al. The At Risk Child Clinic (ARCC): 3 Years of Health Activities in Support of the Most Vulnerable Children in Beira, Mozambique. Int J Environ Res Public Health. 2018;15(7):1350").

- The central role of task shifting to sharing experience and best practice

(Marotta C, Giaquinto C, Di Gennaro F, et al. Pathways of care for HIV infected children in Beira, Mozambique: pre-post intervention study to assess impact of task shifting. BMC Public Health. 2018;18(1):703. Published 2018 Jun 7.)

Authors’ response: we really thank you for supplying us such sources for discussion and conclusion. We have amended these sections as per your recommendation and cited the references.

To Reviewer 2

Reviewer comment: The first time you use an abbreviation, please spell its and then use the abbreviation (i.e. SAM, HIV)

Authors’ response: we used extended form of all abbreviations at their first use as per your recommendation.

Abstract

Reviewer comment: method: who HIV condition is not mentioned?

Authors’ response: among HIV positive children in East Africa

Reviewer comment: Results: why in the abstract do you go in deep regarding the period (2008-2014/ 2015-2019) and no data on malnutrition on HIV negative patients are reported?

Authors’ response: We have revised the method in the abstract removing unnecessary details as per your recommendation. Regarding data on malnutrition on HIV negative patients, all the included studies have done on HIV positive patients. As a result we haven’t extracted data on malnutrition among HIV negative patients since the study population of included studies are HIV positive children.

Background

Reviewer comment: About the definition of under-nutrition (as part of malnutrition) authors should refer to WHO definition that is not that reported

Authors’ response: we have incorporated WHO definition of under-nutrition (as part of malnutrition) as “According to WHO malnutrition, in all its forms, includes under-nutrition (wasting, stunting, underweight), inadequate vitamins or minerals, overweight, obesity, and resulting diet-related non communicable diseases(1, 2).”

Reviewer comment: If the authors focused the review in East Africa, the background should be focused also in East and not in sub-Saharan Africa (especially considering that they are suggesting a further review on Sub-saharan)

the whole background is quite confused with a mix of epidemiological data and possible explanation of interaction between HIV and malnutrition: please reorganise.

Authors’ response: we paraphrased the background as per your comment. We were trying to show the burden from global to local (global – Africa-Sub-Saharan-East Africa) since we have been commented to write it as such. To address your comment we have added data in Eas Africa context.

Reviewer comment: Methods

The Review question “What is the pooled prevalence of under-weight, wasting and stunting in East Africa context?” has no reference on HIV

Authors’ response: we have amended the research question considering your comment as “What is the pooled prevalence of under-weight, wasting and stunting among HIV positive children in East Africa context?”

Reviewer comment: The search strategy again does not contain the HIV term

Authors’ response: Sorry it was typo error, we missed HIV and AIDS during write up of the manuscript. However we used those terms during searching. Now we have revised the search strategy including the term HIV and AIDS as we actually searched.

Results

Reviewer comment: - “A total of 3094 studies were identified; 2050 from PubMed, 12 from Cochrane Library, 1010 from Google Scholar and 22 from other 120 sources. After duplication removed, a total of 970 articles remained” Are authors saying that PubMed database had more than 1000 duplicates?

Authors’ response: the duplicates are not only PubMed database rather the duplicates are from all databases. After collecting studies from all database in endnote library we DEduplicated (removed duplicated studies) in the endnote itself using the following steps. First Edit- preferences-- duplicate –tick all boxes containing author ,year, title……-Apply then –Ok.

Then we gone to reference-Find Duplicate –then we compared the duplicate side by side. Finally we removed duplicates.

Discussion

Reviewer comment: authors should discuss the mutual relationship between HIV and nutrition

Authors’ response: we have revised the discussion as per your and the other reviewers comment. The relationship between HIV and nutrition discussed at the last paragraph of the discussion.

Reviewer comment: why authors divided studies before and after 2014? They should discuss their choice

Authors’ response: we want to assess the trend and the number of studies before and after 2014 is almost balanced to compare the change in magnitude with period changes.

Reviewer comment: Authors should provide data on nutrition status among HIV negative children in the same context

Authors’ response: study subjects of all included studies were HIV positive children. As a result we assessed the pooled nutritional status of HIV positive children. As you said it would be helpful if comparative studies are performed and meta-analysis of those comparative studies is recommended by authors of this study. We have included this in the limitation of the study section of the manuscript.

Reviewer comment: Author should provide limitations and strength of this study (those provided are not enough especially limitations)

Authors’ response: We have now expanded the limitations of the study as per your recommendation as “there are a few limitations to consider in the present study. First, due to the cross-sectional design, the observed results cannot be interpreted as causal. Second, the self-reported measures of variables are subject to measurement, self-report, social desirability, and recall biases. Third, publication bias may occur because all grey literature may not be included and language bias; since all included studies are published in English only. Forth, since only HIV positive children were taken as a study subjects it is difficult to present the result comparing with HIV negative children.”

Reviewer comment: which clinical, political and social implications have these results?

Authors’ response: we have included clinical, political and social implications of the study. “Health professionals working with HIV positive children should routinely screen and manage under nutrition (underweight, wasting and stunting) (clinical implication). Policy makers should incorporate strategies regarding prevention, screening and management of under nutrition in management of HIV/AIDS (political implication). Parents of HIV positive children should improve their feeding practice so as to prevent under nutrition (social implication).”

Reviewer comment: English editing required

Authors’ response: We have consulted native English-speaking colleagues and they have helped editing the paper. We (all authors) have also edited it through repetitive checking and online grammar editor.

Submitted filename: Final response to comments.docx

Click here for additional data file.

17 Aug 2020

Magnitude of underweight, wasting and stunting among HIV positive children in East Africa: a systematic review and meta-analysis

PONE-D-20-09693R1

Dear Dr. Biruk Beletew,

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.

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Kind regards,

Claudia Marotta

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Dear Authors,

you have written a very interesting article

Congratulations

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. 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: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. 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

**********

5. 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: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Authors improved their manuscript. the interaction between authors and reviewers was effective and useful in order to improve the manuscript and give the scientific community a very relevant article on a highly topical issue. I think that can be accepted

Reviewer #2: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (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: Yes: Francesco Di Gennaro

Reviewer #2: No

8 Sep 2020

PONE-D-20-09693R1

Magnitude of underweight, wasting and stunting among HIV positive children in East Africa: a systematic review and meta-analysis

Dear Dr. Abate:

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

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