Co-infection of HIV or HCV among HBsAg positive delivering mothers and its associated factors in governmental hospitals in Addis Ababa, Ethiopia: A cross-sectional study.

BACKGROUND: Blood borne viral infections such as Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human Immunodeficiency virus (HIV) cause substantial mortality and morbidity worldwide. Viral hepatitis during pregnancy is closely related to high risks of maternal and neonatal complications. In Ethiopia, only a little information is available on co-infection of HCV or HIV among Hepatitis B surface Antigen (HBsAg) positive pregnant mothers. Thus, the study aimed to determine HIV or HCV co-infection and associated risk factors among HBsAg positive delivering mothers.
METHOD: A health facility-based cross-sectional study was conducted in five governmental hospitals in Addis Ababa among 265 HBsAg positive delivering mothers in the year 2019 and 2020. A purposive sampling technique was used to select the study participants. Structured questionnaires and laboratory test results were used to collect the data. SPSS version 20 software was used to enter and analyze the data. Multivariable logistic regression was used to identify independent predictors of HIV or HCV co-infections.
RESULTS: Of the HBsAg positive delivering mothers, 9 (3.4%) and 3 (1.1%) were co-infected with HIV and HCV, respectively. None of them were with triplex infection. All of the socio-demographic characteristics were not significantly associated with both HIV and HCV co-infections. Mothers who had a history of sexually transmitted diseases (STDs) were 9.3 times more likely to have HBV-HIV co-infection (AOR = 9.3; 95% CI: 1.84-47.1). Mothers who had multiple sexual partners were 5.96 times more likely to have HIV co-infection (AOR = 5.96; 95% CI: 1.074-33.104). The odds of having HBV-HIV co-infection were 5.5 times higher among mothers who had a history of sharing shavers, razors, and earrings (AOR = 5.5;95% CI: 1.014-29.69). HCV co-infection was not significantly associated with any of the potential risk factors.
CONCLUSION: This dual infection rate of HBsAg positive delivering mother with HIV or HCV indicates that a substantial number of infants born in Ethiopia are at high risk of mother-to-child transmission (MTCT) of HBV, HIV, and HCV. Thus, all pregnant mothers need to be screened for HBV, HCV, and HIV during antenatal care, and also need implementation of prevention mechanisms of MTCT of these viral infections.

Background

Blood-borne viral infections such as HBV, HCV, and HIV cause substantial mortality and morbidity worldwide [1]. HBV infection occurs globally and constitutes a major public health problem. It infects over 20 million people globally every year, and there are around 350–400 million chronic carriers. More than 1.2 million deaths occur annually from HBV-related disease, making it the 10th leading cause of death, and the second most common cause of cancer deaths after tobacco, globally [2, 3]. HBV is an infectious disease, and it mainly transmits through mother-to-child, skin and mucous membrane infections by contaminated blood or body fluids, sexual contacts, and injection drug abuse. In addition, body tattooing, ear piercing, acupuncture, dialysis, and even using a syringe can be the source of infection [4]. HBV acquisition in adulthood commonly leads to acute resolved infection and immunity. But, perinatal/neonatal HBV infection more likely leads to chronic infection and its long-term disease risks [5].

Worldwide the prevalence of HCV infection in pregnant women and children has been estimated at 1–8% and 0.05–5%, respectively. Although, direct percutaneous inoculation is the most efficient mode of transmission of HCV, sexual, household, occupational, and vertical transmission may also be important [6-8]. MTCT of HCV increases to 4–25% times if the mother is also HIV positive [9].

Over the last decades, HIV infection has been one of the largest public health challenges, especially in low and middle-income countries [7]. Among the HIV positive patients, 2–4 million are estimated to have chronic HBV co-infection, and 4–5 million are co-infected with HCV [10]. HIV in pregnancy has adverse outcomes to maternal and fetal health and also to health workers at times of delivery [8].

HBV, HIV, and HCV have similarities in mode of transmission, but there are slight variations in the mode of transmission of these viruses [10-12]. Unlike HIV, HBV is not transmitted by breastfeeding, furthermore, child to child transmission is common for HBV but not for HIV. HBV is 50–100 times and 10 times more infectious than HIV and HCV, respectively [7]. The presence of higher concentrations of HBV in body fluids of persons with acute or chronic HBV infection than persons with HIV infection may cause HBV more infectious than HIV [10].

Co-infection of both HBV and HCV with HIV is associated with low CD4 count, accelerated liver disease progression, higher mortality, and MTCT of the viruses [7, 13–15]. Additionally, the progression rate and complications such as liver fibrosis, cirrhosis, end-stage liver disease, hepatocellular carcinoma (HCC), and mortality due to liver pathology arising from HBV infection are accelerated in patients with HIV co-infected patients than in patients with HBV infection alone [7, 16]. The clinical management of individuals co-infected with those viruses is challenging [17].

Available data suggest that, in resource-rich settings, approximately 10% of the HIV infected population have chronic HBV infection and around a third have chronic HCV infection [13, 16]. However, wide regional variations are observed with co-infection of HIV and HBV prevalence rates estimated to be 5–10% in areas such as North America, Europe and Australia compared to higher prevalence rates of 20–30% in areas such as Sub-Saharan Africa and Asia [16].

HBV/HIV co-infection rates of 12.9% [18] and 16% [19] were reported in people living with HIV in Cameroon. Besides, HBV/HIV co-infection rates of 11.8% [20] and 3.1% [21] were reported in pregnant mothers in Nigeria and South Africa, respectively. HCV/HIV co-infection rates of 0–33% were reported in pregnant mothers in Nigeria [22-24].

HBV/HIV co-infection rates of 19–40% were reported among pregnant mothers according to different studies conducted in Ethiopia [7, 25, 26]. One hundred percent of HCV positive pregnant mothers were also co-infected with HIV in Atat Hopsital, Southern, Ethiopia [7], and 2.9% of HCV/HIV co-infection was reported in pregnant mothers in East Wollega Zone, West Oromia, Ethiopia [9]. None of the pregnant mothers were co-infected with HBV and HCV [27, 28]. Several studies were conducted to determine co-infection of HBV/HIV, HBV/HCV, or HIV/HCV among the general population, general pregnant mothers, or HIV infected pregnant mothers [7, 13, 16, 18–28]. But, only a few studies have been conducted to determine co-infection of HIV or HCV and related risk factors among HBsAg positive delivering mothers globally and particularly in Ethiopia. The study aimed to assess the co-infection of these viruses among HBsAg positive delivering mothers and factors associated.

Methods and materials

Study design and period

A health facility based cross -sectional study design was employed from January 2019 to December 2020.

Study site and population

The study was conducted in Addis Ababa, the capital city of Ethiopia, with an estimated population of 4,591,983 million in 2019 [29]. The city has a higher population of female occupants compared to male occupants. In the city, there are 14 governmental hospitals and 103 health centers. In addition to this, there are many private hospitals and clinics which provide health service for the community of the city and patients from other parts of the country. The study was conducted in 5 of the governmental hospitals that have maternal and child health care services. The hospitals were Zewditu Memorial Hospital, Gandhi Memorial Hospital, Yekatit 12 Hospital Medical College, Armed force Hospital and Menelik II referral Hospital. The study population was HBsAg positive delivering mothers who attended in the selected governmental hospitals in Addis Ababa.

Sample size determination and sampling technique

A single population proportion formula was used. The sample size (n) of this study was determined using 22.2% of HBV/HIV co-infection in pregnant women in Addis Ababa [26] and giving any particular outcome to be with 5% marginal error and 95% confidence interval. Based on this assumption, the actual sample size for this study was computed using one sample population proportion formula indicated below

Where n = sample size, P = 0.222, d = 0.05(5% error of margin), z ∂/2 = 1.96 (standard normal probability for 95% CI) n = 265

After identifying governmental health facilities that have maternal and child health services, study health facilities were selected using the simple random sampling method. A purposive sampling technique was employed to select the study participants.

Eligibility

Inclusion criteria

All HBsAg positive delivering mothers who attended the selected hospitals in Addis Ababa and those who were volunteer to participate and give informed consent were included.

Exclusion criteria

Delivering mothers who had communication problems were excluded.

Study variables

Dependent variables

Co-infection of HIV among HBsAg positive delivering mothers and co-infection of HCV among HBsAg positive delivering mothers were the dependent variables.

Independent variables

Age, marital status, educational status, occupation, religion, and gravidity were socio-demographic independent variables. History of blood transfusion, STDs, abortion, surgical procedure, dental procedure, tattooing, ear piercings, nose piercing, home delivery by traditional birth attendants, multiple sexual partners, female circumcision, hospital admission, Presence of known hepatitis B infected person in a family, sharing shavers, razors, or earrings (at homes, beauty salon or barbershops), sharing toothbrushes, history of jaundice and contact with jaundice patients were the potential risk factor independent variables.

Data collection

To collect the data, questionnaires were developed by the study group in English and then translated to Amharic and back to English and interview was done by the data collectors. Laboratory test results of the blood samples were also used.

Data collection procedures and quality assurance

Delivering mothers who were diagnosed HBsAg positive during screening for HBV as routine antenatal care service were selected based on the status on their medical records. To get information on socio-demographic characteristics of the respondents and risk factors associated with co-infection of the viruses, pre-designed and pretested structured questionnaires were used. Ten midwives and medical laboratory technologists working in the selected hospitals were collected the data. Five supervisors with a second degree in health-related fields who recruited based on their experience in data collection and supervision participated. Two days of training were given on the objective of the study, obtaining consent, confidentiality of the information, and data collection procedures for the data collectors and supervisors. Questionnaires were carefully designed and pre-tested with individuals’ equivalent to 5% of the calculated sample size in Ras Desta Damtew Hospital. Questionnaires were slightly adjusted after pretested results show a lack of clarity. To determine the co-infection of the viruses, 5 ml of venous blood was collected based on the standard collection procedure and placed in ethylene-diamine-tetra-acetic acid (EDTA) tubes. These tubes were labelled with unique identification number and processed at the time of collection. The supervisors and the principal investigator supervised the data collection process.

Laboratory procedures

The blood samples taken from the individuals were centrifuged at 3000 revolutions per minute (RPM) for at least 10 minutes at room temperature. Then the plasma was tested for HBsAg (to re-check the status) and anti-HCV to determine HCV infection using separated rapid test Cassettes (Nantong diagnosis biotechnology co.Ltd P.R.china), which have specificity and sensitivity of greater than 99%.Testing was done following the manufacturer’s protocol. The HIV status of the delivering mothers was used from the antenatal care records since the test is performed on a routine basis.

Data management and analysis

The generated data was cleaned, coded, and uploaded into a computer using SPSS version 20.0 statistical software for analysis and interpretation. Descriptive values were expressed as the frequency, percentage, and mean ± standard deviation (SD). Logistic regression analysis was implemented to explore and determine the relationship of predictors on outcome variables. Variables significant at p <0.25 with the dependent variable were selected for multivariable analysis. Odds ratio with 95% confidence level was computed, and a significant association was declared at p <0.05.

Ethical consideration

Ethical clearance and approval were obtained from the Institutional Review Board of Aklilu Lemma Institute of Pathobiology, Addis Ababa University, and the Addis Ababa Health Bureau. Permission to carry out the study was obtained from the health facilities. After explaining the purpose, written informed consent was obtained from the delivering mothers. Moreover, confidentiality was assured for all the information provided, and the personal identifiers were not included in questionnaires. Results were reported to physicians for treatment management and prevention of MTCT of these viral infections.

Results

Socio-demographic characteristics of the study participants

A total of 265 HBsAg positive delivering mothers who attended governmental hospitals in Addis Ababa were included. The mean age of the study participants was 28.04 years with a SD of 4.62. The majority of the delivering mothers (43.1%) were in the age group of 25–29 years. Most (92.5%) of the delivering mothers were married. About 45.3% of the mothers were housewives, followed by 19.6% who were private employees and 17.7% who were government employees. Respondents were predominantly Orthodox Christians (71.7%) followed by Muslims (16.6%) and Protestants (9.8%). More than half (60%) were multigravida mothers (Table 1).

Table 1

Socio-demographic characteristics of HBsAg positive delivering mothers in governmental hospitals in Addis Ababa, 2019–2020.

Variable	Category	Number	Percentage
Age	<20	4	1.5
	20–24	61	23
	25–29	115	43.4
	30–34	60	22.6
	>35	25	9.4
Marital status	Married	245	92.5
	Single	12	4.5
	Divorced	8	3
Educational status	No formal education	28	10.6
	Primary level (1–8)	98	37
	Secondary level (9–12)	75	28.3
	College diploma and above	64	24.2
Occupation	Government employee	47	17.7
	Private employee	52	19.6
	Self- employee	27	10.2
	House wife	120	45.3
	Others	19	7.2
Religion	Orthodox Christian	190	71.7
	Muslim	44	16.6
	Protestant	26	9.8
	Others	5	1.9
Gravidity	Primigravida	106	40
	Multigravida	159	60

Prevalence of HIV co-infection among HBsAg positive delivering mothers

Out of the 265 HBsAg positive delivering mothers, 9 (3.4%) were co-infected with HIV. Of those, 77.8% were married and multigravida mothers, and 66.7% were between25-29 years old and orthodox Christians. There were no significant differences in HIV co-infection prevalence among all socio-demographic characteristics of the study participants (Table 2).

Table 2

Socio-demographic characteristics and HIV co-infection among HBsAg positive delivering mothers in governmental hospitals in Addis Ababa, 2019–2020.

Variable	Category	HIV status		COR (95%CI)	P value
		Positive (9)	Negative (256)
		N (%)	N (%)
Age	<20	0	4 (1.6)	1.39 (9.658–2.951)	0.386
	20–24	2 (22.2)	59 (23)
	25–29	6 (66.7)	109 (42.6)
	30–34	1 (11.1)	59 (23)
	>35	0	25 (9.8)
Marital status	Married	7 (77.8)	238 (93)	4.86 (.524–44.9)	0.164
	Single	1 (11.1)	11 (4.3)	1.57 (.084–29.4)	0.762
	Divorced	1 (11.1)	7 (2.7)	1
Educational status	Illiterate	2 (22.2)	26 (10.2)	.206 (0.18–2.38)	0.206
	Primary level	4 (44.4)	94 (36.7)	.373 (.041–3.42)	0.383
	Secondary level	2 (22.2)	73 (28.5)	.579 (.051–6.54)	0.659
	College diploma and above	1 (11.1)	63 (24.6)	1
Occupation	Government employee	1 (11.1)	46 (18)	5.75 (.488–67.8)	0.165
	Private employee	2 (22.2)	50 (19.5)	3.13 (.407–24.01)	0.273
	Self- employee	1 (11.1)	27 (10.5)	3.34 (.283–40.25)	0.336
	House wife	3 (33.3)	117 (45.7)	4.88 (.756–31.44)	0.096
	Others	2 (22.2)	16 (6.3)	1
Religion	Orthodox Christian	6 (66.7)	184 (71.9)	7.68 (.741–79.34)	0.088
	Muslim	1 (11.1)	43 (16.8)	10.75 (.560–206.4)	0.115
	Protestant	1 (11.1)	25 (9.8)	6.25 (.322–121.33)	0.226
	Others	1 (11.1)	4 (1.6)	1
Gravidity	Primigravida	2 (22.2)	104 (40.6)	2.39 (.488–11.757)	0.282
	Multigravida	7 (77.8)	152 (59.4)	1

Risk factors associated with HIV co-infection among HBsAg positive delivering mothers

Most (88.9%) of the HIV co-infected mothers had a history of ear piercings, and 44.4% of them had a history of STDs, previous abortion, and female circumcision. About 7 (77.8%) and 6 (66.7%) of them had a history of having multiple sexual partners and sharing shavers, razors or earrings, respectively. In multivariable analysis, history of STDs, having multiple sexual partners, and sharing shavers, razors or earrings were considered as potential risk factors for HIV co-infection. HBsAg positive delivering mothers who had a history of STDs were 9.3 times more likely to have HIV co-infection compared to their counterparts (AOR = 9.3; 95% CI: 1.84–47.1). Mothers who had multiple sexual partners were 5.96 times more likely to have HIV co-infection (AOR = 5.96; 95% CI: 1.074–33.104). The odds of having HBV/HIV co-infection were 5.5 times higher among mothers who had a history of sharing shavers, razors and earrings (at homes, beauty salon or barbershops) (AOR = 5.5;95%CI: 1.014–29.69) (Table 3).

Table 3

Factors associated with HIV co-infection among HBsAg positive delivering mothers in governmental hospitals in Addis Ababa, 2019–2020.

Variables	Category	HIV status		Bivariate analysis		Multivariate analysis
				P value	COR (95%CI)	AOR (95%CI)	P value
		Positive (9)	Negative (256)
		N (%)	N (%)
History of blood transfusion	Yes	1 (11.1)	16 (6.3)	0.565	1.88 (.221–15.93)	NA
	No	8 (88.9)	239 (93.7)		1
History of STDs	Yes	4 (44.4)	11(4.3)	0.000	17.82 (4.19–75.7)	9.3 (1.84–47.1)	0.007
	No	5 (55.6)	246 (95.7)		1	1
History of abortion	Yes	4 (44.4)	44 (17.2)	0.051	3.86 (.995–14.9)	2.69 (.539–13.4)	0.227
	No	5 (55.6)	212 (82.8)		1	1
History of surgical procedure	Yes	1 (11.1)	27 (10.6)	0.926	1.11 (.133–9.19)	NA
	No	8 (88.9)	230 (89.4)		1
History of dental procedure	Yes	1 (11.1)	37 (14.5)	0.779	.74 (.090–6.1)	NA
	No	8 (88.9)	219 (85.5)		1
History of tattooing	Yes	2 (22.2)	44 (17.2)	0.696	1.37 (.277–6.58)	NA
	No	7 (77.8)	212 (82.8)		1
History of ear piercings	Yes	8 (88.9)	249 (97.3)	0.186	.23 (.025–2.05)	0.26 (.019–3.51)	0.308
	No	1 (11.1)	7 (2.7)		1	1
History of nose piercing	Yes	1 (11.1)	12 (4.7)	0.397	2.54 (.294–21.99)	NA
	No	8 (88.9)	244 (95.3)		1
History of home delivery by traditional birth attendants	Yes	1 (11.1)	8 (3.1)	0.226	3.88 (.432–34.79)	0.83 (.042–16.7)	0.905
	No	8 (88.9)	248 (96.9)		1
History of having multiple sexual partners	Yes	7 (77.8)	67 (26.2)	0.005	5.53 (1.345–22.73)	5.96 (1.074–33.104)	0.041
	No	2 (22.2)	189 (73.8)		1
History of female circumcision	Yes	4 (44.4)	123 (48)	0.692	1.31 (.349–5.00)	NA
	No	5 (55.6)	133 (52)		1
History of hospital admission	Yes	2 (22.2)	38 (14.8)	0.552	1.69 (.338–8.46)	NA
	No	7 (77.8)	218 (85.2)		1
Presence of known hepatitis B infected person in a family	Yes	2 (22.2)	26 (10.2)	0.263	2.53 (.499–12.81)	NA
	No	7 (77.8)	230 (89.8)		1
History of sharing shavers, razors, or earrings (at homes, beauty salon or, barber shops)	Yes	6 (66.7)	72 (28.1)	0.022	5.21 (1.269–21.4)	5.5 (1.014–29.69)	0.048
	No	3 (33.3)	184(71.9)		1	1
History of sharing tooth brushes with others	Yes	1 (11.1)	10 (3.9)	0.311	3.08 (.350–27.00)	NA
	No	8 (88.9)	246 (96.1)		1
History of jaundice	Yes	1 (11.1)	12 (4.7)	0.397	2.54 (.294–21.99)	NA
	No	8 (88.9)	244 (95.3)		1
History of contact with jaundice patient	Yes	1 (11.1)	16 (6.3)	0.565	1.88 (.221–15.93)	NA
	No	8 (88.9)	240 (93.7)		1

CI: confidence interval

COR: Crude odds ratio, AOR: adjusted odds ratio

NA: not applicable refers to factors with p-value ≥0.25 at the bivariate analysis which were not considered in Multivariable analysis.

Prevalence of HCV co-infection among HBsAg positive delivering mothers

Only 3 (1.1%) of the HBsAg positive delivering mothers were co-infected with HCV. All of the HCV co-infected mothers were married. Two (66.7%) were between 25–29 years old, had a primary educational level, were orthodox Christians, and multigravida. However, none of the socio-demographic characteristics were significantly associated with co-infection of HCV (Table 4).

Table 4

Socio-demographic characteristics and HCV co-infection among HBsAg positive delivering mothers in governmental hospitals in Addis Ababa, 2019–2020.

Variable	Category	HCV status		P value
		Positive (3)	Negative (262)
		N (%)	N (%)
Age	<20	0	4 (1.5)	0.348
	20–24	0	61 (23.8)
	25–29	2 (66.7)	113 (44.1)
	30–34	0	60 (23.4)
	>35	1 (33.3)	24 (9.2)
Marital status	Married	3 (100)	245 (93.5)	0.999
	Single	0	12 (4.5)
	Divorced	0	8 (3.1)
Educational status	Illiterate	0	28 (10.9)	0.997
	Primary level	2 (66.7)	96 (37.5)
	Secondary level	0	75 (29.3)
	College diploma and above	1 (33.3)	63 (20)
Occupation	Government employee	0	47 (18.4)	0.888
	Private employee	1 (33.3)	51 (19.5)
	Self- employee	1 (33.3)	26 (9.9)
	House wife	1 (33.3)	119 (46.5)
	Others	0	19 (7.3)
Religion	Orthodox Christian	2 (66.7)	188 (73.4)	0.128
	Muslim	0	44 (17.2)
	Protestant	0	26 (9.9)
	Others	1 (33.3)	4 (1.5)
Gravidity	Primigravida	1 (33.3)	105 (40.1)	0.813
	Multigravida	2 (66.7)	157 (59.9)

Risk factors associated with HCV co-infection among HBsAg positive delivering mothers

All (100%) of the HCV co-infected delivering mothers had a history of ear piercings, and 2 (66.7%) had a history of tattooing, female circumcision, sharing shavers, razors, and earrings (at homes, beauty salon or, barber shops), and history of jaundice. About 1 (33.3%) had a history of blood transfusion, previous abortion, surgical procedure, dental procedure, multiple sexual partners, and contact with jaundice patients. Even though the history of blood transfusion, tattooing, home delivery by traditional birth attendants, jaundice, and contact with jaundice patients were candidate variables for multivariate analysis (P<0.25), none of them were significantly associated with HCV co-infection in multivariate analysis (Table 5).

Table 5

Statistical association of predictor variables with HCV co-infection among HBsAg positive delivering mothers in governmental hospitals in Addis Ababa, 2019–2020.

Variables	Category	HCV status		Bivariate analysis		Multivariate analysis
				P value	COR (95%CI)	AOR (95%CI)	P value
		Positive (3)	Negative (262)
		N (%)	N (%)
History of blood transfusion	Yes	1 (33.3)	16 (6.1)	0.103	7.68 (.661–89.36)	1.98 (.045–87.66)	0.722
	No	2 (66.7)	246 (93.9)		1
History of STDs	Yes	0	15 (5.7)
	No	3 (100)	247 (94.3)
History of abortion	Yes	1 (33.3)	48 (18.3)	0.526	2.23 (.198–15.08)	NA
	No	2 (66.7)	214 (81.7)		1
History of surgical procedure	Yes	1 (33.3)	27 (10.3)	0.236	4.35 (.382–49.6)
	No	2 (66.7)	235 (89.7)
History of dental procedure	Yes	1 (33.3)	37 (14.1)	0.369	3.04 (.269–34.38)	NA
	No	2 (66.7)	225 (85.9)		1
History of tattooing	Yes	2 (66.7)	42 (16)	0.057	10.48 (.929–118.2)	4.23 (.222–80.79)	0.338
	No	1 (33.3)	220 (84)		1
History of ear piercings	Yes	3 (100)	254 (96.9)
	No	0	8 (3.1)
History of nose piercing	Yes	0	13 (5)
	No	3 (100)	249 (95)
History of home delivery by traditional birth attendants	Yes	1 (33.3)	8 (3.0)	0.030	15.88(1.30–193.68)	10.92 (.179–665.05)	0.254
	No	2 (66.7)	254 (97)		1
History of having multiple sexual partners	Yes	1 (33.3)	73 (27.9)	0.834	1.3 (.116–14.5)	NA
	No	2 (66.7)	189 (72.1)		1
History of female circumcision	Yes	2 (66.7)	99 (37.8)	0.333	3.293 (.295–36.79)	NA
	No	1 (33.3)	163 (62.2)		1
History of hospital admission	Yes	1 (33.3)	38 (14.5)	0.382	2.95 (.261–33.3)	NA
	No	2 (66.7)	223 (85.5)		1
Presence of known hepatitis B infected person in a family	Yes	0	28 (10.7)
	No	3 (100)	234 (89.3)
History of sharing shavers, razors or earrings (at homes, beauty salon or, barber shops)	Yes	2 (66.7)	75 (28.6)	0.192	4.99(.445–55.32)	6.23(.292–133.3)	0.242
	No	1 (33.3)	187 (71.4)		1
History of sharing tooth brushes with others	Yes	0	11 (4.2)
	No	3 (100)	251 (95.8)
History of jaundice	Yes	2 (66.7)	11 (4.2)	0.002	45.64 (3.84–542.4)	25.16 (.979–646.82)	0.052
	No	1 (33.3)	251 (95.8)		1
History of contact with jaundice patient	Yes	1 (33.3)	16 (6.1)	0.103	7.69 (.661–89.37)	3.22 (.104–99.43)	0.504
	No	2 (66.7)	246 (93.9)

COR: crude odds ratio, AOR: Adjusted odds ratio

CI: confidence interval

NA: not applicable refers to factors with p-value ≥0.25 at the bivariate analysis which were not considered in Multivariable analysis.

HIV and HCV co-infection among the HBsAg positive delivering mothers

None of the HBsAg positive delivering mothers were co-infected with both HIV and HCV. None of them were with triplex infection (Table 6).

Table 6

HIV and HCV co-infection among HBsAg positive delivering mothers in governmental hospitals in Addis Ababa, 2019–2020.

HIV status	HCV status		p-value
	Positive	Negative
Positive	0	9	0.999
Negative	3	253

Discussion

In the present study, 3.4% and 1.1% of the HBsAg positive delivering mothers were co-infected with HIV and HCV, respectively. There is a scarcity of data on co-infection of HIV or HCV among HBsAg positive delivering mothers, and factors associated to compare with our findings. This is due to most of the previous studies were conducted on general or HIV-infected pregnant mothers.

The 3.4% HIV co-infection prevalence in our study is similar to studies in South Africa (3.1%) [21] and Rwanda (4.1%) [10], but it was smaller than HBV and HIV co-infection found among pregnant women in Europe (4.9%) [17], Nigeria (11.8%) [20], Bahir Dar city, Ethiopia (19%) [25], Atat Hospital, Southern Ethiopia (40%) [7] and Addis Ababa, Ethiopia (22.2%) [26]. In contrast it was higher than studies reported in Nigeria (0.24–2%) [23, 30], Southern Ethiopia (0.6%) [31] and 0% in eastern Ethiopia [32]. Furthermore, the 1.1% HCV co-infection in this study is similar to the study in Pakistan (1.3%) [33]. But it is lower than a study in west Iran (7.9%) [11] and higher than a study in Ghana (0.6%) [34]. None of the pregnant mothers were co-infected with HBV and HCV in studies in Ethiopia [28], Nigeria [23], Pakistan [27], and Sana’a, Yemen [35]. These variations might be due to differences in sampling method, laboratory tests used, and cultural and behavioural practices. Even though all of the socio-demographic characteristics were not significantly associated with both HIV and HCV co-infections, the majority (66.7%) of the co-infected mothers were in the age group of 25–29 years old. This is in line with the study conducted in Nigeria [30]. Seven (77.8%) of the HIV co-infected and 66.7% of the HCV co-infected mothers were multigravida. This is supported by studies from Rwanda [13] and Nigeria [6].

In our study, the majority of the potential risk factors were not significantly associated with HCV and HIV co-infections. This might be due to the low number of HBV/HIV and HBV/HCV co-infected study participants in our study, HBV being infectious than HIV and HCV, or early childhood transmission of HBV rather than shared routes of HIV, HCV, and HBV in adulthood [10, 21].

History of having STDs was significantly associated with HIV co-infection. This is in agreement with studies in Rwanda [10] and Brazil [36]. This might be due to STDs being able to increase the susceptibility to infection by both viruses through mucosal disruption, immune changes, and microenvironment effects on the genital tract. History of having multiple sexual partners was another significant risk factor for the HBV/HIV co-infection. This is in agreement with studies in Southern Ethiopia [7], Rwanda [10], and Brazil [36]. This might be due to both HIV and HBV are sexually transmitted infections, and the transmission risk increases with the number of sexual partners. The history of sharing shavers, razors, and earrings (at homes, beauty salons, or barbershops) was also another significant risk factor to HIV co-infection in our study. This is similar to a study in Indonesia, which identified that HIV transmission is possible due to lack of cleanliness of shaving equipment [37]. This might be due to HIV and other blood born infections can be transmitted via the use of sharing sharp material.

Conclusion and recommendation

Of the HBsAg positive delivering mothers, 3.4% and 1.1% were dual infected with HIV and HCV, respectively. This indicates that a substantial number of infants born in Ethiopia are at high risk of mother to child transmission of HBV, HIV and HCV. All of the socio-demographic characteristics of the study participants and the majority of the potential risk factors were not significantly associated with co-infection of the viruses. History of having STDs, having multiple sexual partners, and sharing of shavers, razors, and earrings were potential risk factors significantly associated with co-infection of HIV. All pregnant mothers need to be screened for HBV, HCV, and HIV during antenatal care and also need implementation of prevention mechanisms of MTCT of those viral infections. Furthermore, awareness creation on the transmission of those blood born viral infections is needed.

Strengths and limitations of the study

We included a large number of HBsAg positive delivering mothers than previous studies and, it can help to more determine the rate and potential risk factors of the co-infections. Confirmatory tests like ELISA and PCR were not used because of a lack of laboratory setup.

(DOCX)

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20 Jul 2021

PONE-D-21-13799

Co-infection of HIV or HCV among HBsAg positive delivering mothers and its associated factors in governmental hospitals in Addis Ababa, Ethiopia: a cross-sectional study

PLOS ONE

Dear Mebrihit Arefaine Tesfu,

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.

Reviewer #1: This study dertermines co-infection of HIV, or HCV and related risk factors among HBsAg positive delivering mothers in Ethiopia .HBV, HCV or HIV infection are major public health problems globally, with more than 1.2 million HBV infection-related deaths annually. Many previous studies have explored the co-infection of HBV-HIV, HBV-HCV and HIV-HCV among the general population, general pregnant mothers and pregnant mothers infected with HIV. This study chose another perspective to explore the co-infection of HIV or HCV in Ethiopian among HBsAg positive delivering pregnant mothers. and analyze its risk factors.

This research method is reasonable, the results are clear and complete, the conclusion shows the infection rate of the co-infection of HIV or HCV among HBsAg positive delivering mothers, and risk factors. The suggestions are provided for the clinical, if these viral infection rate of the babes from these delivering pregnant women can be given, that would be more complete and prefect.

Reviewer #2: Overall, I think the paper provides information needed in the field. It just needs some major editing and formatting to make it more presentable and easier to read for the general public.

General Comments

1. There are several parts in the tables where they need to be properly formatted. There are sections of the tables where spacing is off between numbers and percentages.

2. Fix abbreviations throughout the paper. When referring to Hepatitis B Virus, Hepatitis C Virus, and Human Immunodeficiency Virus, you should spell them out at first use in the paper and put the abbreviation in parentheses right after the first spelled out. Then use the abbreviation throughout the rest of the paper. This could also be done to abbreviate mother-to-child-transmission as MTCT.

3. Need to consistently use either "HBV-positive" or "HBV positive" throughout the paper. They are both used but one style of writing that needs to be used. This applies to HIV-positive, HCV-positive, and HBsAg-positive as well.

4. Be sure to indent the beginning of each paragraph throughout paper.

5. Check the formatting of reference list and in-text citations to ensure they adhere to journal guidelines.

6. Be sure to put in-text citations at the end of the sentence, not randomly in the middle.

Specific Comments:

I have attached the PDF of the manuscript with specific comments throughout so that all my comments can be easily seen.

Words that are marked through with a red line are ones I think should be deleted.

ACADEMIC EDITOR:

Typographic errors should be addressed

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Please attend to the many typographic errors

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #2: No

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Reviewer #1: Yes: Binyang Luo

Reviewer #2: Yes: Sarah Gayle Franklin

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Submitted filename: PONE-D-21-13799_reviewer (1).pdf

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6 Aug 2021

We appreciate the time and effort that the Editor and reviewers dedicated to providing feedback on our manuscript and are grateful for the insightful comments on and valuable improvements to our paper. We have incorporated almost all of the comments made by the Editor and reviewers. Those changes are highlighted within the revised manuscript.

Submitted filename: Respone to Reviewers.docx

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9 Jun 2022

24 Jul 2022

1. 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.

Author response: Thank you for pointing this out. We accepted the comment, and we have reviewed the reference list. We found that references number 27 and 29 were retracted papers and replaced with other current references. References number 3 and 24 were wrongly done and corrected in the revised manuscript.

2. The authors should provide key words at the end of the abstract (Reviewer 3)

Author response: Based on the submission guideline format of PLOS ONE journal, keywords should not be included at the end of the abstract. But, they incorporate during online submission. That is why we cannot provide keywords at the end of the abstract.

3. The authors should include the prevalence of cases with triplex infections.

Author response: we accepted the reviewers’ comment and included in the manuscript.

4. REFERENCES

Some references were wrongly done. Example, reference 24 should be: Duru MU, Aluyi HS, Anukam KC. Rapid screening for co-infection of HIV and HCV in pregnant women in Benin City, Edo State, Nigeria. Afr Health Sci. 2009 Sep;9(3):137-42. PMID: 20589140; PMCID: PMC2887022.

Author response: we accept the comment and corrected it.

Submitted filename: Response to reviewers.docx

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8 Aug 2022

Co-infection of HIV or HCV among HBsAg positive delivering mothers and its associated factors in governmental hospitals in Addis Ababa, Ethiopia: a cross-sectional study

PONE-D-21-13799R2

Dear Dr. Tesfu,

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Kind regards,

Hugh Cowley

Staff Editor

PLOS ONE

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When finalizing your manuscript for publication, please check the newly added reference 29 and ensure that enough information is given to enable a reader to locate with certainty the literature you are referencing. Please see our submission guidelines for guidance: https://journals.plos.org/plosone/s/submission-guidelines#loc-references.

Reviewers' comments:

17 Aug 2022

PONE-D-21-13799R2

Co-infection of HIV or HCV among HBsAg positive delivering mothers and its associated factors in governmental hospitals in Addis Ababa, Ethiopia: a cross-sectional study

Dear Dr. Tesfu:

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