Background
Viral hepatitis constitutes a global health burden. Previous studies have affirmed a considerable morbidity and mortality from both acute infections and chronic complications including chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). More than one million people die each year from hepatitis C virus and hepatitis B virus infections. Chronic HBV infection affects over 350 million people worldwide while 150 million people have chronic HCV infection [
1]. On the other hand, the global burden of Human Immunodeficiency Virus (HIV) in 2016 was 0.8% among adults, around 30% of them do not know that they are infected [
2]. Co-infection of HBV/HCV and HIV is characterized by more rapid progression of liver diseases; including accelerated fibrosis, cirrhosis, and HCC [
3]. These viruses share the main transmission routs as they are blood borne pathogens. Transmission occurs from patient to patient via unsafe sexual practices in HIV and HBV while it’s rare in HCV or vertically during pregnancy from mother to child. The viruses can be transmitted from patients to health care personnel via contaminated instruments or accidental needle-stick or sharp injuries [
3‐
5]. Onwards transmission of these viruses could be related to several reasons including: missing opportunities for prevention, lack of awareness about their prevalence and prevention, misdiagnosis, absence of medical care and poor health outcomes in infected people [
3‐
5].
Data exist concerning the epidemiology of HBV, HCV and HIV in several study populations in Sudan. Several studies have provided estimates of the prevalence measures of the three viruses among pregnant women, blood donors and hemodialysis patients as these populations have their impact in estimating the burden of both the wide prevalence among whole population and the prevalence among populations at risk. Chaabna and colleagues have recently (2016) published a systematic review and meta-analysis only for HCV prevalence in Sudan among other neighboring countries. However, although the included studies have been assessed for the risk of bias in their study, all studies were included in the quantitative analysis to estimate the pooled prevalence of the virus antibodies [
6].
The aim of this study was to provide a systematic review and meta-analysis of the results of prevalence studies of the three viruses in different populations and in distinct geographical regions, which will help in determining the population distribution of the viruses and the association of the three infections - if any, contribute in planning national strategies for containment and awareness raising campaigns as well as designing specific preventive measures.
Discussion
The current evidence regarding prevalence of HIV, HBV and HCV infections among general population in Sudan is in need of enforcement. Determining prevalence estimates for all three viruses is crucial for establishing appropriate country specific strategies regarding prevention, diagnosis, and containment. Forty nine studies of seroprevalence targeting the three viruses were - for the first time - quantitatively analyzed to better determine the burden of these infections in the country.
HIV surveillance in Sudan in particular has been described to be of good function according to the assessment of the quality of HIV surveillance in low and middle-income countries [
37]. All included studies determined HIV antibodies prevalence range of 0 to 18.3% among different study populations, three studies concluded a prevalence more than 3% - which is the threshold of HIV infection to be considered as high [
38], however, meta-analysis showed overall pooled prevalence of 1%. This general prevalence estimate is low when compared to the prevalence reported from some neighboring countries; as it was estimated in South Sudan as 3.4%, and Djibouti as 2.1%, data from Somalia indicate almost similar HIV prevalence as 1.1% [
39].
.This result does not agree to the international estimates of HIV in 2011 as they indicate HIV prevalence of 0.5% among adults in Sudan [
40]. However, the fact that this international estimate was almost six years ago is needed to be considered.
HIV pooled prevalence among pregnant women in Sudan was estimated to be 0.4%, which is higher when compared to prevalence data among pregnant women in Morocco (0.2%), and Iran (zero prevalence) [
39]. The pooled prevalence of HIV among female sex workers is showed to be 0.8% according to the national study conducted in fourteen States in Sudan by Elhadi and colleagues [
10]. United States reported prevalence rates among the same population to be from 0.3% up to 32.1% according to the recently (2016) published systematic review, the pooled prevalence was 17.3% (95% CI 13.5–21.9%) [
41]. Moreover, HIV prevalence ranged between 5.4 and 7.4% among Female Sex Workers in Iran [
42].
Only one study conducted at Kassala, Eastern Sudan in 2012 provided HIV prevalence rate among TB patients, prevalence was determined as 18.3% [
16]. This finding is alarming as it showed a high burden of HIV among TB patients in Sudan, as this rate is higher than many known prevalence rates; South Sudan reported a rate of 14.7%, followed by Djibouti 11.3%, Somalia 8.2%, Iran 3.8%, Yemen 1.6%, Morocco 0.8%, 0.4% in Saudi Arabia and zero was reported in both Palestine and Jordan [
39]. However, the fact that the study conducted in Kassala only had 109 TB participants underestimate the significant of this finding.
For HBV, four studies out of the fourteen studies reported prevalence higher than 8%, the pooled prevalence was 9.1% (95% CI 7.11 to 11.04). This prevalence rate is considered very high when compared to the most endemic country in Europe (Italy) which is reported to have prevalence rate of 5.9% as determined by a recently published systematic review in Europe (2016) [
43]. Moreover, according to WHO, this prevalence rate is high (≥8%). This prevalence is with an accordance with the reported prevalence in Africa (8.8%) in the recently published systematic review estimating the worldwide prevalence of hepatitis B virus infection [
44]. Moreover, the same systematic review indicated HBsAg prevalence in Sudan in particular as 9.8 (95% CI 9.03 to 10.54). On the other hand, this estimated prevalence is lower than the prevalence reported in Cameroon as the overall prevalence of HBV infection among 105,601 participants was determined as 11.2% (95% CI 9.7% to 12.8%) [
45].
The rates in the Middle East do vary as reported in the study of Gasim in 2013; a range from 0.6 to 8% in different countries was reported. 5.1% in Yemen, 4.2% in Saudi Arabia [
46], 3.6% in Algeria, 3.5% in Kuwait and Palestine, and 2.1% in Iran [
47].
Close to half of the studies (44%) estimated rate of HCV antibodies prevalence above 2% - the level at which anti-HCV prevalence rate is considered to be high [
48]. The overall pooled prevalence was 2.5% (95% CI 1.42 to 3.53). In developed countries like the US, prevalence of HCV infection has been estimated to be less than 2% [
49]. Even in the Middle East, two recent systematic reviews (2017, 2018) conducted in Iran indicated that the overall seroprevalence of HCV in the general population is 0.6% and 0.3%, respectively [
50,
51], 0.3% is reported in Bahrain, 0.4% in Oman, 1.1% in Qatar, 1.4% in Kuwait, 1.6% in Saudi Arabia and United Arab Emirates [
52] and it is estimated as 1% in Turkey [
53]. This may highlight that the level of HCV infection in Sudan may be relatively high. Nevertheless, this prevalence rate is lower when compared to several countries; recently published systematic reviews concluded HCV antibodies prevalence rate of 3% and 5.9% in Ghana and Italy, respectively [
43,
54]. Moreover, this prevalence rate is much lower when compared to the north neighboring country. Egypt is encountered with a huge HCV infection; it is reported to have a prevalence rate of 14.7% and 11.9% in recently published reviews (2016, 2018, respectively) [
55,
56].
The prevalence of HCV antibodies among pregnant women was estimated as 2.6%, this is considered lower when compared to the prevalence in Ghana 4.6% [
54] and relatively higher or comparable - to some extent - when reference is made to regions like the United States and Europe as general where prevalence of chronic HCV among this group has been estimated to be around 1–2.5% [
57]. The high HCV prevalence among pregnant women emphasizes the need for the adoption of a national program that includes HCV screening for pregnant women at risk [
57].
Only one study; Mudawi and colleagues’ study in 2014 retrieved 358 HIV-infected patients for HCV antibodies detection, the prevalence is estimated to be 1.7% [
31]. Compared to the pooled prevalence conducted in Ghana; this result is lower as it is determined as 2.8% (95% CI = 0.4–6%) [
54]. Furthermore, it is considered very low when compared to the prevalence measure reported in a very recent systematic review from Iran (2018) as HCV antibodies prevalence among HIV-infected patients was determined as 67% [
51]. However, it is to be noted that the systematic review conducted in Iran [
51] included 25 studies concerned of the prevalence of HCV antibodies among HIV-infected patients while only one study was included in the current systematic review.
Two included studies reported a prevalence rate ranges from 15.1 to 20% of OBI among HIV infected patients in Sudan [
31,
32]. This prevalence is higher when compared to the study of Rajat and colleagues in New York in 2013 as they reported a prevalence of 7% [
58]. Moreover, one study determined the prevalence of OBI among hemodialysis patients; group is known to be of high risk, the prevalence was determined as 3.3%, which is higher than a prevalence reported in a study conducted in Iran (0%) among 400 hemodialysis patients [
59]. Nevertheless, it is to be considered that included studies that addressed OBI is scarce to conduct a good quality assessment as only 5 out of 14 included studies concerned of the prevalence of HBV prevalence were provided OBI information. As a result; those differences may be attributed to demographics or sample size of participants.
Based on data reviewed and synthesized; there is no evidence for an HIV endemic in the general population of Sudan. However, both HBV and HCV seroprevalence rates are indicating otherwise. It is to be emphasized that studies toward determining prevalence measures among potential bridging populations (such as truck drivers and military personnel), tea sellers, Men who have Sex with Men (MSM), whip battered individuals and drug users were not included in this review. It is well known that these populations generally express risky behavior.
Several risk factors are to be analyzed to help in firstly understand the situation, then controlling the current critical burden of HBV and HCV consequently. The neighboring Egypt is confronted with a huge HCV infection problem, it has the highest prevalence of HCV in the world, and HCV infection and its complications are among the leading public health threats as Estes and colleagues recently reported (2015) [
60]. To complete the picture; since the 1990s, a new inflow of refugees started arriving in Egypt as a result of wars in the area, especially Sudan, Ethiopia, Eritrea and Somalia. According to official statistics, around 32,000 are granted refugee status in Egypt, among those, 73% are Sudanese [
61]. This situation is overcritical as not only Egyptian as well as Sudanese regular travelers may act as a possible threat of increasing HCV prevalence in Sudan, but both returning legal and illegal Sudanese refugees. For HBV; it is estimated that more than 6% (more than 5 millions) are HBsAg seropositive in Ethiopia and more than 22% (more than 2 millions) are HBsAg seropositive in South Sudan [
44]. Not controlled movements through the Sudanese borders of these countries will have its consequences in the national prevalence of HBV and HCV. Regarding another potential threat from inside; Sudan is reported among other countries in the region to have the highest number of needle-stick-acquired infections (due to mostly lack of sterilization). As a matter of fact, injection practices are reported to be much safer in several countries in the sub-Saharan Africa [
62].
Prevention against HBV infection can be adopted by increasing the distribution of the vaccine, especially in rural areas and in populations at risk. Moreover, when understanding that many people at risk may not know the possible routes of transmission of these viruses or behave in indifference manners due to lack of awareness or social stigma, it is recommended that people at risk should be vaccinated free of charge. Unfortunately, unlike HBV, vaccines for HIV and HCV infections are currently unavailable and therefore disruption of infection transmission would rely primarily on education to improve knowledge and awareness of the transmission dynamics of the viruses. To sum up, reducing the overall burden of HIV, HBV and HCV infections in Sudan will require new measures and national strategies and the recognition of the infections as one of the country’s priority issues.