A systematic review of the epidemiology of hepatitis A in Africa

Hepatitis A is a vaccine preventable disease (VPD) caused by the hepatitis A virus (HAV). The hepatitis A virus is transmitted from person-to-person through the faecal-oral route primarily by ingestion of contaminated food or water and/or contact with infectious persons [1, 2]. Poor hygiene and sanitation pose the greatest risk for HAV infection, particularly in Low and Middle-Income Countries (LMICs) [3]. Infection with HAV causes an immune response which is assessed by measurement of specific antibodies: immunoglobulin class M (IgM) anti-HAV antibodies and immunoglobin class G (IgG) anti-HAV antibodies [4]. Anti-HAV IgM antibodies are detectable following acute infection and antibody titres usually decline to zero within 3–6 months [5, 6]. In contrast, anti-HAV IgG antibodies appear within 2–3 months after infection and persist for a long period of time conferring protective immunity against future infections [2]. A majority of hepatitis A seroprevalence studies, therefore, often report anti-HAV IgG and not anti-HAV IgM seroprevalence data.

Common clinical symptoms of hepatitis A infection include jaundice, fever, malaise, anorexia, nausea and abdominal discomfort [1, 4]. Infection with HAV in early childhood is thought to be largely asymptomatic and results in the development of lifelong protective immunity [4]. In contrast, infection with HAV after early childhood is associated with an increased risk of symptomatic, acute hepatitis A infection [1, 7, 8]. The case fatality rate associated with acute hepatitis A in children and adults < 50 years old ranges from 0.3 to 0.6%, while the case fatality rate in adults ≥50 years old ranges from 1.8 to 5.4% [9]. The high costs associated with management of acute hepatitis A are well appreciated by healthcare providers. Hepatitis A patients typically miss several weeks of work or school and the costs of supportive medical care can be substantial [4]. Therefore, vaccination against hepatitis A has been found to be cost-effective in many LMICs and should be prioritized in settings where hepatitis A is a public health concern [10]. Routine hepatitis A vaccination policies can only be developed based on up-to-date and high-quality contextual evidence that includes the burden of the disease.

The World Health Organization (WHO) describes the epidemiology of hepatitis A according to HAV endemicity levels [2]. Endemicity is measured by HAV seroprevalence; i.e. the proportion of people in the population with anti-HAV IgG antibodies [11]. The levels of HAV endemicity are classified by the WHO as follows: high (≥ 90% IgG seroprevalence by 10 years of age), intermediate (≥ 50% IgG seroprevalence by 15 years of age, < 90% IgG seroprevalence by 10 years of age), and low (≥ 50% IgG seroprevalence by 30 years of age, < 50% IgG seroprevalence by 15 years of age) [2]. The latest global review of HAV endemicity was published in 2010 and included epidemiological data from 1990 to 2005. The review classifies Africa as a high HAV endemic region [12]. Since 2005, many African countries have made significant improvements in water, sanitation and developments in socio-economic status (SES). These improvements are likely to cause changes in the average age of first exposure and infection with HAV as well as in the prevalence of acute hepatitis A. Recent hepatitis A studies conducted in Africa, though few and far between, suggest that some regions on the continent could be experiencing a transition in hepatitis A epidemiology. Our aim in this review is to provide an up-to-date synthesis of hepatitis A epidemiology in Africa.

The WHO does not recommend routine vaccination against hepatitis A in high endemic settings [2]. As of 2018, no African country included routine hepatitis A vaccination as part of its’ Expanded Programme on Immunisation (EPI). The WHO recommendation is that countries should routinely collect and review local factors and epidemiological data needed to guide the development of evidence-based recommendations on hepatitis A vaccination [2]. To the best of our knowledge, an up-to-date, comprehensive synthesis of hepatitis A epidemiological data in Africa is lacking. Though there have been several primary studies on hepatitis A epidemiology published since 2005 in Africa, the review team is not aware of any recent publication that has synthesised data from this setting [13‐16]. The development of effective public health control strategies against hepatitis A require optimal characterisation of the disease epidemiology. Therefore, this systematic review aims to fill the existing knowledge gap to guide considerations of development of public health strategies to control hepatitis A in the region.

The initial database searches yielded 10,598 records, from which 4,334 duplicates were removed. No additional records were found when the search was updated in December 2018. A further 6,264 records were excluded following the screening of titles and abstracts (Fig. 1). The full-text of the remaining 121 records were screened, from which 30 records met the final inclusion criteria. A further two unpublished studies at the time of the search were obtained through personal communication with hepatitis A researchers [11, 21]. Since the time of reciept of these studies, they have since been published. Therefore, a total of 32 studies were included in this review. The included studies were conducted in 13 African countries, a majority of these being from the North, West and Southern regions of the continent (Fig. 2). Figure 2 displays the geographic location of 27 of the included studies conducted on the African continent. Five of the 32 included studies (not shown in Fig. 2) reported hepatitis A data from expatriate communities (adults and children) from the African continent, living in Europe and North America [22‐26].

Twenty-three of the included studies were cross-sectional studies (Table 2). A majority of the included studies were conducted in the public healthcare sectors of lower-middle income countries. Of the 32 included studies, 17 provided data on anti-HAV IgG alone (referred to hereon as HAV seroprevalence), 11 provided data on anti-HAV IgM alone (referred to hereon as IgM anti-HAV seroprevalence) and 4 studies provided data together for IgG anti-HAV and IgM anti-HAV seroprevalence. Our analyses categorize the included studies according to the population age-groups [children & adolescents (1 to 18 years of age), adults (> 18 years of age) and all ages (1 to 99 years of age)], of which children and adolescent populations were most commonly reported on (56% of included studies). Measurement of the anti-HAV antibodies was assessed using ELISA assays for both IgG and IgM positivity in all studies. Real time PCR (RT-PCR) was used in 4 studies, in addition to the ELISA assay (Table 3). Details on the assay detection limits were missing from all included studies.

This systematic review evaluated the epidemiology of hepatitis A in participants > 1 year of age in Africa. The main findings of the review include: 1) the reported HAV seroprevalence data suggests that Africa, as a whole, should not be considered as a high HAV endemic region; 2) the IgM anti-HAV seroprevalence data showed similar risk of acute hepatitis A infection among all age-groups; 3) South Africa could be experiencing a possible transition from high to intermediate HAV endemicity. The results of this review were limited due to lack of detailed age-grouped data from the included studies. Additionally, no included review reported data on the hospitalisation and case fatality rates or co-morbidities occurring with acute hepatitis A which did not allow for the objectives of the paper to be met fully.

Only 13 (24%) out of 54 countries in Africa contributed to the data synthesized in this review. Furthermore, the data included in this review was collected mainly in hospital settings as opposed to from community surveys. A recent study on trends of childhood immunisation research in Africa reported lack of hepatitis A research on the continent [53]. Based on these findings, we believe that more up-to-date research on hepatitis A epidemiology in Africa is needed and will be critical to generate evidence needed to re-think hepatitis A control strategies in the region.

Although limited, the HAV seroprevalence data in this review appear to meet the WHO’s definition of intermediate HAV endemic setting (< 90% IgG seroprevalence by 10 years of age and ≥ 50% IgG seroprevalence by 15 years of age) [54]. The reported HAV seroprevalence estimates for children and adolescents age-groups indicate that the presumed “natural immunisation” during the early childhood is not sufficient to imply high HAV endemicity for the entire continent. Secondly, the reported similarity of IgM anti-HAV seroprevalence among children and adolescents compared with adults was a surprising finding as we expected lower IgM anti-HAV seroprevalence in adults than children due to prior exposure in a high endemic setting. A recent study in China and conducted in a setting undergoing a hepatitis A epidemiological transition, adults aged 20 years and older showed higher disease incidence than children [55]. Thus, our findings corroborate the notion of a HAV epidemiological transition in the African region.

Current global recommendations on hepatitis A vaccination appear to take African countries as homogeneous settings [54]. Our review results showed a large spread in HAV seroprevalence rates as well as IgM anti-HAV seroprevalence rates across the continent. This indicates the heterogeneity of hepatitis A epidemiology, and highly likely, the epidemiology of other VPDs among African countries. For example, in South Africa where comprehensive dataset was available, we reported an increase in IgM anti-HAV seropositivity among all age groups from 2005 to 2015. These results indicate that South Africa is most likely transitioning from high to intermediate endemicity. Previous classifications of South Africa as a high endemic region have been based on limited data published between 1986 and 2002 [56]. This data showed variable HAV seroprevalence rates that were dependent on SES. High HAV seropositivity rates were reported in low SES groups, while high SES groups that were less represented in the data showed low HAV seropositivity rates. Given this and the gradual social economic improvements in South Africa since the collapse of apartheid, it is likely that the HAV epidemiological transition in South Africa has been taking place even before 2005. It would be irrational to extrapolate findings from South Africa to all other African countries as Hepatitis A epidemiology is highly influenced by economic as well as healthcare developments [57]. Our findings suggest that African countries with similar SES developments as South Africa should prioritize generating evidence to guide recommendations on introducing routine immunisation against the disease.

The results of this review must be interpreted with caution due to several limitations. Firstly, the included studies have significant sociocultural, economic and environmental diversity. Secondly, due to the fact that only 13 of 54 countries in Africa contributed to the data synthesized in this review, we were not able to present data for all sub-regions of the continent or by country income category. Thirdly, as data included in this review were collected mainly in hospital settings as opposed to from community surveys, we were unable to stratify our results to urban versus rural areas to assess whether hygiene and sanitation affect the current epidemiology of HAV in Africa. Lastly, although trends in publication of the immunisation research is growing, a lot of research work in Africa still remains unpublished and access to such information is limited [58]. Regardless of these limitations, it is noteworthy to mention that the majority of included studies focused on hepatitis A data in childhood and adolescent populations, which may attest to the anecdotal evidence that children and adolescents are increasingly at risk for acute hepatitis A infection in Africa.

The results of this paper may be an over-estimate of HAV seroprevalence for the general population in Africa as those seeking private healthcare services were not included in this review. Populations seeking private healthcare services are more likely to be of higher social economic status. Higher social economic populations have access to optimal sanitation and are likely to show lower HAV seroprevalence although some may be vaccinated against the disease [27]. Furthermore, the extent of HAV vaccine use in the private sector of Africa is unknown. Future research should include populations seeking both private and private healthcare. Measurement of both IgG and IgM as immunological outcomes should be incorporated in future studies as well as details of the assay detection limits used. Additional missing data such as morbidity, co-morbidity and mortality due to hepatitis A disease should be a research priority. Collectively, complete and high-quality hepatitis A epidemiology data would allow for better pooling of results and meta-analyses. The review team also encourages future studies to incorporate mathematical modelling where the data permits as such an approach could possibly assist health policy decision-makers to better design hepatitis A control strategies in Africa.

This systematic review aimed to generate up-to-date epidemiological data of hepatitis A in Africa with the aim of providing data to better inform hepatitis A public health control measures in the region. We successfully addressed the aim of the study although data on hospitalization, case fatality rates and co-morbidity was missing. With no current routine use of hepatitis A vaccines on the African continent, quality epidemiological data that is currently missing should be compiled and priority be given in re-assessing the current hepatitis A control strategies in the region to prevent possible disease outbreaks in the future.