You are viewing the site in preview mode

Skip to content

Advertisement

  • Research article
  • Open Access
  • Open Peer Review

Epidemiology of hepatitis B, C and D in Malawi: systematic review

BMC Infectious Diseases201818:516

https://doi.org/10.1186/s12879-018-3428-7

  • Received: 27 June 2018
  • Accepted: 1 October 2018
  • Published:
Open Peer Review reports

Abstract

Background

Viral hepatitis is an important public health issue in sub-Saharan Africa. Due to rising mortality from cirrhosis and hepatocellular carcinoma and limited implementation of screening and treatment programmes, it has been characterised as a neglected tropical disease. Synthesis of the existing evidence on the epidemiology of viral hepatitis B, C and D in Malawi is required to inform policy and identify research gaps.

Methods

We searched Pubmed, EMBASE and Scopus for studies reporting the epidemiology of viral hepatitis B, C and D in Malawi from 1990 to 2018. Articles reporting prevalence estimates were included provided they described details of participant selection, inclusion criteria and laboratory methods (detection of HBsAg, anti-HCV or anti-HDV antibody, HCV antigen or HCV RNA or HDV RNA). We assessed study quality using a prevalence assessment tool. Where appropriate, a pooled prevalence was calculated using a DerSimonian Laird random effects model.

Results

Searches identified 199 studies, 95 full text articles were reviewed and 19 articles were included. Hepatitis B surface antigen (HBsAg) seroprevalence was assessed in 14 general population cohorts. The pooled prevalence among adults was 8.1% (95% CI 6.1, 10.3). In 3 studies where HBsAg was stratified by HIV status, no effect of HIV on HBsAg prevalence was observed (OR 1.2 (95% CI: 0.8, 1.6, p = 0.80)). In a single study of HIV/HBV infected individuals, anti-hepatitis D antibody (anti-HDV) prevalence was low (1.5%). HCV antibody prevalence (anti-HCV) ranged from 0.7 to 18.0% among 12 cohorts in general populations. Among three studies which used PCR to confirm current infection, the pooled rate of HCV RNA confirmation among anti-HCV positive individuals was only 7.3% (95% CI: 0.0, 24.3).

Conclusions

Hepatitis B is highly prevalent in Malawi. There is a paucity of epidemiological data from rural areas where 85% of the population reside, and the Northern region. Priority research needs include large-scale representative community studies of HBV, HDV and HCV seroprevalence, assessment of children following introduction of the HBV vaccine in 2002, prevalence estimates of viral hepatitis among individuals with cirrhosis and HCC and data on HCV prevalence using PCR confirmation, to support a viral hepatitis strategy for Malawi.

Keywords

  • Epidemiology
  • Viral hepatitis
  • Hepatitis B
  • Hepatitis C
  • Hepatitis D
  • Malawi
  • Sub-Saharan Africa

Background

Viral hepatitis is the principal cause of liver cirrhosis and hepatocellular carcinoma (HCC) in sub-Saharan Africa [1]. Due to limited availability of screening and treatment programmes, it has been characterised as a neglected tropical disease [2]. In contrast with HIV, malaria and tuberculosis, where public health interventions have resulted in substantial reductions in mortality, viral hepatitis-associated mortality is rising: cirrhosis and HCC were the cause of an estimated 3.2% of adult deaths in 2005, rising to 4% in 2016 [3, 4]. In Malawi, the cirrhosis-associated mortality rate has been ranked in the top global decile [5]. Across Southern Africa, an estimated 50–64% of cases of HCC are attributable to viral hepatitis, and with limited treatment options outcomes are poor with an estimated annual mortality to incidence ratio of 96% [68]. HCC has been shown to occur in a younger age group among individuals in sub-Saharan Africa and in HBV-associated cases (relative to HCV-associated cases), contributing to increased disease impact [9, 10].

Data on the epidemiology of viral hepatitis are required to inform an effective public health response. In the Global Health Sector Strategy on Viral Hepatitis 2016–2021, the World Health Organisation (WHO) has identified the need to define the national disease burden and strategically target limited resources to counter the local epidemic. There is a WHO call for data on transmission and risk factors, to identify specific populations at risk and to quantify the health burden in terms of cirrhosis and hepatocellular carcinoma [11].

The Malawi Ministry of Health (MoH) has resolved to respond to viral hepatitis in a concerted and strategic manner. As part of the response, a National Viral Hepatitis Unit has been created in the MoH to guide the direction of policy and practice. In order to consolidate the current available evidence on epidemiology of viral hepatitis, identify the gaps in knowledge, practice and policy, we aimed to conduct a systematic review of all published epidemiological data on the prevalence of chronic hepatitis B, C and D in Malawi and identify further research needs.

Methods

Searches were performed in Pubmed, Scopus and EMBASE using the search terms Malawi AND (hepatitis or hepatitis B or HBV or HBsAg or hepatitis C or HCV or anti-HCV or HCV antibody or core HCV antigen or HCVcAg or HCV RNA or hepatitis D or HDV or anti-HD or anti-HDV or HDV IgG or HDV RNA or viral hepatitis). (Additional file 1: Table S1) Medical subject headings [MeSH] in Pubmed and EMBASE thesaurus tools were employed. Searches were restricted to publications between 1 Jan 1990 and 1 February 2018 with a search update on 22 June 18, to identify published data from the past 28 years (Fig. 1).
Fig. 1
Fig. 1

Flowchart of literature searches

Data were grouped into two categories: “general populations” which provided data from potentially representative community samples, pregnant women, or blood donors; “HIV positive populations” adults or women, or children receiving routine HIV care, and “special groups”, comprising populations likely to be unrepresentative of the general population such as medical inpatients, prisoners or medical students.

Studies reporting detection of hepatitis B surface antigen (HBsAg), or total or IgG anti-hepatitis delta antibody (anti-HDV) or HDV RNA among HBsAg positive people, or anti-hepatitis C antibody (anti-HCV), hepatitis C core antigen (HCVcAg) or HCV RNA were included, provided they presented details of selection and inclusion criteria and described the laboratory methods used.

Data extraction and quality assessment

We conducted this review in accordance with PRISMA guidelines [12]. We extracted details of study design, participant characteristics (age and gender distribution, population group), sampling method, dates, study locations, laboratory test used and prevalence estimates. A quality assessment tool for prevalence estimates was used and study quality was independently evaluated by two authors (AS, CM) with discordance resolved by discussion [13].

Statistical analysis

Confidence intervals for prevalence were calculated using the Wilson method. Pooled seroprevalence for hepatitis B was calculated with the DerSimonian-Laird random-effects model with Freeman-Tukey double arcsine transformation [14, 15]. A random effects model was applied due to anticipated heterogeneity. Study heterogeneity was assessed using the I2 statistic. Analyses were performed in Stata release 14.2 (College Station, TX, USA) using the metaprop package [16].

Results

The literature search identified 199 studies. Following removal of duplicates, 95 full-text articles were reviewed and 19 studies that reported epidemiological data on hepatitis B, C and D in diverse populations in Malawi were included (Fig. 1).

Description of included studies

The 19 included studies described a total of HBsAg seroprevalence data from 16 different cohorts that were general or HIV-positive populations (Table 1; Fig. 2) and three cohorts from specific unrepresentative subgroups (Table 2); hepatitis D antibody (anti-HDV) data was available from a single study (Table 3) and hepatitis C antibody (anti-HCV) data was available from 15 general or HIV-positive cohorts (Table 4; Fig. 4) and from four cohorts describing specific subgroups (Table 5). Fourteen of 18 studies were from urban centres.
Table 1

Hepatitis B surface antigen (HBsAg) seroprevalence in Malawi: published data from 1990 to 2018

Population

Ref

Year

Location

Laboratory method

Prevalence (n/total)

Prevalence (%), (95% CI)

General Populations

 Pregnant women

[20]

1989–1994

QECH, Blantyre

MONOLISA HBsAg ULTRA (Biorad)

0/70

0.0 (0.0, 5.2)

 Pregnant women, at delivery

[18]

1993–1995

Shire Valley

Bioelisa HBsAg (Biokit, S.A.)

12/100

12.0 (7.0, 19.8)

 Pregnant women

[20]

2004–2008

QECH, Health Centres Blantyre

MONOLISA HBsAg ULTRA (Biorad)

16/134

11.9 (7.5, 18.5)

 Male workers at sugar estate

[17]

1998

Nchalo

Auszyme monoclonal EIA (Abbott)

40/280

14.3 (10.7, 18.9)

 Community, rural adults

[20]

2001

Mwanza District

MONOLISA HBsAg ULTRA (Biorad)

7/98

7.1 (3.5, 14.0)

 Non-pregnant women (intravaginal MTZ gel RCT)

[20]

2003–2005

QECH, Blantyre

MONOLISA HBsAg ULTRA (Biorad)

8/137

5.8 (3.0, 11.1)

 HIV-negative partners in a serodiscordant couple

[19]

2007–2010

Blantyre Lilongwe

HBsAg ELISA NS

26/433

6.0 (4.1, 8.7)

 Blood donors

[21]

2001

Ntechu

HBsAg ELISA NS

13/159

8.2 (4.8, 13.5)

HIV-positive populations

 HIV-positive pregnant women, at delivery

[18]

1993–1995

Shire Valley

Bioelisa HBsAg (Biokit, S.A.)

8/50

16.0 (8.3, 28.5)

 HIV-positive pregnant women

[20]

2000–2004

QECH, Blantyre

MONOLISA HBsAg ULTRA (Biorad)

6/156

3.8 (1.8, 8.1)

 HIV-positive pregnant women

[22]

2004–2009

Lilongwe

Vitros Chemiluminescence Immunoassay (Ortho Clinical Diagnostics)

103/2049

5.0 (4.2, 6.1)

 HIV-positive pregnant women

[23]

2008–2009

Blantyre

Murex HBsAg Version 3 with Confirmatory Assay (Murex Biotech)

27/309

8.7 (6.1, 12.4)

 HIV positive: male workers at sugar estate

[17]

1998

Nchalo

Auszyme monoclonal EIA (Abbott)

32/189

16.9 (12.3, 22.9)

 HIV-positive adults

[24]

2005

QECH, Blantyre

Bioelisa HBsAg (Biokit, S.A.)

20/300

6.7 (4.4, 10.1)

 HIV positive adults, ART starters

[25]

2007–2009

QECH, Blantyre

Bioelisa HBsAg (Biokit, S.A.)

133/1117

11.9 (10.1, 13.9)

 HIV-positive adults in sero-discordant couple

[19]

2007–2010

Blantyre Lilongwe

HBsAg ELISA NS

26/432

6.0 (4.1, 8.7)

 HIV-infected children

[26]

2008–2010

Lilongwe

Genetic Systems HBsAg 3.0 (Bio-Rad)

2/91

2.2 (0.6, 7.7)

Abbreviations: QECH Queen Elizabeth Central Hospital, Blantyre. This is a tertiary referral hospital, MTZ metronidazole, RCT randomised controlled trial. Biorad: HBsAg ELISA, Biorad, Hercules, CA, USA; Bioelisa: HBsAg 3.0 Biokit SA Barcelona, Spain; Ortho Clinical Diagnositics: Raritan, New Jersey, United States: Siemens: ADVIA Centaur, Siemens, Munich, Germany; Abbott: Murex HBsAg, Abbott, Illinois, USA; HBsAg ELISA NS- manufacturer not specified

Fig. 2
Fig. 2

HBsAg seroprevalence in Malawi, published data 1990–2018

Table 2

HBsAg seroprevalence among special unrepresentative populations in Malawi: Published data from 1990 to 2018

Population

Ref

Year

Location

Laboratory method

Prevalence (n/total)

Prevalence (%, (95% CI))

Adult medical inpatients

[27]

2004

Medical ward, QECH, Blantyre

Determine HBsAg Rapid Test (Alere)

34/194

17.5 (12.8, 23.5)

Prisoners

[28]

2007

Chichiri Prison, Blantyre

HBsAg kit (Abbott)

5/164

3.0 (1.3, 6.9)

Medical students

[29]

2013

College of Medicine, Blantyre

SD Bioline Rapid Test (Alere)

0/89

0.0 (0.0, 4.9)

Abbreviations: QECH Queen Elizabeth Central Hospital, ART antiretroviral therapy

Table 3

Published data on hepatitis D seroprevalence in Malawi among HBsAg positive individuals

Population

Ref

Year

Location

Method

Prevalence (n/total)

Prevalence (%, (95% CI))

HIV-HBV infected adults

[30]

2007–2009

HIV clinic, QECH Blantyre

1. ETI-AB-DELTAK (Diasorin)

2/133

1.5 (0.4, 5.3)

2. HDV RNA PCR (in-house)

0/133

0.0 (0.0, 2.8)

Table 4

Published data on hepatitis C seroprevalence in Malawi

Population

Ref

Year

Location

Method

Prevalence (n/total)

Prevalence (%, (95% CI))

General Populations

 Pregnant women

[20]

1989–1994

QECH, Blantyre

Anti-HCV (Biorad)

2/70

2.9 (0.8, 9.8)

 Pregnant women, at delivery

[18]

1993–1995

Shire Valley

Ortho anti-HCV (Ortho Diagnostics)

18/100

18.0 (11.7, 26.7)

 Pregnant women

[20]

2004–2008

QECH, Health Centres Blantyre

Anti-HCV (Biorad)

8/138

5.8 (3.0, 11.0)

 Community, rural adults

[20]

2001

Mwanza District

Anti-HCV (Biorad)

9/99

9.0 (4.9, 16.4)

 Non-pregnant women (intravaginal MTZ gel RCT)

[20]

2003–2005

QECH, Blantyre

Anti-HCV (Biorad)

9/146

6.1 (3.3, 11.3)

 Male workers at sugar estate

[17]

1998

Nchalo

Ortho anti-HCV (Ortho Diagnostics)

35/279

10.0 (7.0, 14.1)

 Blood donors

[32]

1996

KCH, Lilongwe

Anti-HCV EIA (Roche)

Confirmed with Anti-HCV (Abbott)

4/100

4.0 (1.6, 9.8)

 Blood donors

[21]

2001

Ntechu

1. Murex anti-HCV

10/148

6.8 (3.7, 12.0)

2. HCV RNA by in-house PCR

1/140

0.7 (0.1, 3.9)

HIV positive populations

 HIV-positive pregnant women, at delivery

[18]

1993–1995

Shire Valley

Ortho anti-HCV (Ortho Diagnostics)

6/50

12.0 (5.6, 23.8)

 HIV-positive pregnant women

[23]

2008–2009

Blantyre

1. Innotest HCV Ab IV (Innogenetics),

8/309

2.6 (1.3, 5.0)

2. Versant HCV RNA 1.0 assay (Siemens)

1/309

0.3 (0.1, 1.8)

 HIV positive patients

[24]

2005

QECH, Blantyre

Monolisa HCV Ag-Ab (Biorad) confirmed with ADVIA Centaur anti-HCV) and InnoLIA HCV immunoassay (Innogenetics)

17/300

5.7 (3.6, 8.9)

 HIV-positive male workers at sugar estate

[17]

1998

Nchalo

Ortho anti-HCV Ab (Ortho Clinical Diagnostics)

28/280

10.0 (7.0, 14.1)

 HIV-positive pregnant women

[20]

2000–2004

QECH, Blantyre

Anti-HCV (Biorad)

8/148

5.4 (2.8, 10.3)

 HIV positive adults starting ART

[31]

2014–15

Lilongwe

1. HCV IgG Architect (Abbott)

5/227

2.2 (0.9, 5.1)

2. RealTime HCV RNA (Abbott)

0/227

0.0 (0.0, 1.7)

 HIV positive patients on ART for > 10 years

[33]

2014–16

Chiradzulu

OraQuick HCV Rapid antibody test (Orasure)

2/385

0.5 (0.1, 1.9)

Abbreviations: QECH Queen Elizabeth Central Hospital, HCV hepatitis C virus Biorad: Hercules, CA, USA; Ortho Clinical Diagnostics: Raritan, New Jersey, United States; Roche: Basel Switzerland; Abbott: Illinois, USA; Innogenetics: Ghent, Belgium; Siemens: Munich, Germany; Orasure: Bethlehem, Pennsylvania, United States

Table 5

Published data on hepatitis C seroprevalence among special unrepresentative populations in Malawi: Published data from 1990 to 2018

Population

Ref

Year

Location

Method

Prevalence (n/total)

Prevalence (%, (95% CI))

Prisoners

[28]

2007

Chichiri Prison, Blantyre

Anti-HCV (Biotec)

0/164

0.0 (0.0, 2.3)

Adult inpatients (Dermatology, Urology)

[32]

1996

KCH, Lilongwe

Anti-HCV EIA (Roche) Confirmed with Anti-HCV (Abbott)

13/333

3.9 (2.3, 6.6)

Adult medical inpatients

[27]

2004

Medical ward, QECH, Blantyre

HCV Ag/Ab (Monolisa, Biorad) confirmed with Immunoassay (Innogenetics)

9/202

4.5 (2.4, 8.2)

Malawian women and children with childhood malignancies

[34]

2006–10

QECH, Blantyre

HBV ELISA (MP Biomedicals)

Mothers: 2/418

0.5 (0.1, 1.7)

Confirmed by HCV BLOT (MP Biomedicals)

Children: 1/418

0.2 (0.0, 1.3)

Abbreviations: Biotec: Dorset, United Kingdom; Roche: Basel, Switzerland; Abbott: Illinois, USA; Innogenetics: Ghent, Belgium; MP Biomedicals: California, USAKCH Kamuzu Central Hospital, QECH Queen Elizabeth Central Hospital, HCV hepatitis C virus

Hepatitis B prevalence

HBsAg seroprevalence estimates ranged from 0.0 to 14.3% in general populations and 3.8 to 16.0% in HIV positive populations (Table 1). One small study reporting from HIV positive children aged 3 months - 15 years (median 36 months) reported seroprevalence of 2.2% [95% confidence interval (CI) 0.6, 7.7]. This study did not estimate HBV vaccine efficacy as the vaccine was introduced in Malawi in 2002 and both vaccinated and non-vaccinated cohorts were combined. Pooled estimates of HBsAg seroprevalence among adult general populations was 7.6% (95% CI 4.6, 11.2) and 8.5 (95% CI 5.7, 11.7) in HIV positive populations (Fig. 3). The overall pooled estimate of HBsAg seroprevalence in adults was 8.1% (95% CI 6.1, 10.3).
Fig. 3
Fig. 3

Forest plot of HBsAg prevalence in general and HIV-positive populations, Malawi 1990–2018

No significant difference in HBsAg prevalence was noted between HIV-positive and -negative populations (p = 0.74). The effect of HIV status on HBV seroprevalence was assessed directly in three studies, with a total of 1484 participants, that tested HBsAg prevalence, stratified by HIV status within the same population. These populations comprised male workers at a sugar factory (n = 469) [17], pregnant women recruited at delivery (n = 150) [18] and HIV positive and negative serodiscordant couples recruited for a randomised control trial of antiretroviral therapy for prevention of transmission (n = 865) [19]. Among the three groups, the odds ratio of HBsAg positivity among HIV positive compared to HIV negative individuals from within the same population was 1.2 (95% CI 0.8, 1.6, p = 0.80), indicating no evidence of association between HBV infection and HIV infection status. (Fig. 4).
Fig. 4
Fig. 4

Odds ratio of HBsAg seropositivity according to HIV status

Studies among three unrepresentative groups deemed at altered risk of HBV infection: (adult medical inpatients, prisoners and medical students) found HBsAg prevalence rates of 17.5%, 3.0% and 0% respectively (Table 2).

Hepatitis D prevalence

A single study was available reporting HDV prevalence among HIV/HBV co-infected individuals commencing ART in Blantyre [30] (Table 3). This demonstrated anti-HDV prevalence of 2/133 (1.5%) but none of the participants were HDV RNA PCR positive.

Hepatitis C prevalence

Among general populations, anti-HCV prevalence ranged from 0.7 to 18.0% and among HIV-positive populations from 0.0 to 12.0%. (Table 4, Fig. 5) Three studies confirmed active HCV infection using RNA PCR. These comprised a study of HIV-positive adults commencing ART in Lilongwe [31], a study of blood donors in Ntcheu [21] and a study of HIV-positive pregnant women in Blantyre [23]. In these studies, anti-HCV prevalence was 2.2, 6.8 and 2.6% respectively but HCV RNA PCR demonstrated active HCV prevalence of 0, 0.7 and 0.3% respectively, with a pooled rate of HCV RNA confirmation among anti-HCV positive participants of 7.3% (95% CI 0.0–24.3).
Fig. 5
Fig. 5

Prevalence of hepatitis C antibody: published data 1990–2018

Among four studies assessing HCV prevalence in unrepresentative special subgroups comprising: prisoners; medical inpatients in Blantyre and Lilongwe; and children with malignancies and their mothers, the prevalence of anti-HCV was 0; 3.9 and 4.5; 0.2 and 0.5% respectively (Table 5).

Discussion

In this systematic review, we have compiled the existing epidemiological evidence on HBV, HCV and HDV prevalence in Malawi and have highlighted a number of key findings and important knowledge gaps. Data from studies reporting from general and HIV-infected populations showed a pooled HBsAg seroprevalence estimate of 8.1% (95% CI 6.1, 10.3). This finding is in keeping with regional estimates from Mozambique (8.3%), Tanzania (7.2%) and Zambia (6.1%) [35]. Our study has benefitted from the inclusion of significantly more data than previous estimates for Malawi [35, 36]. We noted that available data were biased toward the two main urban centres of Lilongwe and Blantyre, that the Northern region was under-represented and that there were no nationally representative community survey data.

Hepatitis C antibody seroprevalence estimates ranged from 2.9 to 18% from general or HIV-infected populations. Among the three available studies that reported HCV RNA confirmation, only 7.3% of 676 participants with anti-HCV antibody were confirmed to have HCV RNA replication. This finding has been consistent with other cohorts across the region and highlights issues with using anti-HCV as the basis for obtaining epidemiological estimates in the absence of confirmatory testing [37]. Confirmation of anti-HCV results with PCR or core HCV antigen testing are required to obtain reliable prevalence estimates [38]. Accordingly, due to the paucity of studies reporting PCR data, a pooled HCV prevalence estimate was not provided in this review. Furthermore, an assessment of possible association between HCV, HBV and HIV infection was not possible based on the limited data. Based on the available evidence, it is likely that HCV prevalence is low in Malawi, and was below 1% in all studies using RNA confirmation [21, 23, 31], but larger representative samples employing confirmatory PCR testing are required to confirm these findings. Further work to establish whether false positive anti-HCV antibody tests or failure of HCV RNA assays to detect local HCV strains is required, particularly in view of the paucity of available genotypic HCV data from sub-Saharan Africa [39].

Only a single study reporting HDV prevalence was available, demonstrating a low rate of anti-HDV among HIV/HBV co-infected patients in Blantyre (1.5%), with none of the participants showing replication of HDV RNA by PCR. This finding is in keeping with available limited data demonstrating a low rate of HDV seroprevalence from Southern Africa relative to Central or West Africa, though the paucity of available data from the Southern Africa region should be noted [30]. Due to the rapid progression to fatal liver disease associated with HBV/HDV superinfection or co-infection, cross-sectional community estimates of HDV seroprevalence are unlikely to reliably estimate the true burden of disease caused by HDV. Studies of hospitalised patients with well-characterised liver disease are required and will facilitate the ascertainment of the attributable fraction of viral hepatitis to liver disease [40].

There are several limitations in this analysis, highlighted by our assessment of study quality (Additional file 2: Table S2). The epidemiological evidence presented in this study is drawn from predominantly small cohorts studies in diverse populations employing convenience sampling. A striking bias toward urban centres was observed with only four of 18 included studies drawn from rural areas, despite an estimated 85% of the Malawian population residing in rural areas [41]. There were no available data from the Northern region of Malawi, where 13% of the population live [41]. To overcome these issues of lack of nationally representative unbiased community data, the use of the demographic health survey using dried blood spot sampling represents a promising solution. Dried blood spots have excellent diagnostic performance relative to venous blood sampling for HBsAg and anti-HCV screening and this method has been recently recommended for large surveys by the WHO [38]. Use of dried blood spots for hepatitis D screening of the demographic health survey has recently been used in Burkina Faso [42], and represent an efficient method to obtain samples without requiring a cold chain or venepuncture.

The finding of lack of an association between hepatitis B seroprevalence and HIV status is in keeping with previous studies from sub-Saharan Africa [43]. This is likely due to distinct transmission epidemiology, with hepatitis B predominantly acquired perinatally or horizontally in early childhood, and HIV acquired predominantly during adolescence or adulthood by sexual transmission in sub-Saharan Africa. By contrast, recent evidence of incident transmission of HBV in HIV-infected adults has highlighted the risk of HBV acquisition in adulthood [44]. Hepatitis B vaccination is provided as a component of the pentavalent vaccine (also containing, diphtheria, tetanus, pertussis and Haemophilis influenzae type B) in the expanded programme of immunisation schedule for Malawian infants, provided at 6, 10 and 14 weeks since 2002. The Demographic Health Survey 2015–16 estimated 3-dose coverage of the vaccine of 93.0%, with consistently high coverage exceeding 90%, regardless of socioeconomic status or geographic location [45]. The WHO has recently proposed that gathering data on hepatitis B seroprevalence among a vaccinated cohort at 5 years of age is a priority in order to generate evidence on the efficacy of HBV vaccination programmes and this is a priority area for research highlighted by this review [46].

Conclusions

Hepatitis B is highly prevalent in Malawi with an estimated seroprevalence among the general population of 8.1%. HCV prevalence was below 1% in three general population cohorts that used nucleic amplification confirmatory testing. There is a need for representative unbiased community seroprevalence estimates of HBV, HDV and HCV prevalence. These should include confirmatory PCR testing to establish reliable HCV prevalence estimates. Future studies examining seroprevalence among community samples, with a particular focus on rural areas and the Northern region, are required. Assessment of the effectiveness of the hepatitis B vaccination programme introduced in 2002 and data on HDV prevalence among HBsAg positive individuals represent further research priorities. Prevalence estimates of viral hepatitis among people with well-characterised liver disease with cirrhosis and HCC are required to ascertain the attributable fraction and burden of disease. These data will help to support a viral hepatitis strategy for Malawi, facilitate the introduction of screening and treatment programmes for HBV and HCV and begin to reverse the current trend of increasing viral hepatitis-associated mortality.

Abbreviations

Anti-HCV: 

hepatitis C virus antibody

Anti-HDV: 

anti-hepatitis C virus antibody

ART: 

antiretroviral therapy

DNA: 

deoxyribonucleic acid

EIA: 

Enzyme immunoassay

HBsAg: 

hepatitis B surface antigen

HBV: 

hepatitis B virus

HCC: 

hepatocellular carcinoma

HCV: 

hepatitis C virus

HDV: 

hepatitis D virus

KCH: 

Kamuzu Central Hospital, Lilongwe, Malawi (National tertiary referral hospital)

MoH: 

Ministry of Health

PCR: 

polymerase chain reaction

QECH: 

Queen Elizabeth Central Hospital, Blantyre, Malawi (National tertiary referral hospital)

RNA: 

ribonucleic acid

WHO: 

World Health Organisation

Declarations

Funding

AS is supported by a Wellcome Trust Clinical PhD Fellowship, grant 109130/Z/15/Z. The funder had no role in the design of the study and collection, analysis, and interpretation of data nor in writing the manuscript.

Availability of data and materials

All data generated or analysed during this study are included in this published article.

Authors’ contributions

AS performed the literature searches, extracted the data, performed statistical analyses, wrote the manuscript, CM performed quality assessment of included articles, reviewed and revised the manuscript, DE, AMG and MG developed the concept and study design, reviewed and revised the manuscript and assisted in data analysis and interpretation. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Ethical approval was not required for this study as it is a systematic review of aggregate data from previously published studies.

Consent for publication

Not applicable.

Competing interests

The authors declare they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Malawi Liverpool Wellcome Trust Clinical Research Programme, Chichiri 3, PO Box 30096, Blantyre, Malawi
(2)
Institute of Infection and Global Health, University of Liverpool, Ronald Ross Building, 8 West Derby Street, Liverpool, L69 7BE, UK
(3)
HIV and AIDS Department, Malawi Ministry of Health, PO Box 30377, Lilongwe, Malawi
(4)
MRC Centre for Inflammation Research, The Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK

References

  1. Lemoine M, Thursz MR. Battlefield against hepatitis B infection and HCC in Africa. J Hepatol. 2017;66(3):645–54.View ArticleGoogle Scholar
  2. O’Hara GA, McNaughton AL, Maponga T, Jooste P, Ocama P, Chilengi R, Mokaya J, Liyayi MI, Wachira T, Gikungi DM, et al. Hepatitis B virus infection as a neglected tropical disease. PLoS Negl Trop Dis. 2017;11(10):e0005842.View ArticleGoogle Scholar
  3. Global Burden of Disease Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the global burden of disease study 2016. Lancet. 2017;390(10100):1151–210.View ArticleGoogle Scholar
  4. Global Burden of Disease Collaboratorative Network. Global Burden of Disease Study 2016 (GBD 2016) Results. Seattle: Institute for Health Metrics and Evaluation; 2017. http://ghdx.healthdata.org/gbd-results-tool Accessed 24 June 2018Google Scholar
  5. Mokdad AA, Lopez AD, Shahraz S, Lozano R, Mokdad AH, Stanaway J, Murray CJL, Naghavi M. Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis. BMC Med. 2014;12:145.View ArticleGoogle Scholar
  6. Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, Allen C, Al-Raddadi R, Alvis-Guzman N, Amoako Y, Artaman A, et al. The burden of primary liver Cancer and underlying etiologies from 1990 to 2015 at the global, regional, and National Level: results from the global burden of disease study 2015. JAMA Oncol. 2017;3(12):1683–91.View ArticleGoogle Scholar
  7. Parkin DM, Bray F, Ferlay J, Jemal A. Cancer in Africa 2012. Cancer Epidemiol Biomark Prev. 2014;23(6):953–66.View ArticleGoogle Scholar
  8. Yang JD, Mohamed EA, Aziz AO, Shousha HI, Hashem MB, Nabeel MM, Abdelmaksoud AH, Elbaz TM, Afihene MY, Duduyemi BM, et al. Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: a multicountry observational study from the Africa liver Cancer consortium. Lancet Gastroenterol Hepatol. 2017;2(2):103–11.View ArticleGoogle Scholar
  9. de Martel C, Maucort-Boulch D, Plummer M, Franceschi S. World-wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma. Hepatology. 2015;62(4):1190–200.View ArticleGoogle Scholar
  10. Yang JD, Gyedu A, Afihene MY, Duduyemi BM, Micah E, Kingham TP, Nyirenda M, Nkansah AA, Bandoh S, Duguru MJ, et al. Hepatocellular carcinoma occurs at an earlier age in Africans, particularly in association with chronic hepatitis B. Am J Gastroenterol. 2015;110(11):1629–31.View ArticleGoogle Scholar
  11. World Health Organisation. Global health sector strategy on viral hepatitis 2016–2021. Geneva: WHO; 2016.Google Scholar
  12. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.View ArticleGoogle Scholar
  13. Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. Int J Evid Based Healthc. 2015;13(3):147–53.View ArticleGoogle Scholar
  14. Freeman MF, Tukey JW. Transformations related to the angular and the square root. Ann Math Stat. 1950;21(4):607–11.View ArticleGoogle Scholar
  15. Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos T. Meta-analysis of prevalence. J Epidemiol Community Health. 2013;67(11):974–8.View ArticleGoogle Scholar
  16. Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata command to perform meta-analysis of binomial data. Archives Public Health. 2014;72(1):39.View ArticleGoogle Scholar
  17. Sutcliffe S, Taha TE, Kumwenda NI, Taylor E, Liomba GN. HIV-1 prevalence and herpes simplex virus 2, hepatitis C virus, and hepatitis B virus infections among male workers at a sugar estate in Malawi. J Acquir Immune Defic Syndr. 2002;31(1):90–7.View ArticleGoogle Scholar
  18. Ahmed SD, Cuevas LE, Brabin BJ, Kazembe P, Broadhead R, Verhoeff FH, Hart CA. Seroprevalence of hepatitis B and C and HIV in Malawian pregnant women. J Inf Secur. 1998;37(3):248–51.Google Scholar
  19. Greer AE, Ou SS, Wilson E, Piwowar-Manning E, Forman MS, McCauley M, Gamble T, Ruangyuttikarn C, Hosseinipour MC, Kumarasamy N, et al. Comparison of hepatitis B virus infection in HIV-infected and HIV-uninfected participants enrolled in a multinational clinical trial: HPTN 052. J Acquir Immune Defic Syndr. 2017;76(4):388–93.View ArticleGoogle Scholar
  20. Taha TE, Rusie LK, Labrique A, Nyirenda M, Soko D, Kamanga M, Kumwenda J, Farazadegan H, Nelson K, Kumwenda N. Seroprevalence for hepatitis E and other viral Hepatitides among diverse populations. Malawi Emerg Infect Dis. 2015;21(7):1174–82.View ArticleGoogle Scholar
  21. Candotti D, Mundy C, Kadewele G, Nkhoma W, Bates I, Allain JP. Serological and molecular screening for viruses in blood donors from Ntcheu, Malawi: high prevalence of HIV-1 subtype C and of markers of hepatitis B and C viruses. J Med Virol. 2001;65(1):1–5.View ArticleGoogle Scholar
  22. Chasela CS, Kourtis AP, Wall P, Drobeniuc J, King CC, Thai H, Teshale EH, Hosseinipour M, Ellington S, Codd MB, et al. Hepatitis B virus infection among HIV-infected pregnant women in Malawi and transmission to infants. J Hepatol. 2014;60(3):508–14.View ArticleGoogle Scholar
  23. Andreotti M, Pirillo MF, Liotta G, Jere H, Maulidi M, Sagno JB, Luhanga R, Amici R, Mancini MG, Gennaro E, et al. The impact of HBV or HCV infection in a cohort of HIV-infected pregnant women receiving a nevirapine-based antiretroviral regimen in Malawi. BMC Infect Dis. 2014;14:180.View ArticleGoogle Scholar
  24. Moore E, Beadsworth MB, Chaponda M, Mhango B, Faragher B, Njala J, Hofland HW, Davies J, Hart IJ, Beeching NJ, et al. Favourable one-year ART outcomes in adult Malawians with hepatitis B and C co-infection. J Inf Secur. 2010;61(2):155–63.Google Scholar
  25. Aoudjane S, Chaponda M, Gonzalez Del Castillo AA, O'Connor J, Noguera M, Beloukas A, Hopkins M, Khoo S, van Oosterhout JJ, Geretti AM. Hepatitis B virus sub-genotype A1 infection is characterized by high replication levels and rapid emergence of drug resistance in HIV-positive adults receiving first-line antiretroviral therapy in Malawi. Clin Infect Dis. 2014;59(11):1618–26.View ArticleGoogle Scholar
  26. Varo R, Chris Buck W, Kazembe PN, Phiri S, Andrianarimanana D, Weigel R. Seroprevalence of CMV, HSV-2 and HBV among HIV-infected Malawian children: a cross-sectional survey. J Trop Pediatr. 2016;62(3):220–6.View ArticleGoogle Scholar
  27. Nyirenda M, Beadsworth MB, Stephany P, Hart CA, Hart IJ, Munthali C, Beeching NJ, Zijlstra EE. Prevalence of infection with hepatitis B and C virus and coinfection with HIV in medical inpatients in Malawi. J Inf Secur. 2008;57(1):72–7.Google Scholar
  28. Chimphambano C, Komolafe I, Muula A. Prevalence of HIV, HepBsAg and Hep C antibodies among inmates in Chichiri prison, Blantyre. Malawi Malawi Med J. 2007;19(3):107–10.PubMedGoogle Scholar
  29. Chipetah F, Chirambo A, Billiat E, Shawa IT. Hepatitis B virus seroprevalence among Malawian medical students: a cross-sectional study. Malawi Med J. 2017;29(1):29–31.View ArticleGoogle Scholar
  30. Stockdale AJ, Chaponda M, Beloukas A, Phillips RO, Matthews PC, Papadimitropoulos A, King S, Bonnett L, Geretti AM. Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(10):e992–e1003.View ArticleGoogle Scholar
  31. Demir M, Phiri S, Kaiser R, Chaweza T, Neuhann F, Tweya H, Fatkenheuer G, Steffen HM. HIV/hepatitis C virus co-infection among adults beginning antiretroviral therapy, Malawi. Emerg Infect Dis. 2016;22(11):2018–20.View ArticleGoogle Scholar
  32. Maida MJ, Daly CC, Hoffman I, Cohen MS, Kumwenda M, Vernazza PL. Prevalence of hepatitis C infection in Malawi and lack of association with sexually transmitted diseases. Eur J Epidemiol. 2000;16(12):1183–4.View ArticleGoogle Scholar
  33. Loarec A, Carnimeo V, Maman D, Molfino L, Walter K, Nzomukunda Y, Muyindike W, Andrieux-Meyer I, Balkan S, Mwanga-Amumpaire J, et al. Low hepatitis C virus prevalence among human immunodeficiency virus+ individuals in Sub-Saharan Africa. J Hepatol. 2017;66(1):S270–S271.View ArticleGoogle Scholar
  34. Fox JM, Newton R, Bedaj M, Keding A, Molyneux E, Carpenter LM, Martin F, Mutalima N. Prevalence of hepatitis C virus in mothers and their children in Malawi. Tropical Med Int Health. 2015;20(5):638–42.View ArticleGoogle Scholar
  35. Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386(10003):1546–55.View ArticleGoogle Scholar
  36. Rao VB, Johari N, du Cros P, Messina J, Ford N, Cooke GS. Hepatitis C seroprevalence and HIV co-infection in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Infect Dis. 2015;15(7):819–24.View ArticleGoogle Scholar
  37. Sonderup MW, Afihene M, Ally R, Apica B, Awuku Y, Cunha L, Dusheiko G, Gogela N, Lohouès-Kouacou M-J, Lam P, et al. Hepatitis C in sub-Saharan Africa: the current status and recommendations for achieving elimination by 2030. Lancet Gastroenterol Hepatol. 2017;2(12):910–9.View ArticleGoogle Scholar
  38. World Health Organisation. Guidelines of hepatitis B and C testing. Geneva: WHO; 2017. http://www.who.int/hepatitis/publications/guidelines-hepatitis-c-b-testing/en/ Accessed 26 June 18Google Scholar
  39. Niebel M, Singer JB, Nickbakhsh S, Gifford RJ, Thomson EC. Hepatitis C and the absence of genomic data in low-income countries: a barrier on the road to elimination? Lancet Gastroenterol Hepatol. 2017;2(10):700–1.View ArticleGoogle Scholar
  40. Lempp FA, Ni Y, Urban S. Hepatitis delta virus: insights into a peculiar pathogen and novel treatment options. Nat Rev Gastroenterol Hepatol. 2016;13(10):580–9.View ArticleGoogle Scholar
  41. Government of Malawi. Population and housing census. Zomba: National Statistical Office; 2008.Google Scholar
  42. Tuaillon E, Kania D, Gordien E, Van de Perre P, Dujols P. Epidemiological data for hepatitis D in Africa. Lancet Glob Health. 2018;6(1):e33.View ArticleGoogle Scholar
  43. Matthews PC, Geretti AM, Goulder PJ, Klenerman P. Epidemiology and impact of HIV coinfection with hepatitis B and hepatitis C viruses in sub-Saharan Africa. J Clin Virol. 2014;61(1):20–33.View ArticleGoogle Scholar
  44. Seremba E, Ssempijja V, Kalibbala S, Gray RH, Wawer MJ, Nalugoda F, Casper C, Phipps W, Ocama P, Serwadda D, et al. Hepatitis B incidence and prevention with antiretroviral therapy among HIV-positive individuals in Uganda. AIDS. 2017;31(6):781–6.View ArticleGoogle Scholar
  45. Government of Malawi. Malawi demographic and health survey 2015–16. Zomba: National Statistical Office; 2017.Google Scholar
  46. World Health Organisation. World health statistics 2017: monitoring health for the sustainable development goals. Geneva: WHO; 2017.Google Scholar

Copyright

© The Author(s). 2018

Advertisement