Rosemary J. Burnett

Hepatitis B virus and human immunodeficiency virus co-infection in sub-Saharan Africa: a call for further investigation.

Abstract: A growing body of evidence indicates that human immunodeficiency virus (HIV)‐positive individuals are more likely to be infected with hepatitis B virus (HBV) than HIV‐negative individuals, possibly as a result of shared risk factors. There is also evidence that HIV‐positive individuals who are subsequently infected with HBV are more likely to become HBV chronic carriers, have a high HBV replication rate, and remain hepatitis Be antigen positive for a much longer period. In addition, it is evident that immunosuppression brought about by HIV infection may cause reactivation or reinfection in those previously exposed to HBV. Furthermore, HIV infection exacerbates liver disease in HBV co‐infected individuals, and there is an even greater risk of liver disease when HIV and HBV co‐infected patients are treated with highly active anti‐retroviral therapy (HAART). Complicating matters further, there have been several reports linking HIV infection to ‘sero‐silent’ HBV infections, which presents serious problems for diagnosis, prevention, and control. In sub‐Saharan Africa, where both HIV and HBV are endemic, little is known about the burden of co‐infection and the interaction between these two viruses. This paper reviews studies that have investigated HIV and HBV co‐infection in sub‐Saharan Africa, against a backdrop of what is currently known about the interactions between these two viruses.

The first five years of universal hepatitis B vaccination in South Africa: evidence for elimination of HBsAg carriage in under 5-year-olds

South Africa implemented a vaccine against hepatitis B virus (HBV) into the Expanded Programme on Immunisation (EPI) in April 1995. The HBV vaccine is given at 6, 10, and 14 weeks, in parallel with OPV, DTP and Hib vaccines. This study assessed the impact of universal childhood HBV vaccination programme in reducing HBsAg carriage, in the first five years (1995--1999) since its implementation. In parallel, we investigated the current burden of HBV infection in mothers of vaccinees and the adult general population. A total of 598 babies (mean age=23.3 months) who received 3 doses of 1.5 microg/0.5 ml Hepaccine-B (Cheil) were recruited from the Northern Province (one of the nine provinces in South Africa). HBsAg, anti-HBs, anti-HBc, HBeAg and anti-HBe were tested using the IMx or Axsym kits (Abbott Laboratories). PCR assays were performed following established protocols. The overall seroprotection rate (i.e. anti-HBs titre> or =10 mIU/ml) was 86.8% (519/598) in vaccinated babies, while 13.2% had anti-HBs levels<10 mIU/ml. Seroprotection rates and geometric mean titres (GMT) decreased significantly with increasing age, possibly reflecting waning anti-HBs titre over time. Total HBV exposure (positive for either HBsAg, anti-HBs, or anti-HBc) was 31.0% (58/187) in mothers of vaccinees and 40% (72/180) in the adult general population. HBsAg carrier rate was virtually similar in both groups (3.2% in mothers of vaccinees vs. 3.3% in the general population). Against this background, no vaccine failures resulting in HBsAg and HBV DNA positivity were seen in vaccinated babies, including 6 babies born to HBsAg positive carrier mothers (one carrier mother was positive for HBeAg and HBV DNA). However, 0.9% (5/582) babies, aged between 8--11 months, tested positive for anti-HBc, all of whom had anti-HBs titres>10 mIU/ml and were negative for HBV DNA. Anti-HBc positivity was probably maternal in origin, or may represent sub-clinical averted HBV infections. It can be concluded that the HBV vaccine is highly effective within the framework of the South African EPI and already shows a positive impact in the elimination of HBsAg carrier rate in children<5 years.

Increased detection of HBV DNA in HBsAg-positive and HBsAg-negative South African HIV/AIDS patients enrolling for highly active antiretroviral therapy at a tertiary hospital.

This retrospective study investigated the prevalence of hepatitis B virus (HBV) in 192 stored sera from human immunodeficiency virus (HIV) positive South African patients initiating antiretroviral therapy (ART), and explored the implications of HBV–HIV co‐infection on laboratory diagnosis of HBV. HBV serology (HBsAg, anti‐HBs and anti‐HBc) and nested HBV PCR assays targeting the HBV polymerase gene were performed, with HBV DNA positive samples being quantified with Cobas Taqman HBV test 48 assay (Roche Diagnostics). The study found that 63% (121/192) of patients had past or present HBV infection, and 40.6% (78/192) had detectable HBV DNA. Also, 22.9% (44/192) of patients were HBsAg positive and HBV DNA positive, while 23% (34/148) of HBsAG negatives had occult HBV infections. Of the 78 HBV DNA positive samples, 62.8% had viral loads ranging from 102 to ≥108 IU/ml, and 37.2% had HBV viral loads <200 IU/ml. There was a statistically significant positive association between HBsAg‐positivity and high viral loads, with 27% (12/44) of HBsAg positives having HBV viral loads between 104 and ≥108 IU/ml, compared to only 5.9% (2/34) of HBsAg negatives (relative risk: 4.64; 95% confidence interval: 1.11, 19.35; chi‐square P‐value = 0.015). The study shows that the majority of HIV/AIDS patients initiating ART have either acute or chronic HBV infections, and further confirms that HIV remains a risk factor for occult HBV infections in South African patients as previously shown. The findings strongly support HBV screening in all HIV‐positive patients initiating ART in South Africa, considering that current ART regimens include drugs with anti‐HBV activity (e.g., lamivudine). J. Med. Virol. 81:406–412, 2009.

Increased exposure to hepatitis B virus infection in HIV-positive South African antenatal women:

The prevalence of markers for hepatitis B virus (HBV) exposure and active infection in HIV-positive (n = 710) and HIV-negative (n = 710) pregnant South African women was investigated. The following statistically significant increases in the HIV-positive group were found: anti-hepatitis B core antigen (anti-HBc) (37.3% versus 28.6%; odds ratio [OR]: 1.49); anti-hepatitis B surface antigen (anti-HBs) (29.5% versus 20.1%; OR: 1.66); exposure based on hepatitis B surface antigen (HBsAg) and anti-HBc (39.2% versus 30.1 %; OR: 1.49); and exposure based on anti-HBs, anti-HBc and HBsAg (37.1% versus 24.5%; OR: 1.82). However, there was no increase in active HBV infections, with 2.4% of the HIV positives and 2.2% of the HIV negatives being HBV DNA positive. Although the impact that HIV has had on the prevalence of HBV in this population group is not as pronounced as that found in areas of low endemicity (where up to seven-fold increases have been reported), there is a statistically significant increased exposure to HBV.

Reduced detection and levels of protective antibodies to hepatitis B vaccine in under 2-year-old HIV positive South African children at a paediatric outpatient clinic

The study evaluated and compared the prevalence of anti-HBs and exposure to hepatitis B virus (HBV) in vaccinated South African babies aged between 5 and 24 months from the Expanded Programme on Immunisation clinic [EPI group] and paediatric outpatient clinic [OPD group], and results were stratified by HIV status. A total of 303 (243 EPI group and 60 OPD group) babies were studied. All sera were tested for anti-HBs, HBsAg and anti-HBc, while IgM anti-HBc and HBV DNA were only tested in samples positive for HBsAg and/or anti-HBc. Overall, there was a gross difference in the prevalence of anti-HBs marker between the EPI and OPD groups. The EPI group demonstrated higher levels of seroconversion (89.3% vs. 81.7%; p=0.105) and seroprotection rates (86.0% vs. 75.0%; p=0.038), compared to the OPD babies. When the overall results were stratified by HIV status, seroprotection was 85.7% for the HIV-negatives and 78.1% for the HIV-positives, although this was not statistically significant (p=0.125). The seroprotection rates were almost comparable between the HIV-positives (84.3%; n=51) and the HIV-negatives (86.5%; n=192) (p=0.695) in the EPI group. In contrast, reduced seroprotection rates were observed between the HIV-positives (63.6%; n=22) and HIV-negatives (81.6%; n=38) in the OPD group, although this was not statistically significant (p=0.123). Interestingly, no HBsAg or anti-HBc marker was detected in the OPD group, compared to total exposure rate of 4.9% (HBsAg carriage was 1.2%) in the EPI group.

An update after 16 years of hepatitis B vaccination in South Africa.

Hepatitis B (HB) virus (HBV) infection is highly endemic with at least 65 million chronic HB surface antigen (HBsAg) carriers in Africa, 25% of whom are expected to die from liver disease. Before the introduction of the HB vaccine, the prevalence of chronic carriage of HBV in black South Africans was 9.6%, with 76% having been previously exposed to HBV. The major transmission route in South Africa is unexplained horizontal transmission between toddlers, with most transmission occurring before the age of 5 years. During adolescence and early adulthood, sexual transmission becomes the dominant route, while healthcare workers (HCWs) are also at risk for parenteral/percutaneous transmission during occupational exposures. In 1995 the South African Department of Health (SADoH) incorporated the HB vaccine, administered as a monovalent, into the Expanded Programme on Immunisation (EPI) at 6, 10, and 14 weeks of age, and studies conducted thereafter have found it to be safe and highly effective. Catch-up vaccination for adolescents was not introduced and there is no schools-based vaccination programme. The SADoH recommends HB vaccination of HCWs, but this is not mandatory and there is no national policy, thus HB vaccination uptake in HCWs is sub-optimal. Since 1995, studies on children have found that the prevalence of chronic HBsAg carriage has decreased, as has the incidence of paediatric hepatocellular carcinoma and HBV-related membranous nephropathy. The SADoH should focus their efforts on attaining a high infant HB vaccine coverage, prepare for introducing a HB birth dose, and consider using a hexavalent vaccine (DTaP-IPV-Hib-HepB). The department may also want to consider including targeted HB vaccination for 12 year-olds, if their Road to Health Cards show they were not vaccinated as infants. A national policy is needed for HCWs to ensure that they are fully vaccinated and protected against HBV infection.

HPV genotypes in women with squamous intraepithelial lesions and normal cervixes participating in a community-based microbicide study in Pretoria, South Africa

BACKGROUND Little is known regarding the human papillomaviruses (HPV) genotypes prevalent in women in South Africa, a country with a high incidence of cervical cancer. OBJECTIVE To determine the prevalence and HPV genotypes in women with squamous abnormalities and normal cervixes participating in a community-based microbicide study. STUDY DESIGN A total of 159 cervical specimens, including 56 specimens from women with abnormal cytology (cases) and 103 randomly selected specimens from women with normal cytology (controls), were collected. HPV was detected by consensus PCR primers and HPV genotypes were determined by Roche Linear Array HPV genotyping assay. RESULTS HPV genotypes were found in 91% of cases and 40% of controls (p<0.005). High-risk HPV was detected in all high-grade squamous intraepithelial lesions (HSILs), 69% of low-grade squamous intraepithelial lesions (LSILs), 57% of atypical squamous cells of undetermined significance (ASCUS), and 86% of ASCUS in which HSIL could not be excluded (ASCUS-H), and 73% of HPV positive controls. HPV-35 was the predominant genotype in HSILs; HPV-18 in ASCUS; HPV-58 in ASCUS-H and HPV-16 in LSILs and controls. CONCLUSION High-risk HPV prevalence was high in both cases and controls. HPV genotype distribution in HSILs was different from that reported worldwide and from other studies in South Africa.

Hepatitis B vaccination coverage in healthcare workers in Gauteng Province, South Africa.

Hepatitis B (HB) virus (HBV) is highly endemic and HBV infection is a major public health problem in sub-Saharan Africa. Percutaneous/parenteral transmission is an important mode of spread of HBV in the healthcare setting, thus healthcare workers (HCWs) and their patients are at risk for acquiring HBV infections. This study was conducted on three HCW populations in Gauteng Province during 2009, in order to (1) determine HB vaccination coverage of HCWs, and (2) investigate demographic predictors of vaccination uptake. Being a doctor was a statistically significant predictor of vaccination uptake (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.48-6.72; p-value: 0.003), while working in the private sector was also statistically significantly associated with vaccination uptake (OR: 1.73; 95% CI: 1.01-2.98; chi-square p-value: 0.035). The majority (67.9% [491/723]) of HCWs had received at least 1 dose of vaccine, but where data on number of doses was available, only 19.9% (94/472) were fully vaccinated. In conclusion, there is a need to increase HB vaccination uptake in Gauteng HCWs through a policy that is properly implemented and routinely monitored and evaluated, and this policy must ensure that all three doses of vaccine are administered.

Evidence for a change in the epidemiology of hepatitis B virus infection after nearly two decades of universal hepatitis B vaccination in South Africa

The hepatitis B vaccine has been part of the South African Expanded Program on Immunization since April 1995 but its long‐term impact remains unknown. This study tested 1,206 sera collected from patients aged 1–25 years from various health facilities across the country for HBV serological markers and HBV DNA. Based on the year the vaccine was introduced, samples were stratified by age into pre‐ and post‐vaccine introduction populations, which were then compared for evidence of immunity and chronic carriage using the Chi‐square test. Where HIV status was known, subset analyses were performed. Immunity to HBV infection increased from 13.0% in the pre‐ to 57.0% in the post‐vaccine introduction population (P < 0.001). This decreased with increasing age within the post‐vaccine introduction population (76.1% for 1–5 years, 50.0% for 6–10 years, and 46.3% for 11–16 years). In addition, HBV chronic carriage was significantly (P = 0.003) reduced in the post‐ (1.4%) compared to the pre‐vaccine introduction population (4.2%). The difference in prevalence of active HBV infection in the serologically exposed pre‐ and post‐vaccine introduction populations was not statistically significant. Subset analyses showed that evidence of immunity was significantly (P < 0.001) higher in the HIV negative compared to the HIV positive subset in both populations. Universal hepatitis B vaccination has been a remarkable success, with a significant increase in immunity to HBV infection. The observation that HBV chronic carriage increases as immunity wanes over time calls into question whether the time has come to consider a pre‐adolescence vaccine booster dose policy. J. Med. Virol. 86:918–924, 2014.

Hepatitis B vaccination in Africa: mission accomplished?

Hepatitis B more than ever holds a prominent position among the most notorious infectious diseases on a global scale and remains an actual threat to the world population. However, not all countries or continents are equally affected. Sub-Saharan Africa for example is a high-endemic region, with carrier rates of hepatitis B surface antigen (HBsAg) 8% among certain population groups, representing a significant burden to the health and development of a number of societies.