Hepatitis A seroprevalence in Western Cape Province, South Africa: Are we in epidemiological transition?

BACKGROUND: Hepatitis A virus (HAV) is the most common cause of viral hepatitis worldwide. Hepatitis A vaccine is not included in the Expanded Programme on Immunisation in South Africa (EPI-SA), as the country is considered to be highly endemic for hepatitis A. OBJECTIVES: To determine the seroprevalence of hepatitis A infection in Western Cape Province (WCP), South Africa. METHODS: We conducted a cross-sectional seroprevalence study in the 1 - 7-year age group in WCP. Our samples (N=482) were blood specimens left over after laboratory testing obtained from referral hospitals between August and October 2015. A Siemens enzyme immunoassay was used to test for total hepatitis A antibodies. We also analysed hepatitis A immunoglobulin G antibody results from the National Health Laboratory Service (NHLS) Disa*Lab database at Groote Schuur Hospital from 2009 to 2014, and included 2009 - 2014 acute hepatitis A (immunoglobulin M-positive) surveillance data from the National Institute for Communicable Diseases to look at trends in notified acute infections over the same period. RESULTS: Our cross-sectional study showed 44.1% seroprevalence in the 1 - 7-year age group. Hepatitis A data from the NHLS database indicated a seroprevalence of <90% up to age 10 years, indicating intermediate endemicity. The surveillance data showed that a substantial number of symptomatic hepatitis A infections occurred in the 7 - 40-year age group, suggesting that an increasing proportion of the population is susceptible to HAV infection. CONCLUSIONS: These results suggest an urgent need for detailed evidence-based considerations to introduce hepatitis A vaccine into the EPI-SA.

Fulminant hepatitis B virus (HBV) infection in an infant following mother-to-child transmission of an e-minus HBV mutant: Time to relook at HBV prophylaxis in South African infants.

The prevalence of hepatitis B virus (HBV) infection in pregnant women is high in South Africa (SA), yet prophylaxis to prevent mother-to-child transmission (MTCT) falls short of international recommendations. We describe a 10-week-old infant who developed fulminant hepatic failure following MTCT. The mother was hepatitis e-antibody positive and had a viral load of only 760 IU/mL. Genetic analysis of virus from mother and infant showed that both had the G1896A mutation in the preC/C gene, which truncates hepatitis e antigen (HBeAg) during translation, causing an HBeAg-negative phenotype. HBeAg attenuates antiviral immune responses, and its absence was probably responsible for the infant's fulminant hepatitis, due to an uncontrolled immune attack on infected liver cells. Pregnant women are not tested for HBV infection in SA and MTCT rates are unknown. Addition of a birth dose of vaccine, HBV screening of pregnant women and antiviral prophylaxis to positive mothers should be prioritised.

Relation between HLA antigens and skin cancer in renal transplant recipients in Queensland, Australia.

On the basis of previous studies that showed a negative association between HLA-A11 and skin cancer in renal transplant recipients and a positive association with HLA-B27 and HLA-DR7, we performed a study in Queensland with 1098 recipients to address the question of whether the same associations could be found. The influence of HLA mismatching and HLA homozygosity on the risk of skin cancer was also studied. In contrast to earlier studies, HLA-A11 was associated with an increased risk of skin cancer. On the other hand, we confirmed that the HLA-B27 antigen was associated with the development of skin cancer, but only when the development of basal cell carcinomas alone was considered, and we confirmed that there is a weak but not statistically significant association with HLA-DR7. No association between HLA mismatching or HLA homozygosity and the development of skin cancer was observed. Environmental factors such as different levels of exposure to sunlight and infection with human papillomaviruses are factors that are most likely to be involved. We hypothesize that human papillomavirus-induced antigens prevail in the skin cancers in the recipients living in the Netherlands, whereas antigens induced by solar radiation, the so-called "photo-antigens," may be more common in the skin cancers of the recipients living in Queensland. Exposure to sunlight can also induce immunologic unresponsiveness, and excessive exposure to sunlight in Australia may, therefore, simply override the risk factors that are important in countries with a more temperate climate.

Analysis of the preS1 gene of hepatitis B virus (HBV) to define epidemiologically linked and un-linked infections in South Africa.

Analysis of the preS1 gene of hepatitis B virus was used to define two nosocomial outbreaks of HBV infection. In an outbreak in an oncology unit we had previously shown by single stranded conformational polymorphism (SSCP) analysis of a 189 bp fragment of the preS1 gene, that 52 children were infected with HBV strains that displayed only 5 different SSCP profiles. Sequencing of a 383 bp fragment encompassing the entire preS1 gene, revealed that isolates with same SSCP profile were identical in sequence across the entire preS1 gene, confirming that those patients with the same SSCP pattern had epidemiologically linked infections. A second outbreak involved 8 liver transplant patients from two different hospitals, 5 of whom were from the same hospital at which the oncology outbreak had occurred. Two of these 5 patients had HBV strains that were identical to strains from the oncology unit and nosocomial transmission probably accounted for the infections in these two, while diversity of both SSCP profiles and sequence data of remaining 6 patients supported the conclusion that they had not been infected from a common source. The donor liver is believed to be the most likely source of infection in these patients. HBV isolates from patients infected in the community were used as a standard for the general degree of preS1 sequence variation of local HBV strains. Phylogenetic analysis and comparison with reference HBV clones revealed that of 27 local HBV strains, genotypes A and D occurred most frequently and were identified in 14 and 12 patients respectively, while genotype C was detected in one patient.

DNA single strand conformation polymorphism identifies five defined strains of hepatitis B virus (HBV) during an outbreak of HBV infection in an oncology unit.

An outbreak of hepatitis B virus (HBV) infection in a children's oncology unit was identified in which 61 children were shown to have been infected, 59 of them asymptomatically. In order to establish whether intra-unit cross infection had occurred, we used the single strand conformational polymorphism (SSCP) technique to analyse viral isolates from 57 of the infected children and 40 unrelated controls. HBV-specific primers were designed to amplify a 189 bp fragment of DNA encompassing part of the hypervariable pre-S1 region of the HBV genome. Denatured PCR products were compared after electrophoresis through polyacrylamide gels and staining with silver. By SSCP analysis, the unrelated infections each yielded a unique electrophoretic banding pattern, indicative of a variety of distinct virus strains. In contrast, most of the oncology patients had been infected with one of only five different strains. Three major groups comprising 19, 16, and 9 patients, respectively, and two minor groups of 5 and 3 patients were identified. Results indicate the occurrence of multiple episodes of cross infection, and demonstrate the sensitivity and value of SSCP as a technique to establish common sources of infection.

The risk of skin cancer in renal transplant recipients in Queensland, Australia. A follow-up study.

A long-term retrospective follow-up study was performed to evaluate the risk of skin cancer in 1098 renal transplant recipients in Queensland, Australia. In a subgroup, we also assessed the influence of immunosuppressive therapy on the risk of developing skin cancer: cyclosporine alone or in combination with prednisolone; azathioprine alone or in combination with prednisolone; or the combination of cyclosporine and azathioprine with or without prednisolone. The cumulative incidence of developing skin cancer, calculated by life table analysis, increased progressively from 7% after 1 year of immunosuppression to 45% after 11 years and to 70% after 20 years of immunosuppression. Multivariate analysis in a subgroup comparing the risk of developing skin cancer in patients on either long-term cyclosporine or azathioprine (each with or without prednisolone) and in patients on the combination of cyclosporine and azathioprine (with or with- out prednisolone) showed no differences between the groups. We conclude that it is likely that the increased risk of skin cancer associated with immunosuppression is independent of the agent(s) used and is a result of the immunosuppression per se.

Routine use of indwelling ureteral stents in renal transplantation.

An extravesical ureteral implantation with the routine use of an internal stent was performed in 358 transplants (351 cadaveric and 7 living related). The 1-year patient and graft survival was 93% and 87%, respectively, with a minimum followup of 2 years. Ureteral complications developed in 9 patients (2.6%), with 3 fistulas, 2 of which resolved spontaneously, and 6 stenoses following stent removal. Nephrostomy drainage and antegrade stenting were initially attempted in all cases of stenosis, and were successful in 4. Revision of the ureteral anastomosis was required in 1 case of fistula and 2 cases of stenosis (0.9%). Extrinsic compression resulted in ureteral obstruction in 3 cases (2 lymphoceles and 1 hematoma), which resolved following drainage. Stent related complications occurred in 8 patients (2.2%), including obstruction due to the stent in 2 cases, breakage during removal in 3 leaving fragments in the upper urinary tract, proximal migration of 2 stents that were retrieved via percutaneous nephrostomy and calculus formation on 1 stent in a patient with hyperparathyroidism, necessitating extracorporeal shock wave lithotripsy for stent removal. In the cases with ureteral or stent related complications 1-year patient and graft survival was 100%. These results suggest that ureteral stents used routinely in renal transplantation are associated with a low incidence of urinary leaks, early postoperative obstruction and subsequent surgery for urological complications. However, a small number of unique problems related to stent use or malfunction may occur. Minimally invasive strategies using percutaneous nephrostomy and antegrade stenting are effective in managing the majority of complications that occur following ureteral stenting in renal transplant recipients.

An Fc receptor for human immunoglobulin G is located within the tegument of human cytomegalovirus.

Immunogold electron microscopy has demonstrated that human immunoglobulin G (IgG) can bind to the tegument of human cytomegalovirus virions by the Fc portion of the molecule. This binding was inhibited by preincubation of the Fc probes with protein A. Treatment of AD169 virions with Triton X-100 allowed release of the Fc-binding proteins, which were precipitated and characterized by polyacrylamide gel electrophoresis (PAGE). Polypeptides of approximately 69 and 33 kDa were recovered and shown by immunoblotting to retain their capacity to bind Fc-gold after separation under both reducing and nonreducing conditions. The combined results of blocking experiments, PAGE of precipitates, and Western blots (immunoblots) indicate that the tegument proteins which bind IgG-Fc are identical to those which bind beta 2 microglobulin.