Masters Degrees (Medical Virology)
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Browsing Masters Degrees (Medical Virology) by browse.metadata.advisor "Andersson, Monique I."
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- ItemAn investigation of hepatitis B virus in antenatal women tested for human immunodeficiency virus, in the Western Cape Province of South Africa(Stellenbosch : Stellenbosch University, 2012-03) Maponga, Tongai Gibson; Andersson, Monique I.; Preiser, Wolfgang; Stellenbosch University. Faculty of Health Sciences. Dept. of Pathology.ENGLISH ABSTRACT: Hepatitis B virus (HBV) immunisation protocols in much of Africa are based on data from the pre-human immunodeficiency virus (pre-HIV) era that indicated that HBV transmission occurs predominantly horizontally between siblings and play-mates rather than vertically from mother to child. The immunosuppression associated with HIV infection however may release HBV from immune control resulting in higher HBV viral loads, which may increase the risk of perinatal mother to child transmission of HBV. The aim of this study was to determine the prevalence and characteristics of chronic HBV infection in HIV-infected pregnant women compared to HIV-uninfected pregnant women in the Western Cape province of South Africa. Ethical approval was obtained to conduct a retrospective, matched case-control, unlinked anonymous study using residual plasma samples from the 9355 pregnant women included in the Western Cape's 2008 National HIV and Syphilis Antenatal Survey. Samples were tested for HBsAg on the AxSYM (Abbott, Chicago, IL) and confirmed by neutralization. Confirmed HBsAg-positive samples were tested for HBeAg, anti-HBe and anti-HD (Diasorin, Saluggia, Italy) and had HBV viral load and genotyping done. In addition, HBsAg-negative samples were tested for anti-HBc. Samples from 1549 HIV-infected pregnant women were included and matched to the same number of samples from age- and race-matched HIV-uninfected women. Median age of 26 years, parity and education were similar in the two groups. The prevalence of HBsAg was 3.4% for the HIV-infected group and 2.9% for the HIV-uninfected group. HBV DNA loads of greater than 104 IU/ml were detected in 32.1% of HBsAg-positive, HIV/HBV co-infected women, and in 14.3% HBsAg positive, HBV mono-infected women. Among the HIV-infected group 18.9% of HBsAg-positive were HBeAg positive, with a median viral load of 7.93 log10 IU/ml; whilst 15.5% HIV-uninfected women were positive for HBeAg with a median viral load of 6.07 log10 IU/ml. Genotype A was seen in 92.6% of the isolates while 7.4% of the isolates were genotype D. Serum total anti-HBc antibodies that are a marker of past infection were detected in 42.2% of HIV-infected and in 24.1% of HIV-uninfected women that were negative for HBsAg. No positive sample for anti-HD was seen among all HBsAg-positive samples. This data indicates that there is increased exposure to HBV in HIV-infected pregnant women than in HIV-uninfected women and that a greater proportion of HIV-infected pregnant women compared to HBV mono-infected pregnant women may be at increased risk of transmitting HBV to their infants. Further studies are needed to determine the rate of vertical transmission of HBV in the HIV era.
- ItemPrevalence and risks of Hepatitis E virus infection in blood donors from the Western Cape, South Africa(Stellenbosch : Stellenbosch University, 2016-03) Lopes, Tatum; Andersson, Monique I.; Preiser, Wolfgang; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Medical Virology.ENGLISH ABSTRACT: Hepatitis E virus (HEV) is an important cause of enterically transmitted acute hepatitis worldwide and is a locally acquired disease in both developing and developed nations. Different genotypes in these two regions display the different characteristics of this interesting infection. HEV is classified into four major genotypes and it can present as two contrasting clinical entities. HEV genotypes 1 (HEV1) and 2 (HEV 2) are related to waterborne transmission and poor sanitation. Whereas genotypes 3 (HEV3) and 4 (HEV4) are associated with zoonotic transmission mainly through pigs, wild boar and deer. HEV infections in Africa are thought to be caused by HEV1 and HEV2. The seroprevalence of HEV has been described in Southern Africa, but all more than 10 years ago when assays were not well developed. South Africa has three HEV reports, describing a hospital outbreak, and the seroprevalence in specific communities of South Africa. The seroprevalence from these studies ranged from 2% to 10.7% however no genotyping was done. Researchers have reported evidence of direct and indirect transfusion-transmitted HEV infection being a potential risk to recipients of blood transfusions. Asymptomatic HEV infections in blood donors increase the likelihood that blood or blood products are contaminated with HEV viral particles. Hence, there is a greater chance of infecting high-risk recipient groups with compromised immune systems. Therefore, the main aim of this study was to determine the prevalence of past and active HEV infection in blood donors from the Western Cape. We also investigated which risk factors are associated with infection. Our study population consisted of 10,250 blood donors that were tested as two sub-studies. For study group 1 we recruited 250 donors to complete an HEV risk questionnaire. Thereafter these donors were tested using an indirect Wantai ELISA (Fortress Diagnostics) for anti-HEV IgG detection. Statistical analysis was done to determine which demographics and risk factors were associated with past HEV infection. In addition, to this, their plasma donations were pooled, prior to extraction and amplified with an in-house real-time reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) to detect HEV RNA. The 10,000 blood donors of study group 2 were tested as individual donations using a commercial Procleix HEV nucleic acid testing (NAT) assay to qualitatively detect HEV RNA by transcription-mediated amplification (TMA). Thereafter repeat-reactive donations were quantified using our in-house real-time RT-qPCR. The total anti-HEV IgG seroprevalence of our study was found to be 42.4% in blood donors (study group 1). Risk analysis revealed that eating turkey (p=0.001) and organ meat (p=0.026) and canoeing (p=0.017) were significantly associated with past HEV infection. Whereas direct contact with rabbits (p=0.045) or chickens (p=0.020) were statistically significantly different means of HEV exposure associated with HEV3 and HEV4. Furthermore, we found that the total HEV RNA prevalence was 0.009% (1/10,250). Studies are needed to further assess the risk of HEV blood-borne transmission and to understand the epidemiology of HEV in our setting.
- ItemThe prevalence of Hepatitis B virus infection in an HIV-exposed paediatric cohort from the Western Cape, South Africa(Stellenbosch : Stellenbosch University, 2012-12) Chotun, Bibi Nafiisah; Andersson, Monique I.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology Medical Virology..ENGLISH ABSTRACT: Despite the availability of Hepatitis B virus (HBV) vaccination for over three decades, this infection remains a major public health problem. Whilst the WHO recommends giving a birth dose of the vaccine, in South Africa, routine infant HBV vaccination commences at six weeks of age. This schedule is based on data from the pre-HIV era which showed transmission occurred via the horizontal, rather than the vertical route. In the era of HIV however, maternal HIV co-infection may release HBV from immune control, resulting in higher HBV loads and increasing the risk of vertical transmission. The aim of this study was to determine the prevalence and character of HBV infection in HIV-exposed infected and uninfected infants. Residual plasma samples from routine HIV nucleic acid testing of 1000 HIV-exposed infants aged between 0 and 18 months from the Western Cape were tested. Samples were tested for HBsAg by ELISA (Murex HBsAg Version 3) and confirmed by neutralisation. HBV DNA was quantified using an in-house real-time PCR assay. Infants with HBsAg positive samples were followed up and a blood sample was collected from mother and child. Those HBsAg positive samples were tested for HBeAg/antiHBe (Diasorin) and HBsAg negative samples were tested for antiHBs. HBV DNA was quantified. The surface gene was sequenced and the HBV genotype determined by phylogenetic analysis using HepSEQ (www.hepseq.org.uk). Whole genome sequencing was also performed. Of 1000 samples tested, four samples were positive for HBsAg and/or HBV DNA, indicating a prevalence of HBV transmission of 0.4%. At follow-up, two of three infected infants were positive for HBsAg, with HBV viral loads of greater than 108 IU/ml. The third infant was found to have cleared his infection and the fourth child was lost to follow up. These infected infants had all received HBV vaccination. All four mothers were HBeAg positive. Sequencing analysis showed the HBV strains from the two infants and four mothers belonged to subgenotype A1. The two mother-child paired sequences were identical. The data from this study shows that vertical transmission of HBV infection in HIV-exposed infants from the Western Cape is occurring, despite vaccination. Data from the Western Cape, showing an HBV prevalence of 3.4% in HIV-infected pregnant women, and those presented here suggest a vertical transmission rate of HBV of 12%. This is despite the widespread use of tenofovir and lamivudine in HIV-infected women with low CD4 counts. This study provides data supporting calls to bring HBV vaccination closer to the time of birth. Further work is urgently needed to confirm these findings and to determine the rates of transmission in HIV-unexposed infants.
- ItemA study of the prevalence of Hepatitis B virus infection in the infants of HIV-positive mothers participating in P1041 in South Africa(Stellenbosch : Stellenbosch University, 2014-12) Tamandjou Tchuem, Cynthia Raissa; Andersson, Monique I.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Medical Virology.ENGLISH ABSTRACT: Despite the decreased rate of HBV horizontal transmission in South Africa (SA) due to the HB vaccine, the risk of perinatal transmission remains of concern, especially in HIV/HBV co-infected women. Loss of HBV immune control, resulting in higher HBV replication and thus increasing the risk of transmission is described in HIV/HBV co-infected women. Chronic hepatitis is a well-recognized risk factor for hepatocellular carcinoma (HCC). The presence of specific HBV mutations has been reported in chronic and HCC patients and is used in algorithms for the prediction of HCC in CHB patients in Asia. While these mutations are extensively described in male patients, little is known regarding the antenatal and paediatric populations. This study aimed to determine the prevalence of HBV infection in HIV-exposed infants and to investigate the presence of HCC-related mutations in pregnant women and HIV-exposed children in SA. Residual samples of infants born to HIV-infected mothers were collected from the P1041 study previously conducted in SA. HBV markers (HBsAg, anti-HBs and anti-HBc) were tested on the Architect (Abbott). HBsAg positive samples were tested for HBV DNA to determine HBV viral loads. HBV strains were characterised by sequencing of the HBsAg gene and genotypes were determined by phylogenetic analysis using HepSEQ (www.hepseq.org.uk). For the HCC-related mutations investigation, samples and data were collected from three HBV-related studies: the NHLS Paediatric Study, an Antenatal Study and the current study. Pre-S, basal core promoter (BCP) and pre-core data was collected from all samples. Multiple alignments were formed and the nucleotide sequences of these extracts were translated into protein sequences. These protein sequences were compared manually to the HBV reference genes to identify HCC-related mutations. Of 850 HIV-exposed infants tested, three infants were positive for both HBsAg and HBV DNA. Two samples show evidence of past, but cleared HBV infection. Sequence analysis showed that the infants were infected with a subgenotype A1. At follow up, only one infant and mother were able to be traced and contacted. The infant was HIV-infected and had been on an ART regimen, including lamivudine for two years. HBV testing showed that the infant was HBsAg positive and had an undetectable viral load. Core sequence analysis showed clustering between mother and infant sequences. Transmission of mutant HBV previously associated with HCC prompted the question of what the prevalence of mutations in the antenatal and paediatric population is. In this investigation of HCC-related mutations study, a higher prevalence of combined pre-S, BCP and pre-core mutations was found in HIV-infected as compared to HIV-uninfected women. This study shows that vertical transmission is occurring in HIV-exposed infants in SA despite HB vaccination. Data described in this study suggests the importance of HB vaccination closer to the time of birth in SA. Moreover, data on the higher prevalence of HCC-related mutations in HIV-infected pregnant women provide a background for further longitudinal studies to confirm these findings and their implications in SA.