Biology subjects

Goedhals, D.

Publications and source records attributed to Goedhals, D..

6 recordsLinked to original sources

bioRxiv2024

Preliminary report on the molecular epidemiology of mpox, South Africa 2024

Mpox is an emerging viral infection and has since May 2022 been reported in a multi-country outbreak involving predominantly previously non-endemic countries. In addition, the number of cases of mpox is also rising in some endemic countries in Western and Central Africa. The disease is a notifiable medical condition in South Africa, with no cases reported before 2022. However, in 2022, coinciding with the peak of a multi-country mpox outbreak, five mpox cases were diagnosed in the country. Genomic sequencing and analysis revealed the presence of a monkeypox virus variant, which was circulating during the multi-country outbreak, namely Clade IIb sub-lineage B.1.7 (hMPXV). After the fifth case was reported in 2022, there were no cases detected for the following 20 months. In May 2024, mpox cases were again detected in South Africa leading to concerns that the virus may have been silently transmitting in the country since 2022. Genomic sequencing and analysis for 22 mpox cases reported during May to September 2024, were compared with sequences obtained from mpox cases reported in South Africa in 2022, and cases that have been reported globally. It was found that the sequences of the 2024 cases analysed in this study, clustered with Clade IIb hMPXV and sub-lineage B.1.20 and B.1.6 sequences. The results indicate that the detection of mpox cases in South Africa was an extension of the ongoing multi-country outbreak. Detection of different sub-lineages of hMPXV indicates reintroductions of the virus in the country since 2022, with local transmission of Clade IIb B1.20 hMPXV.

microbiology↗

bioRxiv2019

HBV seroepidemiology data for Africa provides insights into transmission and prevention

International goals for elimination of hepatitis B virus (HBV) infection set ambitious targets for 2030. In many African populations, HBV prevalence remains high ([≥]8%) despite the roll-out of infant HBV immunisation from the mid-1990s onwards. Enhanced efforts are now urgently required to improve an understanding of population epidemiology, in order to determine which interventions are most likely to be effective in advancing populations towards elimination goals. In populations with a high prevalence of infection, catch-up HBV vaccination of adults has sometimes been deployed as a preventive strategy. An alternative approach of test and treat could be applied as a tool to interrupt transmission. We used a systematic approach to investigate the relationship between prevalence of HBV infection (HBsAg) and exposure (anti-HBc) in Africa, and then applied a mathematical model to investigate the impact of catch-up vaccination and a test and treat strategy in Uganda, representing a high prevalence setting. We demonstrate a strong relationship between the prevalence of HBsAg and anti-HBc (p<0.0001), but with region-specific differences that may reflect different patterns of transmission. In high prevalence settings, catch-up vaccination may have a transient effect but this intervention does not contribute to a sustained decline in prevalence. In contrast, diagnosing and treating infection has a marked impact on reducing prevalence, equivalent to that of infant immunisation. Conclusion: We have developed a high-resolution picture of HBV epidemiology across Africa. Developing insights into regional differences provides an evidence base for the most effective interventions. In combination with robust neonatal immunisation programmes, testing and treating infection is likely to be of most impact in making advances towards elimination targets.

epidemiology↗

bioRxiv2018

Modelling cost-effectiveness of tenofovir for prevention of mother to child transmission of hepatitis B virus infection in South Africa

In light of sustainable development goals for 2030, an important priority for Africa is to have affordable, accessible and sustainable hepatitis B virus (HBV) prevention of mother to child transmission (PMTCT) programmes, delivering screening and treatment for antenatal women and implementing timely administration of HBV vaccine for their babies. We developed a decision-analytic model simulating 10,000 singleton pregnancies to assess the cost-effectiveness of three possible strategies for deployment of tenofovir in pregnancy, in combination with routine infant vaccination: S1: no screening nor antiviral therapy; S2: screening and antiviral prophylaxis for all women who test HBsAg-positive; S3: screening for HBsAg, followed by HBeAg testing and antiviral prophylaxis for women who are HBsAg-positive and HBeAg-positive. Our outcome was cost per infant HBV infection avoided and the analysis followed a healthcare perspective. S1 predicts 45 infants would be HBV-infected at six months of age, compared to 21 and 28 infants in S2 and S3, respectively. Relative to S1, S2 had an incremental cost of $3,940 per infection avoided. S3 led to more infections and higher costs. Given the long-term health burden for individuals and economic burden for society associated with chronic HBV infection, screening pregnant women and providing tenofovir for all who test HBsAg+ may be a cost-effective strategy for South Africa.

epidemiology↗

bioRxiv2018

PhyloPi: an affordable, purpose built phylogenetic pipeline for the HIV drug resistance testing facility

Phylogenetic analysis plays a crucial role in quality control in the HIV drug resistance testing laboratory. If previous patient sequence data is available sample swaps can be detected and investigated. As Antiretroviral treatment coverage is increasing in many developing countries, so is the need for HIV drug resistance testing. In countries with multiple languages, transcription errors are easily made with patient identifiers. Here a self-contained blastn integrated phylogenetic pipeline can be especially useful. Even though our pipeline can run on any unix based system, a Raspberry Pi 3 is used here as a very affordable and integrated solution.\n\nThe computational capability of this single board computer is demonstrated as well as the utility thereof in the HIV drug resistance laboratory. Benchmarking analysis against a large public database shows excellent time performance with minimal user intervention. This pipeline also contains utilities to find previous sequences as well as phylogenetic analysis and a graphical sequence mapping utility against the pol area of the HIV HXB2 reference genome. Sequence data from the Los Alamos HIV database was analyzed for inter- and intra-patient diversity and logistic regression was conducted on the calculated genetic distances. These findings show that allowable clustering and genetic distance between viral sequences from different patients is very dependent on subtype as well as the area of the viral genome being analyzed.\n\nThe Raspberry Pi image for PhyloPi, source code of the pipeline, sequence data, bash-, python- and R-scripts for the logistic regression, benchmarking as well as helper scripts are available at http://scholar.ufs.ac.za:8080/xmlui/handle/11660/7638 and https://github.com/ArmandBester/phylopi.\n\nThe PhyloPi image and the source code are published under the GPLv3 license. A demo version of the PhyloPi pipeline is available at http://phylopi.hpc.ufs.ac.za/.

bioinformatics↗

bioRxiv2018

A systematic review of Hepatitis B virus (HBV) drug and vaccine escape mutations in Africa: a call for urgent action

International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the pressing need to optimize strategies for prevention, diagnosis and treatment. Selected or transmitted resistance associated mutations (RAMs) and vaccine escape mutations (VEMs) in hepatitis B virus (HBV) may reduce the success of existing treatment and prevention strategies. These issues are particularly pertinent for many settings in Africa where there is high HBV prevalence and co-endemic HIV infection, but lack of robust epidemiological data and limited education, diagnostics and clinical care. The prevalence, distribution and impact of RAMs and VEMs in these populations are neglected in the current literature. We therefore set out to assimilate data for sub-Saharan Africa through a systematic literature review and analysis of published sequence data, and present these in an on-line database (https://livedataoxford.shinyapps.io/1510659619-3Xkoe2NKkKJ7Drg/). The majority of the data were from HIV/HBV coinfected cohorts. The commonest RAM was rtM204I/V, either alone or in combination with compensatory mutations, and identified in both reportedly treatment-naive and treatment-experienced adults. We also identified the suite of mutations rtM204V/I + rtL180M + rtV173L, that has been associated with vaccine escape, in over 1/3 of cohorts. Although tenofovir has a high genetic barrier to resistance, it is of concern that emerging data suggest polymorphisms that may be associated with resistance, although the precise clinical impact of these is unknown. Overall, there is an urgent need for improved diagnostic screening, enhanced laboratory assessment of HBV before and during therapy, and sustained roll out of tenofovir in preference to lamivudine alone. Further data are needed in order to inform population and individual approaches to HBV diagnosis, monitoring and therapy in these highly vulnerable settings.\n\nAuthors summaryThe Global Hepatitis Health Sector Strategy is aiming for the elimination of viral hepatitis as a public health threat by 2030. However, mutations associated with drug resistance and vaccine escape may reduce the success of existing treatment and prevention strategies. In the current literature, the prevalence, distribution and impact of hepatitis B virus (HBV) mutations in many settings in Africa are neglected, despite the high prevalence of HBV and co-endemic HIV infection. This systematic review describes the frequency, prevalence and co-occurrence of mutations associated with HBV drug resistance and vaccine escape mutations in Africa. The findings suggest a high prevalence of these mutations in some populations in sub-Saharan Africa. Scarce resources have contributed to the lack of HBV diagnostic screening, inconsistent supply of drugs, and poor access to clinical monitoring, all of which contribute to drug and vaccine resistance. Sustainable long-term investment is required to expand consistent drug and vaccine supply, to provide screening to diagnose infection and to detect drug resistance, and to provide appropriate targeted clinical monitoring for treated patients.

epidemiology↗

bioRxiv2017

Mapping the drivers of within-host pathogen evolution using massive data sets

Differences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution. Identifying such interactions can potentially be achieved through genetic association studies. However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses. Moreover, the multiple testing burden of interaction scanning can potentially limit power. To address these problems, we have developed a Bayesian approach for detecting host influences on pathogen evolution that makes use of vast existing data sets of pathogen diversity to improve power and control for stratification. The approach models key processes, including recombination and selection, and identifies regions of the pathogen genome affected by host factors. Using simulations and empirical analysis of drug-induced selection on the HIV-1 genome we demonstrate the power of the method to recover known associations and show greatly improved precision-recall characteristics compared to other approaches. We build a high-resolution map of HLA-induced selection in the HIV-1 genome, identifying novel epitope-allele combinations.

genetics↗