The Milnor-Witt motivic ring spectrum and its associated theories

We build a ring spectrum representing Milnor-Witt motivic cohomology, as well as its \'etale local version and show how to deduce out of it three other theories: Borel-Moore homology, cohomology with compact support and homology. These theories, as well as the usual cohomology, are defined for singular schemes and satisfy the properties of their motivic analog (and more), up to considering more general twists. In fact, the whole formalism of these four theories can be functorially attached to any ring spectrum, giving finally maps between the Milnor-Witt motivic ones to the classical motivic ones.Comment: 28 pages. Comments welcom

The prevalence of Hepatitis B virus infection in an HIV-exposed paediatric cohort from the Western Cape, South Africa

Thesis (MScMedSc))--Stellenbosch University, 2012.Includes bibliographyENGLISH 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.AFRIKAANSE OPSOMMING: Ten spyte van die beskikbaarheid van die Hepatitis B virus (HBV) inenting vir meer as drie dekades, hierdie infeksie bly 'n groot openbare gesondheid probleem. Terwyl die WGO aan beveel dat'n geboorte dosis van die entstof, in Suid-Afrika, roetine baba HBV inenting op die ouderdom van ses weke gegee word. Hierdie skedule is gebaseer op data van die pre-MIV era wat getoon het dat die oordrag plaasgevind het via die horisontale, eerder as die vertikale roete. In die era van MIV egter, moeder MIV ko-infeksie kan HBV vrylaat van immuun beheer, wat lei in hoër HBV vlakke en die verhoging van die risiko van vertikale oordrag. Die doel van hierdie studie was om die voorkoms en karakter van die HBV infeksie in MIV-besmette en onbesmette babas te bepaal. Residuele plasma monsters van roetine-MIV-nukleïensuur toetse van 'n 1000 MIV-blootgestelde babas tussen die ouderdomme van 0 en 18 maande van die Wes-Kaap was getoets. Monsters was getoets vir HBsAg deur ELISA (Murex HBsAg Version 3) en bevestig deur neutralisering. HBV DNA is gekwantifiseer deur gebruik te maak van 'n in-huis real-time PCR assay. Babas met HBsAg positiewe monsters was opgevolg en 'n bloedmonster is versamel van moeder en kind. Die HBsAg positiewe monsters was getoets vir HBeAg/antiHBe (Diasorin) en HBsAg negatiewe monsters was getoets vir antiHBs. HBV DNA was gekwantifiseer. Die oppervlak gene volgorde en genotipes was bepaal deur filogenetiese analise met behulp van HepSEQ (www.hepseq.org.uk). Die hele genoom-volgordebepaling was ook uitgevoer. Van die 1000 monsters wat getoets was, was vier monsters positief vir HBsAg en of HBV DNA, dit dui op 'n voorkoms van HBV oordrag van 0.4%. By op volg, twee van die drie besmette babas was positief vir HBsAg, met HBV virale vlakke van groter as 108 IE/ml. Die derde baba was gevind dat sy infeksie opgeklaar het en die vierde kind was verlore as gevolg van op volg. Hierdie besmette babas het almal HBV inenting ontvang. Al vier moeders was HBeAg positief. Volgordebepaling analise het getoon die HBV stamme van die twee babas en vier moeders behoort aan subgenotype A1. Die twee moeder-kind gepaarde rye was homoloë. Die data van hierdie studie toon dat die vertikale oordrag van HBV infeksie in MIV-blootgestelde babas van die Wes-Kaap vind plaas, ten spyte van inenting. Data van die Wes-Kaap, wat 'n HBV voorkoms van 3.4% in MIV-besmette swanger vroue, en dié wat hier aangebied is dui op 'n vertikale oordrag koers van 12% van die HBV. Dit is ten spyte van die wydverspreide gebruik van tenofovir en lamivudine in MIV-geïnfekteerde vroue met 'n lae CD4-telling. Hierdie studie bied data wat ondersteunende oproepe van HBV inenting nader aan die tyd van die geboorte bring. Verdere werk is dringend nodig om die bevindinge te bevestig en die pryse van die oordrag in MIV-blootgestelde babas te bepaal.National Health Laboratory Service Research TrustPoliomyelitis Research Foundation (PRF)Harry Crossley FoundationStellenbosch Universit

Hepatitis b virus-related hepatocellular carcinoma in south africa: investigations into the risk profile of a previously unscreened population from the Western Cape

Thesis (PhD)--Stellenbosch University, 2018.ENGLISH ABSTRACT: Hepatocellular carcinoma (HCC) is a neglected major public health problem worldwide. In SubSaharan Africa (SSA), most HCC cases are diagnosed with advanced disease, well past the timing of possible treatment. Most HCC cases worldwide are caused by chronic infection with hepatitis B virus (HBV). Although the bulk of the burden of HBV is in SSA, there are no screening programmes implemented in the general African population so only 0.8% of HBV-infected individuals are diagnosed. Most research on HBV-related HCC has been conducted in Asia, where HBV is also endemic, but where there are differences in disease progression and presentation. The present study investigated HBV and HCC from an African perspective and tackled these public health issues by incorporating three key components for early diagnosis of HBV-related HCC: HBV screening, HCC biomarkers, and HBV-related HCC genomics. The HBV screening study found the prevalence of HBV in a South African community-based cohort using a validated point-of-care test to be 2.2% (95% CI: 1.4%–3.3%). The test performed well in the field and had a sensitivity, specificity, negative and positive predictive values of 100%. The test was also accepted by the community (93% uptake) and health care providers. The results of the present study support the case for the implementation of HBV screening in South Africa by demonstrating the magnitude of the HBV health problem in South Africa and new evidence that the POCT test performs well in the field, is accepted by the community and health care providers, and that patients diagnosed with the test can be successfully linked to treatment and long-term follow-up. The HCC biomarker study found significant differences in methylation expression levels in CpG islands in the promoter region of the tumour suppressor gene RASSF1A between HCC cases and normal liver tissue controls as well as a significant association between HBV genotype A and HCC. Although the sample size was small, it showed that there are biomarkers that may be used to identify HCC, paving the way for future studies looking into developing HCC risk scores for early diagnosis of HCC. Using whole-exome sequencing, the HBV-related HCC genomics study identified two novel germline variants in the SMARCA1 and RAB19 genes that in the absence of other risk factors besides HBV infection, could have contributed to early-onset HBV-related HCC in their respective hosts. Overall, these data provide evidence that early diagnosis of HBV-related HCC in an African setting is possible especially if a multi-targeted approach is taken. The simplest approach to minimise the incidence of HCC in SSA would be to implement HBV screening, at the very least in pregnant women, to break the transmission cycle of HBV. Moreover, the biomarkers of interest identified in the present study should be investigated further in larger cohorts and non-invasive patient samples to determine their utility in stratifying HCC risk. Lastly, the WES study showed that there are germline variants that could predispose carriers to HCC although these results need to be further investigated in in-silico and proteomic studies.AFRIKAANSE OPSOMMING: Hepatosellulêre karsinoom (HCC) is ‘n omvangryke maar verontagsame publieke gesondheid probleem wêreldwyd. In sub-Sahara Afrika (SSA) word meeste HCC gevalle eers gediagnoseer met reeds-gevorderde siekte, lank nadat moontlike behandeling toegepas kon word. Meeste HCC gevalle word deur kroniese hepatitis B virus (HBV) infeksie veroorsaak. Alhoewel die grootste HBV las op SSA is, bestaan daar geen siftingsprogramme vir die algemene populasie in Afrika nie, wat veroorsaak dat slegs 0.8% van HBV positiewe individuele gediagnoseer word. Meeste HBV verwante HCC navorsing is tot dusvêr in Asië uitgevoer waar HBV ook endemies is, maar daar is verskille in siekte ontwikkeling en voordoening. Hierdie studie het HBV en HCC uit ‘n Akrika perspektief benader en die publieke gesondheid kwessies ondersoek deur drie sleutelkomponente in ag te neem om HBV verwante HCC vroeg te identifiseer, naamlik: HBV sifting, HCC biomerkers en HBV verwante HCC genomika. In die HBV sifting studie, het ‘n geverifieërde punt-van-sorg toets gevind dat die voorkoms van HBV in ‘n Suid Afrikaanse gemeenskap gebaseerde kohort 2.2% (95% CI: 1.4%–3.3%) is. Die toets was suksesvol uitgevoer en het sensitiwiteit, spesifisiteit, negatiewe en positiewe voorspellende waardes van 100% behaal. Die toets is ook deur die gemeenskap (93% opname) en gesondheidsorgverskaffers aanvaar. Die bevindings van die huidige studie ondersteun die implementering van HBV sifting in Suid Afrika deur die omvang van HBV as ‘n meenigte gesondheids probleem te bevestug is en deur nuwe bevindings dat the punt-van-sorg toets gebruiklik in die veld is en aanvaar word deur die gemeenskap en gesondheidsorgverskaffers. Pasiënte gediagnoseer met die toets kan ook behandeling en langtermyn nasorg ontvang. Die HCC biomerker studie het bekenisvolle verskille in metilering uitdrukking-vlakke in CpG eilande in die promotor area van die tumor onderdrukking geen RASSFIA tussen HCC gevalle en normale lewer weefsel kontroles gevind, asook ‘n betekenisvolle verwantskap tussen HBV genotype A en HCC. Alhoewel die steekproefgrootte klein was, het dit daartoe aanduiding gegee dat sekere biomerkers gebruik kan word vir die identifikasie van HCC, wat die pad voorberei vir verdere studies om HCC risiko-gradering te gebruik om HCC vroegtydig te diagnoseer. Met die gebruik van heel-eksoom nukleïensuurvolgordebepaling het die HBV-verwante HCC genomika studie twee nuwe kiemlyn variante in die SMARCA1 en RAB19 gene geïdentifiseer, wat onafhanklik van ander risiko faktore, HBV uitgesluit, kon bydra tot vroeë HBV-verwante HCC aanvang in hulle onderskeie gashere. In samevatting, verskaf hierdie data bewyse dat vroeë diagnose van HBV-verwante HCC in ‘n Afrika-omgewing moontlik is, veral wanneer ‘n multi-geteikende benadering geneem word. Die eenvoudigste benadering tot die vermindering van HCC in SSA is om HBV-sifting te implementer, minstens in swanger vroue om die oordragsiklus te verhoed. Verder moet die biomerkers wat in hierdie studie geïdentifiseer is, in meer omvattende studies ondersoek met gebruik van nie-indringende pasiënt monsters. Laastens het die WES studie aangedui dat daar sekere kiemlyn variante is wat draers kan vatbaar maak aan HCC, hoewel hierdie resultate verder ondersoek moet word in ‘in-silico’ en proteomiese studies

Hepatitis B virus infection in HIV-exposed infants in the Western Cape, South Africa

CITATION: Chotun, N. et al. 2015. Hepatitis B virus infection in HIV-exposed infants in the Western Cape, South Africa. Vaccine, 33(36):4618–4622, doi:10.1016/j.vaccine.2015.06.076.The original publication is available at http://www.sciencedirect.com/science/journal/0264410XHepatitis B virus infection (HBV) is a significant public health problem in sub-Saharan Africa. Universal infant vaccination with the hepatitis B (HB) vaccine has been implemented within the South African Expanded Programme of Immunization since April 1995 with concomitant reduction in HBV infection in children. However, the first vaccine dose is only administered at six weeks of age. This delay may lead to a failure to reduce the risk of perinatal HBV transmission to infants born to HIV/HBV co-infected women, in whom HBV infection is often upregulated. The aim of this study was to determine the prevalence of HBV infection in babies born to HIV-infected mothers in the Western Cape, South Africa. HBV serological markers were tested in all infant serum samples and following HB viral load testing, sequencing and genotyping were also performed. Three of 1000 samples screened tested positive for HBsAg and HBV DNA. An additional infant tested positive for HBV DNA alone. All babies had received the HB vaccine at 6, 10 and 14 weeks. The prevalence of HBV infection was therefore 4/1000 (0.4%; 95% CI, 0.01–0.79%). Three of four infants and all four mothers were followed-up. Two infants were persistently positive for HBsAg with viral loads above 108 International Units per millilitre. All four maternal samples were positive for HBsAg and HBeAg and one was also positive for anti-HBe. Sequencing analysis of two mother–child HBV pairs showed 100% sequence identity. This study demonstrates HBV infection in HIV-exposed infants despite HB vaccination from 6 weeks of age. A more strategic approach is needed to prevent mother to child transmission of HBV, including screening of pregnant women, HBV-targeted antiviral therapy and HB birth dose vaccine.http://www.sciencedirect.com/science/article/pii/S0264410X15008774Publisher's versio

EVALUATION OF THE DETERMINE™ HBsAG RAPID TEST AS A POINT-OF-CARE SCREENING TOOL FOR THE DIAGNOSIS OF HEPATITIS B VIRUS INFECTION

The aim of this study was to compare the performance characteristics of the Determine HBsAg Rapid test with the automated AxSYM® HBsAg assay (Abbott Laboratories, Abbott Park, IL USA) and the manual Murex HBsAg Version 3 (DiaSorin S.p.A, Saluggia, Italy) assay

Availability, accessibility and use of antivenom for snakebite envenomation in Africa with proposed strategies to overcome the limitations

Africa remains one of the regions with the highest incident and burden of snakebite. The goal of the World Health Organization to halve the global burden of snakebite by 2030 can only be achieved if sub-optimal access to antivenoms in the most affected regions is addressed. We identified upstream, midstream, and downstream factors along the antivenom value chain that prevent access to antivenoms in the African region. We identified windows of opportunities that could be utilized to ensure availability, accessibility, and affordability for snakebite endemic populations in Africa. These include implementation of multicomponent strategies such as intensified advocacy, community engagement, healthcare worker trainings, and leveraging the institutional and governance structure provided by African governments to address the challenges identified

Serological and molecular infant results.

<p>Serological and molecular infant results.</p

Serological and molecular maternal results.

<p>Serological and molecular maternal results.</p