Prevalence and risks of Hepatitis E virus infection in blood donors from the Western Cape, South Africa

Lopes, Tatum (2016-03)

Thesis (MSc)--Stellenbosch University, 2016.

Thesis

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.

AFRIKAANSE OPSOMMING: Hepatitis E virus (HEV) is een van die grootste oorsake van akute hepatitis wêreldwyd en is algemeen bekend as 'n plaaslike siekte in baie ontwikkelende lande. Maar HEV infeksie wat oorgedra word in ontwikkelde lande word nie net meer verbind met reise na ander lande waar HEV infeksie dikwels voorkom nie. HEV word geklassifiseer in vier hoof genotipes en dit kom voor as twee kontrasterende kliniese entiteite. HEV genotipes 1 (HEV1) en (HEV 2) is verwant aan water oordrag en swak sanitasie, terwyl genotipes 3 (HEV3) en 4 (HEV4) geassosieer word met soönotiese oordrag wat hoofsaaklik plaasvind deur varke, wilde varke en takbokke. HEV infeksies in Afrika is vermoedelik veroorsaak deur HEV1 en HEV2. Verskeie gevalle is beskryf in Suider-Afrika, maar dit was reeds meer as 10 jaar gelede, toe toetse nog nie goed ontwikkel was nie. Suid-Afrika het drie HEV uitbrake gerapporteer; 'n hospitaal uitbraak, en twee serologiese voorkoms verslae in spesifieke gemeenskappe van Suid-Afrika. Die serologiese voorkoms van hierdie studies het gewissel vanaf 2% tot 10,7% en geen genotipering was gedoen nie. Navorsers het bewys dat direkte en indirekte-bloedoortapping oordraagbare infeksie van HEV moontlik is en 'n potensiële risiko vir ontvangers van bloedoortappings beskryf. Asimptomatiese HEV infeksies in bloed skenkers verhoog die waarskynlikheid dat die bloed of bloed produkte geïnfekteer is met HEV virale partikels. As gevolg daarvan is daar 'n groter kans dat hoë-risiko ontvanger groepe met verswakte immuunstelsels geïnfekteer mag word. Daarom was die hoofdoel van hierdie studie om die voorkoms van vorige en aktiewe HEV infeksie in bloed skenkers van die Wes-Kaap te bepaal. Ons het ook ondersoek watter risiko faktore verband hou met infeksie. Ons studie het bestaan uit 10,250 bloed skenkers wat getoets was as deel van twee sub-studies. Vir studie groep 1 het ons 250 skenkers gewerf om 'n HEV risiko vraelys te voltooi. Hierdie skenkers was getoets met behulp van 'n indirekte Wantai toets (Fortress Diagnostics) vir die identifisering van anti-HEV IgG. Daarna was statistiese analise gedoen om te bepaal wat die demografie en risiko faktore is wat verband hou met die voorkoms van vorige HEV infeksie. Benewens hierdie was hul plasma monsters saamgevoeg, voor ekstraksie en amplifikasie met 'n in-huis intydse omgekeerde transkriptase-kwantitatiewe polimerase kettingreaksie (PKR) om HEV RNS te spoor. Die 10,000 bloed skenkers van studie groep 2 was getoets as individuele skenkings met die gebruik van 'n kommersiële Procleix HEV NST toets om HEV RNS deur transkripsie amplifikasie te kwantifiseer. Daarna is herhaalde reaktiewe skenkings gekwantifiseer met behulp van ons in-huis intydse omgekeerde transkriptase-kwantitatiewe PKR. Die totale serologiese voorkoms van antiliggame teen HEV vir ons studie was 42,4% in bloedskenkers (studie groep 1). Risiko analise het aan die lig gebring dat om kalkoen (p=0.001) en orgaan vleis te eet (p=0.026) wat aanleiding gee tot ‘n voedselverwante oordrag van HEV3, en kanovaart (p=0.017) wat deur middel van water lei tot oordrag van HEV1, hou beduidend verband met die voorkoms van vorige HEV infeksie. Direkte kontak met hase (p=0.045) of hoenders (p=0.020) was beduidend statisties ‘n metode van HEV blootstelling wat verband hou met HEV3 of HEV4. Verder het ons gevind dat die totale HEV RNS voorkoms vir ons studie 0,009% (1/10,250) was. Studies is nodig om die risiko van HEV stygende oordrag verder te evalueer en om die epidemiologie in ons omgewing te verstaan.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/98691
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