Department of Microbiology / PhD (Microbiology) / Human herpes virus type 8 (HHV-8), also known as Kaposi’s sarcoma associated
herpes virus (KSHV), is the etiologic agent of Kaposi’s sarcoma (KS), and AIDS
related Kaposi’s sarcoma (AIDS-KS). HHV-8 which is a member of the Herpesviridae
family, exhibits extensive genetic diversity globally. In endemic regions, infection with
HHV-8 occurs very early on in life, which is an indication of both environmental and
vertical routes of transmission. The advent of HIV leads to the classification of an
AIDS-KS defining condition in HIV infections. This suggests that in regions where HIV
and HHV-8 are endemic, KS may become common in a mature HIV epidemic. Just
like the prevalence of HIV in Northern South Africa is generally high as in most regions
of the country, as the HIV epidemic matures in South Africa, it is important to
understand the burden and distribution of HHV-8 infection, and the likely genotypes
infecting the population. The main objective of the thesis was to establish the
epidemiology and infecting genotypes of HHV-8 in Northern South Africa (Limpopo
Province), where no data exists.
First, a systematic review of the literature was carried out for the entire African
continent to determine the seroprevalence and genotype distribution of HHV-8 in all
African countries (n=53). In this review, Sudan and South Sudan were considered as
one country. Articles were searched using the PRISMA guideline and exported using
an article grid. More than two-thirds (64%) of the studies reported on seroprevalence,
29.3% on genotypes; and 9.5% were on both seroprevalence and genotypes. About
45% (24/53) of the African countries had data on HHV-8 seroprevalence exclusively,
and more than half (53%) had data on either seroprevalence or genotypes. Almost
half (47%) of the countries had no data on HHV-8 infection. There was high
heterogeneity in the types of tests and interpretation algorithms used in determining
HHV-8 seropositivity across the different studies.
Generally, seroprevalence ranged from 2.0% in a group of young children in Eritrea to
100% in a small group of individuals with KS in the Central Africa Republic and a larger
group of KS in individuals in Morocco. Approximately, 16% of all the studies reported
on children. The difference in seroprevalence across the African region was not
significant (95% CI, X2 =0.86; p =0.35), although specifically, a relatively significant
ETTA MASHU ELIZABETH, PHD IN MICROBIOLOGY|UNIVERSITY OF VENDA, 2019|VIII
level of infection was observed in HIV-infected children. About 38% of the countries
had data on K1 genotypes A, A5, B, C, F and Z which occurred at frequencies of 5.3%,
26.3%, 42.1%, 18.4%, 5.3% and 2.6% respectively. Twenty-three percent of the
countries had data for K15 genotypes, whereas genotypes P, M and N occurred at
frequencies of 52.2%, 39.1% and 8.7% respectively. Data on HHV-8 inter-genotype
recombinant is scanty. Our finding suggests that HHV-8 is endemic on the entire
African continent, and in HIV endemic regions, but there is need for a harmonized
testing protocol for better understanding of HHV-8 seropositivity. HHV-8 genotype A5
and B for K1 gene and genotype P and M for K15 gene are the most predominant
genotypes in Africa. The review, for the first time, has provided information on HHV-8
burden on the entire African continent, and suggests that vaccine development efforts
for Africa should focus on genotypes B and P.
The second component of the investigation focused on the burden of HHV-8 in an HIV
population in Northern South Africa (Limpopo Province). Plasma from 3501 HIV
infected individuals from 5 districts in Limpopo Province were assessed for antibodies
to both the lytic antigen (ORFK8.1) and the latent antigen (ORF73). The distribution of
infection was analyzed based on demographic, socioeconomic, and immunological
parameters. Statistical inferences for significant differences were determined by Chisquare
at a confidence interval of 95%. P-values less than 0.05 were considered
significant. About 19.0% of the study population was positive for antibodies to either
the lytic or latent antigens or both. Prevalence of antibodies to the lytic antigen was
significantly higher than prevalence of antibodies to the latent antigen (17.3% vs 4.1%;
p=0.0001). Significant differences were observed for age groups, racial population
groups, districts and year of sample collection (p=<0.0001, p=<0.0001, p=<0.0001 and
p=0.0385) respectively. Associations were found between both antigens in
comparison to the different variables such as age group, racial population groups and
districts (R2 value ranging between 0.886 and 1.0). The burden of HHV-8 has now
been established for the first time in Northern South Africa.
The third aspect of the investigation was a meta-analysis of HHV-8 seroprevalence in
Southern Africa in order to understand the impact of geographical location (urban vs
rural) on infection. The analysis revealed a significant association between urban
settings and HHV-8 infection (p=0.0001).
ETTA MASHU ELIZABETH, PHD IN MICROBIOLOGY|UNIVERSITY OF VENDA, 2019|IX
The fourth component of the thesis examined the detection of HHV-8 antigen through
polymerase chain reaction (PCR) in 534 participants in HIV infected and HIV noninfected
populations. A selection of mouthwash DNA samples were subjected to Next
Generation Sequencing (NGS) for subsequent genotype inference. Mouth wash
samples were obtained from each consenting individual before eating or smoking, and
their DNA was purified. A 233bp fragment of the ORF26 gene of HHV-8 was amplified
by PCR. HHV-8 was detected in 150 of the 534 participants (28.1%). A significant
difference in detection was observed for gender, HIV status, district and the level of
education (p=0,0003; p=0.0094; p=0.0002 and p=0.0095) respectively. Consensus
sequences were derived from NGS reads for 13 samples. The genotyping results
revealed that genotype Q, B, E and N are the genotypes predominant in the study
population. As such no mixed infections were detected.
Therefore, from the investigations foregoing have demonstrated for the first time the
following: (1) HHV-8 is endemic in the entire African continent, which suggest a coendemicity
in regions already endemic for HIV; (2) HHV-8 is endemic in Northern
South Africa; (3) Urban settings in Southern Africa are associated with high HHV-8
infection; (4) HHV-8 genotypes Q, B, E and N may be predominant in Northern South
Africa, with B and P common on the entire African continent. Hence, studies should
focus on the generation of full length HHV-8 genomes of the common genotypes to
support the selection of genes for vaccine design and development. / NRF
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:univen/oai:univendspace.univen.ac.za:11602/1287 |
| Date | 16 May 2019 |
| Creators | Etta, Elizabeth Mashu |
| Contributors | Bessong, Pascal Obong, Mavhandu - Ramarumo, Lufuno Grace |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 1 online resource (xxi, 191 leaves : color illustrations, color maps) |
| Rights | University of Venda |
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