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Item Open Access Enteric pathogen co-infections in the paediatric population from rural communities in the Vhembe District, South Africa(2018-06-18) Ledwaba, S. E.; Kabue, J. P.; Barnard, T. G.; Traore, A. N.; Potgieter, N.Background. Enteric pathogens co-infections are a serious health risk in children under the age of 5 years. Objective. The study aimed to determine the prevalence of diarrhoea-causing pathogens in children suffering from diarrhoea in rural communities of the Vhembe District. Methods. A cross-sectional study was conducted from July 2014 to June 2015. Diarrhoeal stool specimens (N=237) were collected from children attending primary healthcare facilities in rural communities of the Vhembe District. Stools were screened for enteric viral adenovirus 40/41, rotavirus and norovirus pathogens by means of enzyme immuno-assay (EIA) and enteric bacterial Escherichia coli spp. (diarrhoeagenic pathotypes), Shigella spp., Salmonella spp. and Vibrio spp. pathogens by means of multiplex polymerase chain reaction. Results. A total of 59.1% (140/237) were positive for at least one or more enteric pathogens. Enterotoxigenic E. coli (ETEC) (27.9%), enteroaggregative E. coli (EAEC) (26.8%) and atypical enteropathogenic E. coli (EPEC) (17.9%) were frequently detected in children less than 2 years of age. Bacterial-bacteria co-infections were detected in 24.5% (n=58) and bacterial-viral co-infections in 14.3% (n=34) of the stool specimens. Conclusion. The findings indicated that enteric pathogen co-infections are major causes of diarrhoea in children less than 2 years of age in the Vhembe District.Item Open Access Ethnobotanical evaluation of selected medicinal plants used in treatment of diseases around Venda: A literature review(2017-07) Sigidi, Muendi; Traore, Afsatou-Ndama; Tshisikhawe, Milingoni Peter; Potgieter, NatashaThe importance of traditional medicine has been recorded throughout the world. It has also been practiced throughout Africa by more than 80 % of rural communities. Traditional medicine has since been imbedded in the culture of many rural communities. People of the world continues to use traditional medicine because of their accessibility and affordability. The use of medicinal plants around the Venda region is vast, yet the published data on the various plants is scanty. The review aims to bring forth the knowledge of the most widely used plants among the Vhavenda population. The data was compiled from peer reviewed and non-peer reviewed journals, textbooks, thesis and also by interviews conducted with the traditional healers. The review revealed that there are a number of traditional medicines that are being preferred by traditional healers in their practice, the use of the selected plants in literature has never reported to be used in curing HIV/AIDS and its related illnesses. Most of the plants recorded were found to have active compounds in most of their organs. Plants are great sources for the discovery of new medicines. Natural products and their synthetics can be utilized in the development of highly useful drugs through chemical procedures and isolation followed by analog synthesis through modern medicinal mechanisms. The knowledge and understanding of each utilized medicinal plant is of great importance for it is through the discovery of newer potential drugs that the emerging life threatening infections can be effectively combated. With the increasing rate of people migrating from either rural – urban or vice versa, the natural habitats for such herbal plants is in the process of being completely destroyed without preservation of the naturally important plant species. The fear is of losing such important plant from the local communities thus losing valuable and future vital drugs. (Less)Item Open Access Further screening of Venda medicinal plants for activity against HIV type 1 reverse transcriptase and integrase(2006-03-15) Bessong, Pascal O.; Rojas, Luis B; Obi, Larry C.; Tshisikhawe, Peter M.; Igunbor, Eunice O.The use of medicinal plants for AIDS-related conditions is common in South Africa. In order to establish an antiviral rationale for the use of these plants we screened fractions of the methanol extracts of medicinal plants for activity against HIV-1 reverse transcriptase (RT) and integrase (IN). The n-butanol fraction obtained from the crude methanol extracts of the roots of Bridelia micrantha (Hochst) Baill. (Euphorbiaceae) was observed to be as the most active inhibiting the RNA-dependent-DNA polymerization (RDDP) activity of HIV-1 RT with an IC50 of 7.3 g/ml. However, it had no activity on the 3’-end processing activity of HIV integrase. Bioassay-guided fractionation of the n-butanol fraction yielded friedelin and -sistosterol, which did not inhibit the RDDP of RT or 3’-end processing functions of IN even at a concentration of 500 M. An uncharacterized fraction obtained in the bioassay-guided fractionating process inhibited the RDDP with an IC50 of 9.6 g/ml, but had no inhibition on IN. Phytochemical screening indicated the presence of flavonoids and tannins in the uncharacterized fraction.Item Open Access Serologic and genotypic characterization of hepatitis B virus in HIV-1 infected patients from South West and Littoral Regions of Cameroon(BioMed Central, 2016) Magoro, Tshifhiwa; Gachara, George; Mavhandu, Lufuno; Lum, Emmaculate; Kimbi, Helen K.; Ndip, Roland N; Bessong, Pascal ObongBackground: HBV and HIV share similar transmission routes. Concurrent infection with the two viruses usually results in more severe and progressive liver disease, and a higher incidence of cirrhosis, liver cancer and mortality. Further, this co-infection may lead to cross-resistance between HIV and HBV drugs and increased liver injury, either due to direct hepatotoxicity or drug-related immune-reconstitution hepatitis. These challenges necessitate continuous surveillance for HBV among HIV infected individuals to guide patient management. We conducted this study to understand the serologic and genotypic characteristics of HBV among HIV/HBV infected patients in South West and Littoral Regions of Cameroon. Methods: Plasma samples were screened for HBsAg, HBeAg, Anti-HBs and anti-HBc using ELISA followed by DNA extraction from all HBsAg positive samples. A 366 bp region covering the overlapping surface/polymerase gene was amplified by a nested PCR and the product sequenced using Big Dye sequencing chemistry. The resulting sequences were then analyzed for genotypes and both escape and drug resistance mutations. Results: Of the 455 samples in this study, 25.5 % (n = 116) were HBsAg positive and 46 of these had their DNA successfully amplified. Genotype E was found in 32 samples (69.6 %) and genotype A in the rest of the samples. Escape mutations associated with failure of diagnosis (Y100C, R122K and Q129H) and with vaccine escape (Q129R and T131N) were detected in varying frequencies in the population. Polymerase mutations implicated in resistance to lamivudine and other ʟ-nucleoside analogues were detected in seven patients (15.2 %), while all the samples lacked mutations associated with resistance to adefovir and tenofovir. Conclusions: These findings suggest the endemicity of HBV and the predominance of genotypes A and E in the study population. Also, drug resistance findings support the use of tenofovir based ART regimens among HIV/HBV co-infected persons. There is need for continuous HBV screening and monitoring in HIV infected individuals in these regionsItem Open Access Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: an Individual-Patient-and Sequence-Level-Meta-Analysis(2015-04-07) Rhee, Soo-Yon; Blanco, Jose Luis; Jordan, Michael R.; Taylor, J.; Lemmey, Philippe; Varghese, ViciBackground Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and de- signing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. Methods and Findings We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study se- quences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/ Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05–1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse tran- scriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06–1.25), North America (OR = 1.19; 95% CI: 1.12–1.26), Europe (OR = 1.07; 95% CI: 1.01–1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12–1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92–1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-asso- ciated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevira- pine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resis- tance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent lim- itations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. Conclusions Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resis- tance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimenItem Open Access Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED)(Lancet Glob Health, 2015) Platts-Mills, James A.Background Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specifi c diarrhoea burdens in the community. Methods We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defi ned as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identifi ed through twice-weekly home visits by fi eldworkers over a follow-up period of 24 months. Non-diarrhoeal stool specimens were also collected for surveillance for months 1–12, 15, 18, 21, and 24. Stools were analysed for a broad range of enteropathogens using culture, enzyme immunoassay, and PCR. We used the adjusted attributable fraction (AF) to estimate pathogen-specifi c burdens of diarrhoea. Findings Between November 26, 2009, and February 25, 2014, we tested 7318 diarrhoeal and 24 310 non-diarrhoeal stools collected from 2145 children aged 0–24 months. Pathogen detection was common in non-diarrhoeal stools but was higher with diarrhoea. Norovirus GII (AF 5·2%, 95% CI 3·0–7·1), rotavirus (4·8%, 4·5–5·0), Campylobacter spp (3·5%, 0·4–6·3), astrovirus (2·7%, 2·2–3·1), and Cryptosporidium spp (2·0%, 1·3–2·6) exhibited the highest attributable burdens of diarrhoea in the fi rst year of life. The major pathogens associated with diarrhoea in the second year of life were Campylobacter spp (7·9%, 3·1–12·1), norovirus GII (5·4%, 2·1–7·8), rotavirus (4·9%, 4·4–5·2), astrovirus (4·2%, 3·5–4·7), and Shigella spp (4·0%, 3·6–4·3). Rotavirus had the highest AF for sites without rotavirus vaccination and the fi fth highest AF for sites with the vaccination. There was substantial variation in pathogens according to geography, diarrhoea severity, and season. Bloody diarrhoea was primarily associated with Campylobacter spp and Shigella spp, fever and vomiting with rotavirus, and vomiting with norovirus GII. Interpretation There was substantial heterogeneity in pathogen-specifi c burdens of diarrhoea, with important determinants including age, geography, season, rotavirus vaccine usage, and symptoms. These fi ndings suggest that although single-pathogen strategies have an important role in the reduction of the burden of severe diarrhoeal disease, the eff ect of such interventions on total diarrhoeal incidence at the community level might be limited.Item Open Access A putative HIV-1 subtype C/CRF11_cpx unique recombinant from South Africa(Springer, 2016) Bessong, Obong Pascal; Iweriebor, BensonThe HIV epidemic in South Africa is overwhelmingly driven by HIV-1 subtype C viruses. The HIV gag, pol, env (C2-V5) and nef sequences of virus 08MB26ZA, obtained from a 47 year old woman, were studied by phylogenetic analysis, REGA and the jumping Profile Hidden Markov Model (jPHMM) tools. The pol gene was further analyzed for recombination by Simplot. The pol and env sequences were examined for genetic drug resistance mutations and predicted co-receptor usage respectively. There was agreement in the assignment of the gag sequence as pure HIV-1 subtype C by phylogenetic, REGA and jPHMM analyses. The pol sequence clustered with CRF11_cpx and in the J-clade by phylogenetic analysis; and to a CRF11_cpx/subtype C recombinant by REGA. The assignment of pol to CRF11_cpx and subtype C was confirmed by Simplot. The recombinant was of the R5 biotype, with no important drug resistance mutations in the pol region. The epidemiologic and biologic significance of the virus are unknown. The finding suggests that complex viruses are being introduced into South Africa with potential implications for diagnosis. This is apparently the first report from South Africa of a putative unique recombinant involving CRF11_cpx and subtype C genomes.Item Open Access Genetic Variants of APOC3 Promoter and HLA-B genes in an HIV Infected Cohort in Northern South Africa: A Pilot Study(Molecular Diversity Preservation International (MDPI), 2014-06-26) Masebe, Tracy; Bessong, Obong Pascal; Ndip, Roland Ndip; Meyer, DebraMetabolic disorders and hypersensitivities affect tolerability and impact adherence to highly active antiretroviral therapy (HAART). The aim of this study was to determine the prevalence of C-482T/T-455C variants in the Apolipoprotein C3 (APOC3) promoter gene and Human leukocyte antigen (HLA)-B*57:01, known to impact lipid metabolic disorders and hypersensitivity respectively; and to correlate genotypes with gender, CD4+ cell count and viral load in an HIV infected cohort in northern South Africa. Frequencies of C-482 and T-455 polymorphisms in APOC3 were determined by restriction fragment length polymorphism analysis. Allele determination for HLA-B was performed with Assign SBT software in an HLA library. Analysis of APOC3 C-482 site revealed a prevalence of 196/199 (98.5%) for CC, 1/199 (0.5%) for CT and 2/199 (1.0%) for TT genotype (p = 0.000 with 1° of freedom; χ2 = 126.551). For the T-455 site, prevalences were: 69/199 (35%) for TT and 130/199 (65%) for the CC genotype (p = 0.000 with 1° of freedom; χ2 = 199). There was no association between gender and the presence of −482 (p = 1; χ2 = 0.00001) or −455 genotypes (p = 0.1628; χ2 = 1.9842). There was no significant difference in the increase in CD4+ cell count irrespective of genotypes. Significant increases in CD4+ cell count were observed in males and females considering the −455C OPEN ACCESS Int. J. Mol. Sci. 2014, 15 11404 genotype, but not in males for the −455T genotype. Viral load decreases were significant with the −455C and −482C genotypes irrespective of gender. HLA-B*57:01 was not identified in the study cohort. The apparently high prevalence of APOC3 T-455CC genotype needs confirmation with a larger samples size and triglyceride measurements to support screening of patients to pre-empt HAART associated lipid disorders.Item Open Access Malaria infection and anaemia in HIV-infected children in Mutengene, South west Cameroon: a cross sectional study(BioMed Central, 2016) Bate, Ayukenchengamba; Kimbi, Helen K.; Lum, Emmaculate; Lehman, Leopold G.; Onyoh, Elias F.; Ndip, Lucy M.; Njabi, Conica M.; Tonga, Calvin; Wempnje, Godlove B.; Ndip, Roland N; Bessong, Pascal O.Background: Malaria is one of the leading causes of morbidity and mortality in children and HIV infection as well as other factors may worsen the situation. This study was aimed at determining the factors influencing malaria parasite prevalence and density as well as anaemia in HIV-infected children in Mutengene, Cameroon from November, 2012 to April, 2013. Methods: A semi-structured questionnaire was used to record information on socio-demographic factors and use of preventive measures by caregivers of HIV-infected children aged 1–15 years and of both sexes. Venous blood was collected; blood films were prepared and Giemsa-stained for parasite detection and speciation. Haemoglobin concentration was measured and the anaemic status determined. Data was analysed using Epi Info 7 software. Results: A total of 234 children were studied. The overall malaria parasite prevalence was 24.8 % (58) and was significantly higher (31.9 %, P = 0 .004) in females, those who did not implement any preventive measure at all (66.7 %, P = 0.03) and children who used antiretroviral therapy (ART) (28.6 %, P = 0.02) when compared with their respective counterparts. Geometric mean parasite density (GMPD) was significantly higher (3098.4, P = 0.02) in children who presented with fever, had CD4 T cells ≥500 cells/μL (491.3, P = 0.003) and those with moderate anaemia (1658.8, P = 0.03) than their respective counterparts. Although there was no significant difference, GMPD was however higher in males (549.0); those not on ART (635.0) and highest in children <5 years old (633.0) than their respective counterparts. The overall prevalence of anaemia was 49.6 % (116). The value was significantly highest (58.3 %, P = 0.01) in the 11–15 years age group; those with CD4 T cell level 200–499 (72.7 %, P = 0.001) and children with fever (85.7 %, P = 0.01). Conclusion: Implementation of proper and integrated malaria preventive measures as well as frequent monitoring of anaemia on prescription of ART could likely improve the health conditions of HIV-infected children thus avoiding malaria-related morbidity and mortality.Item Open Access Genetic analysis of HIV-1 integrase sequences from treatment naive individuals in Northeastern South Africa(Molecular Diversity Preservation International (MDPI), 2013-03-01) Bessong, Pascal Obong; Nwobegahay, JuliusRaltegravir, an integrase inhibitor, is not a component of the current South African antiretroviral treatment guidelines, but it could be introduced in the near future as cases of virological failures from current treatment regimens begin to occur. The aim of this study was to analyze the complete HIV integrase gene obtained from individuals at two treatment sites in northeastern South Africa for the presence of Raltegravir associated drug resistant mutations and viral subtypes based on the integrase gene. Examination for mutations against other integrase inhibitors, such as Elvitegravir and Dolutegravir, was also done. Viruses from 127 treatment naive individuals were analyzed. Genetic drug resistance mutations were determined using the Stanford HIV Drug Resistance Interpretation program and the International AIDS society-USA guidelines. Viral subtyping was done by phylogenetic analysis, and recombinants were determined using the REGA, jpHMM and RIP tools. No major resistance mutations were detected. However, 7% of the sequences had minor mutations and polymorphisms. The majority (99%) of the viruses were HIV-1 C. Recombination analysis showed that the polymerase gene of one virus was likely composed of HIV-1 subtype A1 and C sequences. The present study indicates that Raltegravir, Elvitegravir and Dolutegravir resistant mutations may be absent in the study communities and further indicates the presence of recombinant viruses in northeastern South Africa.