A study of the genital microbiotas of black South African women and men: associations with human papillomavirus and HIV infections

Persistent genital infection with oncogenic or high-risk human papillomavirus (HPV) is causally associated with cervical cancer in women and some penile cancers in men. The role of the complex genital microbiota in HPV infection has not been extensively addressed. This study characterised the genital microbiotas of heterosexually-active Black South African women and men, predominantly of the Xhosa ethnicity, recruited from a community in Cape Town, South Africa. The association of the genital microbiotas with prevalent HPV, HIV, demographic, behavioural, and clinical characteristics of the participants was examined. In Chapter 2 the bacterial communities in cervicovaginal samples from 62 HIVseronegative South African women were profiled by Ion Torrent PGM sequencing of the V4 hypervariable region of the bacterial 16S rRNA gene (IT-V4 method). The cervicovaginal microbiotas (CVMs) were found to cluster into three distinct community state types (CSTs): Lactobacillus iners-dominated CVMs (CST I (38.7%, 24/62)), unclassified Lactobacillusdominated CVMs (CST II (4.8%, 3/62)), and diverse CVMs (CST III (56.5%, 35/62)) with an array of heterogeneous bacteria, predominantly the bacterial vaginosis (BV)-associated Gardnerella, Prevotella, Sneathia, and Shuttleworthia. The majority of the women had nonLactobacillus-dominated CVMs. Lactobacilli are recognised as protective against sexually transmitted infections. Among the Lactobacillus species detected in the women, L. iners was the most prevalent and abundant. This species is recognised as the least protective amongst the vaginal lactobacilli. Women in CST I were more likely to be on hormonal contraception compared to women in CST III (relative risk (RR): 2.6 [95% CI 1.3-5.3]; p=0.005). Further research is required to confirm this association and to determine the biological mechanism. Microbiome research methodologies are constantly improving and in Chapter 3 the performance of two bacterial 16S rRNA gene amplicon-based methodologies were compared. The CVMs of 19 women were characterised using the IT-V4 method (Chapter 2) and using the Illumina 16S rRNA metagenomics method (IM-V3/V4 method). The latter method involves sequencing the V3 and V4 hypervariable regions of the 16S rRNA gene on the Illumina MiSeq platform. The two methods showed a high degree of correlation (r=0.89, p3, p3, p3, p 2, p<0.05) Men with BV-negative female sexual partners (66.5% (157/236)) had higher relative abundances of Lactobacillus in their penile microbiotas than men with BV-positive female partners (p=0.007). Atopobium, Sneathia, and Saccharofermentans were significantly more prevalent in men with BV-positive female partners than men with BV-negative partners (p<0.020). The main limitations of our study include relatively small sample size of women, insufficient participant information such as host genetics, other STIs (e.g., herpes simplex virus) and abnormal vaginal flora (e.g., aerobic vaginitis), using a less sensitive method to diagnose BV in women, and inherent biases evident in any retrospective study. Moreover, we did not adjust for confounding factors in our analysis due to the small sample size. Despite the underscored limitations, our findings provide insight into the baseline genital microbiotas of the Black South African women and men. The associations identified in this cross-sectional study between specific microbiota members and HPV infection, particularly the association between Sneathia and HPV/high-risk HPV infection, identified in both women and men, are hypothesis-generating and warrant further investigation. The study forms a critical starting point for future longitudinal confirmatory association studies and studies examining these bacteria as potential biomarkers or risk factors for HPV infection

An in vitro investigation of the phytochemical contents of Marsdenia macrantha root and its antibacterial activity against selected foodborne pathogens

Introduction:&nbsp;Marsdenia macrantha&nbsp;is a crucial source of traditional medicine in Northern Namibia. Its roots are used to treat various health conditions ranging from mouth infections to urinary retention. Despite its medicinal application, there is no known knowledge of its therapeutic properties. Thus, we investigated the phytochemical content and antibacterial activity of&nbsp;M. macrantha. Methods:&nbsp;M. macrantha&nbsp;root extracts were obtained using three different solvents (distilled water, methanol and acetone) - in the soxhlet and maceration extraction methods. Total phytochemical (terpenoid, alkaloid and/or flavonoid) content was determined by spectrophotometry. Antibacterial activity against common foodborne pathogens (Staphylococcus aureus,&nbsp;Escherichia coli&nbsp;and&nbsp;Salmonella typhi) was determined by both well and disc diffusion method. Results:&nbsp;we detected the presence of all the tested phytochemicals. Methanol gave the highest percentage yield of extraction (mean: 13.95 ± standard deviation: 0.41%) followed by water (10.92 ± 0.11%) and acetone (6.85 ± 0.23%), F-ratio=326.71 and p&lt;0.0003. The total content determined showed that&nbsp;M. macrantha&nbsp;root extract contained more flavonoids than alkaloids (mg of standard per grams of the dry material). Antibacterial analyses showed inhibitory activity against all the selected pathogens, with the highest inhibition zone against&nbsp;S. typhi&nbsp;(19.7 ± 0.3 mm) - for the acetone-prepared root extract. There were variations in minimum inhibitory concentrations of the extracts prepared by the different solvents. Conclusion:&nbsp;this is the first study demonstrating the presence of phytochemicals and antibacterial properties of&nbsp;M. macrantha&nbsp;roots. Further studies are needed to isolate and characterize the phytochemicals for antibacterial application

Influence of non-synonymous sequence mutations on the architecture of HIV-1 clade C protease receptor site : docking and molecular dynamics studies

Despite the current interventions to avert contagions and AIDS-related deaths, sub-Saharan Africa is still the region most severely affected by the HIV/AIDS pandemic, where clade C is the dominant circulating HIV-1 strain. The pol-encoded HIV-1 protease enzyme has been extensively exploited as a drug target. Protease inhibitors have been engineered within the framework of clade B, the commonest in America, Europe and Australia. Recent studies have attested the existence of sequence and catalytic disparities between clades B and C proteases that could upset drug susceptibilities. Emergence of drug-resistant associated mutations and combinatorial explosions due to recombination thwarts the attempt to stabilize the current highly active antiretroviral therapy (HAART) baseline. The project aimed at identifying the structural and molecular mechanisms hired by mutants to affect the efficacies of both FDA approved and Rhodes University (RU)-synthesized inhibitors, in order to define how current and or future drugs ought to be modified or synthesized with the intent of combating drug resistance. The rationale involved the generation of homology models of the HIV-1 sequences from the South African infants failing treatment with two protease inhibitors: lopinavir and ritonavir (as monitored by alterations in surrogate markers: CD4 cell count decline and viral load upsurge). Consistent with previous studies, we established nine polymorphisms: 12S, 15V, 19I, 36I, 41K, 63P, 69K, 89M, and 93L, linked to subtype C wild-type; some of which are associated with protease treatment in clade B. Even though we predicted two occurrence patterns of M46I, I54V and V82A mutations as V82A→I54V→M46I and I54V→V82A→M46V, other possibilities might exist. Mutations either caused a protracted or contracted active site cleft, which enforced differential drug responses. The in silico docking indicated susceptibility discordances between clades B and C in certain polymorphisms and non-polymorphisms. The RU-synthesized ligands displayed varied efficacies that were below those of the FDA approved protease inhibitors. The flaps underwent a wide range of structural motions to accommodate and stabilize the ligands. Computational analyses unravelled the need for these potential drugs to be restructured by (de novo) drug engineers to improve their binding fits, affinities, energies and interactions with multiple key protease residues in order to target resilient HIV-1 assemblages. Accumulating evidences on contrasting drug-choice interpretations from the Stanford HIVdb should act as an impetus for the customization of a HIVdb for the sub-Saharan subcontinent

The need for a balanced hospital-based care (HBC) and home- and community-based care (HCBC) approach for COVID-19 pandemic in sub-Saharan Africa

The onslaught of COVID-19 pandemic has greatly overwhelmed some of the best healthcare systems in the world. Medical practitioners working in hospitals at the epicenters of COVID-19 pandemic have emphasized on the need to manage mildly ill and convalescent COVID-19 patients at home or community facilities rather than at hospitals during a pandemic. In this article, we highlight that a standardized home- and community-based (HCBC) approach for management of COVID-19 patients will be a key component for preparing hospitals in sub-Saharan Africa (SSA) for a potential surge in COVID-19 cases. So far, based on the trajectory of infection, we think that SSA seems to have a window of opportunity, albeit narrowing, for implementing HCBC. However there are challenges that will need to be addressed in order to implement and maintain HCBC. Successful implementation and maintenance of HCBC in SSA will require international agencies and key donors to work closely with the national governments; providing them with policy, technical, and financial assistance. HCBC is also important because it can play a role in advocacy, education, training, and health promotion during COVID-19 pandemic. We further underscore the need for a delicate balance between HCBC and hospital-based care (HBC) approach as well as with COVID-19 mitigation and suppression measures in order to reduce the risk of SARS-CoV-2 community transmission and allow optimal continuity of the HBC. We conclude by emphasizing once again that, for countries in SSA to adequately prepare for the worst-case scenario of COVID-19 pandemic in the absence of a cure, policy makers of member states need to act collectively and fast.https://deepblue.lib.umich.edu/bitstream/2027.42/156028/1/REV_Onywera et al_AFM.pdfDescription of REV_Onywera et al_AFM.pdf : Main Articl

Evidence of negative energy balance using doubly labelled water in elite Kenyan endurance runners prior to competition

Previous studies have found Kenyan endurance runners to be in negative energy balance during training and prior to competition. The aim of the present study was to assess energy balance in nine elite Kenyan endurance runners during heavy training. Energy intake and expenditure were determined over 7d using weighed dietary intake and doubly labelled water, respectively. Athletes were on average in negative energy balance (mean energy intake 13 241 (SD 1330) kJ/d v. mean energy expenditure 14 611 (SD 1043) kJ/d; P=0·046), although there was no loss in body mass (mean 56·0 (SD 3·4) kg v. 55·7 (SD 3·6) kg; P=0·285). The calculation of underreporting was 13; (range −24 to +9%) and almost entirely accounted for by undereating (9% (range −55 to +39%)) as opposed to a lack of significant underrecording (i.e. total water intake was no different from water loss (mean 4·2 (SD 0·6) l/d v. 4·5 (SD 0·8) l/d; P=0·496)). Fluid intake was modest and consisted mainly of water (0·9 (SD 0·5) l/d) and milky tea (0·9 (SD 0·3) l/d). The diet was high in carbohydrate (67·3 (SD 7·8) %) and sufficient in protein (15·3 (SD 4·0) %) and fat (17·4 (SD 3·9) %). These results confirm previous observations that Kenyan runners are in negative energy balance during periods of intense training. A negative energy balance would result in a reduction in body mass, which, when combined with a high carbohydrate diet, would have the potential in the short term to enhance endurance running performance by reducing the energy cost of runnin

Prevalence of Overweight and Obesity among Primary School Children Aged 8-13 Years in Dar es Salaam City, Tanzania

Background. The understanding of obesity as a growing health problem in Africa and Tanzania in particular is hampered by lack of data as well as sociocultural beliefs in which overweight and obesity are revered. This study sought to determine the prevalence of overweight and obesity among primary school children aged 8-13 years in Dar es Salaam, Tanzania. Method. A cross-sectional analytical research design was used to study overweight and obesity in primary schools in Dar es Salaam, Tanzania. The target population was 150,000 children aged 8-13 years. Stratified random sampling was used to select 1781 children. Weight and height were taken and WHO standards for children were used to determine weight status. Results. Findings showed that the prevalence of overweight and obesity was 15.9% and 6.7%, respectively ( = 1781). However, 6.2% of the children were underweight. There were significant differences in mean BMI between children in private and public schools ( = 0.021), between male and female ( &lt; 0.001), and across age groups of 8-10 and 11-13 years ( &lt; 0.001). Conclusion. The prevalence of overweight and obesity among primary school children is significant and requires management and prevention strategies

Comparative study of physical activity patterns among school children in Kenya and Canada: Results from the ISCOLE Project

Abstract Examination of the timing and patterns of daily activity are crucial in understanding when children accumulate the highest levels of physical activity. The objectives of this study were to examine moderate-to-vigorous physical activity (MVPA) patterns accrued by time of day among Kenyan children, and compare activity patterns in Kenya to those of Canadian children. Physical activity and body weights of participating children were measured by accelerometry and anthropometry, while supplementary self-report data were captured by questionnaires. Data were collected as part of a larger International Study of Childhood Obesity, Lifestyle and Environment (ISCOLE) in Nairobi for ISCOLE-Kenya and in the Ottawa Region for ISCOLE-Canada. A total of 555 Kenyan and 541 Canadian children 9 to 11 years were included in the analyses. In Kenya, boys, under/healthy weight, and children attending public (lower socioeconomic status (SES)) schools were found to have significantly higher MVPA levels compared to girls, overweight/obese, and children attending private (higher SES) schools respectively. MVPA on weekdays was higher than on weekend-days. Activity profiles among Kenyan and Canadian children were very similar; however, Kenyan children had significantly higher MVPA and lower sedentary time on weekend-days. MVPA patterns among urban Kenyan children were largely similar to those of urban Canadian children when assessed by sex, BMI category, and weekday/weekend days. However, in the Kenyan sample, unlike in many higher income countries, lower SES was associated with higher MVPA

NEWS for Africa : adaptation and reliability of a built environment questionnaire for physical activity in seven African countries

This study reports on the adaptation and test-retest reliability of the Neighborhood Environment Walkability Scale in seven sub-Saharan African countries (NEWS-Africa). The measure will be useful for surveillance of built environment conditions for planning purposes, and to evaluate physical activity and policy interventions in Africa, two effective strategies for controlling deaths from physical inactivity-related non-communicable diseases. This report includes data collection and analysis, as well as a discussion of findings

Sleep characteristics and health-related quality of life in 9- to 11-year-old children from 12 countries

IntroductionPrevious studies have linked short sleep duration, poor sleep quality, and late sleep timing with lower health-related quality of life (HRQoL) in children. However, almost all studies relied solely on self-reported sleep information, and most studies were conducted in high-income countries. To address these gaps, we studied both device-measured and self-reported sleep characteristics in relation to HRQoL in a sample of children from 12 countries that vary widely in terms of economic and human development.MethodsThe study sample included 6,626 children aged 9-11 years from Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, the United Kingdom, and the United States. Waist-worn actigraphy was used to measure total sleep time, bedtime, wake-up time, and sleep efficiency on both weekdays and weekends. Children also reported ratings of sleep quantity and quality. HRQoL was measured by the KIDSCREEN-10 survey. Multilevel regression models were used to determine the relationships between sleep characteristics and HRQoL.ResultsResults showed considerable variation in sleep characteristics, particularly duration and timing, across study sites. Overall, we found no association between device-measured total sleep time, sleep timing or sleep efficiency, and HRQoL. In contrast, self-reported ratings of poor sleep quantity and quality were associated with HRQoL.ConclusionsSelf-reported, rather than device-based, measures of sleep are related to HRQoL in children. The discrepancy related to sleep assessment methods highlights the importance of considering both device-measured and self-reported measures of sleep in understanding its health effects