Epidemiology and Biostatistics

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Acute pain in the African prehospital setting : a scoping review
(Hindawi, 2019) Lourens, Andrit; McCaul, Michael; Parker, Romy; Hodkinson, Peter
Background. Acute pain is a common reason for seeking prehospital emergency care. Regrettably, acute pain is often underestimated and poorly managed in this setting. The scoping review was conducted to gain insight into existing research on the topic and to make recommendations for future work. Objectives. To identify all available evidence related to acute pain assessment and management in the African prehospital setting, describe the extent of the evidence, encapsulate findings, and identify research gaps. Methods. The scoping review considered primary and secondary research related to acute pain assessment and management of both medical and traumatic origins in all age groups in the African prehospital setting. The search strategy aimed to identify published, unpublished, and ongoing research which met the inclusion criteria. Potentially eligible studies were identified by a comprehensive search of electronic databases, trial registers, dissertation/thesis databases, grey literature databases, and conference proceedings. Screening and data extraction were conducted independently and in duplicate. Results. The comprehensive search identified 3823 potential studies, duplicate titles were removed, and 3358 titles/abstracts were screened. Full text of 66 potentially eligible titles was screened, 60 were excluded, and six publications met the inclusion criteria. Despite recommendations for pain assessment during general patient care, most studies reported no/limited pain assessment. In general, pain management was concluded to be insufficient and not conforming to best practice. Conclusions. Only six publications addressing prehospital acute pain care in Africa could be identified, possibly indicative of a knowledge gap. Future research is indicated to enable a better understanding of the epidemiology of acute pain and barriers and enablers of acute pain care and to develop evidence-based clinical practice guidelines (CPGs) catering for all EMS systems in Africa. Additionally, educational initiatives should be implemented to improve the quality of acute pain care and to monitor quality through continuous quality improvement (CQI) programs.
Adherence to isoniazid preventive therapy among child contacts in Rwanda : a mixed-methods study
(Public Library of Science, 2019-02-11) Birungi, Francine Mwayuma; Graham, Stephen Michael; Uwimana, Jeannine; Musabimana, Angele; Van Wyk, Brian
Background: The World Health Organization recommends isoniazid preventive therapy (IPT) for six months for child contacts without tuberculosis (TB), who are exposed to an adult with active TB. The effectiveness of IPT depends on 80% or greater adherence to medication. In the current study, we assessed IPT adherence and explored barriers to and facilitators of adherence among eligible child contacts in Kigali, Rwanda. Methods: A mixed method study design was used to prospectively assess adherence to IPT among eligible child contacts and its associated factors through a quantitative, observational cohort study, and to explore barriers to and facilitators of adherence to IPT through a descriptive qualitative study. Results: Of the 84 child contacts who started IPT, 74 (88%) had complete adherence and ten (12%) had incomplete adherence. There were no factors (individual characteristics of index cases, households and or health facility characteristics) found to be significantly associated with IPT adherence in the bivariate and multivariate analysis. In the qualitative analysis, we identified factors relating to parents/caregivers, disease, household and health-care providers as major themes determining IPT adherence. Conclusion: There was a high rate of IPT completion in this cohort of eligible child contacts living in Kigali. However, structural factors (poverty and relocation) were found to be the main barriers to IPT adherence that could be addressed by health-care providers.
Alcohol marketing and adolescent alcohol consumption : results from the International Alcohol Control study (South Africa)
(Health & Medical Publishing Group, 2018-08-28) Morojele, N. K.; Lombard, C.; Harker Burnhams, N.; Petersen Williams, P.; Nel, E.; Parry, C. D. H.
Background. A complete ban on alcohol advertisements has been proposed for South Africa (SA), but there has been limited local research on the association between exposure to alcohol advertisements and alcohol consumption. Objectives. To examine the role of demographic factors, exposure to alcohol marketing and liking of alcohol advertisements in predicting use of alcohol in the past 6 months among older adolescents in Tshwane, Gauteng Province, SA. Methods. Participants comprised the adolescent sub-sample (N=869) of the International Alcohol Control study survey that was conducted in SA. They consisted of 408 males and 461 females aged 16 and 17 years who took part in structured interviews on their alcohol consumption and various alcohol-related attitudes and behaviours. A multiple survey logistic regression analysis of the dependent variable alcohol use in the past 6 months on the independent variables age, gender, educational status, socioeconomic status, exposure to alcohol brand marketing and liking of alcohol advertisements was used. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Results. The prevalence of drinking in the past 6 months was 10.6% (95% CI 5.9 - 18.3). The number of modes of alcohol brand/product advertising to which the adolescents were exposed was positively associated with alcohol use in the past 6 months. An additional mode of alcohol brand/product advertising exposure led to a relative increase of 1.13 (95% CI 1.01 - 1.28) in the odds of alcohol use in the past 6 months (e.g. a participant who was exposed to advertisements via seven different channels was 2.08 times more likely to have used alcohol in the past 6 months than a participant with exposure via a single channel). Having a strong dislike of alcohol advertisements was associated negatively (protective) with alcohol use in the past 6 months, with the odds ratio being 0.35 (95% CI 0.19 - 0.64). Having only a moderate dislike or a liking of alcohol advertisements was positively associated with alcohol use in the past 6 months among the study participants (OR 2.90 and 2.84, respectively). Age, gender, educational status and socioeconomic status were not independently associated with alcohol consumption. Conclusions. Exposure to alcohol marketing and not being strongly averse to advertisements of alcohol brands and products were associated with alcohol use among adolescents. The results have implications for policies on alcohol marketing in SA.
Ambient air pollution and health in Sub-Saharan Africa : current evidence, perspectives and a call to action
(Elsevier, 2019) Katoto, Patrick D. M. C.; Byamungu, Liliane; Brand, Amanda S.; Mokaya, Jolynne; Strijdom, Hans; Goswami, Nandu; De Boever, Patrick; Nawrot, Tim S.; Nemery, Benoit
Background: People from low- and middle-income countries are disproportionately affected by the global burden of adverse health effects caused by ambient air pollution (AAP). However, data from Sub-Saharan Africa (SSA) are still scarce. We systematically reviewed the literature to describe the existing knowledge on AAP and health outcomes in SSA. Methods: We searched PubMed, Medline-OVID, EMBASE and Scopus databases to identify studies of AAP and health outcomes published up to November 15, 2017. We used a systematic review approach to critically analyze and summarize levels of outdoor air pollutants, and data on health effects associated with AAP. We excluded occupational and indoor exposure studies. Results: We identified 60 articles, with 37 only describing levels of AAP and 23 assessing the association between air pollution and health outcomes. Most studies (75%) addressing the relation between AAP and disease were cross-sectional. In general, exposure data were only obtained for selected cities in the framework of temporary international collaborative research initiatives without structural long-term continuation. Measurements of AAP revealed 10–20 fold higher levels than WHO standards. Of the 23 studies reporting health effects, 14 originated from South Africa, and most countries within SSA contributed no data at all. No studies, except from South Africa, were based on reliable morbidity or mortality statistics at regional or country level. The majority of studies investigated self-reported respiratory symptoms. Children and the elderly were found to be more susceptible to AAP. Conclusion: AAP and its negative health effects have been understudied in SSA compared with other continents. The limited direct measurements of air pollutants indicate that AAP in SAA cities is high compared with international standards. Efforts are needed to monitor AAP in African cities, to identify its main sources, and to reduce adverse health effects by enforcing legislation.
Analytical methods used in estimating the prevalence of HIV/AIDS from demographic and cross-sectional surveys with missing data : a systematic review
(BMC (part of Springer Nature), 2020-03-14) Mosha, Neema R.; Aluko, Omololu S.; Todd, Jim; Machekano, Rhoderick; Young, Taryn
Background: Sero- prevalence studies often have a problem of missing data. Few studies report the proportion of missing data and even fewer describe the methods used to adjust the results for missing data. The objective of this review was to determine the analytical methods used for analysis in HIV surveys with missing data. Methods: We searched for population, demographic and cross-sectional surveys of HIV published from January 2000 to April 2018 in Pub Med/Medline, Web of Science core collection, Latin American and Caribbean Sciences Literature, Africa-Wide Information and Scopus, and by reviewing references of included articles. All potential abstracts were imported into Covidence and abstracts screened by two independent reviewers using pre-specified criteria. Disagreements were resolved through discussion. A piloted data extraction tool was used to extract data and assess the risk of bias of the eligible studies. Data were analysed through a quantitative approach; variables were presented and summarised using figures and tables. Results: A total of 3426 citations where identified, 194 duplicates removed, 3232 screened and 69 full articles were obtained. Twenty-four studies were included. The response rate for an HIV test of the included studies ranged from 32 to 96% with the major reason for the missing data being refusal to consent for an HIV test. Complete case analysis was the primary method of analysis used, multiple imputations 11(46%) was the most advanced method used, followed by the Heckman’s selection model 9(38%). Single Imputation and Instrumental variables method were used in only two studies each, with 13(54%) other different methods used in several studies. Forty-two percent of the studies applied more than two methods in the analysis, with a maximum of 4 methods per study. Only 6(25%) studies conducted a sensitivity analysis, while 11(46%) studies had a significant change of estimates after adjusting for missing data. Conclusion: Missing data in survey studies is still a problem in disease estimation. Our review outlined a number of methods that can be used to adjust for missing data on HIV studies; however, more information and awareness are needed to allow informed choices on which method to be applied for the estimates to be more reliable and representative.
Assessing the uncertainty around age-mixing patterns in HIV transmission inferred from phylogenetic trees
(Public Library of Science, 2021) Niyukuri, David; Nyasulu, Peter S.; Delva, Wim
Understanding age-mixing patterns in Human Immunodeficiency Virus (HIV) transmission networks can enhance the design and implementation of HIV prevention strategies in sub-Saharan Africa. Due to ethical consideration, it is less likely possible to conduct a benchmark study to assess which sampling strategy, and sub-optimal sampling coverage which can yield best estimates for these patterns. We conducted a simulation study, using phylogenetic trees to infer estimates of age-mixing patterns in HIV transmission, through the computation of proportions of pairings between men and women, who were phylogenetically linked across different age groups (15–24 years, 25–39 years, and 40–49 years); and the means, and standard deviations of their age difference. We investigated also the uncertainty around these estimates as a function of the sampling coverage in four sampling strategies: when missing sequence data were missing completely at random (MCAR), and missing at random (MAR) with at most 30%—50%—70% of women in different age groups being in the sample. The results suggested that age-mixing patterns in HIV transmission can be unveiled from proportions of phylogenetic pairings between men and women across age groups; and the mean, and standard deviation of their age difference. A 55% sampling coverage was sufficient to provide the best values of estimates of age-mixing patterns in HIV transmission with MCAR scenario. But we should be cautious in interpreting proportions of men phylogenetically linked to women because they may be overestimated or underestimated, even at higher sampling coverage. The findings showed that, MCAR was the best sampling strategy. This means, it is advisable not to use sequence data collected in settings where we can find a systematic imbalance of age and gender to investigate age-mixing in HIV transmission. If not possible, ensure to take into consideration the imbalance in interpreting the results.
Assessment of point-of-care testing for prediction of aromatase inhibitor-associated side effects in obese postmenopausal breast cancer patients screened for cardiovascular risk factors
(Stellenbosch : Stellenbosch University, 2021-12) Milambo, Jean Paul Muambangu; Akudugu, John M.; Nyasulu, Peter S.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY : Background: Aromatase inhibitors (AIs) constitute a standard of care for post- and premenopausal patients with estrogen receptor-positive breast cancer (BC). Obesity and mediators of inflammation have been identified as the most important risk and predictive factors in postmenopausal breast cancer survivors (BCS) using AIs. However, data on the feasibility of point-of-care (POC) genotyping using high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI) as predictors of drug toxicity among postmenopausal BCS in African clinical settings are lacking. Aim: The study was conducted to assess the impact of AIs on hs-CRP and BMI, which are used at POC for prediction of therapy-associated side effects among obese postmenopausal breast cancer patients in Africa. Methods: One hundred and twenty-six female BC patients with cancer stages ranging from 0-III were recruited at Tygerberg Hospital (TBH) in the Western Cape Province of South Africa, between August 2014 and February 2017, for the study. A Quasi-experimental study was conducted. Patients were initially subjected to AIs and subsequently followed up at months 4, 12, and 24. Baseline clinical and biomedical assessments were conducted at commencement of study to predict hs-CRP and BMI at months 12 and 24, using a multiple imputation model. A random effects model was used to monitor the changes over the time. Statistical analyses were performed using SPSS 18.0 software (SPSS Inc., Chicago, IL, USA) and STATA version 16. Analyses were two-tailed and a p-value < 0.05 was considered statistically significant. Results: The mean age of the participants was 61 years (SD = 7.11 years; 95% CI: 60-62 years). Linear regression revealed that hs-CRP was associated with waist circumference (OR: 7.5; p= 0. 0116; 95%CI: 1.45 to 39.61) and BMI (OR: 2.15; p=0.034, 95%CI: 1.02 to 4.56). Waist circumference was associated with hypertension (OR: 3, 83; p= 0.003, 95%CI: 1.56 to 9.39), and chemotherapy was associated with waist circumference by (p= 0. 016; 95%CI: 0.11 to 0. 79). hs-CRP levels were significantly correlated with BMI and total body fat (TBF) among postmenopausal using aromatase inhibitors. Random linear effects modelling revealed stronger statistical association between BMI and homocysteine (p=0.021, 95%CI: 0.0083 to 0.1029). Weight and TBF were strongly associated after 24 months of follow-up. In addition, hs-CRP was associated with BMI (p=0.0001) and other inflammatory markers such as calcium (p=0.021, 95%CI: 0.0083 to 0.1029), phosphate (p=0.039, 95%CI: 0.0083 to 0.1029), and ferritin (p=0.002, 95%CI: 0.0199 to 0.084). Multiple imputation modelling indicated that there were statistically significant variations in TBF, weight, homocysteine, ferritin, and calcium between baseline and after 24 months of follow-up. Mathematical modeling Comparison of genotyping from HyBeacon® probe technology to Sanger sequencing showed that yielded sensitivity of 99% (95% CI: 94.55 to 99.97%), specificity of 89.44% (95% CI: 87.25 to 91.38%), PPV of 51% (95%: 43.77 to 58.26%), and NPV of 99.88% (95% CI: 99.31 to 100.00%). Based on the mathematical model, the assumptions revealed that incremental cost-effective ratio (ICER) was R7 044.55. Conclusion: This study revealed that hs-CRP and BMI are predictors of CVD-related adverse events in obese postmenopausal patients. Calcium, phosphate, homocysteine, and ferritin should also be incorporated in POCT. There were statistically significant variations in TBF, weight, hs-CRP, BMI, homocysteine, ferritin, and calcium between baseline and after 24 months of follow-up. HyBeacon® probe technology at POC for AI-associated adverse events maybe cost-effective in Africa while adjunct to standard practice. The appropriate pathways for implementation of POC testing in postmenopausal breast cancer survivors need further investigation in different clinical settings with real data for external validation.
The association between taking HAART and hypertension
(Stellenbosch : Stellenbosch University, 2017-12) Mangunda, Tichatonga John; Machekano, Rhoderick; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY: Prevalence of hypertension in patients on HAART compared to pre-ART patients at Sithobela Hospital. Background: The use of Highly Active Anti-retroviral Therapy (HAART) has improved the quality of life among people with HIV/AIDS, but there are concerns about its effect on hypertension and other cardiovascular diseases. Objectives: In this study we sought to find out if HAART is associated with hypertension and to describe lifestyle and socio-demographic factors among people on pre-ART and HAART. Methods: We conducted a cross sectional study of HIV infected patients initiated on HAART and pre-ART at Sithobela health centre. Results: We enrolled a total of 410 participants, 205 in the ART group and 205 in the pre-ART group. The estimated prevalence of hypertension among those on ART was 14.2% [95% CI: 9.3-18.9] and 19%[95% CI: 13.6-24.4] among pre-ART patients. There was no significant difference in the prevalence of hypertension between the two groups (p=0.185). However, after adjusting for age, marital status, level of education, stage of disease, smoking history, waist to hip ratio, occupation, income level, history of smoking and alcohol use, HAART was significantly associated with hypertension (AOR= 0.43 [95% CI: 0.23-0.83]). Patients who reported drinking alcohol were likely to be hypertensive (AOR 10.96 [95% CI: 2.36-50.92]). Smokers were 3 times more likely to be hypertensive compared to non-smokers but this association was found not to be statistically significant on multivariate analysis. Conclusion: our study demonstrated a potential beneficial effect of HAART in reducing hypertension among HIV infected people in Sithobela, Swaziland.
Association of home hygienic practice and diarrhoeal presence in low-cost housing in Cape Town, South Africa
(Stellenbosch : Stellenbosch University, 2017-12) Brand, Amanda; Esterhuizen, Tonya; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY: Background: Good home hygiene in key high-risk areas shows potential to be a simple and cost-effective intervention for preventing infectious disease transmission in low income homes. Knowledge of good home hygiene does not, however, always translate to practice due to complex factors which hinder translation. The objective of the study was to investigate whether an association between cleanliness and diarrhoeal disease exists, and to understand the factors which impede knowledge translation. Method: This cross-sectional study in low-income areas in Cape Town, South Africa took the format of an administered questionnaire focusing on health, and hygienic behaviour. Interviewer-assessed cleanliness was also recorded for each home. Results: Gastrointestinal symptoms were significantly associated with unclean kitchens and toilets (odds ratio (OR)=5.93 (1.98 – 19.78) and OR=17.67 (5.20 – 63.90), respectively). The presence of diarrhoea was significantly associated with dirty toilet areas (OR=8.94 (2.34 – 40.96)), despite its relatively low prevalence (17% (11 – 25%)). While knowledge of home hygiene and health was high, a lack of association between knowledge and observed cleanliness indicated a gap in the translation of knowledge to practice. Proposed emotional drivers of this process could not be substantiated, but evidence suggested that lack of understanding of underlying reasons plays an important role, but it may be effectively overcome by education. Conclusions: Good home hygiene shows potential for preventing infectious disease risk in low-income areas, but knowledge does not translate to effective practice. This is likely attributable to a lack of understanding of underlying principles, specifically among persons with low levels of formal schooling.
Barriers and facilitators to linkage, adherence and retention in care among HIV positive patients : an overview of qualitative systematic reviews using mega-aggregation framework synthesis
(Stellenbosch : Stellenbosch University, 2019-04) Hendricks, Lynn Avril; Rohwer, Anke; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY : Background: People living with Human Immunodeficiency Virus (PLHIV) continue to struggle with the complexities related to having a chronic disease and integrating antiretroviral treatment (ART) and care into their daily lives. This overview aimed to assess existing evidence related to self-reported barriers and facilitators to linkage to ART, adherence to ART and retention in care for PLHIV and to identify gaps in the evidence. Methods: The novel pragmatic approach of mega-aggregation framework synthesis was developed, described and applied in this overview using Kaufman’s interpretation of the socio-ecological framework. We included qualitative systematic reviews, up to July 2018, and used a systematic and rigorous approach to select reviews and extract data. We assessed methodological quality using an amended version of the Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews. Results: We included 33 systematic reviews, from low, middle and high income countries and included 1 111 964 HIV positive children and adults. Methodological quality varied considerably across reviews. Using the mega-aggregative framework approach, we found 544 unique third order concepts, from the included systematic reviews, and reclassified the third order concepts into 45 fourth order themes within the individual, interpersonal, community, institutional and structural levels of the Kaufman HIV Behaviour Change model. Our overview found that the main barriers and facilitators to linkage, adherence and retention such as psychosocial personal characteristics of perceptions of ART, desires, fears, experiences of HIV and ART, coping strategies and mental health, were interwoven with other factors on the interpersonal, community, institutional and structural level. Conclusions: High quality qualitative review level evidence on self-reported barriers and facilitators of linkage, adherence and retention in care is lacking for adults and even more so for children. Overviews are useful in the identification of evidence gaps to inform new review questions and researchers are encouraged to build on the method of mega-aggregative framework synthesis as the place of overviews become more prominent with the growing body of qualitative reviews. Systematic review registration: The protocol of this overview was registered on PROSPERO (CRD42017078155) on 17 December 2017.
Being HIV positive and staying on antiretroviral therapy in Africa : a qualitative systematic review and theoretical model
(PLoS, 2019-01-10) Eshun-Wilson, Ingrid; Rohwer, Anke; Hendricks, Lynne; Oliver, Sandy; Garner, Paul
Background : Adherence to antiretroviral therapy (ART) and long-term uninterrupted engagement in HIV care is difficult for HIV-positive people, and randomized trials of specific techniques to promote adherence often show small or negligible effects. Understanding what influences decision-making in HIV-positive people in Africa may help researchers and policy makers in the development of broader, more effective interventions and policies. Methods: We used thematic synthesis and a grounded theory approach to generate a detailed narrative and theoretical model reflecting life with HIV in Africa, and how this influences ART adherence and engagement decisions. We included qualitative primary studies that explored perspectives, perceptions and experiences of HIV-positive people, caregivers and healthcare service providers. We searched databases from 1 January 2013 to 9 December 2016, screened all studies, and selected those for inclusion using purposeful sampling methods. Included studies were coded with Atlas.ti, and we assessed methodological quality across five domains. Results: We included 59 studies from Africa in the synthesis. Nine themes emerged which we grouped under three main headings. First, people who are HIV-positive live in a complicated world where they must navigate the challenges presented by poverty, competing priorities, unpredictable life events, social identity, gender norms, stigma, and medical pluralism—these influences can make initiating and maintaining ART difficult. Second, the health system is generally seen as punishing and uninviting and this can drive HIV-positive people out of care. Third, long-term engagement and adherence requires adaptation and incorporation of ART into daily life, a process which is facilitated by: inherent self-efficacy, social responsibilities, previous HIV-related illnesses and emotional, practical or financial support. These factors together can lead to a “tipping point”, a point in time when patients choose to either engage or disengage from care. HIV-positive people may cycle in and out of these care states in response to fluctuations in influences over time. Conclusion: This analysis provides a practical theory, arising from thematic synthesis of research, to help understand the dynamics of adherence to ART and engagement in HIV care. This can contribute to the design of service delivery approaches, and informed thinking and action on the part of policy makers, providers, and society: to understand what it is to be HIV-positive in Africa and how attitudes and the health service need to shift to help those with HIV lead ‘normal’ lives.
Better virological outcomes among people living with human immunodeficiency virus (HIV) initiating early antiretroviral Tteatment (CD4 Counts ≥500 Cells/µL) in the HIV Prevention Trials Network 071 (PopART) trial in South Africa
(Oxford University Press, 2020-01-16) Fatti, Geoffrey; Grimwood, Ashraf; Nachega, Jean B.; Nelson, Jenna A.; LaSorda, Kelsea; van Zyl, Gert; Grobbelaar, Nelis; Ayles, Helen; Hayes, Richard; Beyers, Nulda; Fidler, Sarah; Bock, Peter
Background: There have been concerns about reduced adherence and human immunodeficiency virus (HIV) virological suppression (VS) among clinically well people initiating antiretroviral therapy (ART) with high pre-ART CD4 cell counts. We compared virological outcomes by pre-ART CD4 count, where universal ART initiation was provided in the HIV Prevention Trials Network 071 (PopART) trial in South Africa prior to routine national and international implementation. Methods: This prospective cohort study included adults initiating ART at facilities providing universal ART since January 2014. VS (<400 copies/mL), confirmed virological failure (VF) (2 consecutive viral loads >1000 copies/mL), and viral rebound were compared between participants in strata of baseline CD4 cell count. Results: The sample included 1901 participants. VS was ≥94% among participants with baseline CD4 count ≥500 cells/µL at all 6-month intervals to 30 months. The risk of an elevated viral load (≥400 copies/mL) was independently lower among participants with baseline CD4 count ≥500 cells/µL (3.3%) compared to those with CD4 count 200-499 cells/µL (9.2%) between months 18 and 30 (adjusted relative risk, 0.30 [95% confidence interval, .12-.74]; P = .010). The incidence rate of VF was 7.0, 2.0, and 0.5 per 100 person-years among participants with baseline CD4 count <200, 200-499, and ≥500 cells/µL, respectively (P < .0001). VF was independently lower among participants with baseline CD4 count ≥500 cells/µL (adjusted hazard ratio [aHR], 0.23; P = .045) and 3-fold higher among those with baseline CD4 count <200 cells/µL (aHR, 3.49; P < .0001). Conclusions: Despite previous concerns, participants initiating ART with CD4 counts ≥500 cells/µL had very good virological outcomes, being better than those with CD4 counts 200-499 cells/µL. Clinical trials registration: NCT01900977.
Burden of congenital rubella syndrome and potential impact of rubella vaccine introduction in South Africa
(Stellenbosch : Stellenbosch University, 2021-12) Motaze, Nkengafac Villyen; Wiysonge, Charles S.; Suchard, Melinda S.; Metcalf, C. Jessica E.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY : Background: Introduction of rubella vaccines into public vaccination schedules of all countries is necessary if global rubella elimination is to be achieved. Rubella is targeted for elimination in five World Health Organization (WHO) regions and several international organizations, under the stewardship of the WHO, are working towards this goal. Although there is no rubella elimination or control target for the WHO Africa region, there has been accelerated introduction of rubella vaccination on the continent. South African government is planning to introduce rubella vaccination in its Expanded Programme on Immunization (EPI) schedule and several epidemiological studies have been conducted to aid preparation of this public health intervention. In the absence of vaccination, rubella is mainly a mild endemic childhood viral illness that is asymptomatic in up to 50% of cases. The most severe consequences of rubella occur when infection occurs during pregnancy. These include miscarriages, stillbirths, intra-uterine growth restriction and congenital rubella syndrome. Rubella vaccines are therefore intended to prevent rubella and associated complications. In South Africa, rubella vaccines are not part of the EPI schedule and there is limited information on the epidemiology of rubella and its complications. In addition, the South African government has to cover the cost of introducing rubella vaccination. Therefore, the aim of this research project was to characterize the epidemiology of rubella and congenital rubella syndrome in South Africa, to assess the potential impact of introducing rubella vaccination in the EPI schedule. Methods: Four different studies were carried out as part of this PhD project: a cross-sectional descriptive study, a sero-survey, a mathematical modelling study and a systematic review. Results: The findings of a newly established CRS surveillance system to provide data on disease trends in the absence of rubella vaccination are presented in the first research component. We provided baseline data on laboratory-confirmed CRS that will enable planning and monitoring of RCV implementation in the South African EPI program. Ninety-eight percent of mothers of infants with CRS were young women 14 to 30 years old, indicating a potential immunity gap in this age group for consideration during introduction of RCV. In the second research component, we present results of testing on residual samples collected from public health facilities to identify immunity gaps in various age groups and genders. The bulk of individuals susceptible to rubella are children under sixteen years old and about 20% of individuals 16 to 49 years old are susceptible to rubella. In multivariable logistic regression, age and province of residence were found to be associated with rubella susceptibility.Webuilt on a previously published mathematical model adapted to the South African context in the third research component and provide insights into optimal scenarios for RCV introduction into the South African public immunization schedule. We simulated a number of scenarios that combined infant vaccination with vaccination of older individuals. Routine vaccination at 12 months of age coupled with vaccination of nine-year-old children was associated with the lowest RCV cost per CRS case averted for a similar percentage CRS reduction. Interestingly, at 80% RCV coverage, all vaccine introduction scenarios could achieve rubella and CRS elimination in South Africa.In the final research component, we systematically reviewed mathematical modelling studies to identify the most effective approach for countries introducing RCV into their public immunization schedules. There were variations in the manner in which individual studies reported outcomes. However, we found that better outcomes are obtained when rubella vaccination is introduced into public vaccination schedules at coverage figures of 80%, as recommended by WHO, or higher. Conclusion: The results from these different studies support the implementation of a strategy involving infant vaccination in combination with vaccination of older individuals. Further research projects are required to provide more detail on the burden of CRS and the economic impact of RCV introduction into the EPI schedule.
Burden of seasonal influenza in sub- Saharan Africa : a systematic review protocol
(BMJ Publishing Group, 2018-10) Sambala, Evanson Zondani; Mdolo, Aaron; Banda, Richard; Phiri, Arthur; Wiyeh, Alison B.; Wiysonge, Charles Shey
Introduction Measures of epidemiological burdens are an important contribution to estimating disease severity and determining the at-risk populations for seasonal influenza. In the absence of these data, it is extremely difficult for policy-makers to decide on how to distribute limited resources. This systematic review will synthesise the literature on reported burden of seasonal influenza (eg, morbidity and mortality) in sub-Saharan Africa. Method and analysis We will include published epidemiological studies that capture the burden estimation of seasonal influenza between 1 January 2000 and 31 August 2018. Studies that have reported disease burden estimates associated to influenza-like illness, acute respiratory illness, acute lower respiratory illness, severe acute respiratory illness and severe or very severe pneumonia using laboratory-confirmed influenza cases will be included. We will perform a multiple electronic database search in PubMed, Embase, African Journals Online, Cochrane, Web of science, CINAHL and Google scholar for eligible studies. The reference lists of relevant studies will also be hand-searched for potentially eligible studies. The titles and abstracts of identified records will be screened independently by two authors. The full-text articles of potentially eligible studies will be assessed independently by two authors. Discrepancies will be resolved by discussion, and by a third author if the first two authors fail to come to a consensus. The measures of the burden of influenza will be aggregated using a meta-analysis for homogeneous studies and narrative synthesis if the studies are heterogeneous. The strength of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.
Clinical evolution, management and outcomes of patients with COVID-19 admitted at Tygerberg Hospital, Cape Town, South Africa : a research protocol
(BMJ Publishing Group, 2020-08-06) Allwood, Brian W.; Koegelenberg, Coenraad F. N.; Irusen, Elvis; Lalla, Usha; Davids, Razeen; Chothia, Yazied; Davids, Ryan; Prozesky, Hans; Taljaard, Jantjie; Parker, Arifa; Decloedt, Eric; Jordan, Portia; Lahri, Sa'ad; Moosa, Rafique; Schrueder, Neshaad; Du Toit, Riette; Viljoen, Abraham; English, Rene; Ayele, Birhanu; Nyasulu, Peter; COVID-19 Research Response Team
Introduction The outbreak of the SARS-CoV-2 virus causing COVID-19, declared a global pandemic by the WHO, is a novel infection with a high rate of morbidity and mortality. In South Africa, 55 421 cases have been confirmed as of 10 June 2020, with most cases in the Western Cape Province. Coronavirus leaves us in a position of uncertainty regarding the best clinical approach to successfully manage the expected high number of severely ill patients with COVID-19. This presents a unique opportunity to gather data to inform best practices in clinical approach and public health interventions to control COVID-19 locally. Furthermore, this pandemic challenges our resolve due to the high burden of HIV and tuberculosis (TB) in our country as data are scarce. This study endeavours to determine the clinical presentation, severity and prognosis of patients with COVID-19 admitted to our hospital. Methods and analysis The study will use multiple approaches taking into account the evolving nature of the COVID-19 pandemic. Prospective observational design to describe specific patterns of risk predictors of poor outcomes among patients with severe COVID-19 admitted to Tygerberg Hospital. Data will be collected from medical records of patients with severe COVID-19 admitted at Tygerberg Hospital. Using the Cox proportional hazards model, we will investigate the association between the survival time of patients with COVID-19 in relation to one or more of the predictor variables including HIV and TB. Ethics and dissemination The research team obtained ethical approval from the Health Research Ethics Committee of the Faculty of Medicine and Health Sciences, Stellenbosch University and Research Committee of the Tygerberg Hospital. All procedures for the ethical conduct of scientific investigation will be adhered to by the research team. The findings will be disseminated in clinical seminars, scientific forums and conferences targeting clinical care providers and policy-makers.
Clinical practice guideline adaptation methods in resource-constrained settings : four case studies from South Africa
(BMJ Publishing, 2020-12) McCaul, Michael; Ernstzen, Dawn; Temmingh, Henk; Draper, Beverly; Galloway, Michelle; Kredo, Tamara
Developing a clinical practice guideline (CPG) is expensive and time-consuming and therefore often unrealistic in settings with limited funding or resources. Although CPGs form the cornerstone of providing synthesised, systematic, evidence-based guidance to patients, healthcare practitioners and managers, there is no added benefit in developing new CPGs when there are accessible, good-quality, up-to-date CPGs available that can be adapted to fit local needs. Different approaches to CPG development have been proposed, including adopting, adapting or contextualising existing high-quality CPGs to make recommendations relevant to local contexts. These approaches are attractive where technical and financial resources are limited and high-quality guidance already exists. However, few examples exist to showcase such alternative approaches to CPG development. The South African Guidelines Excellence project held a workshop in 2017 to provide an opportunity for dialogue regarding different approaches to guideline development with key examples and case studies from the South African setting. Four CPGs represented the topics: mental health, health promotion, chronic musculoskeletal pain and prehospital emergency care. Each CPG used a different approach, however, using transparent, reportable methods. They included advisory groups with representation from content experts, CPG users and methodologists. They assessed CPGs and systematic reviews for adopting or adapting. Each team considered local context issues through qualitative research or stakeholder engagement. Lessons learnt include that South Africa needs fit-for-purpose guidelines and that existing appropriate, high-quality guidelines must be taken into account. Approaches for adapting guidelines are not clear globally and there are lessons to be learnt from existing descriptions of approaches from South Africa.
Colorectal cancer incidence and mortality trends by sex and population group in South Africa : 2002–2014
(BMC (part of Springer Nature), 2021-02-06) Motsuku, Lactatia; Chen, Wenlong C.; Muchengeti, Mazvita M.; Naidoo, Megan; Quene, Tamlyn M.; Kellett, Patricia; Mohlala, Matshediso I.; Chu, Kathryn M.; Singh, Elvira
Background: South Africa (SA) has experienced a rapid transition in the Human Development Index (HDI) over the ast decade, which had an effect on the incidence and mortality rates of colorectal cancer (CRC). This study aims to provide CRC incidence and mortality trends by population group and sex in SA from 2002 to 2014. Methods: Incidence data were extracted from the South African National Cancer Registry and mortality data obtained from Statistics South Africa (STATS SA), for the period 2002 to 2014. Age-standardised incidence rates (ASIR) and age-standardised mortality rates (ASMR) were calculated using the STATS SA mid-year population as the denominator and the Segi world standard population data for standardisation. A Joinpoint regression analysis was computed for the CRC ASIR and ASMR by population group and sex. Results: A total of 33,232 incident CRC cases and 26,836 CRC deaths were reported during the study period. Of the CRC cases reported, 54% were males and 46% were females, and among deaths reported, 47% were males and 53% were females. Overall, there was a 2.5% annual average percentage change (AAPC) increase in ASIR from 2002 to 2014 (95% CI: 0.6–4.5, p-value < 0.001). For ASMR overall, there was 1.3% increase from 2002 to 2014 (95% CI: 0.1–2.6, p-value < 0.001). The ASIR and ASMR among population groups were stable, with the exception of the Black population group. The ASIR increased consistently at 4.3% for black males (95% CI: 1.9–6.7, p-value < 0.001) and 3.4% for black females (95% CI: 1.5–5.3, p-value < 0.001) from 2002 to 2014, respectively. Similarly, ASMR for black males and females increased by 4.2% (95% CI: 2.0–6.5, p-value < 0.001) and 3.4% (, 95%CI: 2.0–4.8, p-value < 0.01) from 2002 to 2014, respectively. Conclusions: The disparities in the CRC incidence and mortality trends may reflect socioeconomic inequalities across different population groups in SA. The rapid increase in CRC trends among the Black population group is concerning and requires further investigation and increased efforts for cancer prevention, early screening and diagnosis, as well as better access to cancer treatment.
Combination antiretroviral treatment use in prevention of mother-to-child transmission programmes : 6-week HIV prevalence and relationship to time of antiretroviral treatment initiation and mixed feeding
(AOSIS, 2019) Ndarukwa, Victoria; Zunza, Moleen
Background: In Zimbabwe, 16% of pregnant women aged 15–49 years are infected with HIV. More than 90% of HIV infection in children is through mother-to-child transmission (MTCT). We investigated the effectiveness of the Option B+ in reducing HIV infection and factors associated with HIV transmission among infants born to mothers enrolled in the prevention of mother-to-child transmission (PMTCT) programme. Methods: We randomly selected 1204 early infant HIV diagnosis test results for HIV-exposed infants and linked these results to maternal clinical records at primary healthcare clinics in Harare to estimate the prevalence of MTCT and to determine the clinical factors associated with MTCT of HIV at 6 weeks. Results: Of the 1204 infants in the study, 2.5% (95% confidence interval [CI], 1.7–3.5) were infected with HIV at 6 weeks post-delivery. Antiretroviral adherence reduced the odds of HIV infection by about 99% (odds ratio [OR] 0.01 [95% CI, 0.00–0.06]). Both mixed feeding (OR 3.89 [95% CI, 0.92–16.50]) and late initiation of antiretroviral treatment (ART) (after delivery) (OR 3.18 [95% CI, 0.42–23.94]) increased the odds of HIV infection. Conclusion: Early initiation of combination ART reduces 6-week MTCT of HIV in PMTCT programmes to levels similar to those found in controlled trial settings. Exclusive breastfeeding remains important even in the presence of ART.
A comparative evaluation of PDQ-Evidence
(BioMed Central, 2018-03-15) Johansen, Marit; Rada, Gabriel; Rosenbaum, Sarah; Paulsen, Elizabeth; Motaze, Nkengafac Vilyen; Opiyo, Newton; Wiysonge, Charles S.; Ding, Yunpeng; Mukinda, Fidele K.; Oxman, Andrew D.
Background: A strategy for minimising the time and obstacles to accessing systematic reviews of health system evidence is to collect them in a freely available database and make them easy to find through a simple ‘Google-style’ search interface. PDQ-Evidence was developed in this way. The objective of this study was to compare PDQ-Evidence to six other databases, namely Cochrane Library, EVIPNet VHL, Google Scholar, Health Systems Evidence, PubMed and Trip. Methods: We recruited healthcare policy-makers, managers and health researchers in low-, middle- and highincome countries. Participants selected one of six pre-determined questions. They searched for a systematic review that addressed the chosen question and one question of their own in PDQ-Evidence and in two of the other six databases which they would normally have searched. We randomly allocated participants to search PDQ-Evidence first or to search the two other databases first. The primary outcomes were whether a systematic review was found and the time taken to find it. Secondary outcomes were perceived ease of use and perceived time spent searching. We asked open-ended questions about PDQ-Evidence, including likes, dislikes, challenges and suggestions for improvements. Results: A total of 89 people from 21 countries completed the study; 83 were included in the primary analyses and 6 were excluded because of data errors that could not be corrected. Most participants chose PubMed and Cochrane Library as the other two databases. Participants were more likely to find a systematic review using PDQ-Evidence than using Cochrane Library or PubMed for the pre-defined questions. For their own questions, this difference was not found. Overall, it took slightly less time to find a systematic review using PDQ-Evidence. Participants perceived that it took less time, and most participants perceived PDQ-Evidence to be slightly easier to use than the two other databases. However, there were conflicting views about the design of PDQ-Evidence. Conclusions: PDQ-Evidence is at least as efficient as other databases for finding health system evidence. However, using PDQ-Evidence is not intuitive for some people.
Comparative, cross-sectional study describing agreement and accuracy of emergency centre triage using either a mobile application or manual triage
(Stellenbosch : Stellenbosch University, 2016-03) Khan, Yaseen; Govender, Thashlin; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY: Background and Purpose: Unacceptable patient waiting times and misidentification of critically ill patients are significant problems within Emergency Centres (ECs). Triage, when performed correctly, is acritical process to address this. The South African Triage Scale (SATS) is widely used. Manually performed triage may be prone to inaccuracies and prolonged triage time. A mobile tablet application to facilitate use of the SATS by automating triage calculation and guiding nurses has been developed. Methods: This is a comparative cross-sectional study to observe the accuracy of triage using the mobile tablet application compared with triage performed manually. Under classroom examination conditions, nurses calculated triage scores on written case scenarios of typical EC presentations. A total of 59 nurses across five hospitals in the Western Cape Province, South Africa were randomized into an ‘app group’ and a ‘manual group’. Results: The app group scored a 23% higher level of agreement with the expert-validated results than the manual group. Kappa of 0.735 (0.719 - 0.770) and 0.597 (0.545 - 0.656) were found respectively. One in five patients are triaged more correctly using the app. Sensitivity for emergency cases was 65.5% and 53% respectively, with and without the app. Conclusions: Nurses triaging written scenarios with the aid of the app were observed to have a higher agreement with the expert-validated results than nurses performing traditional manual triage. The effect size is considerable and of practical relevance. The app could have significant benefit in busy Emergency Centres of public sector hospitals. A larger study involving real patients is recommended.

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