Browsing by Author "Lesosky, Maia"
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- ItemOpen AccessA study of the association of prenatal inflammatory diet and adverse infant birth outcomes in a birth cohort in Uganda(2022) Ndlovu, Davies; Lesosky, MaiaBackground: Low birth weight (LBW) and low infant lung capacity among others are risk factors for childhood and adulthood chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma. These respiratory diseases are among the leading causes of death and disability worldwide. The aetiology of these respiratory diseases and other inflammatory conditions has recently been linked to maternal diet during pregnancy. As such it has been important to study the role of maternal diet during pregnancy to find any association with maternal and infant outcomes. Highly diverse diets have been thought to be a proxy to maternal nutrient adequacy as well as healthy diet. Diverse diets may offer protection from inflammatory airway diseases and other inflammatory diseases by evening out inflammatory and anti-inflammatory food components. Purpose: To investigate the effect of Dietary diversity (DD) and Dietary inflammatory index (DII), on infant birth outcomes particularly birth weight and lung function and to determine if there is any association. Methods: In this study we analysed data obtained from 564 women who attended antenatal care facilities in Kalungu district of rural Uganda. These women were recruited by convenience sampling as they walked into the facilities for antenatal care. Those who gave consent were asked about their diets and socioeconomic statuses by means of questionnaires. Infant outcomes were measured by healthcare professionals at presentation for postnatal care at 6 weeks ofage. Dietary scores were created as the number of unique food groups obtained from the data collected. The scores ranged from 0-14, with 14 representing those who consumed all 14 unique food groups identified in the study. Dietary inflammatory index was also calculated from the data obtained. The methods for calculating the DII will be explained in detail under methods. The data collection for this purpose was based on 24hr recall. Results: The mean Dietary Diversity score was 4.61 +/- 1.79 SD. In the previous 24 h, 84.8% of the participating women had consumed tubers such as cassava, 57.1% reported consuming grains or cereal, 12.6% vegetables, 19.3% Fruits, 1.2% meat and 7.4% eggs. There were statistically significant differences in dietary practices of the women according to their level of education, with 81% of those who attained tertiary education having adequate dietary diversity. Starches were the most consumed food group with an average of 16 servings per week while meat, processed starches (samosas, etc), fruits and vegetables were consumed at=<2 serving per week, with meat the least consumed at an average of less than 1 serving per week. Although marginal, the diets of the participants were mostly anti-inflammatory with an average dietary inflammatory score of -1.2. Those with the lowest inflammatory score were associated with more servings of legumes, green leafy vegetables, fish and less servings of processed starches and animal oil. There was no association observed between dietary diversity and infant birth outcomes, birth weight and lung function. No association was also observed between Dietary inflammatory scores and infant lung function.
- ItemOpen AccessAir pollution exposure during pregnancy among rural Ugandan women(2022) Mahlaba, Harmony Boiketlo; Lesosky, MaiaIntroduction: Air pollution monitoring of hazardous pollutants such as CO (Carbon Monoxide) and PM (Particulate Matter) are important for assessing whether air pollution thresholds are not exceeded in the environment. There is sparce data that has been collected in the African region for air pollution monitoring. In this study PM and CO are measured. Air pollution in pregnancy is associated with poor lung function in infants, in later life. The overall aim of this dissertation is to investigate air pollution exposure during pregnancy among rural Ugandan women. Methods: This mini-dissertation covers two components; the research protocol (Part A) and a manuscript section (Part B). We measured the CO and PM 2.5 levels in the study location of the Kyamulibwa Health Demographic Surveillance Site (HDSS), with a total population size of 22,000. Our study population were pregnant women. Household energy use was measured using personal monitoring tools. The Dylos tool was used to measure PM 2.5 in the households, while the Lascar tool was used to measure CO once a week at two different points at the HDSS. Boxplots were used to compare the relationship between air pollution exposures (CO and PM 2.5) and respiratory symptoms. Boxplots were further used to compare the relationship between air pollution exposure and infant birth weight. Furthermore, logistic regression models were used to show associations between air pollution exposure levels and infant birth weight as well as respiratory symptoms respectively. Results: The boxplots and regression models showing the relationship between air pollution exposure and respiratory symptoms suggest that mothers who presented no respiratory symptoms had lower levels of air pollution exposure compared to mothers who presented one or more symptoms. The boxplots and regression models also showed that air pollution exposure may not be a factor in low birthweight. Infants with low birth weight had lower air pollution exposure compared to infants with normal and high birth weight. Conclusion: Although it is evident through the results that there is a relationship between air pollution exposure and respiratory symptoms, further research is necessary to understand context specific ways in which exposure to air pollution can be reduced in both households and the general outside environment.
- ItemOpen AccessAn investigation in the seasonal patterns of bacterial colonisation in childhood pneumonia(2022) Auckloo, Marie Belle Kathrina Mendoza; Lesosky, MaiaGlobally, pneumonia is a leading cause of morbidity and mortality in children younger than the age of 5 years, especially in low- and middle-income countries. The aetiology of paediatric pneumonia is complex, and its definitive determination remains challenging. S. pneumoniae, H. influenzae, M. catarrhalis, and S. aureus are among the most frequent bacterial causes of childhood pneumonia. Common to such recognised bacterial pathogens is the occurrence of asymptomatic bacterial colonisation or carriage of the nasopharynx, which in turn precedes disease development and progression. This study investigates the trends and patterns of bacterial carriage in the development of pneumonia in South African infants up to one year of life. It is hypothesised that respiratory bacterial carriage is considerably influenced by age and seasonality. Based on previously collected time-series data from the Drakenstein Child Health Study conducted in Paarl, South Africa, this study focuses on exploring the effects of season on nasopharyngeal carriage of pathogens occurring in the nasopharynx of young children with and without the occurrence of lower respiratory tract infection. Using logistic mixed effects models and taking into account the repeated measure structure of the data as well as seasonal components, we found that seasonal variations occur in the prevalence of nasopharyngeal carriage of respiratory pathogens in infants, with and without lower respiratory tract infection. With the inclusion of age-effects, these associations appeared to be highly complex. Understanding the factors that influence bacterial carriage, asymptomatic or not, is necessary to better understand the opportunities for and impact of intervention strategies against lower respiratory tract illness.
- ItemOpen AccessBlood cultures taken from patients attending emergency departments in South Africa are an important antibiotic stewardship tool, which directly influences patient management(2015-10-06) Boyles, Tom H; Davis, Kelly; Crede, Thomas; Malan, Jacques; Mendelson, Marc; Lesosky, MaiaAbstract Background Febrile illness with suspected blood stream infection (BSI) is a common reason for admission to hospital in Africa and blood cultures are therefore an important investigation. Data on the prevalence and causes of community acquired BSI in Africa are scarce and there are no studies from South Africa. There are no validated clinical prediction rules for use of blood cultures in Africa. Methods A prospective observational cohort study of patients attending 2 urban emergency departments in Cape Town, South Africa. The decision to take a blood culture was made by the attending clinician and information available at the time of blood draw was collected. Bottles were weighed to measure volume of blood inoculated. Results 500 blood culture sets were obtained from 489 patients. 39 (7.8 %) were positive for pathogens and 13 (2.6 %) for contaminants. Significant independent predictors of positive cultures were diastolic blood pressure <60 mmHg, pulse >120 bpm, diabetes and a suspected biliary source of infection, but not HIV infection. Positive results influenced patient management in 36 of 38 (95 %) cases with the organism being resistant to the chosen empiric antibiotic in 9 of 38 (24 %). Taking <8 ml of blood was predictive of a negative culture. The best clinical prediction rule had a negative predictive value (NPV) of 92 % which is unlikely to be high enough to be clinically useful. Discussion Blood cultures taken from patients attending emergency departments in a high HIV prevalent city in South Africa are frequently positive and almost always influence patient management. At least 8 ml of blood should be inoculated into each bottle. Conclusion Blood cultures should be taken from all patients attending EDs in South Africa suspected of having BSI particularly if diabetic, with hypotension, tachycardia or if biliary sepsis is suspected.
- ItemOpen AccessCOVID-19 and the Gaping Wounds of South Africa’s Suboptimal Immunisation Coverage: An Implementation Research Imperative for Assessing and Addressing Missed Opportunities for Vaccination(2021-06-23) Nnaji, Chukwudi A; Wiysonge, Charles S; Lesosky, Maia; Mahomed, Hassan; Ndwandwe, DuduzileDespite South Africa’s substantial investments in and efforts at ensuring universal access to immunisation services, progress has stalled and remains suboptimal across provinces and districts. An additional challenge is posed by the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has disrupted immunisation services globally, including in South Africa. While there is growing evidence that missed opportunities for vaccination (MOV) are a major contributor to suboptimal immunisation progress globally, not much is known about the burden and determinants of MOV in the South African context. Herein, we make a case for assessing MOV as a strategy to address current immunisation coverage gaps while mitigating the adverse impacts of the COVID-19 pandemic on immunisation services. We illustrate a practical implementation research approach to assessing the burden of MOV among children in primary care settings; for understanding the factors associated with MOV; and for designing, implementing, and evaluating context-appropriate quality improvement interventions for addressing missed opportunities. Such efforts are vital for building health system resilience and maintaining immunisation programme capacity to optimally deliver essential health services such as routine childhood immunisation, even during pandemics.
- ItemOpen AccessThe development of simple anthropometric measures to diagnose antiretroviral therapy-associated lipodystrophy in resource limited settings(BioMed Central, 2014-08-04) Abrahams, Zulfa; Dave, Joel A; Maartens, Gary; Lesosky, Maia; Levitt, Naomi SAbstract Background Lipohypertrophy does not appear to be an adverse ART reaction while lipoatrophy is clearly associated with the use of stavudine (d4T) and zidovudine (AZT). In low and middle income countries d4T has only recently been phased out and AZT is still widely being used. Several case definitions have been developed to diagnose lipodystrophy, but none of them are generalizable to sub-Saharan Africa where black women have less visceral adipose tissue and more subcutaneous adipose tissue than white women. We aimed to develop a simple, objective measure to define lipoatrophy and lipohypertrophy by comparing patient report to anthropometric and dual-energy X-ray absorptiometry (DXA) -derived variables. Methods DXA and anthropometric measures were obtained in a cross sectional sample of black HIV-infected South African men (n = 116) and women (n = 434) on ART. Self-reported information on fat gain or fat loss was collected using a standard questionnaire. Receiver operating characteristic (ROC) curves were used to describe the performance of anthropometric and DXA-derived variables using patient reported lipoatrophy and lipohypertrophy as the reference standard. Results Lipoatrophy and lipohypertrophy were more common in women (25% and 33% respectively) than in men (10% and 13% respectively). There were insufficient numbers of men with DXA scans for meaningful analysis. The best predictors of lipoatrophy in women were the anthropometric variables tricep (AUC = 0.725) and thigh skinfold (AUC =0.720) thicknesses; and the DXA-derived variables percentage lower limb fat (AUC = 0.705) and percentage lower limb fat/height (AUC = 0.713). The best predictors of lipohypertrophy in women were the anthropometric variable waist/hip ratio (AUC = 0.645) and the DXA-derived variable percentage trunk fat/percentage limb fat (AUC = 0.647). Conclusions We were able to develop simple, anthropometric measures for defining lipoatrophy and lipohypertrophy, using a sample of black HIV-infected South African women with DXA scans. This is of particular relevance in resource limited settings, where health professionals need simple and inexpensive methods of diagnosing patients with lipoatrophy and lipohypertrophy.
- ItemOpen AccessFamily planning behaviours among South African HIV-infected and HIV-negative women during the post partum period(2018) Oosthuizen, Jenna; Lesosky, MaiaThere has been growing research on the impact of HIV on family planning and fertility behaviours with studies showing conflicting results. However, these relationships have been understudied in sub-Saharan Africa, especially during the postpartum period. Based on the differences reported in different studies as well as the lack of studies performed in South Africa during the postpartum period, further research is required to investigate differences in fertility desire and use and need for family planning among and between HIV-infected and HIV-uninfected women. The aim of this study was to compare family planning use, fertility desires and unmet family planning need at 12 months postpartum in a population of HIV-infected and HIV-uninfected women from Gugulethu, Cape Town. The thesis components include a study protocol, a literature review investigating previous work on family planning uptake, fertility desire and unmet family planning need in sub-Saharan Africa, and an analysis of secondary data from three contributing studies performed in Gugulethu, Cape Town of HIV-infected and HIV-uninfected women who participated at 12 months postpartum. Logistic regression was used to model associations between HIV status and family planning use, fertility desires and unmet family planning need. Of the 854 women included in this analysis, 497 (58.0%) were HIV-infected and 357 (42.0%) were HIV-uninfected. Family planning prevalence was 62.3%, injectable contraceptives were the most common FP methods used among participants (>90.0%) and 37.2% of participants had an unmet family planning need. Only 8 participants (0.9%) had an immediate fertility desire (wanted to have a child within the next 12 months) and 20.9% wanted to have a child sometime in the future. Family planning use and unmet family planning need did not differ by HIV status however, fertility desires significantly differed by HIV status. In multivariable analysis, HIV status was not associated with family planning use or unmet family planning need. HIV status was significantly associated with future fertility desire. HIV-infected women were significantly less likely to have a future fertility desire than HIV-uninfected women (OR=0.3, 95% CI=0.2 to 0.4, p<0.001). Age, parity, intended pregnancy and discussed family planning/ pregnancy with partner were also significantly associated with future fertility desire. HIV status appears to be associated with fertility desires in this population. No significant association was found between family planning use and unmet family planning need in this population by HIV status. Family planning services need to be strengthened for all women in this population and access to a larger variety of family planning methods is needed.
- ItemOpen AccessHIV-related knowledge and antiretroviral therapy outcomes (ART) in HIV infected women initiating ART during pregnancy(2018) Brown, Karryn; Lesosky, MaiaThe characteristics of South Africa’s HIV epidemic mean that approximately 28% of women presenting for antenatal care, are HIV-infected. Maternal HIV-infection can lead to mother-to-child transmission (MTCT) of HIV during pregnancy, labour, delivery or breastfeeding if viral load (VL) is not well controlled by antiretroviral therapy (ART). Globally, 90% of pediatric infections occur via MTCT, though lifelong ART is reducing the rate of new infections. Full benefits of ART can only be realized when ART adherence is high. Evidence from South Africa and elsewhere has shown that ART adherence in pregnant and postpartum women is suboptimal. Potential drivers of suboptimal adherence may include poor or inadequate knowledge of HIV and ART. This thesis investigates how HIV-infected pregnant and postpartum women’s knowledge of HIV and ART-related information may be associated with ART adherence as evaluated by HIV VL measures. Components of this thesis include the research protocol, a literature review of previous studies exploring the relationship between knowledge and HIV-related health outcomes in Sub-Saharan Africa and a manuscript describing the results of an investigation into predictors of HIV and ART-related knowledge and the association of knowledge with maternal vireamia (VL>1000copies/mL). This data for analysis came from a cohort of 376 HIV-infected pregnant women, initiating ART during pregnancy, at a primary care antenatal facility in Gugulethu, South Africa. Participants were followed from their first antenatal visit until twelve months postpartum. Knowledge of HIV and ART-related information were assessed at three time points by two knowledge inventories and items were classified as either relating to general knowledge or prevention of MTCT. HIV VL was measured at delivery and twelve months postpartum. Demographic characteristics were surveyed at the first antenatal visit. Analyses included univariable and multivariable regression models to estimate potential predictors of knowledge among demographic and clinical characteristics, as well as to estimate the association between knowledge and maternal vireamia at delivery and twelve months postpartum. We found that HIV and ART knowledge increased marginally over the repeated study visits. Knowledge relating to general HIV or ART information was typically good while knowledge on PMTCT was lacking. Education (OR=-0.52; 95% CI=-0.83- -0.21; P=0.001), previous HIV diagnoses (OR=-0.36; 95% CI=-0.09- 0.63; P=0.009), and weeks on ART at delivery (OR=-0.03; 95% CI=0.00-0.06; P=0.047) were statistically significant predictors of HIV knowledge in adjusted analyses. The associations between the various knowledge outcomes and vireamia at delivery and twelve months postpartum were mixed and generally not statistically significant. In summary, HIV and ART knowledge both increased with increasing time in care and general knowledge was better than knowledge specific to MTCT. Education, timing of HIV diagnoses and time on ART were identified as potential predictors of HIV-related knowledge. Generally, knowledge of HIV or ART was not meaningfully associated with vireamia at delivery or at twelve months postpartum. There remain significant gaps in the knowledge of HIV-infected women, of childbearing age, around how HIV is transmitted and how to reduce the risk of MTCT.
- ItemOpen AccessHost adapted intramammary infections in pregnant heifers which were co-housed and reared on fresh milk as calves(BioMed Central Ltd, 2013) Petzer, Inge-Marie; Karzis, Joanne; Lesosky, Maia; Watermeyer, Johanna; Badenhorst, RenetteBACKGROUND:Heifers can calve down with intramammary infections (IMI) and udder damage. This will have a negative impact on their longevity, future milk yield and financial return. Co-housed pre-weaned calves that are fed fresh milk have the opportunity to suckle each other's teats and may infect udders of fellow heifer calves with pathogens present in milk. The prevalence of IMI in pregnant heifers in South Africa (SA) which were co-housed and reared on fresh milk as calves, is not known. Quarter secretion samples from both pregnant heifers (n=2065) and dry cows (n=5365) were collected for microbiological analysis from eight SA dairy herds. All heifers tested in this study were co-housed pre-weaning and were fed fresh milk as calves. RESULTS: The prevalence of coagulase negative staphylococci, Staphylococcus aureus, Streptococcus agalactiae, environmental streptococci, coliforms and samples with no bacterial growth in heifers was 26%, 0.9%, 0.08%, 1.4%, 0.4% and 66%, respectively. The overall prevalence ratio between heifers and cows for Staphylococcus aureus IMI was 0.76 (95% CI: 0.59, 0.98). Four of the individual herds had prevalence ratios of less than one (p<0.05), one herd had a prevalence ratio of 3.15 (95% CI: 1.52, 6.32), and the remaining 3 herds had a prevalence ratio not significantly different from 1.0. Marginally significant differences were found between Staphylococcus aureus IMI in pregnant heifers compared to cows in their second and later lactations (p=0.06, p=0.05, respectively) but no significant differences between heifers and cows in their first lactation. CONCLUSIONS: The presence of Streptococcus agalactiae IMI in heifers came as a surprise, especially as herd infection rates were low. The high prevalence ratio of Staphylococcus aureus between heifers and cows in one herd warrants further investigation due to the potential danger of udder damage in a young cow at the start of her productive life. The IMI in heifers with host adapted pathogens can also act as a source of new IMI for lactating dairy cows.
- ItemOpen AccessInvestigating associations between maternal mental health on wheeze through two years of age in a South African birth cohort study(2017) Macginty, Rae; Lesosky, Maia; Zar, Heather J; Stein, Dan J; Barnett, WhitneyBackground: Wheezing is one of the most common respiratory illnesses in children worldwide. Severe wheeze can result in significant morbidity, caregiver burden and increased health care costs. In addition, early childhood wheeze may be associated with reduced lung function, diminished airway responsiveness, increased risk of asthma in late childhood and subsequent respiratory disease including asthma in adulthood. This is particularly true in those experiencing recurrent wheeze episodes, which in the presence of viral respiratory tract infections, are believed to lead to asthma diagnosis. Thus, it is imperative to understand the risk factors for early childhood wheeze to reduce the increasing burden of respiratory illness. Recent research has seen a shift to maternal psychosocial risk factors and the impact these have on child respiratory health outcomes, such as wheeze. Various studies, largely conducted in High Income Countries (HIC), have found associations between antenatal or postnatal psychosocial risk factors, such as depression, psychological distress, and Intimate Partner Violence (IPV), and child wheeze and/or asthma diagnosis in early stages of life. However, these studies predominantly considered those in low-income urban regions that were predisposed to respiratory illnesses, including wheeze and asthma. Utilising the techniques and knowledge gained from previous studies, this research considers the relationship between antenatal or postnatal maternal psychosocial exposures and the onset and recurrence of child wheeze in a South African setting. In the study population used for this research, the reported prevalence of antenatal psychological distress and depression was 23% and 20%, respectively, while 34% of the women were exposed to antenatal IPV. Often those suffering from poor mental health in these contexts are not recognised and therefore remain untreated. In addition, service provision in these settings is also generally poor. The combination of low levels of social and psychiatric support, with unique political and socio-economic risk factors, may result in more persistent and severe forms of psychosocial exposure in Low Middle Income Countries (LMIC). Given the high prevalence of psychosocial risk factors, as well as the high prevalence of child wheeze, South Africa provides an excellent platform to investigate the association between maternal antenatal or postnatal psychosocial exposure and the development and recurrence of child wheeze in an LMIC context. Methods: The data used for this research was provided by the Drakenstein Child Health Study (DCHS), a prospective birth cohort study conducted in the Drakenstein region, a peri-urban region outside of Paarl in the Western Cape of South Africa. Pregnant women over 18 years old, between 20-28 weeks' gestation, living in the region were enrolled in a parent study, in order to investigate the epidemiology and aetiology of respiratory illnesses in children. The parent study considered various risk factors, including psychosocial risk factors such as maternal depression, psychological distress and IPV, which were measured antenatally and postnatally by validated questionnaires. In the context of this research, wheeze was considered to be present if it was identified during any routine study follow-up visit, as well as at an unscheduled lower respiratory tract infection (LRTI) episode visit during the first two years of life. Recurrent wheeze was defined as experiencing two or more episodes of wheeze in a 12-month period. Logistic regression was used to investigate the relationship between antenatal and postnatal psychosocial risk factors and child wheeze. Results: From the results, postnatal psychological distress and IPV were associated with experiencing at least one episode of child wheeze (adjusted OR = 2.10, 95% CI: 1.16-3.79 and 1.60, 95% CI: 1.11-2.29 respectively) and recurrent wheeze (adjusted OR = 2.33, 95% CI: 1.09- 4.95 and 2.22, 95% CI: 1.35-3.63 respectively), within the first two years of life. No associations were found between antenatal psychosocial risk factors and child wheeze. Of clinical covariates explored, maternal smoking and household smoke exposure, birth weight, gestational age, sex and population group were associated with the presence of wheeze. All of these clinical covariates, as well as alcohol consumption were associated with recurrent child wheeze. Conclusion: Maternal postnatal psychological distress and postnatal IPV had the strongest impact on predicting wheeze outcomes. These findings suggest that screening and treatment programs which address maternal postnatal psychosocial risk factors may lessen the burden of childhood wheeze in LMIC settings.
- ItemOpen AccessMissed Opportunities for Vaccination and Associated Factors among Children Attending Primary Health Care Facilities in Cape Town, South Africa: A Pre-Intervention Multilevel Analysis(2022-05-16) Nnaji, Chukwudi A; Wiysonge, Charles S; Adamu, Abdu A; Lesosky, Maia; Mahomed, Hassan; Ndwandwe, DuduzileDespite the substantial efforts at ensuring universal access to routine immunisation services among children in South Africa, major gaps in immunisation coverage remain. This study assessed the magnitude of missed opportunities for vaccination (MOV) and associated factors among children aged 0–23 months attending primary health care (PHC) facilities in Cape Town. We used multilevel binomial logistic regression models to explore individual and contextual factors associated with MOV, with children aged 0–23 months at Level 1, nested within PHC facilities (Level 2). A total of 674 children and their caregivers were enrolled. MOV prevalence was 14.1%, ranging from 9.1% to 18.9% across sub-districts. Dose-specific MOV prevalence was highest for the second dose of measles vaccine (9.5%) and lowest for the first dose of rotavirus vaccine (0.6%). The likelihood of a child experiencing MOV was significantly associated with caregivers’ low level of education (Odds ratio (OR) = 3.53, 95% credible interval (CrI): 1.13–11.03), recent receipt of immunisation messages (OR = 0.46, 95%CrI: 0.25–0.87), shared immunisation decision making by both parents (OR = 0.21, 95%CrI: 0.07–0.62) and health facility staff number (OR = 0.18, 95%CrI: 0.06–0.61). The burden of MOV among children in Cape Town is influenced by individual and contextual factors, which provide important opportunities for quality improvement and broader strategies to improve routine immunisation service delivery.
- ItemOpen AccessMulti-state models for the analysis of Wheeze in a birth cohort of Western Cape children(2019) Hannan, Patrick Luke; Lesosky, Maia; Zar, HeatherIntroduction Wheezing is common in young children. By the age of six, approximately 50% of children in high-income countries will have experienced at least one episode of wheezing in their life. Furthermore, childhood wheezing may be associated with reduced lung function and increased risk of asthma in later life. Determining the epidemiology of wheeze is complex given that the risk factors vary based on the age of the child and the phenotype of wheeze. Little is known regarding the recurrent nature of childhood wheezing in low- and middle-income contexts. This study aimed to use multi-state models to estimate the rate of transition among various states of wheeze in children from birth to the age of three years. This study also aimed to investigate the association between possible risk factors for childhood wheezing and the estimated transition intensities. Methods The rationale for conducting the study, as well as the objectives of the study, methods and data analysis plan are outlined in the study protocol (Part A). A summary of what is currently known about childhood wheezing is presented as part of the literature review (Part B). The aim of the literature review was to identify known risk factors for childhood wheeze and the methods used to analyse recurrent childhood wheezing, as well as identify the limitations of the current methods used to analyse recurrent childhood wheezing. A manuscript presenting the results of the study is included as Part C. This study was a secondary analysis of data from 1086 children from birth to three years, born to mothers in the Drakenstein area of the Western Cape, South Africa, enrolled at one of two pri- mary care clinics. The data were collected as part of a prospective birth cohort, the Drakenstein Child Health Study. Cox proportional hazards models were used to investigate the association of risk factors with time to first wheezing event and time to recurrent wheezing. Two multistate models investigating the progression of childhood wheezing were constructed. Multiple definitions of childhood wheeze as an outcome were investigated for all constructed models. A simple unidirectional multi-state model and a complex multi-state model with three states (never wheeze, wheeze not associated with lower respiratory tract infection (LRTI), and, lower respiratory tract infection associated wheeze) were constructed. The multi-state model allowed four possible transitions: 1) from “never wheeze” to “wheeze not associated with LRTI” or from 2) “never wheeze” to “LRTI-associated wheeze” or from 3) “wheeze not associated with LRTI” to “LRTI-associated wheeze” and from 4) “LRTI-associated wheeze” to “wheeze not associated with LRTI”. Transition intensities between wheeze states were estimated using discrete time multi-state models. The association of risk factors with transition intensities were estimated using multivariable proportional hazards models. Results Of the 1086 children included in the study, 476 (44%) experienced at least one episode of wheezing, and 227 (21%) experienced more than one episode of wheezing in the first three years of life. A total of 951 episodes of wheezing were recorded in the 36 months of follow-up time. In the multi-state analysis, LRTI-associated wheeze and wheeze not associated with LRTI were equally likely to be the first wheeze event. However, recurrent wheezing events were more likely to follow LRTI-associated wheeze as the first event (0.0020033 vs 8.6683754 × 10−4 ). Male children were at significantly higher risk of experiencing wheeze associated with an LRTI as the first wheezing event and at significantly higher risk of subsequent recurrent wheezing. Children exposed to maternal smoking prenatally had a significantly higher risk of transition to the wheeze state compared to unexposed children. Conclusion Multi-state models provide a novel method for the analysis of wheezing and recurrent wheezing in a cohort of children in South Africa. Multi-state models successfully predicted the progression of children through discrete states of wheeze and produced results consistent with existing literature on childhood wheeze, while accounting for recurrent events and interval-censored data.
- ItemOpen AccessPositive attitudes toward adoption of a multi-component intervention strategy aimed at improving HIV outcomes among adolescents and young people in Nampula, Mozambique: perspectives of HIV care providers(2023-06-06) Mogoba, Phepo; Lesosky, Maia; Mukonda, Elton E.; Zerbe, Allison; Falcao, Joana; Zandamela, Ricardino; Myer, Landon; Abrams, Elaine J.Background Service providers' attitudes toward interventions are essential for adopting and implementing novel interventions into healthcare settings, but evidence of evaluations in the HIV context is still limited. This study is part of the CombinADO cluster randomized trial (ClinicalTrials.gov NCT04930367), which is investigating the effectiveness of a multi-component intervention package (CombinADO strategy) aimed at improving HIV outcomes among adolescents and young adults living with HIV (AYAHIV) in Mozambique. In this paper we present findings on key stakeholder attitudes toward adopting study interventions into local health services. Methods Between September and December 2021, we conducted a cross-sectional survey with a purposive sample of 59 key stakeholders providing and overseeing HIV care among AYAHIV in 12 health facilities participating in the CombinADO trial, who completed a 9-item scale on attitudes towards adopting the trial intervention packages in health facilities. Data were collected in the pre-implementation phase of the study and included individual stakeholder and facility-level characteristics. We used generalized linear regression to examine the associations of stakeholder attitude scores with stakeholder and facility-level characteristics. Results Overall, service-providing stakeholders within this setting reported positive attitudes regarding adopting intervention packages across study clinic sites; the overall mean total attitude score was 35.0 ([SD] = 2.59, Range = [30–41]). The study package assessed (control or intervention condition) and the number of healthcare workers delivering ART care in participating clinics were the only significant explanatory variables to predict higher attitude scores among stakeholders (β = 1.57, 95% CI = 0.34–2.80, p = 0.01 and β = 1.57, 95% CI = 0.06–3.08, p = 0.04 respectively). Conclusions This study found positive attitudes toward adopting the multi-component CombinADO study interventions among HIV care providers for AYAHIV in Nampula, Mozambique. Our findings suggest that adequate training and human resource availability may be important in promoting the adoption of novel multi-component interventions in healthcare services by influencing healthcare provider attitudes.
- ItemOpen AccessPrediction of post-tuberculosis lung damage using CT lung imaging measures among adults in Malawi(2018) Gunsaru, Vester Poyamba; Lesosky, MaiaThe burden of tuberculosis (TB) is high globally and in sub-Saharan Africa (SSA). Although TB treatment regimens are now widely available, and with high success rates in most parts of the world, TB can lead to long-term health consequences. Evidence has shown that completion of TB treatment can mark the beginning of chronic lung damage and other sequelae. There is a need for early identification of individuals at risk of post-tuberculosis lung damage (PTLD) to necessitate its appropriate management. This study evaluated the significance of radiological features from computed tomography (CT) scan in describing PTLD patterns at treatment completion and predicting PTLD outcomes at 12 months post treatment, as a possible tool to detect risk of PTLD at an early stage. This thesis comprises three parts. Part A is the study protocol, which outlines the purpose, methods and ethical considerations of the proposed study. Part B is the literature review, which summarizes the existing literature on PTLD, the risk factors for PTLD, and the relationship between imaging data and PTLD. The objective of the literature review was to identify gaps in literature which would provide context for further research. Part C is the journal-ready manuscript, which provides the results of the conducted study and a discussion on the implication of these results. The results of the study showed that CT imaging features were important in determining concurrent abnormal spirometry at baseline in post-TB individuals. These features were not useful in predicting spirometry outcomes at 12 months after treatment completion. However, there is need for further validation of these results in other settings and the consideration of other lung damage outcomes.
- ItemOpen AccessProlonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factors(BioMed Central, 2016-09-27) Bana, Tasnim M; Lesosky, Maia; Pepper, Dominique J; van der Plas, Helen; Schutz, Charlotte; Goliath, Rene; Morroni, Chelsea; Mendelson, Marc; Maartens, Gary; Wilkinson, Robert J; Meintjes, GraemeBackground: In a proportion of patients with HIV-associated tuberculosis who develop paradoxical immune reconstitution inflammatory syndrome (IRIS), the clinical course of IRIS is prolonged necessitating substantial health care utilization for diagnostic and therapeutic interventions. Prolonged TB-IRIS has not been prospectively studied to date. We aimed to determine the proportion of patients with prolonged TB-IRIS, as well as the clinical characteristics and risk factors for prolonged TB-IRIS. Methods: We pooled data from two prospective observational studies and a randomized controlled trial conducted in Cape Town, South Africa, that enrolled patients with paradoxical TB-IRIS. We used the same diagnostic approach and clinical case definitions for TB-IRIS in the 3 studies. Prolonged TB-IRIS was defined as TB-IRIS symptoms lasting > 90 days. Risk factors for prolonged TB-IRIS were analysed using Wilcoxon rank sum test, Fisher’s exact test, multivariate logistic regression and Cox proportional hazards models. Results: Two-hundred and sixteen patients with TB-IRIS were included. The median duration of TB-IRIS symptoms was 71.0 days (IQR 41.0–113.2). In 73/181 patients (40.3 %) with adequate follow-up data, IRIS duration was > 90 days. Six patients (3.3 %), mainly with lymph node involvement, had IRIS duration > 1 year. In univariate logistic regression analysis the following were significantly associated with IRIS duration > 90 days: lymph node involvement at initial TB diagnosis, drug-resistant TB, lymph node TB-IRIS, and not being hospitalised at time of TB-IRIS diagnosis. In our multivariate logistic regression model lymph node TB-IRIS (aOR 2.27, 95 % CI 1.13–4.59) and not being hospitalised at time of TB-IRIS diagnosis (aOR for being hospitalised 0.5, 95 % CI 0.25-0.99) remained significantly associated with prolonged TB-IRIS, and drug-resistant TB was of borderline significance (aOR 3.26, 95 % CI 0.97–12.99). The association of not being hospitalised with longer duration of IRIS might be related to 1 of the 3 cohorts in which all patients were hospitalised at ART initiation with close inpatient follow-up. This could have resulted in diagnosis of milder cases and earlier IRIS treatment potentially resulting in shorter TB-IRIS duration in these hospitalised patients. Conclusions: Around 40 % of patients with TB-IRIS have symptoms for more than 90 days. Involvement of lymph nodes at time of TB-IRIS is an independent risk factor for prolonged TB-IRIS. Future studies should address whether more prompt anti-inflammatory treatment of lymph node TB-IRIS reduces the risk of prolonged TB-IRIS. Trial registration: The randomized controlled trial was registered with Current Controlled Trials ISRCTN21322548 on 17 August 2005.
- ItemOpen AccessPsychological distress and its relationship with non-adherence to TB treatment: a multicentre study(Biomed Central Ltd, 2015) Theron, Grant; Peter, Jonny; Zijenah, Lynn; Chanda, Duncan; Mangu, Chacha; Clowes, Petra; Rachow, Andrea; Lesosky, Maia; Hoelscher, Michael; Pym, Alex; Mwaba, Peter; Mason, Peter; Naidoo, Pamela; Pooran, Anil; Sohn, Hojoon; Pai, Madhukar; Stein, DanBACKGROUND:The successful cure of tuberculosis (TB) is dependent on adherence to treatment. Various factors influence adherence, however, few are easily modifiable. There are limited data regarding correlates of psychological distress and their association with non-adherenceto anti-TB treatment. METHODS: In a trial of a new TB test, we measured psychological distress (K-10 score), TB-related health literacy, and morbidity (TBscore), prior to diagnosis in 1502 patients with symptoms of pulmonary TB recruited from clinics in Cape Town (n = 419), Harare (n = 400), Lusaka (n = 400), Durban (n = 200), and Mbeya (n = 83). Socioeconomic, demographic, and alcohol usage-related data were captured. Patients initiated on treatment had their DOTS cards reviewed at two-and six-months. RESULTS: 22 %(95 % CI: 20 %, 25 %) of patients had severe psychological distress (K-10 [greater than or equal to] 30). In a multivariable linear regression model, increased K-10 scorewas independently associated with previous TB [estimate (95 % CI) 0.98(0.09-1.87); p = 0.0304], increased TBscore [1(0.80, 1.20); p <0.0001], and heavy alcohol use [3.08(1.26, 4.91); p = 0.0010], whereas male gender was protective [-1.47(2.28, 0.62); p = 0.0007]. 26 % (95 % CI: 21 %, 32 %) of 261 patients with culture-confirmed TB were non-adherent. In a multivariable logistic regression modelfor non-adherence, reduced TBscore [OR (95 % CI) 0.639 (0.497, 0.797); p = 0.0001], health literacy score [0.798(0.696, 0.906); p = 0.0008], and increased K-10 [1.082(1.033, 1.137); p = 0.0012], and heavy alcohol usage [14.83(2.083, 122.9); p = 0.0002], were independently associated. Culture-positive patients with aK-10 score[greater than or equal to] 30 were more-likely to be non-adherent (OR = 2.290(1.033-5.126); p = 0.0416]. CONCLUSION: Severe psychological distress is frequent amongst TB patients in Southern Africa. Targeted interventions to alleviate psychological distress, alcohol use, and improve health literacy in newly-diagnosed TB patients could reduce non-adherenceto treatment.
- ItemOpen AccessRenal safety of lithium in HIV-infected patients established on tenofovir disoproxil fumarate containing antiretroviral therapy: analysis from a randomized placebo-controlled trial(BioMed Central, 2017-02-04) Decloedt, Eric H; Lesosky, Maia; Maartens, Gary; Joska, John ABackground: The prevalence of bipolar disorder in HIV-infected patients is higher than the general population. Lithium is the most effective mood stabiliser, while tenofovir disoproxil fumarate (TDF) is frequently used as part of combination antiretroviral therapy (ART). Both TDF and lithium are associated with renal tubular toxicity, which could be additive, or a pharmacokinetic interaction may occur at renal transporters with a decrease in TDF elimination. Objective: We report on the change in estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula in participants who received ART including TDF and were enrolled in a 24 week randomised trial of lithium versus placebo in patients with HIV-associated neurocognitive impairment. Methods: We included HIV-infected adults with cognitive impairment established on ART for at least 6 months with a suppressed viral load attending public sector ART clinics in Cape Town, South Africa. We excluded participants with an eGFR or increase in potassium between the two arms during the 24 weeks. Conclusions: We found that 24-week treatment of HIV-infected patients with lithium and TDF did not result in increased nephrotoxicity.
- ItemOpen AccessSafety of licensed vaccines in HIV-infected persons: a systematic review protocol(2014-09-11) Kagina, Benjamin M; Wiysonge, Charles S; Lesosky, Maia; Madhi, Shabir A; Hussey, Gregory DAbstract Background Safety of vaccines remains a cornerstone of building public trust on the use of these cost-effective and life-saving public health interventions. In some settings, particularly Sub-Saharan Africa, there is a high prevalence of HIV infection and a high burden of vaccine-preventable diseases. There is evidence suggesting that the immunity induced by some commonly used vaccines is not durable in HIV-infected persons, and therefore, repeated vaccination may be considered to ensure optimal vaccine-induced immunity in this population. However, some vaccines, particularly the live vaccines, may be unsafe in HIV-infected persons. There is lack of evidence on the safety profile of commonly used vaccines among HIV-infected persons. We are therefore conducting a systematic review to assess the safety profile of routine vaccines administered to HIV-infected persons. Methods/Design We will select studies conducted in any setting where licensed and effective vaccines were administered to HIV-infected persons. We will search for eligible studies in PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Africa-Wide, PDQ-Evidence and CINAHL as well as reference lists of relevant publications. We will screen search outputs, select studies and extract data in duplicate, resolving discrepancies by discussion and consensus. Discussion Globally, immunisation is a major public health strategy to mitigate morbidity and mortality caused by various infectious disease-causing agents. In general, there are efforts to increase vaccination coverage worldwide, and for these efforts to be successful, safety of the vaccines is paramount, even among people living with HIV, who in some situations may require repeated vaccination. Results from this systematic review will be discussed in the context of the safety of routine vaccines among HIV-infected persons. From the safety perspective, we will also discuss whether repeat vaccination strategies may be feasible among HIV-infected persons. Systematic review registration PROSPERO CRD42014009794 .
- ItemOpen AccessSimulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial(BioMed Central, 2017-06-07) Lesosky, Maia; Joska, John; Decloedt, EricBackground: Therapeutic drug monitoring (TDM) is essential practice when dosing drugs with a narrow therapeutic index in order to achieve a plasma drug concentration within a narrow target range above the efficacy concentration but below the toxicity concentration. However, TDM with dose individualisation is challenging during a double-blind clinical trial with laboratory staff and investigators blinded to treatment arm allocation. Methods: Drug concentrations were simulated for participants in the placebo arm by an unblinded independent statistician, utilising the measured values from the treatment arm participants. Simulated and actual concentrations were re-blinded and passed on to a dose-adjusting investigator, who made dose adjustment recommendations but was not directly responsible for clinical care of participants. Results: A total of 257 sham lithium plasma concentrations were simulated utilising 242 true lithium plasma concentrations in real time as the trial progressed. The simulated values had a median (interquartile range) of 0.59 (0.46, 0.72) compared to 0.53 (0.39, 0.72) in the treatment arm. Blinding of the laboratory staff and dose-adjusting investigator was maintained successfully. Conclusions: We succeeded in simulating sham lithium plasma concentrations while maintaining blinding. Our simulated values have a smaller range than the observed data, which can be explained by the challenges with respect to drug adherence and dose timing that were experienced. Trial registration: Pan African Clinical Trials Registry, PACTR201310000635418. Registered on 30 August 2013.
- ItemOpen AccessSimultaneous clustering with mixtures of factor analysers(2013) O'Donnell, Warwick; Lesosky, MaiaThis work details the method of Simultaneous Model-based Clustering. It also presents an extension to this method by reformulating it as a model with a mixture of factor analysers. This allows for the technique, known as Simultaneous Model-Based Clustering with a Mixture of Factor Analysers, to be able to cluster high dimensional gene-expression data. A new table of allowable and non-allowable models is formulated, along with a parameter estimation scheme for one such allowable model. Several numerical procedures are tested and various datasets, both real and generated, are clustered. The results of clustering the Iris data find a 3 component VEV model to have the lowest misclassification rate with comparable BIC values to the best scoring model. The clustering of Genetic data was less successful, where the 2-component model could successfully uncover the healthy tissue, but partitioned the cancerous tissue in half.