OpenUCT :: Browsing by Author "Hussey, Gregory D"

Browsing by Author "Hussey, Gregory D"

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Open Access
A systematic review of the epidemiology of hepatitis A in Africa
(2019-07-22) Patterson, Jenna; Abdullahi, Leila; Hussey, Gregory D; Muloiwa, Rudzani; Kagina, Benjamin M
Abstract Background Hepatitis A, caused by the hepatitis A virus (HAV), is a vaccine preventable disease. In Low and Middle-Income Countries (LMICs), poor hygiene and sanitation conditions are the main risk factors contributing to HAV infection. There have been, however, notable improvements in hygiene and sanitation conditions in many LMICs. As a result, there are studies showing a possible transition of some LMICs from high to intermediate HAV endemicity. The World Health Organization (WHO) recommends that countries should routinely collect, analyse and review local factors (including disease burden) to guide the development of hepatitis A vaccination programs. Up-to-date information on hepatitis A burden is, therefore, critical in aiding the development of country-specific recommendations on hepatitis A vaccination. Methods We conducted a systematic review to present an up-to-date, comprehensive synthesis of hepatitis A epidemiological data in Africa. Results The main results of this review include: 1) the reported HAV seroprevalence data suggests that Africa, as a whole, should not be considered as a high HAV endemic region; 2) the IgM anti-HAV seroprevalence data showed similar risk of acute hepatitis A infection among all age-groups; 3) South Africa could be experiencing a possible transition from high to intermediate HAV endemicity. The results of this review should be interpreted with caution as the reported data represents research work with significant sociocultural, economic and environmental diversity from 13 out of 54 African countries. Conclusions Our findings show that priority should be given to collecting HAV seroprevalence data and re-assessing the current hepatitis A control strategies in Africa to prevent future disease outbreaks.
Open Access
A bibliometric analysis of childhood immunization research productivity in Africa since the onset of the Expanded Program on Immunization in 1974
(BioMed Central, 2013-03-14) Wiysonge, Charles S; Uthman, Olalekan A; Ndumbe, Peter M; Hussey, Gregory D
Background: The implementation of strategic immunization plans whose development is informed by available locally-relevant research evidence should improve immunization coverage and prevent disease, disability and death in Africa. In general, health research helps to answer questions, generate the evidence required to guide policy and identify new tools. However, factors that influence the publication of immunization research in Africa are not known. We, therefore, undertook this study to fill this research gap by providing insights into factors associated with childhood immunization research productivity on the continent. We postulated that research productivity influences immunization coverage. Methods: We conducted a bibliometric analysis of childhood immunization research output from Africa, using research articles indexed in PubMed as a surrogate for total research productivity. We used zero-truncated negative binomial regression models to explore the factors associated with research productivity. Results: We identified 1,641 articles on childhood immunization indexed in PubMed between 1974 and 2010 with authors from Africa, which represent only 8.9% of the global output. Five countries (South Africa, Nigeria, The Gambia, Egypt and Kenya) contributed 48% of the articles. After controlling for population and gross domestic product, The Gambia, Guinea-Bissau and Sao Tome and Principe were the most productive countries. In univariable analyses, the country's gross domestic product, total health expenditure, private health expenditure, and research and development expenditure had a significant positive association with increased research productivity. Immunization coverage, adult literacy rate, human development index and physician density had no significant association. In the multivarable model, only private health expenditure maintained significant statistical association with the number of immunization articles. Conclusions: Immunization research productivity in Africa is highly skewed, with private health expenditure having a significant positive association. However, the current contribution of authors from Africa to global childhood immunization research output is minimal. The lack of association between research productivity and immunization coverage may be an indication of lack of interactive communication between health decision-makers, program managers and researchers; to ensure that immunization policies and plans are always informed by the best available evidence.
Open Access
Building evidence for improving childhood immunisation coverage in Africa.
(2012) Wiysonge, Shey Umaru Charles; Hussey, Gregory D; Schoub, Barry D
The Expanded Programme on Immunisation has the potential to substantially reduce child mortality and contribute to achieving the Millennium Development Goals. We assessed the programme’s performance in Africa, the reasons for poor performance, and effective interventions for improving its performance on the continent. We used a combination of methods including systematic reviews, bibliometric analyses, generalised linear models, and grading of the quality of evidence. We found that African countries have made extraordinary advances since childhood immunisation programmes began in 1974. However, there exist wide inter-country and intra-country differences, and the quality of immunisation data is poor. Besides, vaccines are administered well after the recommended ages in many countries; leaving children exposed to deadly vaccine-preventable diseases for long periods. In addition, Africa’s contribution to the global immunisation research output is minimal. There is no association between research productivity and immunisation coverage in Africa, which may signal lack of interactive communication between policymakers and researchers. Furthermore, individual and contextual factors (defined at community and country levels) are independently associated with low immunisation coverage; suggesting that immunisation system strengthening should address people and the communities and societies in which they live. Lastly, we found moderate-to-high quality evidence that interactive educational meetings, audit and feedback, supportive supervision; and use of community health workers, parent reminders, home visits, interactive communication, mass media, and material incentives have the potential to improve childhood immunisation coverage in Africa.
Open Access
A descriptive study of the attitudes of doctors, working at clinics and day hospitals in the Cape Metropole to patients with HIV/AIDS
(1998) Fransman, Desireé Christine; Hussey, Gregory D; Henley, Lesley
HIV/AIDS is a fairly new condition. Despite a large amount of published literature regarding its clinical aspects, there is a paucity of South African research and information relating to the attitudes and feelings of the physicians who diagnose, care for and make decisions with regard to these patients, especially children. Several studies suggest that health care workers who provide clinical care for Persons with HIV/AIDS (PWA's) may have an intolerant attitude towards them. As the number of children with HIV/AIDS increases, the burden of care will shift to health care workers at primary level care. It was therefore decided to assess the attitudes of doctors at primary level care facilities in Cape Town, towards paediatric patients with HIV/AIDS. The results of this study are crucial given the increasing exposure of doctors at this level to HIV/AIDS patients and understanding their response to its management. The objectives of the study were to: assess whether doctors' knowledge of the patient's HIV positive status affects their attitudes and management of the patient; assess doctors' perceived competency with regard to the management of paediatric AIDS; determine doctors' opinions with regard to HIV testing, the utilisation of diagnostic investigations and treatment; determine doctors' main concerns with regard to the management of paediatric patients with HIV/AIDS. A descriptive, cross-sectional survey was conducted amongst all doctors working at the clinics and day hospitals in Cape Town during the period February to April 1997. Seventy-eight doctors (51 % response rate) working in the clinics and day hospitals in Cape Town each completed an anonymous self-administered questionnaire. Doctors in this survey generally displayed a positive, humanistic attitude towards children with HIV/AIDS. In the majority of cases the knowledge of the child 's HIV positive status did not impact negatively on their management of the child. Interestingly, 86% of respondents felt that they would always/mostly take extra care in applying universal precautions when they know that the child is HIV positive. There is a lack of confidence in their counselling and clinical competency in the management of children with HIV/AIDS. The main source of information with regard to paediatric HIV/AIDS is journals (69%), followed by in-service training (53%) and colleagues (49%). In contrast, the preferred sources of information were in-service training (68%) and organised discussion groups/workshops (65%). Most were in favour of routine HIV testing of pregnant women and informed consent for HIV testing. However, not everyone agreed that pre-HIV test counselling was necessary in the case of children. Confidentiality of positive test results was not favoured in the majority of cases (65%) and disclosure even without the consent of the patient/carer was supported. Priority concerns relating to the management of paediatric HIV/AIDS, were lack of support in the community for parents and children, lack of policy and management guidelines and the lack of resources in the health services to cope with the burden of care. This study identifies the need for specific training in HIV/AIDS for medical doctors at primary level care facilities. The foundation of this training must begin with medical students during their clinical years but training and support should continue through in-service training. Training strategies, which address the clinical and psychological challenges presented by this disease, should be employed. In addition, clinical guidelines, which are relevant to South Africa and evidence-based, should be adopted nationally. Resources should be available to support these guidelines. It is further recommended that policies be underpinned by appropriate legislation which protects the rights of patients and health care workers in order to minimise the effects of individual attitudes and biases with regard to the treatment of PWAs.
Open Access
Determinants of vaccine hesitancy in Africa: a systematic review
(2017) Paone, Alexander; Kagina, Benjamin M; Muloiwa, Rudzani; Hussey, Gregory D
This MPH dissertation is a systematic review of the factors contributing to vaccine hesitancy in Africa. The dissertation comprises of the following three parts: The research protocol (Part A) outlines the background and proposed methods of the research. The protocol outlines the search strategy used to identify research eligible for this review according to defined criteria. The objective of this research was to identify determinants of vaccine hesitancy in Africa. The protocol describes data collection methods and the analysis plan of this research in order to address the objective. The literature review (Part B) provides a summary and interpretation of the current literature on barriers to vaccination, specifically vaccine hesitancy and its impacts on immunisation programs. The literature review identifies discord among literature in defining vaccine hesitancy and evaluating its presence and impact on varying populations, and reviews the attempts for standardisation by the Strategic Advisory Group of Experts Working Group on Vaccine Hesitancy. Lastly, the literature review identifies gaps in the literature, and suggests filling them ideally with a standardised metric. The manuscript (Part C) is presented in a format suitable for Vaccine journal submission. The manuscript includes a background, a description of the methods used, and a presentation and discussion of the results of the systematic review.
Open Access
Epidemiology of pertussis in children hospitalised with respiratory tract infection
(2021) Muloiwa, Rudzani; Zar, Heather J; Hussey, Gregory D
The availability of an effective vaccine against Bordetella pertussis substantially reduced the morbidity and mortality from pertussis, however, in the last decade there appears to have been a substantial increase in pertussis cases as reported mainly in high income countries. Although it is believed that the greatest burden of pertussis, including deaths, is in low- and middle-income countries (LMICs), there seem to be little data available to back this up. This thesis set out to find data that will give some insight into the burden of pertussis in a low- and middle-income setting in infants and children with severe lower respiratory tract infection (LRTI). Given the paucity of data in LMICs, the thesis starts by systematically searching for existing data that will give some indication of the possible extent of the pertussis problem in these countries. Secondly, a prospective study was conducted at a children's hospital. As hospital admission is a marker of severe disease, these children were targeted as the appropriate population in which to meaningfully conduct a primary study on the burden of pertussis. In addition to quantifying the burden by describing the prevalence of confirmed pertussis in this group of children, the study set out to look for potential factors that may be associated with increased risk of pertussis. LRTI are now commonly known to be associated with identification of multiple organisms in respiratory samples, this study aimed to also look at organisms that are detected with Bordetella pertussis; and investigate whether this association was in any way associated with severe disease or negative outcomes. Finally, as data has been emerging that in the context of immunisation, the clinical presentation of pertussis may no longer be following a classical pattern, this study hoped to identify clinical features that could be used to develop a more reliable clinical case definition of pertussis. 2 Chapter 1 gives a background that justifies the undertaking of this study as well as give a summary of the methods used to answer the question of the thesis. The chapter also gives an indication of the structure that the thesis follows. In chapter 2 a systematic review quantifies the burden of pertussis in LMICs using the best available data. In chapter 3 the burden of pertussis due to the two organisms known to cause the disease, Bordetella pertussis and Bordetella parapertussis, is described in some detail. In both this chapter and the earlier mentioned systematic review (chapter 2), the burden of pertussis is stratified by subgroups to identify potential risk factors. The issue of risk is formally and specifically taken up in the chapter that follows (chapter 4) where potential risk factors are analysed, and the independent impact for some of these factors is established. The last two results chapters (chapters 5 and 6) deal respectively with the conundrum of finding other respiratory organism in the same specimen with Bordetella pertussis and failure to find useful clinical criteria that can help with improved diagnosis of pertussis, specifically in children presenting with acute severe lower respiratory tract infection. While there is no established pattern noted between pertussis and most organisms, a few give signals of being independently associated with Bordetella pertussis even if the clinical relevance is not clear at the moment. In the final chapter of the thesis (chapter 7) I conclude the thesis by making an argument that although there are still knowledge gaps, the thesis gives a clear indication that pertussis remains a serious problem in LMICs especially for some groups that show increased risk of the disease or its severe consequences.
Open Access
Hepatitis A seroprevalence in South Africa: Are we in epidemiological transition?
(2018) Enoch, Annabel; Kagina, Benjamin M; Hussey, Gregory D; Andersson, Monique; Hardie, Diana
Hepatitis A virus (HAV) is the most common cause of viral hepatitis worldwide. Infection with HAV is vaccine preventable, however, a vaccine against HAV is not included in the Expanded Programme on Immunization in South Africa (SA). South Africa was considered to be a high endemic country for hepatitis A in the past, hence there was no need for routine immunization against the virus. Our hypothesis is that SA is changing from high to intermediate endemic setting for hepatitis A. To test our hypothesis, we conducted a cross-sectional seroprevalence study in the 1-7 year age group in the Western Cape Province. Our samples for this study were from specimens, collected between August and October 2015, sent for routine diagnosis to referral hospitals in the Western Cape Province. We tested remaining serum of 482 samples sent for routine tests. A Siemens enzyme immunoassay was used to test for hepatitis A antibodies. We also analysed hepatitis A test results from the National Health Laboratory Services (NHLS) Disa*Lab database at Groote Schuur hospital from 2009-2014, as well as hepatitis A surveillance data from the National Institute for Communicable Diseases (NICD) from 2009-2014, to look at the past hepatitis A prevalence trend. Our cross-sectional study showed the seroprevalence to be 44.1% in the 1-7 year age group. The NHLS data showed a seroprevalence of <90% up to age 10 years, indicating intermediate endemicity. The NICD data showed that a substantial number of symptomatic hepatitis A infections occurred in the 7-40 year age group, suggesting an increasing proportion of a susceptible population to HAV infection. Taken together, these results indicate the need for further studies designed to aid the development of vaccination policies against HAV infection in South Africa.
Open Access
Individual and contextual factors associated with low childhood immunisation coverage in sub-Saharan Africa: a multilevel analysis
(Public Library of Science, 2012) Wiysonge, Charles S; Uthman, Olalekan A; Ndumbe, Peter M; Hussey, Gregory D
BACKGROUND: In 2010, more than six million children in sub-Saharan Africa did not receive the full series of three doses of the diphtheria-tetanus-pertussis vaccine by one year of age. An evidence-based approach to addressing this burden of un-immunised children requires accurate knowledge of the underlying factors. We therefore developed and tested a model of childhood immunisation that includes individual, community and country-level characteristics. Method and FINDINGS: We conducted multilevel logistic regression analysis of Demographic and Health Survey data for 27,094 children aged 12-23 months, nested within 8,546 communities from 24 countries in sub-Saharan Africa. According to the intra-country and intra-community correlation coefficient implied by the estimated intercept component variance, 21% and 32% of the variance in unimmunised children were attributable to country- and community-level factors respectively. Children born to mothers (OR 1.35, 95%CI 1.18 to 1.53) and fathers (OR 1.13, 95%CI 1.12 to 1.40) with no formal education were more likely to be unimmunised than those born to parents with secondary or higher education. Children from the poorest households were 36% more likely to be unimmunised than counterparts from the richest households. Maternal access to media significantly reduced the odds of children being unimmunised (OR 0.94, 95%CI 0.94 to 0.99). Mothers with health seeking behaviours were less likely to have unimmunised children (OR 0.56, 95%CI 0.54 to 0.58). However, children from urban areas (OR 1.12, 95% CI 1.01 to 1.23), communities with high illiteracy rates (OR 1.13, 95% CI 1.05 to 1.23), and countries with high fertility rates (OR 4.43, 95% CI 1.04 to 18.92) were more likely to be unimmunised. CONCLUSION: We found that individual and contextual factors were associated with childhood immunisation, suggesting that public health programmes designed to improve coverage of childhood immunisation should address people, and the communities and societies in which they live.
Open Access
Knowledge, attitudes and practices on adolescent vaccination among parents, teachers and adolescents in Africa: a systematic review protocol
(BioMed Central, 2014-09-09) Abdullahi, Leila H; Kagina, Benjamin M; Cassidy, Tali; Adebayo, Esther F; Wiysonge, Charles S; Hussey, Gregory D
Background: Vaccines are the most successful and cost-effective public health interventions available to avert vaccine-preventable diseases and deaths. Despite progress in the field of adolescent health, many young people in Africa still get sick and die from vaccine-preventable diseases due to lack of vaccination. Parents, adolescents and teachers are key players with regard to implementation of adolescent vaccination policies. Therefore, understanding their knowledge, attitudes and practices towards adolescent vaccination may provide clues on what can be done to improve vaccine uptake among adolescents. The aim of this study is to conduct a qualitative and quantitative systematic review on knowledge, attitudes and practices on adolescent vaccination among parents, teachers and adolescents in Africa. Methods: We will include both quantitative and qualitative primary studies. Eligible quantitative studies include both intervention and observational studies. Qualitative studies to be included are focus group discussions, direct observations, in-depth interviews and case ethnographic studies. We will search PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, WHOLIS, Africa Wide and CINAHL for eligible studies with no time and language limits. We will also check reference lists of included studies for other eligible reports. Two authors will independently screen the search output, select studies and extract data, resolving discrepancies by consensus and discussion. We will analyse qualitative data using thematic analysis where applicable, and quantitative studies findings will be presented in a narrative synthesis form based on the outcomes. Discussion: The findings from this systematic review will guide the identification of gaps on knowledge, attitudes and practices among the key role players on adolescent vaccination. We anticipate that our findings will guide the development of adolescent-focused vaccination policy in Africa, which is virtually non-existent at present. Systematic review registration: This review is registered with PROSPERO, registration number CRD42014010395. .
Open Access
Mobile phone text messaging for promoting adherence to anti-tuberculosis treatment: a systematic review protocol
(BioMed Central Ltd, 2013) Nglazi, Mweete; Bekker, Linda-Gail; Wood, Robin; Hussey, Gregory D; Wiysonge, Charles S
BACKGROUND: In 2010, there were approximately 8.8 million incident cases of tuberculosis (TB) worldwide. The treatment of TB is at least six months long and may be complicated by a high pill burden. In addition, TB patients often do not take their medication on schedule simply because they forget. Mobile phone text messaging has the potential to help promote TB treatment adherence. We, therefore, propose to conduct a review of current best evidence for the use of mobile phone text messaging to promote patient adherence to TB treatment. METHODS: This is a systematic review of the literature. We will preferably include randomized controlled trials (RCTs). However, non-randomized studies (NRS) will be considered if there is an inadequate number of RCTs.We will search PubMed, EMBASE, CINAHL, CENTRAL, Science Citation Index, Africa-Wide Information, and WHOLIS electronic databases for eligible studies available by 30 November 2012 regardless of language or publication status. We will also check reference lists for additional studies, identify abstracts from conference proceedings and communicate with authors for any relevant material.At least two authors will independently screen search outputs, select studies, extract data and assess the risk of bias (using separate criteria for RCTs and NRS); resolving discrepancies by discussion and consensus. We will assess clinical heterogeneity by examining the types of participants, interventions and outcomes in each study and pool studies judged to be clinically homogenous. We will also assess statistical heterogeneity using the chi-square test of homogeneity and quantify it using the I-square statistic. If study results are found to be statistically homogeneous (that is heterogeneity P > 0.1), we will pool them using the fixed-effect meta-analysis. Otherwise, we will use random-effects meta-analysis. We will calculate risk ratios and their corresponding 95% confidence intervals for dichotomous outcomes, and mean differences for continuous outcomes. For other outcomes without quantitative data, a descriptive analysis will be used.DISCUSSION:Our results can be used by researchers and policy-makers to help inform them of the efficacy of mobile phone text messaging interventions to promote patient adherence to TB treatment.
Open Access
Passive smoking and meningococcal disease
(1997) Moodley, Jennifer R; Coetzee, Nicol; Hussey, Gregory D
Neiserria meningitidis remains an important cause of morbidity and mortality in South Africa (SA). It is the sixth commonest cause of notified disease with a case fatality rate of 11% for the period 1990 1994. Identification of preventable risk factors is critical as no effective vaccine exists for serogroup B, the most prevalent serogroup in SA. A case control study was undertaken to determine the risk factors associated with meningococcal disease. The study population consisted of all children under the age of 14 years who were residents of the Cape Town City Council and Cape Metropolitan Council areas of jurisdiction. Cases were identified from weekly notification reports and from admissions to the City Hospital for Infectious Diseases. Controls were selected from the trauma wards at Red Cross War Memorial Children's Hospital. Data was analyzed using EPI INFO and SAS statistical software. During the period October 1993 to January 1995 70 cases and 210 controls were interviewed. Cases were significantly younger than controls (p = 0.0001). On univariate analysis significant risk factors for meningococcal disease included: a household where 2 or more members smoked (odds ratio (OR) =1.8), recent upper respiratory tract infection (OR= 1.8), poor nutritional status (OR= 3.6), being breastfed for less than 3 months (OR= 2.7) and overcrowding (OR= 2.8). After adjusting for confounders, the main force of passive smoking as a risk factor for meningococcal disease appeared to be in the presence of a recent upper respiratory tract infection. Other factors that remained significant after adjusting for confounders included: being breastfed for less than three months (adjusted OR= 2.4) and being less than 4 years old (adjusted OR= 2.3). This is the first case control study in South Africa examining risk factors associated with meningococcal disease. The study provides further evidence for the reduction of smoking, reduction of overcrowding and the promotion of breast-feeding as important public health measures. It also identifies children under the age of 4 years as an important target group should an effective vaccine become available.
Open Access
A retrospective study assessing the clinical outcomes and costs of acute hepatitis A in Cape Town, South Africa
(2022-01-11) Patterson, Jenna; Cleary, Susan; Silal, Sheetal P; Hussey, Gregory D; Enoch, Annabel; Korsman, Stephen; Goddard, Elizabeth; Setshedi, Mashiko; Spearman, Wendy C; Kagina, Benjamin M; Muloiwa, Rudzani
Background While some evidence has been demonstrated the cost-effectiveness of routine hepatitis A vaccination in middle-income countries, the evidence is still limited in other settings including in South Africa. Given this, the evidence base around the cost of care for hepatitis A needs to be developed towards considerations of introducing hepatitis A vaccines in the national immunisation schedule and guidelines. Objectives To describe the severity, clinical outcomes, and cost of hepatitis A cases presenting to two tertiary healthcare centers in Cape Town, South Africa. Methods We conducted a retrospective folder review of patients presenting with hepatitis A at two tertiary level hospitals providing care for urban communities of metropolitan Cape Town, South Africa. Patients included in this folder review tested positive for hepatitis A immunoglobulin M between 1 January 2008 and 1 March 2018. Results In total, 239 folders of hepatitis A paediatric patients < 15 years old and 212 folders of hepatitis A adult patients $$\ge$$ ≥ 15 years old were included in the study. Before presenting for tertiary level care, more than half of patients presented for an initial consultation at either a community clinic or general physician. The mean length of hospital stay was 7.45 days for adult patients and 3.11 days for paediatric patients. Three adult patients in the study population died as a result of hepatitis A infection and 29 developed complicated hepatitis A. One paediatric patient in the study population died as a result of hepatitis A infection and 27 developed complicated hepatitis A, including 4 paediatric patients diagnosed with acute liver failure. The total cost per hepatitis A hospitalisation was $1935.41 for adult patients and $563.06 for paediatric patients, with overhead costs dictated by the length of stay being the largest cost driver. Conclusion More than 1 in every 10 hepatitis A cases (13.3%) included in this study developed complicated hepatitis A or resulted in death. Given the severity of clinical outcomes and high costs associated with hepatitis A hospitalisation, it is important to consider the introduction of hepatitis A immunisation in the public sector in South Africa to potentially avert future morbidity, mortality, and healthcare spending.
Open Access
Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis
(BioMed Central Ltd, 2009) Schaaf, Hendrik S; Willemse, Marianne; Cilliers, Karien; Labadarios, Demetre; Maritz, Johannes S; Hussey, Gregory D; McIlleron, Helen; Smith, Peter; Donald, Peter R
BACKGROUND: Rifampin is a key drug in antituberculosis chemotherapy because it rapidly kills the majority of bacilli in tuberculosis lesions, prevents relapse and thus enables 6-month short-course chemotherapy. Little is known about the pharmacokinetics of rifampin in children. The objective of this study was to evaluate the pharmacokinetics of rifampin in children with tuberculosis, both human immunodeficiency virus type-1-infected and human immunodeficiency virus-uninfected. METHODS: Fifty-four children, 21 human immunodeficiency virus-infected and 33 human immunodeficiency virus-uninfected, mean ages 3.73 and 4.05 years (P = 0.68), respectively, admitted to a tuberculosis hospital in Cape Town, South Africa with severe forms of tuberculosis were studied approximately 1 month and 4 months after commencing antituberculosis treatment. Blood specimens for analysis were drawn in the morning, 45 minutes, 1.5, 3.0, 4.0 and 6.0 hours after dosing. Rifampin concentrations were determined by liquid chromatography tandem mass spectrometry. For two sample comparisons of means, the Welch version of the t-test was used; associations between variables were examined by Pearson correlation and by multiple linear regression. RESULTS: The children received a mean rifampin dosage of 9.61 mg/kg (6.47 to 15.58) body weight at 1 month and 9.63 mg/kg (4.63 to 17.8) at 4 months after commencing treatment administered as part of a fixed-dose formulation designed for paediatric use. The mean rifampin area under the curve 0 to 6 hours after dosing was 14.9 and 18.1 mug/hour/ml (P = 0.25) 1 month after starting treatment in human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children, respectively, and 16.52 and 17.94 mug/hour/ml (P = 0.59) after 4 months of treatment. The mean calculated 2-hour rifampin concentrations in these human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children were 3.9 and 4.8 mug/ml (P = 0.20) at 1 month after the start of treatment and 4.0 and 4.6 mug/ml (P = 0.33) after 4 months of treatment. These values are considerably less than the suggested lower limit for 2-hour rifampin concentrations in adults of 8.0 mug/ml and even 4 mug/mlCONCLUSION:Both human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children with tuberculosis have very low rifampin serum concentrations after receiving standard rifampin dosages similar to those used in adults. Pharmacokinetic studies of higher dosages of rifampin are urgently needed in children to assist in placing the dosage of rifampin used in childhood on a more scientific foundation.
Open Access
Safety 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 D
Abstract 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 .
Open Access
School based versus supplemental vaccination strategies in the delivery of vaccines to 5-19 year olds in Africa - a systematic review
(2017) Haddison, Christiana Eposi; Kagina, Benjamin M; Abdullahi, Leila H; Muloiwa, Rudzani; Hussey, Gregory D
Background: Some vaccine preventable diseases still remain a public health burden in many African countries. The occurrence of vaccine preventable diseases in all age groups has led to the realization of the need to extend routine immunisation services to school age children and adolescents. Supplemental immunisation activities (SIAs) and school based vaccination (SBV) are two common strategies used to complement the EPI in vaccine delivery. Therefore, this review aimed to assess the effectiveness of SIAs compared to SBV in the administration of vaccines to 5-19 year olds in Africa. Methods and findings: Systematic review methods (protocol number CRD42017057475) were used to address our study aim. Electronic databases were searched up to March 30, 2017 for primary studies investigating the delivery of vaccines via SIAs or SBV to 5-19 year olds. To be included in the review, studies must have reported any of the following outcomes: vaccination coverage, cost of the vaccination strategy or effect of the strategy on routine immunisation. During the search, no restriction was placed on language or the study period. The search was complemented by browsing reference lists of potential studies. Out of the 4938 studies identified, 31 studies met our inclusion criteria. Both SIAs and SBV showed high vaccination coverage. This result should be interpreted with caution due to the high heterogeneity observed across the included studies. The SIAs reported a higher coverage of 91% (95% CI: 84%, 98%) than SBV which had a coverage of 75% (95% CI: 67%, 83%). In most settings, SBV was reported to be more expensive than SIAs. The SIAs were found to negatively affect routine immunisation services. Conclusions: Both SIAs and SBV are routinely used to complement the EPI in the delivery of vaccines in Africa. In settings where school enrolment is suboptimal as is the case in many African countries, our results show SIAs may be more effective in reaching school age children and adolescents than SBV. The SBV has only been tested in the delivery of two or three dose HPV vaccine to adolescent girls, whereas SIAs have been tested in the delivery of different types of vaccines. Our results re-iterate the importance of systematic evidence to best inform African authorities on the optimal delivery strategies of vaccines targeting school age children and adolescents into their immunisation programme.
Open Access
A situation analysis of street children in Harare, Zimbabwe
(1996) Pascoe, Margaret Joy; Powell, Greg; Hussey, Gregory D
The problem of children on the streets of Harare has been increasing over the last five years. The majority of these children appear to be of school-going age. Who are these children? Where do they live? Why are they not attending school? This study is an attempt to provide answers for these questions, to evaluate current policy and programmes for street children and to promote appropriate and effective policy measures. A convenience sample of two hundred and eight children, who fulfilled the definition of street child used in the study, were interviewed using a questionnaire and focus group discussions. A number of children's homes, a probation centre and a remand home were visited and personnel from non-governmental organisations working with street children were interviewed. The study found that the majority of children were male (89%), and the age distribution ranged from six to seventeen years. The mean time period spent on the street was 18,4 months. The most common reason for leaving home was that the family was unable to support the child. Most of the children slept in a nearby squatter settlement or at the city railway station. The most popular income generating activity was guarding motor vehicles. Five of the children were attending alternative education programmes and one third had never attended school. The most common medical conditions were acute respiratory infections, diarrhoeal disease and skin rashes. Some of the children had suffered physical (12) and /or sexual (10) abuse while on the street. Substance abuse, notably glue sniffing, was widespread with 78% of the children admitting to this activity. A general attitude of hopelessness prevailed among the children and few could envisage brighter prospects for the future. Short term measures to improve the children's lives on the street must be taken, but the long-term solution requires a broad attack on poverty in order to eradicate the root problems that force children onto the streets. Recommendation were aimed at the major role players in the lives of street children - the Government, the Department of Social Welfare, the Zimbabwe Republic Police and Non-Governmental Organisations.
Open Access
Strengthening the expanded programme on immunization in Africa: looking beyond 2015
(Public Library of Science, 2013) Machingaidze, Shingai; Wiysonge, Charles S; Hussey, Gregory D
Shingai Machingaidze and colleagues reflect on the successes and shortfalls of the Expanded Programme on Immunization (EPI) in Africa, and the considerable challenges that must now be addressed to improve immunization systems.
Open Access
The burden of laboratory-confirmed pertussis in low- and middle-income countries since the inception of the Expanded Programme on Immunisation (EPI) in 1974: a systematic review and meta-analysis
(2020-08-28) Muloiwa, Rudzani; Kagina, Benjamin M; Engel, Mark E; Hussey, Gregory D
Abstract Background An effective vaccine against Bordetella pertussis was introduced into the Expanded Programme on Immunisation (EPI) by WHO in 1974, leading to a substantial global reduction in pertussis morbidity and mortality. In low- and middle-income countries (LMICs), however, the epidemiology of pertussis remains largely unknown. This impacts negatively on pertussis control strategies in these countries. This study aimed to systematically and comprehensively review published literature on the burden of laboratory-confirmed pertussis in LMICs over the 45 years of EPI. Methods Electronic databases were searched for relevant literature (1974 to December 2018) using common and MeSH terms for pertussis. Studies using PCR, culture or paired serology to confirm Bordetella pertussis and parapertussis in symptomatic individuals were included if they had clearly defined numerators and denominators to determine prevalence and mortality rates. Results Eighty-two studies (49,167 participants) made the inclusion criteria. All six WHO regions were represented with most of the studies published after 2010 and involving mainly upper middle-income countries (n = 63; 77%). PCR was the main diagnostic test after the year 2000. The overall median point prevalence of PCR-confirmed Bordetella pertussis was 11% (interquartile range (IQR), 5–27%), while culture-confirmed was 3% (IQR 1–9%) and paired serology a median of 17% (IQR 3–23%) over the period. On average, culture underestimated prevalence by 85% (RR = 0.15, 95% CI, 0.10–0.22) compared to PCR in the same studies. Risk of pertussis increased with HIV exposure [RR, 1.4 (95% CI, 1.0–2.0)] and infection [RR, 2.4 (95% CI, 1.1–5.1)]. HIV infection and exposure were also related to higher pertussis incidences, higher rates of hospitalisation and pertussis-related deaths. Pertussis mortality and case fatality rates were 0.8% (95% CI, 0.4–1.4%) and 6.5% (95% CI, 4.0–9.5%), respectively. Most deaths occurred in infants less than 6 months of age. Conclusions Despite the widespread use of pertussis vaccines, the prevalence of pertussis remains high in LMIC over the last three decades. There is a need to increase access to PCR-based diagnostic confirmation in order to improve surveillance. Disease control measures in LMICs must take into account the persistent significant infant mortality and increased disease burden associated with HIV infection and exposure.
Open Access
The burden of pertussis in low- and middle-income countries since the inception of the Expanded Programme on Immunization (EPI) in 1974: a systematic review protocol
(2015-05-01) Muloiwa, Rudzani; Kagina, Benjamin M; Engel, Mark E; Hussey, Gregory D
Abstract Background Vaccine against pertussis has been in use for several decades. Despite the widespread use of pertussis vaccine, evidence shows resurgence of pertussis in high-income countries. Pertussis surveillance data is largely missing from low- and middle-income countries (LMICs). Without data on trends of pertussis, it is difficult to review and amend pertussis control policies in any country. We propose conducting a systematic review to evaluate the burden and trends of pertussis in LMICs since 1974. Methods/design Common and medical subject heading (MeSH) terms for pertussis and LMICs will be used to search electronic databases for the relevant literature published between 1974 and December 2014. Only studies from LMICs that fulfils World Health Organisation (WHO) or CDC pertussis case definitions will be included. The studies must have a clear numerator and denominator in a well-defined population. Risk of bias will be evaluated by assessing all qualifying full-text articles for quality and eligibility using a modified quality score assessment tool. Standardised data extraction will be carried out after which descriptions of trends in the prevalence, incidence, as well as mortality rate and case fatality rate, will be done. Where sufficient data is available, the results will be stratified by age group, geography, location, vaccination and HIV status. Discussion The systematic review proposed by this protocol seeks to address the knowledge gap in the epidemiology of pertussis in LMICs for the first time. It is anticipated that the background epidemiological trends of pertussis in LMICs that our study will provide could be used in the planning for the control of pertussis. Systematic review registration PROSPERO CRD42015015159
Open Access
Trends in the types and quality of childhood immunisations research output from Africa 1970–2010: mapping the evidence base
(2014-02-04) Machingaidze, Shingai; Hussey, Gregory D; Wiysonge, Charles S
Abstract Background Over the past four decades, extraordinary progress has been made in establishing and improving childhood immunization programmes around Africa. In order to ensure effective and sustainable positive growth of these childhood immunisations programmes, the development, adaptation and implementation of all interventions (programme activities, new vaccines, new strategies and policies) should be informed by the best available local evidence. Methods An assessment of the peer-reviewed literature on childhood immunization research published in English from 1970 to 2010 was conducted in PubMed and Africa-Wide databases. All study types were eligible for inclusion. A standard form was used to extract information from all studies identified as relevant and entered into a Microsoft Access database for analysis. Results Our initial search yielded 5436 articles from the two databases, from which 848 full text articles were identified as relevant. Among studies classified as clinical research (417), 40% were clinical trials, 24% were burden of disease/epidemiology and 36% were other clinical studies. Among studies classified as operational research (431), 77% related to programme management, 18% were policy related and 5% were related to vaccine financing. Studies were conducted in 48 African countries with six countries (South Africa, The Gambia, Nigeria, Senegal, Guinea-Bissau and Kenya) accounting for 56% of the total research output. Studies were published in 152 different journals with impact factors ranging from 0.192 to 53.29; with a median impact factor of 3.572. Conclusion A similar proportion of clinical versus operational research output was found. However, an uneven distribution across Africa was observed with only six countries accounting for over half of the research output. The research conducted was of moderate to high quality, with 62% being published in journals with 2010 impact factors greater than two. Urgent attention should be given to the development of research capacity in low performing countries around Africa, with increased focus on the process of turning immunisations programme research evidence into policy and practice, as well as increased focus on issues relating to vaccine financing and sustainability in Africa.