The self-controlled case series method: performance and design in studies of vaccine safety

The self-controlled case series method (SCCSM) is a novel study design to investigate associations between acute responses with transient point exposures (for example vaccination). The method provides an attractive alternative to cohort and case-control designs. The method is unusual in that it requires data only on individuals who experience a response (the ‘cases’). The method works as follows. Prior to the study a post-exposure risk period is defined, which corresponds to the period in which responses causally related to exposure are likely to occur. An observation period is also defined, and individuals with responses arising within this observation period are sampled. The data are then analysed using a Poisson model, conditional on the total number of events occurring for each individual. This conditioning ensures that including only cases does not bias the relative risk estimator. The self-controlled case series method has been used to good effect in many settings, particularly in investigating putative associations between adverse events and paediatric vaccines. However, so far only limited research has been undertaken on the statistical properties of the method in finite samples, and virtually no work has been undertaken on design issues. The method also needs to be extended in various directions, for example application in surveillance methods. This thesis provides detailed investigations of these topics. To this end, expressions for the asymptotic bias, variance and mean square error of the log-relative incidence are derived. Simulation studies taking account of age are carried out to study small and medium sample performance. Sample size formulae are obtained and validated via simulations, thus improving the design of self-controlled case series studies. The method is extended to applications in surveillance and simulation studies are conducted to evaluate this use of the method. The methods are illustrated using data on intussusception and oral polio vaccine

Impact of Public Health Expenditure on Infant and Under-five Mortality in Tanzania (1995-2013): An Application of Bayesian Approach.

The main purpose of this study was to examine the impact of public health expenditure on health outcomes (infant and under five mortality rate) in Tanzania over the period 1995 to 2013. Per capital GDP as an indicator of income level and improved sanitation facilities were used as explanatory variables. A full Bayesian time series approach based on Markov Chain Monte Carlo (MCMC) was used to estimate the impact of public health expenditure on health outcomes (infant and under five mortality). The results shows that, despite changing patterns on government health expenditure over the period 1995 to 2013, still government health expenditure had no impact on health outcomes (infant and under five mortality) in Tanzania. The results further shows that, the mean for income levels represented by (GDP per capital) had positive significant effect on both infant and under-five mortality decline. The failure to bring impact on health outcomes (infant and under five mortality) was probably due to its low level of public health spending. The paper recommends the policy that aim to increase GDP per capital and public health expenditure. Since public health expenditure is still low, re-prioritisation is also needed in the public expenditure system for resource allocation during budgeting to favour health budget to be given first priority. Keywords: Bayesian Approach, Health Outcomes, Government Health Expenditur

Determinants of Infants and Under-Five Mortality Differentials in Tanzanian Zones: Evidence from Panel Data Analysis.

Infant and under-five mortality have shown a substantial decline of 49% and 47% respectively in Tanzania over the period (1992-2010). Despite these declines, under-five and infant mortality rates in Tanzania across regions/zones are heterogeneous and unequally distributed. The main purpose of this study was to identify factors determining infant and under-five mortality differentials in Tanzanian Zones using four rounds of Demographic Health Surveys (1992, 1996, 2004 and 2010) over the period 1992 to 2010. A panel data was used to estimate factors determining infants and under-five mortality differentials across zones/regions. Spearman correlation was used for association between explanatory variables and dependent variables. The results show attendant’s birth skills, antenatal care providers, mothers education levels, ever breastfeeding and immunization coverage (vaccine measles) to contribute a strong role in improving child health and reducing infant and under-five mortality across Tanzanian zones over time. The results reveal that, zones with higher attendant’s birth skills, immunization coverage (vaccine measles), mothers education levels, antenatal care providers and ever breastfeeding have better health outcomes. The highest and lowest infant and under-five mortality over time were observed in southern and northern zones respectively. The paper recommends the importance of expanding schooling and access to quality education to all levels, educating more women in primary, secondary or higher levels and strengthening stronger health system in the access to health care services including immunizations coverage, attendants’ birth skills and antenatal care providers in the country to avoid health inequity within Tanzanian zones to achieve sustainable development goals. Keywords: Fixed effects; Panel Data, Infant and under -five Mortalit

Parent-child communication about sexual issues in Zambia: a cross sectional study of adolescent girls and their parents

Background Parent-child communication about sexual issues can reduce risky sexual behaviour amongst adolescents. Risky sexual behaviour is of concern in sub-Saharan Africa where the prevalence of early pregnancy, unsafe abortion and HIV are high. Parent-child communication about sexual issues presents a feasible approach for reducing sexual risk amongst adolescents in sub-Saharan Africa but limited research exists from the region. This study from Zambia examines the sociodemographic and psychosocial factors that are associated with whether parents communicate with their daughters about sexual issues. Methods Data from a cluster randomized controlled trial examining the effect of interventions aiming to reduce teenage pregnancy and school drop out in Zambia was used. The data was collected between January–July in 2018 and consists of structured, face to face interviews with 4343 adolescent girls and 3878 parents. Cross sectional analyses examined the associations between parent-child communication about sexual issues and sociodemographic and psychosocial characteristics using univariate and multivariable logistic regression models. Results Adolescent girls who felt connected to their parents and those who perceived their parents to be comfortable in communicating about sex, were more likely to speak to their parents about sexual issues than those who did not (AOR 1.23, 95% CI 1.01–1.52; and AOR 2.94, 95% CI 2.45–3.54, respectively). Girls whose parents used fear-based communication about sexual issues, and those who perceived their parents as being opposed to education about contraception, were less likely to communicate with their parents about sex than those who did not (AOR 0.76, 95% CI 0.65–0.89; and AOR 0.76, 95% CI 0.63–0.91, respectively). Girls enrolled in school were less likely to communicate with their parents about sex than those out of school (AOR 0.56, 95% CI 0.44–0.71). Conclusion Parenting style, children’s perception of parental attitudes and parental communication styles are associated with whether parents and children communicate about sexual issues. This may imply that parents can improve the chances of communicating with their children about sex by conveying non-judgemental attitudes, using open communication styles with neutral messages and appearing comfortable whilst displaying positive attitudes towards communication around sex and contraceptive use.publishedVersio

Determinants of public health expenditure growth in Tanzania: an application of Bayesian Model

This paper identifies some major drivers of per capita public health expenditure growth in Tanzania using nationally representative annual data between 1995 and 2014. It used Bayesian model based on Markov Chain Monte Carlo (MCMC) simulation. The empirical result shows that both the real GDP per capita and population age 65 years and older exert a positive effect on per capita public health expenditure growth in Tanzania. Advances in medical technologies represented by life expectancy seem to reduce real per capita public health expenditure growth in Tanzania. However, the credible intervals for life expectancy and population age 65 years and older are very wide suggesting a lot of uncertainty with these estimates. The results imply that, future trends in per capita public health spending would mainly depend on the development of the economy such as real per capita gross domestic product. The result suggests the rapid growth in real per capita public health expenditure is likely to continue in future when the country economy becomes more robust and increase of population age 65 years and above.Keywords: Bayesian Approach, per capita GDP and Real per capita public health expenditur

Implementation effectiveness of revised (post-2010) World Health Organization guidelines on prevention of mother-to-child transmission of HIV using routinely collected data in sub-Saharan Africa: A systematic literature review.

BACKGROUND: To synthesize and evaluate the impact of implementing post-2010 World Health Organization (WHO) prevention of mother-to-child transmission (PMTCT) guidelines on attainment of PMTCT targets. METHODS: Retrospective and prospective cohort study designs that utilized routinely collected data with a focus on provision and utilization of the cascade of PMTCT services were included. The outcomes included the proportion of pregnant women who were tested during their antenatal clinic (ANC) visits; mother-to-child transmission (MTCT) rate; adherence; retention rate; and loss to follow-up (LTFU). RESULTS: Of the 1210 references screened, 45 met the inclusion criteria. The studies originated from 14 countries in sub-Saharan Africa. The highest number of studies originated from Malawi (10) followed by Nigeria and South Africa with 7 studies each. More than half of the studies were on option A while the majority of option B+ studies were conducted in Malawi. These studies indicated a high uptake of human immunodeficiency virus (HIV) testing ranging from 75% in Nigeria to over 96% in Zimbabwe and South Africa. High proportions of CD4 count testing were reported in studies only from South Africa despite that in most of the countries CD4 testing was a prerequisite to access treatment. MTCT rate ranged from 1.1% to 15.1% and it was higher in studies where data were collected in the early days of the WHO 2010 PMTCT guidelines. During the postpartum period, adherence and retention rate decreased, and LTFU increased for both HIV-positive mothers and exposed infants. CONCLUSION: Irrespective of which option was followed, uptake of antenatal HIV testing was high but there was a large drop off along later points in the PMTCT cascade. More research is needed on how to improve later components of the PMTCT cascade, especially of option B+ which is now the norm throughout sub-Saharan Africa

Educational Attainment as a Predictor of HIV Testing Uptake Among Women of Child-Bearing Age: Analysis of 2014 Demographic and Health Survey in Zambia.

Background: Globally, an estimated 150,000 children were newly infected with HIV in 2015, over 90% of them in Sub-Saharan Africa. In Zambia, ~500,000 babies are born to HIV positive mothers every year, and without intervention 40,000 of them would acquire the infection. Studies have shown a strong association between education and HIV prevalence, but in Zambia, this association has not been demonstrated. There is little published information on the association between educational attainment and HIV testing uptake among pregnant women, which is fundamental in understanding the mother to child transmission of HIV. This study investigated whether educational attainment was associated with uptake of HIV testing among women of reproductive age in Zambia. Methods: Data were taken from Zambia Demographic and Health Survey in 2014 (ZDHS14). The analysis consisted of all women aged 15-49 years, who responded to the question on HIV testing in the ZDHS. Multivariable logistic regression was used to determine whether educational attainment was associated with uptake of HIV testing among women of reproductive age in Zambia. Results: Educational attainment was strongly associated with HIV testing among 15,388 women of child bearing age [AOR 3.8, 95% CI 1.7-8.2; p = 0.001]. HIV testing differed greatly by socioeconomic social status with an increased uptake among women with higher wealth index [AOR 4.4, 95% CI 1.9-9.9; p = 0.001]. Additionally, HIV testing was observed to be higher among the older women 25-34 years compared to the young women 15-19 years [AOR 2.3, 95% CI 1.3-4.3; p = 0.007]. Conclusions: This study revealed educational attainment to be a strong predictor of HIV testing among women of child bearing age in this population. High HIV testing uptake among educated pregnant women indicated that low-educated women may not fully realize the benefits of testing for HIV. Therefore, strengthening HIV testing in rural health facilities and providing initiatives to overcome barriers to testing among women with no formal education may help reduce vertical transmission of HIV

Estimating levels of HIV testing coverage and use in prevention of mother-to-child transmission among women of reproductive age in Zambia.

BACKGROUND: Mother to child transmission of HIV (MTCT) still remains a challenge affecting many countries. Globally, an estimated 150,000 children were newly infected with HIV in 2015, over 90% of them in Sub-Saharan Africa through MTCT. In Zambia approximately 500,000 babies are born and 40,000 acquire the infection vertically if there is no intervention annually. This study estimated the HIV testing coverage and associated factors among Zambian women of reproductive age 15-49 years. METHODS: A cross-sectional study based on data extracted from the Zambia Demographics and Health Survey [Zambia Demographic and Health Survey. Central Statistical Office (CSO), Ministry of Health (MOH), Tropical Diseases Research Centre (TDRC), University of Zambia, and Macro International Inc. 2009. 2014]. Women aged 15-49 years, 15,388 who reported having ever tested for HIV or not comprised the de facto eligible sample. Extracted data comprised women's demographic characteristics; their full birth history and records of antenatal care for the most recent birth within a 5 year period preceding the survey. A weighted multiple logistic regression model was done to determine factors associated with the odds of HIV testing coverage among women of reproductive age. RESULTS: Out of 15,388 women in the study, 12,413 (81%) reported ever tested for HIV. Of the 6461 women who attended antenatal care (ANC) 6139 (95%) reported ever tested for HIV. Additionally, 6139 (95%) out of 6461 of the women were given information on PMTCT during ANC sessions. Testing coverage was higher among women aged 20-24 years compared to women aged 15-19 years [AOR 2.1, 95% CI 1.14-3.84; p = 0.017]. Women with higher socio-economic status had 6.6 times the odds of having ever tested compared to women with lower status [AOR 6.6, 95% CI 3.04-14.14; p < 0.001]. CONCLUSIONS: In this study we have demonstrated that HIV testing coverage is higher among women of reproductive age. HIV testing among women attending ANC is also higher. Older women with higher socio-economic status are more likely to take up HIV testing compared to their young counterparts

Effectiveness of Lifelong ART (Option B+) in the Prevention of Mother-to-Child Transmission of HIV Programme in Zambia: Observations Based on Routinely Collected Health Data.

Background: Mother to child transmission of HIV (MTCT) is a global challenge affecting many countries especially in sub-Saharan Africa. In 2009 about 370,000 infants were infected with HIV mainly through MTCT and most of them in sub-Saharan Africa. We aimed to determine the effectiveness of Option B+ compared to other options in reducing rates of early MTCT of HIV infections in Zambia. Methods: This was a retrospective cohort study based on routinely collected data using SmartCare in Zambia. Survival analysis with Cox Proportional Hazard regression was used to determine association between MTCT and regimen type of mothers. Kaplan-Meier (K-M) curves were used to compare MTCT for infants born to mothers option B+ to those on other options, and Wilcoxon (Breslow) test was used to establish statistical significance. Results: Overall (n = 1,444), mother-baby pairs with complete data were included in the analysis, with the median age of mothers being 33 (28-38) years; and 57% of these women were on Option B+. MTCT rate was estimated at 5% (73/1,444) [P = 0.025]. A Kaplan-Meier estimate showed that HIV Exposed Infants (HEI) of mothers on Option B+ had lower MTCT rate than those who were on other MTCT prevention interventions [Wilcoxon test; chi2 = 4.97; P = 0.025]. Furthermore, The Nelson Aalen cumulative hazard estimates indicated similar evidence of option B+ being more effective than other options with some statistical significance [HR = 0.63, P = 0.068]. HEI of option B+ mothers had 50% reduced risk of having HIV infection compared to option A/B [adjusted HR = 0.4; 95% CI = 0.28-0.84; P = 0.010]. HEI to women who were married had an increased risk 50% of getting infected compared to those not married [adjusted HR = 1.5; 95% CI = 3.43-6.30; P < 0.001]. Exposed infants whose mothers had assisted delivery had 3 times increased risk of getting infected compared to those born through normal vaginal delivery [Adjusted HR = 3.2; 95% CI = 0.98-10.21; P = 0.050]. Conclusions: The use of Option B+ as PMTCT intervention was found to be more effective in reducing MTCT of HIV compared to other options. Scaling up access to life-long ART and improving retention for women on treatment can potentially reduce further vertical transmission

Duration of cART Before Delivery and Low Infant Birthweight Among HIV-Infected Women in Lusaka, Zambia

To estimate the association between duration of combination antiretroviral therapy (cART) during pregnancy and low infant birthweight (LBW), among women ≥37 weeks gestation