Factors influencing the implementation of TB screening among PLHIV in selected HIV clinics in Ghana: a qualitative study.

BACKGROUND: Decreasing the burden of Tuberculosis (TB) among PLHIV through TB screening is an effective intervention recommended by the World Health Organization (WHO). However, after over a decade of implementation in Ghana, the intervention does not realize the expected outcomes. It is also not well understood whether this lack of success is due to implementation barriers. Our study, therefore, sought to examine the factors influencing the implementation of the intervention among people living with HIV (PLHIV) attending HIV clinics at district hospitals in Ghana. METHODS: This was a qualitative study conducted from 6th to 31 May 2019 in three regions of Ghana. We conducted 17 in-depth interviews (IDIs - comprising two regional, six districts and nine facility TB/HIV coordinators) and eight focus group discussions (FGD - consisting of a total of 65 participants) with HIV care providers. The Consolidated Framework for Implementation Research (CFIR) guided the design of interview guides, data collection and analysis. All responses were digitally audio-recorded and transcribed verbatim for coding and analysis using the Framework Approach. Participants consented to the interview and recording. RESULTS: The main barriers to TB screening relate to the low commitment of the implementers to screen for TB and limited facility infrastructure for the screening activities. Facilitators of TB screening include (1) ease in TB screening, (2) good communication and referral channels, (3) effective goals and feedback mechanisms, (4) health workers recognizing the need for the intervention and (5) the role of chemical sellers. CONCLUSIONS: Key barriers and facilitators to the intervention are revealed. The study has shown that there is a need to increase HIV care providers and institutional commitment towards TB screening interventions. In addition, cost issues need to be assessed as they are drivers of sustainability. Our study also advances the field of implementation science through CFIR to better understand the factors influencing the implementation.

Analysis of Recurrent Times-to-Clinical Malaria Episodes and Plasmodium falciparum Parasitemia: A Joint Modeling Approach Applied to a Cohort Data.

Background: Recurrent clinical malaria episodes due to Plasmodium falciparum parasite infection are common in endemic regions. With each infection, acquired immunity develops, making subsequent disease episodes less likely. To capture the effect of acquired immunity to malaria, it may be necessary to model recurrent clinical disease episodes jointly with P. falciparum parasitemia data. A joint model of longitudinal parasitemia and time-to-first clinical malaria episode (single-event joint model) may be inaccurate because acquired immunity is lost when subsequent episodes are excluded. This study's informativeness assessed whether joint modeling of recurrent clinical malaria episodes and parasitemia is more accurate than a single-event joint model where the subsequent episodes are ignored. Methods: The single event joint model comprised Cox Proportional Hazards (PH) sub-model for time-to-first clinical malaria episode and Negative Binomial (NB) mixed-effects sub-model for the longitudinal parasitemia. The recurrent events joint model extends the survival sub-model to a Gamma shared frailty model to include all recurrent clinical episodes. The models were applied to cohort data from Malawi. Simulations were also conducted to assess the performance of the model under different conditions. Results: The recurrent events joint model, which yielded higher hazard ratios of clinical malaria, was more precise and in most cases produced smaller standard errors than the single-event joint model; hazard ratio (HR) = 1.42, [95% confidence interval [CI]: 1.22, 2.03] vs. HR = 1.29, [95% CI:1.60, 2.45] among participants who reported not to use LLINs every night compared to those who used the nets every night; HR = 0.96, [ 95% CI: 0.94, 0.98] vs. HR = 0.81, [95% CI: 0.75, 0.88] for each 1-year increase in participants' age; and HR = 1.36, [95% CI: 1.05, 1.75] vs. HR = 1.10, [95% CI: 0.83, 4.11] for observations during the rainy season compared to the dry season. Conclusion: The recurrent events joint model in this study provides a way of estimating the risk of recurrent clinical malaria in a cohort where the effect of immunity on malaria disease acquired due to P. falciparum parasitemia with aging is captured. The simulation study has shown that if correctly specified, the recurrent events joint model can give risk estimates with low bias.

Adherence of HIV clinics to guidelines for the delivery of TB screening among people living with HIV/AIDS in Ghana.

BACKGROUND: Tuberculosis screening of people living with HIV (PLHIV) - an intervention to reduce the burden of TB among PLHIV - is being implemented at HIV clinics in Ghana since 2007, but TB screening coverage remains low. Facility adherence to intervention guidelines may be a factor but is missing in implementation science literature. This study assesses the level of HIV clinic adherence to the guidelines and related facility characteristics in selected district hospitals in Ghana. METHODS: This cross-sectional study was conducted in all 27 district hospitals with HIV clinics, X-ray and geneXpert machines in Ghana. These hospitals are in 27 districts representing about 27% of the 100 district hospitals with HIV clinics in Ghana. A data collection tool with 18-items (maximum score of 29) was developed from the TB/HIV collaborative guidelines to assess facility adherence to four interrelated components of the TB screening programme as stated in the guidelines: intensive TB case-finding among PLHIV (ITCF), Isoniazid preventive therapy initiation (IPT), TB infection control (TIC), and programme review meetings (PRM). Data were collected through record review and interviews with 27 key informants from each hospital. Adherence scores per component were summed to determine an overall adherence score per facility and summarized using medians and converted to proportions. Facility characteristics were assessed and compared across facilities with high (above median) versus low (below median) overall adherence scores, using nonparametric test statistics. RESULTS: From the 27 key interviews and facility records reviewed, the median adherence scores for ITCF, IPT, TIC, and PRM components were 85.7% (IQR: 85.5-100.0), 0% (IQR: 0-66.7), 33.3% (IQR: 33.3-50.0), and 90.0% (IQR: 70.0-90.0), respectively. The overall median adherence score was 62.1% (IQR: 58.6-65.1), and 17 clinics (63%) with overall adherence score above the median were categorized as high adherence. Compared to low adherence facilities, high adherence facilities had statistically significant lower PLHIV clinic attendees per month (256 (IQR: 60-904) vs. 900 (IQR: 609-2622); p = 0.042), and lower HIV provider workloads (28.6 (IQR: 8.6-113) vs. 90 (IQR: 66.7-263.5); p = 0.046), and most had screening guidelines (76%, p < 0.01) and questionnaire (80%, p < 0.01) available on-site. CONCLUSION: PRM had highest score while the IPT component had the lowest score. Almost a third of the facilities implemented the TB screening programme activities with a high level of adherence to the guidelines. We suggest to ensure adherence to all four components, reducing staff workloads and making TB screening questionnaires and guidelines available on-site would increase facility adherence to the intervention and ultimately achieve intervention targets.

Fidelity of implementation of TB screening guidelines by health providers at selected HIV clinics in Ghana.

INTRODUCTION: Tuberculosis screening of people living with human immunodeficiency virus is an intervention recommended by the WHO to control the dual epidemic of TB and HIV. The extent to which the intervention is adhered to by the HIV healthcare providers (fidelity) determines the intervention's effectiveness as measured by patient outcomes, but literature on fidelity is scarce. This study assessed provider implementation fidelity to national guidelines on TB screening at HIV clinics in Ghana. METHODS: It was a cross-sectional study that used structured questionnaires to gather data, involving 226 of 243 HIV healthcare providers in 27 HIV clinics across Ghana. The overall fidelity score comprised sixteen items with a maximum score of 48 grouped into three components of the screening intervention (TB diagnosis, TB awareness and TB symptoms questionnaire). Simple summation of item scores was done to determine fidelity score per provider. In this paper, we define the level of fidelity as low if the scores were below the median score and were otherwise categorized as high. Background factors potentially associated with implementation fidelity level were assessed using cluster-based logistic regression. Odds ratio with 95% confidence interval (CI) was used as the measure of association. RESULTS: Of the 226 healthcare providers interviewed, 60% (135) were females with a mean age of 34.5 years (SD = 8.3). Most of them were clinicians [63% (142)] and had post-secondary non-tertiary education [62% (141)]. Overall, 53% (119) of the healthcare providers were categorized to have implemented the intervention with high fidelity. Also, 56% (126), 53% (120), and 59% (134) of the providers implemented the TB diagnosis, TB awareness and TB symptoms questionnaire components respectively with high fidelity. After adjusting for cluster effect, female providers (AOR = 2.36, 95%CI: 1.09-5.10, p = <0.029), those with tertiary education (AOR = 4.31, 95%CI: 2.12-9.10, p = 0.040), and clinicians (AOR = 1.78, 95%CI: 1.07-3.50, p = 0.045) were more likely to adhere to the guidelines compared to their counterparts. CONCLUSION: The number of providers with fidelity scores above the median was marginally greater (6%) than the number with fidelity score below the median. Similarly, for each of the components, the number of providers with fidelity scores higher than the median was marginally higher. This could explain the existing fluctuations in the intervention outcomes in Ghana. We found gender, profession and education were associated with provider implementation fidelity. To improve fidelity level among HIV healthcare providers, and realize the aims of the TB screening intervention among PLHIV in Ghana, further training on implementing all components of the intervention is critical.

Markov modelling of viral load adjusting for CD4 orthogonal variable and multivariate conditional autoregressive mapping of the HIV immunological outcomes among ART patients in Zimbabwe.

BACKGROUND: This study aimed to jointly model HIV disease progression patterns based on viral load (VL) among adult ART patients adjusting for the time-varying "incremental transients states" variable, and the CD4 cell counts orthogonal variable in a single 5-stage time-homogenous multistate Markov model. We further jointly mapped the relative risks of HIV disease progression outcomes (detectable VL (VL ≥ 50copies/uL) and immune deterioration (CD4 < 350cells/uL) at the last observed visit) conditional not to have died or become loss to follow-up (LTFU). METHODS: Secondary data analysis of individual-level patients on ART was performed. Adjusted transition intensities, hazard ratios (HR) and regression coefficients were estimated from the joint multistate model of VL and CD4 cell counts. The mortality and LTFU transition rates defined the extent of patients' retention in care. Joint mapping of HIV disease progression outcomes after ART initiation was done using the Bayesian intrinsic Multivariate Conditional Autoregressive prior model. RESULTS: The viral rebound from the undetectable state was 1.78times more likely compared to viral suppression among patients with VL ranging from 50-1000copies/uL. Patients with CD4 cell counts lower than expected had a higher risk of viral increase above 1000copies/uL and death if their VL was above 1000copies/uL (state 2 to 3 (λ23): HR = 1.83 and (λ34): HR = 1.42 respectively). Regarding the time-varying effects of CD4 cell counts on the VL transition rates, as the VL increased, (λ12 and λ23) the transition rates increased with a decrease in the CD4 cell counts over time. Regardless of the individual's VL, the transition rates to become LTFU decreased with a decrease in CD4 cell counts. We observed a strong shared geographical pattern of 66% spatial correlation between the relative risks of detectable VL and immune deterioration after ART initiation, mainly in Matabeleland North. CONCLUSION: With high rates of viral rebound, interventions which encourage ART adherence and continual educational support on the barriers to ART uptake are crucial to achieve and sustain viral suppression to undetectable levels. Area-specific interventions which focus on early ART screening through self-testing, behavioural change campaigns and social support strategies should be strengthened in heavily burdened regions to sustain the undetectable VL. Sustaining undetectable VL lowers HIV transmission in the general population and this is a step towards achieving zero HIV incidences by 2030.

A review of multistate modelling approaches in monitoring disease progression: Bayesian estimation using the Kolmogorov-Chapman forward equations.

There are numerous fields of science in which multistate models are used, including biomedical research and health economics. In biomedical studies, these stochastic continuous-time models are used to describe the time-to-event life history of an individual through a flexible framework for longitudinal data. The multistate framework can describe more than one possible time-to-event outcome for a single individual. The standard estimation quantities in multistate models are transition probabilities and transition rates which can be mapped through the Kolmogorov-Chapman forward equations from the Bayesian estimation perspective. Most multistate models assume the Markov property and time homogeneity; however, if these assumptions are violated, an extension to non-Markovian and time-varying transition rates is possible. This manuscript extends reviews in various types of multistate models, assumptions, methods of estimation and data features compatible with fitting multistate models. We highlight the contrast between the frequentist (maximum likelihood estimation) and the Bayesian estimation approaches in the multistate modeling framework and point out where the latter is advantageous. A partially observed and aggregated dataset from the Zimbabwe national ART program was used to illustrate the use of Kolmogorov-Chapman forward equations. The transition rates from a three-stage reversible multistate model based on viral load measurements in WinBUGS were reported.

Considerations for an integrated population health databank in Africa: lessons from global best practices.

Background: The rising digitisation and proliferation of data sources and repositories cannot be ignored. This trend expands opportunities to integrate and share population health data. Such platforms have many benefits, including the potential to efficiently translate information arising from such data to evidence needed to address complex global health challenges. There are pockets of quality data on the continent that may benefit from greater integration. Integration of data sources is however under-explored in Africa. The aim of this article is to identify the requirements and provide practical recommendations for developing a multi-consortia public and population health data-sharing framework for Africa. Methods: We conducted a narrative review of global best practices and policies on data sharing and its optimisation. We searched eight databases for publications and undertook an iterative snowballing search of articles cited in the identified publications. The Leximancer software © enabled content analysis and selection of a sample of the most relevant articles for detailed review. Themes were developed through immersion in the extracts of selected articles using inductive thematic analysis. We also performed interviews with public and population health stakeholders in Africa to gather their experiences, perceptions, and expectations of data sharing. Results: Our findings described global stakeholder experiences on research data sharing. We identified some challenges and measures to harness available resources and incentivise data sharing.  We further highlight progress made by the different groups in Africa and identified the infrastructural requirements and considerations when implementing data sharing platforms. Furthermore, the review suggests key reforms required, particularly in the areas of consenting, privacy protection, data ownership, governance, and data access. Conclusions: The findings underscore the critical role of inclusion, social justice, public good, data security, accountability, legislation, reciprocity, and mutual respect in developing a responsive, ethical, durable, and integrated research data sharing ecosystem.

Developing excellence in biostatistics leadership, training and science in Africa: How the Sub-Saharan Africa Consortium for Advanced Biostatistics (SSACAB) training unites expertise to deliver excellence.

The increase in health research in sub-Saharan Africa (SSA) has generated large amounts of data and led to a high demand for biostatisticians to analyse these data locally and quickly.  Donor-funded initiatives exist to address the dearth in statistical capacity, but few initiatives have been led by African institutions. The Sub-Saharan African Consortium for Advanced Biostatistics (SSACAB) aims to improve biostatistical capacity in Africa according to the needs identified by African institutions, through (collaborative) masters and doctoral training in biostatistics. We describe the SSACAB Consortium, which comprises 11 universities and four research institutions- supported by four European universities. SSACAB builds on existing resources to strengthen biostatistics for health research with a focus on supporting biostatisticians to become research leaders; building a critical mass of biostatisticians, and networking institutions and biostatisticians across SSA.  In 2015 only four institutions had established Masters programmes in biostatistics and SSACAB supported the remaining institutions to develop Masters programmes. In 2019 the University of the Witwatersrand became the first African institution to gain Royal Statistical Society accreditation for a Biostatistics MSc programme. A total of 150 fellows have been awarded scholarships to date of which 123 are Masters fellowships (41 female) of which with 58 have already graduated. Graduates have been employed in African academic (19) and research (15) institutions and 10 have enrolled for PhD studies. A total of 27 (10 female) PhD fellowships have been awarded; 4 of them are due to graduate by 2020. To date, SSACAB Masters and PhD students have published 17 and 31 peer-reviewed articles, respectively. SSACAB has also facilitated well-attended conferences, face-to-face and online short courses. Pooling the limited biostatistics resources in SSA, and combining with co-funding from external partners is an effective strategy for the development and teaching of advanced biostatistics methods, supervision and mentoring of PhD candidates.

HIV Disease Progression Among Antiretroviral Therapy Patients in Zimbabwe: A Multistate Markov Model.

Background: Antiretroviral therapy (ART) impact has prolonged survival of people living with HIV. We evaluated HIV disease progression among ART patients using routinely collected patient-level data between 2004 and 2017 in Zimbabwe. Methods: We partitioned HIV disease progression into four transient CD4 cell counts states: state 1 (CD4 ≥ 500 cells/µl), state 2 (350 cells/µl ≤ CD4 < 500 cells/µl), state 3 (200 cells/µl ≤ CD4 < 350 cells/µl), state 4 (CD4 < 200 cells/µl), and the absorbing state death (state 5). We proposed a semiparametric time-homogenous multistate Markov model to estimate bidirectional transition rates. Covariate effects (age, gender, ART initiation period, and health facility level) on the transition rates were assessed. Results: We analyzed 204,289 clinic visits by 63,422 patients. There were 24,325 (38.4%) patients in state 4 (CD4 < 200) at ART initiation, and 7,995 (12.6%) deaths occurred by December 2017. The overall mortality rate was 3.9 per 100 person-years. The highest mortality rate of 5.7 per 100 person-years (4,541 deaths) was from state 4 (CD4 < 200) compared to other states. Mortality rates decreased with increase in time since ART initiation. Health facility type was the strongest predictor for immune recovery. Provincial or central hospital patients showed a diminishing dose-response effect on immune recovery by state from a hazard ratio (HR) of 8.30 [95% confidence interval (95% CI), 6.64-10.36] (state 4 to 3) to HR of 3.12 (95% CI, 2.54-4.36) (state 2 to 1) compared to primary healthcare facilities. Immune system for male patients was more likely to deteriorate, and they had a 32% increased mortality risk (HR, 1.32; 95% CI, 1.23-1.42) compared to female patients. Elderly patients (45+ years) were more likely to immune deteriorate compared to 25-34 years age group: HR, 1.35; 95% CI, 1.18-1.54; HR, 1.56; 95% CI, 1.34-1.81 and HR, 1.53; 95% CI, 1.32-1.79 for states 1 to 2, state 2 to 3, and states 3 to 4, respectively. Conclusion: Immune recovery was pronounced among provincial or central hospitals. Male patients with lower CD4 cell counts were at a higher risk of immune deterioration and mortality, while elderly patients were more likely to immune deteriorate. Early therapeutic interventions when the immune system is relatively stable across gender and age may contain mortality and increase survival outcomes. Interventions which strengthen ART services in primary healthcare facilities are essential.

Systematic review of analytical methods applied to longitudinal studies of malaria.

BACKGROUND: Modelling risk of malaria in longitudinal studies is common, because individuals are at risk for repeated infections over time. Malaria infections result in acquired immunity to clinical malaria disease. Prospective cohorts are an ideal design to relate the historical exposure to infection and development of clinical malaria over time, and analysis methods should consider the longitudinal nature of the data. Models must take into account the acquisition of immunity to disease that increases with each infection and the heterogeneous exposure to bites from infected Anopheles mosquitoes. Methods that fail to capture these important factors in malaria risk will not accurately model risk of malaria infection or disease. METHODS: Statistical methods applied to prospective cohort studies of clinical malaria or Plasmodium falciparum infection and disease were reviewed to assess trends in usage of the appropriate statistical methods. The study was designed to test the hypothesis that studies often fail to use appropriate statistical methods but that this would improve with the recent increase in accessibility to and expertise in longitudinal data analysis. RESULTS: Of 197 articles reviewed, the most commonly reported methods included contingency tables which comprised Pearson Chi-square, Fisher exact and McNemar's tests (n = 102, 51.8%), Student's t-tests (n = 82, 41.6%), followed by Cox models (n = 62, 31.5%) and Kaplan-Meier estimators (n = 59, 30.0%). The longitudinal analysis methods generalized estimating equations and mixed-effects models were reported in 41 (20.8%) and 24 (12.2%) articles, respectively, and increased in use over time. A positive trend in choice of more appropriate analytical methods was identified over time. CONCLUSIONS: Despite similar study designs across the reports, the statistical methods varied substantially and often represented overly simplistic models of risk. The results underscore the need for more effort to be channelled towards adopting standardized longitudinal methods to analyse prospective cohort studies of malaria infection and disease.

Joint modelling of time-to-clinical malaria and parasite count in a cohort in an endemic area.

BACKGROUND: In malaria endemic areas such as sub-Saharan Africa, repeated exposure to malaria results in acquired immunity to clinical disease but not infection. In prospective studies, time-to-clinical malaria and longitudinal parasite count trajectory are often analysed separately which may result in inefficient estimates since these two processes can be associated. Including parasite count as a time-dependent covariate in a model of time-to-clinical malaria episode may also be inaccurate because while clinical malaria disease frequently leads to treatment which may instantly affect the level of parasite count, standard time-to-event models require that time-dependent covariates be external to the event process. We investigated whether jointly modelling time-to-clinical malaria disease and longitudinal parasite count improves precision in risk factor estimates and assessed the strength of association between the hazard of clinical malaria and parasite count. METHODS: Using a cohort data of participants enrolled with uncomplicated malaria in Malawi, a conventional Cox Proportional Hazards (PH) model of time-to-first clinical malaria episode with time-dependent parasite count was compared with three competing joint models. The joint models had different association structures linking a quasi-Poisson mixed-effects of parasite count and event-time Cox PH sub-models. RESULTS: There were 120 participants of whom 115 (95.8%) had >1 follow-up visit and 100 (87.5%) experienced the episode. Adults >15 years being reference, log hazard ratio for children <5 years was 0.74 (95% CI: 0.17, 1.26) in the joint model with best fit vs. 0.62 (95% CI: 0.04, 1.18) from the conventional Cox PH model. The log hazard ratio for the 5-15 years was 0.72 (95% CI: 0.22, 1.22) in the joint model vs.0.63 (95% CI: 0.11, 1.17) in the Cox PH model. The area under parasite count trajectory was strongly associated with the risk of clinical malaria, with a unit increase corresponding to-0.0012 (95% CI: -0.0021, -0.0004) decrease in log hazard ratio. CONCLUSION: Jointly modelling longitudinal parasite count and time-to-clinical malaria disease improves precision in log hazard ratio estimates compared to conventional time-dependent Cox PH model. The improved precision of joint modelling may improve study efficiency and allow for design of clinical trials with relatively lower sample sizes with increased power.

The prevalence of human papillomavirus infections and associated risk factors in men-who-have-sex-with-men in Cape Town, South Africa.

BACKGROUND: We investigated the prevalence of human papillomavirus (HPV) infection and associated behavioural risk factors in men-who-have-sex-with-men (MSM) attending a clinical service in Cape Town, South Africa. METHODS: MSM were enrolled at the Ivan Toms Centre for Men's Health in Cape Town. A psychosocial and sexual behavioral risk questionnaire was completed for each participant and urine, oro-pharyngeal and anal swabs were collected for HPV testing using the Linear Array HPV Genotyping Test. Logistic regression analyses were performed to determine sexual risk factors associated with HPV infection at the three anatomical sites. RESULTS: The median age of all 200 participants was 32 years (IQR 26-39.5), of which 31.0 % were black, 31.5 % mixed race/coloured and 35.5 % white. The majority of the participants (73.0 %) had completed high school, 42.0 % had a tertiary level qualification and 69.0 % were employed. HPV genotypes were detected in 72.8 % [95 % CI: 65.9-79.0 %], 11.5 % [95 % CI: 7.4-16.8 %] and 15.3 % [95 % CI: 10.5-21.2 %] of anal, oro-pharyngeal and urine specimens, respectively. Prevalence of high-risk (HR)-HPV types was 57.6 % [95 % CI: 50.3-64.7 %] in anal samples, 7.5 % [95 % CI: 4.3-12.1 %] in oro-pharyngeal samples and 7.9 % [95 % CI: 4.5-12.7 %] in urine, with HPV-16 being the most common HR-HPV type detected at all sites. HPV-6/11/16/18 was detected in 40.3 % [95 % CI: 33.3-47.6 %], 4.5 % [95 % CI: 2.1-8.4 %] and 3.2 % [95 % CI: 1.2-6.8 %] of anal, oro-pharyngeal and urine samples, respectively. Multiple HPV types were more common in the anal canal of MSM while single HPV types constituted the majority of HPV infections in the oropharynx and urine. Among the 88 MSM (44.0 %) that were HIV positive, 91.8 % [95 % CI: 83.8-96.6 %] had an anal HPV infection, 81.2 % [95 % CI: 71.2-88.8 %] had anal HR-HPV and 85.9 % [95 % CI: 76.6-92.5 %] had multiple anal HPV types. Having sex with men only, engaging in group sex in lifetime, living with HIV and practising receptive anal intercourse were the only factors independently associated with having any anal HPV infection. CONCLUSIONS: Anal HPV infections were common among MSM in Cape Town with the highest HPV burden among HIV co-infected MSM, men who have sex with men only and those that practiced receptive anal intercourse. Behavioural intervention strategies and the possible roll-out of HPV vaccines among all boys are urgently needed to address the high prevalence of HPV and HIV co-infections among MSM in South Africa.

An exploratory spatial analysis of geographical inequalities of birth intervals among young women in the Democratic Republic of Congo (DRC): a cross-sectional study.

BACKGROUND: The length of time between two successive live births (birth interval), is associated with child survival in the developing world. Short birth intervals (<24 months) contribute to infant and child mortality risks. Contraceptive use contributes to a reduction in short birth intervals, but evidence is lacking in the DRC. We aimed to investigate the proportion of short birth intervals at the provincial level among young women in the DRC. METHODS: Data from the Demographic and Health Survey undertaken in the DRC in 2007 were analyzed. Logistic regression and Bayesian geo-additive models were used to explain provincial inequalities in short birth intervals among women of reproductive age and young women. Posterior odds ratio (OR) and 95% credible region (CR) were estimated via Markov chain Monte Carlo (MCMC) techniques. Posterior spatial effects and the associated posterior probability maps were produced at the provincial-level to highlight provinces with a significant higher risk of short birth interval. RESULTS: The overall proportion of short birth intervals among all women of reproductive age (15-49 years) and young women (15-24 years) were 30.2% and 38.7% respectively. In multivariate Bayesian geo-additive regression analyses, among the whole sample of women, living in rural areas [OR = 1.07, 95% CR: (0.97, 1.17)], exclusive breastfeeding [1.08 (1.00, 1.17)] and women with primary education [1.06 (1.00, 1.16)], were consistently associated with a higher risk of short birth intervals. For the young women, none of the factors considered were associated with the risk of short birth interval except a marginal effect from the lack of education. There was a spatial variation in the proportion of women reporting short birth intervals and among all women of reproductive age across provinces, with Nord-Kivu [1.12 (1.02, 1.24)], Sud Kivu [1.17 (1.05, 1.29)] and Kasai Occidental [1.18 (1.06, 1.32)] reporting a higher risk of short birth intervals. For young women, the higher risk provinces were Nord-Kivu [1.22 (1.00, 1.54)] and Sud Kivu [1.34 (1.14, 1.63)]. CONCLUSIONS: This study suggests distinct geographic patterns in the proportion of short birth intervals among Congolese women, as well as the potential role of demographic and geographic location factors driving the ongoing higher youth fertility, higher childhood and maternal mortality in the DRC.

Urethritis/cervicitis pathogen prevalence and associated risk factors among asymptomatic HIV-infected patients in South Africa.

BACKGROUND: To determine sexually transmitted infection (STI) prevalence, and patient characteristics associated with detection of urethritis/cervicitis pathogens, among HIV-infected individuals offered voluntary STI screening at a South African HIV treatment center. METHODS: Individuals, asymptomatic for genital discharge, were screened for Neisseria gonorrhoeae (NG), Chlamydia trachomatis, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) infections (real-time polymerase chain reaction assay), for syphilis and herpes simplex type 2 (serologically), and for bacterial vaginosis and Candida (microscopy, women only). Patients' most recent CD4 and viral load results were recorded. Demographic, clinical, and behavioral data were collected by nurse-administered questionnaire. RESULTS: Compared with men (n = 551), women (n = 558) were younger (mean age, 35.0 vs. 37.9 years; P < 0.001), reported more STIs in the past year (65.5% vs. 56.5%; P = 0.002), had more urethritis/cervicitis pathogens detected (21.3% vs.16.4%, P = 0.035), and were less aware of their partner's HIV status (53.1% vs. 62.3%; P = 0.007). The overall prevalence of individual urethritis/cervicitis pathogens was TV (7.6%), MG (6.1%), NG (5.4%), and C. trachomatis (2.1%). Multivariate analysis highlighted 4 significant factors associated with the detection of specific urethritis/cervicitis pathogens, namely female gender (TV, adjusted odds ratio [aOR] 2.53, 95% confidence interval [CI]: 1.47-4.37), having a regular sexual partner in the past 3 months (NG, aOR 2.26, 95% CI: 1.01-5.08), suboptimal condom use with regular partners (TV, aOR 2.07, 95% CI: 1.25-3.42), and a history of genital warts in the past year (NG, 2.25, 95% CI: 1.26-4.03). CONCLUSIONS: Asymptomatic urethritis/cervicitis pathogens were highly prevalent in this population. Few urethritis/cervicitis pathogen-associated patient characteristics were identified, emphasizing the need for affordable STI diagnostics to screen HIV-infected patients.

Evaluating the potential of the sterile insect technique for malaria control: relative fitness and mating compatibility between laboratory colonized and a wild population of Anopheles arabiensis from the Kruger National Park, South Africa.

BACKGROUND: The successful suppression of a target insect population using the sterile insect technique (SIT) partly depends on the premise that the laboratory insects used for mass rearing are genetically compatible with the target population, that the mating competitiveness of laboratory reared males is at least comparable to that of their wild counterparts, and that mass rearing and sterilization processes do not in themselves compromise male fitness to a degree that precludes them from successfully competing for mates in the wild. This study investigated the fitness and sexual cross-compatibility between samples of field collected and laboratory reared An. arabiensis under laboratory conditions. RESULTS: The physiological and reproductive fitness of the MALPAN laboratory strain is not substantially modified with respect to the field population at Malahlapanga. Further, a high degree of mating compatibility between MALPAN and the Malahlapanga population was established based on cross-mating experiments. Lastly, the morphological characteristics of hybrid ovarian polytene chromosomes further support the contention that the MALPAN laboratory colony and the An. arabiensis population at Malahlapanga are genetically homogenous and therefore compatible. CONCLUSIONS: It is concluded that the presence of a perennial and isolated population of An. arabiensis at Malahlapanga presents a unique opportunity for assessing the feasibility of SIT as a malaria vector control option. The MALPAN laboratory colony has retained sufficient enough measures of reproductive and physiological fitness to present as a suitable candidate for male sterilization, mass rearing and subsequent mass release of sterile males at Malahlapanga in order to further assess the feasibility of SIT in a field setting.

Infant mortality in South Africa--distribution, associations and policy implications, 2007: an ecological spatial analysis.

BACKGROUND: Many sub-Saharan countries are confronted with persistently high levels of infant mortality because of the impact of a range of biological and social determinants. In particular, infant mortality has increased in sub-Saharan Africa in recent decades due to the HIV/AIDS epidemic. The geographic distribution of health problems and their relationship to potential risk factors can be invaluable for cost effective intervention planning. The objective of this paper is to determine and map the spatial nature of infant mortality in South Africa at a sub district level in order to inform policy intervention. In particular, the paper identifies and maps high risk clusters of infant mortality, as well as examines the impact of a range of determinants on infant mortality. A Bayesian approach is used to quantify the spatial risk of infant mortality, as well as significant associations (given spatial correlation between neighbouring areas) between infant mortality and a range of determinants. The most attributable determinants in each sub-district are calculated based on a combination of prevalence and model risk factor coefficient estimates. This integrated small area approach can be adapted and applied in other high burden settings to assist intervention planning and targeting. RESULTS: Infant mortality remains high in South Africa with seemingly little reduction since previous estimates in the early 2000's. Results showed marked geographical differences in infant mortality risk between provinces as well as within provinces as well as significantly higher risk in specific sub-districts and provinces. A number of determinants were found to have a significant adverse influence on infant mortality at the sub-district level. Following multivariable adjustment increasing maternal mortality, antenatal HIV prevalence, previous sibling mortality and male infant gender remained significantly associated with increased infant mortality risk. Of these antenatal HIV sero-prevalence, previous sibling mortality and maternal mortality were found to be the most attributable respectively. CONCLUSIONS: This study demonstrates the usefulness of advanced spatial analysis to both quantify excess infant mortality risk at the lowest administrative unit, as well as the use of Bayesian modelling to quantify determinant significance given spatial correlation. The "novel" integration of determinant prevalence at the sub-district and coefficient estimates to estimate attributable fractions further elucidates the "high impact" factors in particular areas and has considerable potential to be applied in other locations. The usefulness of the paper, therefore, not only suggests where to intervene geographically, but also what specific interventions policy makers should prioritize in order to reduce the infant mortality burden in specific administration areas.

Determinants of survival in very low birth weight neonates in a public sector hospital in Johannesburg.

BACKGROUND: Audit of disease and mortality patterns provides essential information for health budgeting and planning, as well as a benchmark for comparison. Neonatal mortality accounts for about 1/3 of deaths < 5 years of age and very low birth weight (VLBW) mortality for approximately 1/3 of neonatal mortality. Intervention programs must be based on reliable statistics applicable to the local setting; First World data cannot be used in a Third World setting. Many neonatal units participate in the Vermont Oxford Network (VON); limited resources prevent a significant number of large neonatal units from developing countries taking part, hence data from such units is lacking. The purpose of this study was to provide reliable, recent statistics relevant to a developing African country, useful for guiding neonatal interventions in that setting. METHODS: This was a retrospective chart review of 474 VLBW infants admitted within 24 hours of birth, between 1 July 2006 and 30 June 2007, to the neonatal unit of Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in Johannesburg, South Africa. Binary outcome logistic regression on individual variables and multiple logistic regression was done to identify those factors determining survival. RESULTS: Overall survival was 70.5%. Survival of infants below 1001 grams birth weight was 34.9% compared to 85.8% for those between 1001 and 1500 grams at birth. The main determinant of survival was birth weight with an adjusted survival odds ratio of 23.44 (95% CI: 11.22 - 49.00) for babies weighing between 1001 and 1500 grams compared to those weighing below 1001 grams. Other predictors of survival were gender (OR 3. 21; 95% CI 1.6 - 6.3), birth before arrival at the hospital (BBA) (OR 0.23; 95% CI: 0.08 - 0.69), necrotising enterocolitis (NEC) (OR 0.06; 95% CI: 0.02 - 0.20), hypotension (OR 0.05; 95% CI 0.01 - 0.21) and nasal continuous positive airways pressure (NCPAP) (OR 4.58; 95% CI 1.58 - 13.31). CONCLUSIONS: Survival rates compare favourably with other developing countries, but can be improved; especially in infants < 1001 grams birth weight. Resources need to be allocated to preventing the birth of VLBW babies outside hospital, early neonatal resuscitation, provision of NCPAP and prevention of NEC.

Human papillomavirus (HPV) infection in heterosexual South African men attending sexual health services: associations between HPV and HIV serostatus.

OBJECTIVES: To investigate the distribution of human papillomavirus (HPV) genotypes and determine the associations between HPV infection and HIV coinfection in sexually active heterosexual men with anogenital warts (GW), male urethral discharge or asymptomatic men. METHODS: Valid specimens for HPV genotyping were obtained from three patient groups consisting of 108 men with GW, 56 men with urethral discharge syndrome and 50 asymptomatic men attending for HIV voluntary counselling and testing. The Linear Array HPV Genotyping Test was used to determine the HPV genotype distribution among study participants. Sera were tested for HIV antibodies using two commercial rapid tests. RESULTS: The prevalence of anogenital HPV among study participants was 78% (166). HPV DNA was detected in 100% (108) of GW, 48% (27) of men with urethral discharge syndrome and 62% (31) of voluntary counselling and testing participants. HPV types 6, 11, 16 and 18 were prevalent as either single or combined infections in 81% (134) of all HPV-positive study participants. HPV types 6 and/or 11 were significantly higher among GW patients (p<0.001). After adjusting for patient groups, HIV seropositivity was significantly associated with multiple HPV infections (OR=3.98, 95% CI 1.58 to 10.03) but not with the presence of a foreskin (OR=0.67, 95% CI 0.32 to 1.40). CONCLUSIONS: Infections with HPV were prevalent among sexually active heterosexual men attending the men's sexual health clinic. Associations were observed between HIV coinfection and multiple HPV infections. Further population-based studies on the prevalence of HPV genotypes are required to determine if men should be included in any future national HPV vaccination programme in South Africa.

Applications of Bayesian approach in modelling risk of malaria-related hospital mortality.

BACKGROUND: Malaria is a major public health problem in Malawi, however, quantifying its burden in a population is a challenge. Routine hospital data provide a proxy for measuring the incidence of severe malaria and for crudely estimating morbidity rates. Using such data, this paper proposes a method to describe trends, patterns and factors associated with in-hospital mortality attributed to the disease. METHODS: We develop semiparametric regression models which allow joint analysis of nonlinear effects of calendar time and continuous covariates, spatially structured variation, unstructured heterogeneity, and other fixed covariates. Modelling and inference use the fully Bayesian approach via Markov Chain Monte Carlo (MCMC) simulation techniques. The methodology is applied to analyse data arising from paediatric wards in Zomba district, Malawi, between 2002 and 2003. RESULTS AND CONCLUSION: We observe that the risk of dying in hospital is lower in the dry season, and for children who travel a distance of less than 5 kms to the hospital, but increases for those who are referred to the hospital. The results also indicate significant differences in both structured and unstructured spatial effects, and the health facility effects reveal considerable differences by type of facility or practice. More importantly, our approach shows non-linearities in the effect of metrical covariates on the probability of dying in hospital. The study emphasizes that the methodological framework used provides a useful tool for analysing the data at hand and of similar structure.