Defining operational strengths and gaps relevant to post licensure Group B Streptococcus vaccine effectiveness studies: an expert stakeholder evaluation of the United Kingdom and Uganda

A future Group B Streptococcal (GBS) vaccine for pregnant women to protect neonates is likely to be licensed based on evidence of vaccine induced protective antibody levels. Post licensure surveillance to monitor the impact of any future vaccine on GBS disease therefore needs to be clearly defined (in both high and low income settings). A priority research gap is understanding health system preparedness for a GBS vaccine evaluation This expert stakeholder evaluation aimed to describe the UK and Uganda's operational strengths and gaps relevant to post-licensure GBS vaccine studies

Considerations for post-licensure group B streptococcus vaccine effectiveness studies.

Post-licensure studies of a Group B streptococcal vaccines for pregnant women in low and middle-income countries will require investment in electronic health records

Increased use of malaria rapid diagnostic tests improves targeting of anti-malarial treatment in rural Tanzania: implications for nationwide rollout of malaria rapid diagnostic tests.

ABSTRACT: BACKGROUND: The World Health Organization recommends parasitological confirmation of all malaria cases. Tanzania is implementing a phased rollout of malaria rapid diagnostic tests (RDTs) for routine use in all levels of care as one strategy to increase parasitological confirmation of malaria diagnosis. This study was carried out to evaluated artemisinin combination therapy (ACT) prescribing patterns in febrile patients with and without uncomplicated malaria in one pre-RDT implementation and one post-RDT implementation area. METHODS: A cross-sectional health facility surveys was conducted during high and low malaria transmission seasons in 2010 in both areas. Clinical information and a reference blood film on all patients presenting for an initial illness consultation were collected. Malaria was defined as a history of fever in the past 48 hours and microscopically confirmed parasitaemia. Routine diagnostic testing was defined as RDT or microscopy ordered by the health worker and performed at the health facility as part of the health worker-patient consultation. Correct diagnostic testing was defined as febrile patient tested with RDT or microscopy. Over-testing was defined as a febrile patient tested with RDT or microscopy. Correct treatment was defined as patient with malaria prescribed ACT. Over-treatment was defined as patient without malaria prescribed ACT. RESULTS: A total of 1,247 febrile patients (627 from pre-implementation area and 620 from post-implementation area) were included in the analysis. In the post-RDT implementation area, 80.9% (95% CI, 68.2-89.3) of patients with malaria received recommended treatment with ACT compared to 70.3% (95% CI, 54.7-82.2) of patients in the pre-RDT implementation area. Correct treatment was significantly higher in the post-implementation area during high transmission season (85.9% (95%CI, 72.0-93.6) compared to 58.3% (95%CI, 39.4-75.1) in pre-implementation area (p=0.01). Over-treatment with ACT of patients without malaria was less common in the post-RDT implementation area (20.9%; 95% CI, 14.7-28.8) compared to the pre-RDT implementation area (45.8%; 95% CI, 37.2-54.6) (p<0.01) in high transmission. The odds of overtreatment was significantly lower in post- RDT area (adjusted Odds Ratio (OR: 95%CI) 0.57(0.36-0.89); and much higher with clinical diagnosis adjusted OR (95%CI) 2.24(1.37-3.67) CONCLUSION: Implementation of RDTs increased use of RDTs for parasitological confirmation and reduced over-treatment with ACT during high malaria transmission season in one area in Tanzania. Continued monitoring of the national RDT rollout will be needed to assess whether these changes in case management practices will be replicated in other areas and sustained over time. Additional measures (such as refresher trainings, closer supervisions, etc) may be needed to improve ACT targeting during low transmission seasons

Correct Dosing of Artemether-Lumefantrine for Management of Uncomplicated Malaria in Rural Tanzania: Do facility and Patient Characteristics Matter?

Use of artemisinin-based combination therapy (ACT), such as artemether-lumefantrine (AL), requires a strict dosing schedule that follows the drugs' pharmacokinetic properties. The quality of malaria case management was assessed in two areas in rural Tanzania, to ascertain patient characteristics and facility-specific factors that influence correct dosing of AL for management of uncomplicated malaria. Exit interviews were conducted with patients attending health facilities for initial illness consultation. Information about health workers' training and supervision visits was collected. Health facilities were inventoried for capacity and availability of medical products related to care of malaria patients. The outcome was correct dosing of AL based on age and weight. Logistic regression was used to assess health facility factors and patient characteristics associated with correct dosing of AL by age and weight. A total of 1,531 patients were interviewed, but 60 pregnant women were excluded from the analysis. Only 503 (34.2%) patients who received AL were assessed for correct dosing. Most patients who received AL (85.3%) were seen in public health facilities, 75.7% in a dispensary and 91.1% in a facility that had AL in stock on the survey day. Overall, 92.1% (463) of AL prescriptions were correct by age or weight; but 85.7% of patients received correct dosing by weight alone and 78.5% received correct dosing by age alone. In multivariate analysis, patients in the middle dosing bands in terms of age or weight, had statistically significant lower odds of correct AL dosing (p < 0.05) compared to those in the lowest age or weight group. Other factors such as health worker supervision and training on ACT did not improve the odds of correct AL dosing. Although malaria treatment guidelines indicate AL dosing can be prescribed based on age or weight of the patient, findings from this study show that patients within the middle age and weight dosing bands were least likely to receive a correct dose by either measure. Clinicians should be made aware of AL dosing errors for patients aged three to 12 years and advised to use weight-based prescriptions whenever possible

Access to Artemisinin-Based Anti-Malarial Treatment and its Related Factors in Rural Tanzania.

Artemisinin-based combination treatment (ACT) has been widely adopted as one of the main malaria control strategies. However, its promise to save thousands of lives in sub-Saharan Africa depends on how effective the use of ACT is within the routine health system. The INESS platform evaluated effective coverage of ACT in several African countries. Timely access within 24 hours to an authorized ACT outlet is one of the determinants of effective coverage and was assessed for artemether-lumefantrine (Alu), in two district health systems in rural Tanzania. From October 2009 to June 2011we conducted continuous rolling household surveys in the Kilombero-Ulanga and the Rufiji Health and Demographic Surveillance Sites (HDSS). Surveys were linked to the routine HDSS update rounds. Members of randomly pre-selected households that had experienced a fever episode in the previous two weeks were eligible for a structured interview. Data on individual treatment seeking, access to treatment, timing, source of treatment and household costs per episode were collected. Data are presented on timely access from a total of 2,112 interviews in relation to demographics, seasonality, and socio economic status. In Kilombero-Ulanga, 41.8% (CI: 36.6-45.1) and in Rufiji 36.8% (33.7-40.1) of fever cases had access to an authorized ACT provider within 24 hours of fever onset. In neither of the HDSS site was age, sex, socio-economic status or seasonality of malaria found to be significantly correlated with timely access. Timely access to authorized ACT providers is below 50% despite interventions intended to improve access such as social marketing and accreditation of private dispensing outlets. To improve prompt diagnosis and treatment, access remains a major bottle neck and new more innovative interventions are needed to raise effective coverage of malaria treatment in Tanzania

Predictors of Antibiotics Co-prescription with Antimalarials for Patients Presenting with Fever in Rural Tanzania.

Successful implementation of malaria treatment policy depends on the prescription practices for patients with malaria. This paper describes prescription patterns and assesses factors associated with co-prescription of antibiotics and artemether-lumefantrine (AL) for patients presenting with fever in rural Tanzania. From June 2009 to September 2011, a cohort event monitoring program was conducted among all patients treated at 8 selected health facilities in Ifakara and Rufiji Health and Demographic Surveillance System (HDSS).It included all patients presenting with fever and prescribed with AL. Logistic regression was used to model the predictors on the outcome variable which is co-prescription of AL and antibiotics on a single clinical visit. A cohort of 11,648 was recruited and followed up with 92% presenting with fever. Presumptive treatment was used in 56% of patients treated with AL. On average 2.4 (1 -- 7) drugs was prescribed per encounter, indicating co-prescription of AL with other drugs. Children under five had higher odds of AL and antibiotics co-prescription (OR = 0.63, 95% CI: 0.46 -- 0.85) than those aged more than five years. Patients testing negative had higher odds (OR = 2.22, 95%CI: 1.65 -- 2.97) of AL and antibiotics co-prescription. Patients receiving treatment from dispensaries had higher odds (OR = 1.45, 95% CI: 0.84 -- 2.30) of AL and antibiotics co-prescription than those from served in health centres even though the deference was not statistically significant. Regardless the fact that Malaria is declining but due to lack of laboratories and mRDT in most health facilities in the rural areas, clinicians are still treating malaria presumptively. This leads them to prescribe more drugs to treat all possibilities

Gestational age data completeness, quality and validity in population-based surveys: EN-INDEPTH study.

BACKGROUND: Preterm birth (gestational age (GA) <37 weeks) is the leading cause of child mortality worldwide. However, GA is rarely assessed in population-based surveys, the major data source in low/middle-income countries. We examined the performance of new questions to measure GA in household surveys, a subset of which had linked early pregnancy ultrasound GA data. METHODS: The EN-INDEPTH population-based survey of 69,176 women was undertaken (2017-2018) in five Health and Demographic Surveillance System sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda. We included questions regarding GA in months (GAm) for all women and GA in weeks (GAw) for a subset; we also asked if the baby was 'born before expected' to estimate preterm birth rates. Survey data were linked to surveillance data in two sites, and to ultrasound pregnancy dating at <24 weeks in one site. We assessed completeness and quality of reported GA. We examined the validity of estimated preterm birth rates by sensitivity and specificity, over/under-reporting of GAw in survey compared to ultrasound by multinomial logistic regression, and explored perceptions about GA and barriers and enablers to its reporting using focus group discussions (n = 29). RESULTS: GAm questions were almost universally answered, but heaping on 9 months resulted in underestimation of preterm birth rates. Preference for reporting GAw in even numbers was evident, resulting in heaping at 36 weeks; hence, over-estimating preterm birth rates, except in Matlab where the peak was at 38 weeks. Questions regarding 'born before expected' were answered but gave implausibly low preterm birth rates in most sites. Applying ultrasound as the gold standard in Matlab site, sensitivity of survey-GAw for detecting preterm birth (GAw <37) was 60% and specificity was 93%. Focus group findings suggest that women perceive GA to be important, but usually counted in months. Antenatal care attendance, women's education and health cards may improve reporting. CONCLUSIONS: This is the first published study assessing GA reporting in surveys, compared with the gold standard of ultrasound. Reporting GAw within 5 years' recall is feasible with high completeness, but accuracy is affected by heaping. Compared to ultrasound-GAw, results are reasonably specific, but sensitivity needs to be improved. We propose revised questions based on the study findings for further testing and validation in settings where pregnancy ultrasound data and/or last menstrual period dates/GA recorded in pregnancy are available. Specific training of interviewers is recommended

Vulnerability to high risk sexual behaviour (HRSB) following exposure to war trauma as seen in post-conflict communities in eastern uganda: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Much of the literature on the relationship between conflict-related trauma and high risk sexual behaviour (HRSB) often focuses on refugees and not mass in-country displaced people due to armed conflicts. There is paucity of research about contexts underlying HRSB and HIV/AIDS in conflict and post-conflict communities in Uganda. Understanding factors that underpin vulnerability to HRSB in post-conflict communities is vital in designing HIV/AIDS prevention interventions. We explored the socio-cultural factors, social interactions, socio-cultural practices, social norms and social network structures that underlie war trauma and vulnerability to HRSB in a post-conflict population.</p> <p>Methods</p> <p>We did a cross-sectional qualitative study of 3 sub-counties in <it>Katakwi </it>district and 1 in <it>Amuria </it>in Uganda between March and May 2009. We collected data using 8 FGDs, 32 key informant interviews and 16 in-depth interviews. We tape-recorded and transcribed the data. We followed thematic analysis principles to manage, analyse and interpret the data. We constantly identified and compared themes and sub-themes in the dataset as we read the transcripts. We used illuminating verbatim quotations to illustrate major findings.</p> <p>Results</p> <p>The commonly identified HRSB behaviours include; transactional sex, sexual predation, multiple partners, early marriages and forced marriages. Breakdown of the social structure due to conflict had resulted in economic destruction and a perceived soaring of vulnerable people whose propensity to HRSB is high. Dishonour of sexual sanctity through transactional sex and practices like incest mirrored the consequence of exposure to conflict. HRSB was associated with concentration of people in camps where idleness and unemployment were the norm. Reports of girls and women who had been victims of rape and defilement by men with guns were common. Many people were known to have started to display persistent worries, hopelessness, and suicidal ideas and to abuse alcohol.</p> <p>Conclusions</p> <p>The study demonstrated that conflicts disrupt the socio-cultural set up of communities and destroy sources of people's livelihood. Post-conflict socio-economic reconstruction needs to encompass programmes that restructure people's morals and values through counselling. HIV/AIDS prevention programming in post-conflict communities should deal with socio-cultural disruptions that emerged during conflicts. Some of the disruptions if not dealt with, could become normalized yet they are predisposing factors to HRSB. Socio-economic vulnerability as a consequence of conflict seemed to be associated with HRSB through alterations in sexual morality. To pursue safer sexual health choices, people in post-conflict communities need life skills.</p

“Every Newborn-INDEPTH” (EN-INDEPTH) study protocol for a randomised comparison of household survey modules for measuring stillbirths and neonatal deaths in five Health and Demographic Surveillance sites

Background: Under-five and maternal mortality were halved in the Millennium Development Goals (MDG) era, with slower reductions for 2.6 million neonatal deaths and 2.6 million stillbirths. The Every Newborn Action Plan aims to accelerate progress towards national targets, and includes an ambitious Measurement Improvement Roadmap. Population-based household surveys, notably Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys, are major sources of population-level data on child mortality in countries with weaker civil registration and vital statistics systems, where over two-thirds of global child deaths occur. To estimate neonatal/child mortality and pregnancy outcomes (stillbirths, miscarriages, birthweight, gestational age) the most common direct methods are: (1) the standard DHS-7 with Full Birth History with additional questions on pregnancy losses in the past 5 years (FBH+) or (2) a Full Pregnancy History (FPH). No direct comparison of these two methods has been undertaken, although descriptive analyses suggest that the FBH+ may underestimate mortality rates particularly for stillbirths. Methods: This is the protocol paper for the Every Newborn-INDEPTH study (INDEPTH Network, International Network for the Demographic Evaluation of Populations and their Health Every Newborn, Every Newborn Action Plan), aiming to undertake a randomised comparison of FBH+ and FPH to measure pregnancy outcomes in a household survey in five selected INDEPTH Network sites in Africa and South Asia (Bandim in urban and rural Guinea-Bissau; Dabat in Ethiopia; IgangaMayuge in Uganda; Kintampo in Ghana; Matlab in Bangladesh). The survey will reach >68 000 pregnancies to assess if there is ≥15% difference in stillbirth rates. Additional questions will capture birthweight, gestational age, birth/death certification, termination of pregnancy and fertility intentions. The World Bank's Survey Solutions platform will be tailored for data collection, including recording paradata to evaluate timing. A mixed methods assessment of barriers and enablers to reporting of pregnancy and adverse pregnancy outcomes will be undertaken. Conclusions: This large-scale study is the first randomised comparison of these two methods to capture pregnancy outcomes. Results are expected to inform the evidence base for survey methodology, especially in DHS, regarding capture of stillbirths and other outcomes, notably neonatal deaths, abortions (spontaneous and induced), birthweight and gestational age. In addition, this study will inform strategies to improve health and demographic surveillance capture of neonatal/child mortality and pregnancy outcomes.Children’s Investment Fund Foundation (CIFF

Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9–3·0) for men and 3·5 years (3·4–3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78–0·92) and 1·2 years (1·1–1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum. Funding Bill &amp; Melinda Gates Foundation