Feasibility, safety, and impact of the RTS,S/AS01E malaria vaccine when implemented through national immunisation programmes: evaluation of cluster-randomised introduction of the vaccine in Ghana, Kenya, and Malawi.

BACKGROUND: The RTS,S/AS01E malaria vaccine (RTS,S) was introduced by national immunisation programmes in Ghana, Kenya, and Malawi in 2019 in large-scale pilot schemes. We aimed to address questions about feasibility and impact, and to assess safety signals that had been observed in the phase 3 trial that included an excess of meningitis and cerebral malaria cases in RTS,S recipients, and the possibility of an excess of deaths among girls who received RTS,S than in controls, to inform decisions about wider use. METHODS: In this prospective evaluation, 158 geographical clusters (66 districts in Ghana; 46 sub-counties in Kenya; and 46 groups of immunisation clinic catchment areas in Malawi) were randomly assigned to early or delayed introduction of RTS,S, with three doses to be administered between the ages of 5 months and 9 months and a fourth dose at the age of approximately 2 years. Primary outcomes of the evaluation, planned over 4 years, were mortality from all causes except injury (impact), hospital admission with severe malaria (impact), hospital admission with meningitis or cerebral malaria (safety), deaths in girls compared with boys (safety), and vaccination coverage (feasibility). Mortality was monitored in children aged 1-59 months throughout the pilot areas. Surveillance for meningitis and severe malaria was established in eight sentinel hospitals in Ghana, six in Kenya, and four in Malawi. Vaccine uptake was measured in surveys of children aged 12-23 months about 18 months after vaccine introduction. We estimated that sufficient data would have accrued after 24 months to evaluate each of the safety signals and the impact on severe malaria in a pooled analysis of the data from the three countries. We estimated incidence rate ratios (IRRs) by comparing the ratio of the number of events in children age-eligible to have received at least one dose of the vaccine (for safety outcomes), or age-eligible to have received three doses (for impact outcomes), to that in non-eligible age groups in implementation areas with the equivalent ratio in comparison areas. To establish whether there was evidence of a difference between girls and boys in the vaccine's impact on mortality, the female-to-male mortality ratio in age groups eligible to receive the vaccine (relative to the ratio in non-eligible children) was compared between implementation and comparison areas. Preliminary findings contributed to WHO's recommendation in 2021 for widespread use of RTS,S in areas of moderate-to-high malaria transmission. FINDINGS: By April 30, 2021, 652 673 children had received at least one dose of RTS,S and 494 745 children had received three doses. Coverage of the first dose was 76% in Ghana, 79% in Kenya, and 73% in Malawi, and coverage of the third dose was 66% in Ghana, 62% in Kenya, and 62% in Malawi. 26 285 children aged 1-59 months were admitted to sentinel hospitals and 13 198 deaths were reported through mortality surveillance. Among children eligible to have received at least one dose of RTS,S, there was no evidence of an excess of meningitis or cerebral malaria cases in implementation areas compared with comparison areas (hospital admission with meningitis: IRR 0·63 [95% CI 0·22-1·79]; hospital admission with cerebral malaria: IRR 1·03 [95% CI 0·61-1·74]). The impact of RTS,S introduction on mortality was similar for girls and boys (relative mortality ratio 1·03 [95% CI 0·88-1·21]). Among children eligible for three vaccine doses, RTS,S introduction was associated with a 32% reduction (95% CI 5-51%) in hospital admission with severe malaria, and a 9% reduction (95% CI 0-18%) in all-cause mortality (excluding injury). INTERPRETATION: In the first 2 years of implementation of RTS,S, the three primary doses were effectively deployed through national immunisation programmes. There was no evidence of the safety signals that had been observed in the phase 3 trial, and introduction of the vaccine was associated with substantial reductions in hospital admission with severe malaria. Evaluation continues to assess the impact of four doses of RTS,S. FUNDING: Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid.

Acute lower respiratory infections among children under five in Sub-Saharan Africa: a scoping review of prevalence and risk factors.

BACKGROUND: Acute lower respiratory tract infections (ALRTIs) among children under five are still the leading cause of mortality among this group of children in low and middle-income countries (LMICs), especially countries in sub-Saharan Africa (SSA). This scoping review aims to map evidence on prevalence and risk factors associated with ALRTIs among children under 5 years to inform interventions, policies and future studies. METHODS: A thorough search was conducted via four main databases (PubMed, JSTOR, Web of Science and Central). In all, 3,329 records were identified, and 107 full-text studies were considered for evaluation after vigorous screening and removing duplicates, of which 43 were included in this scoping review. FINDINGS: Findings indicate a high prevalence (between 1.9% to 60.2%) of ALRTIs among children under five in SSA. Poor education, poverty, malnutrition, exposure to second-hand smoke, poor ventilation, HIV, traditional cooking stoves, unclean fuel usage, poor sanitation facilities and unclean drinking water make children under five more vulnerable to ALRTIs in SSA. Also, health promotion strategies like health education have doubled the health-seeking behaviours of mothers of children under 5 years against ALRTIs. CONCLUSION: ALRTIs among children under five still present a significant disease burden in SSA. Therefore, there is a need for intersectoral collaboration to reduce the burden of ALRTIs among children under five by strengthening poverty alleviation strategies, improving living conditions, optimising child nutrition, and ensuring that all children have access to clean water. There is also the need for high-quality studies where confounding variables in ALRTIs are controlled.

Effect of iron fortification on anaemia and risk of malaria among Ghanaian pre-school children with haemoglobinopathies and different ABO blood groups.

BACKGROUND: Haemoglobinopathies such as sickle cell disorder and glucose-6-phosphate dehydrogenase (G6PD) deficiency as well as differences in ABO blood groups have been shown to influence the risk of malaria and/or anaemia in malaria-endemic areas. This study assessed the effect of adding MNP containing iron to home-made weaning meals on anaemia and the risk of malaria in Ghanaian pre-school children with haemoglobinopathies and different ABO blood groups. METHODS: This study was a double-blind, randomly clustered trial conducted within six months among infants and young children aged 6 to 35 months in rural Ghana (775 clusters, n = 860). Participants were randomly selected into clusters to receive daily semiliquid home-prepared meals mixed with either micronutrient powder without iron (noniron group) or with iron (iron group; 12.5 mg of iron daily) for 5 months. Malaria infection was detected by microscopy, blood haemoglobin (Hb) levels were measured with a HemoCue Hb analyzer, the reversed ABO blood grouping microtube assay was performed, and genotyping was performed by PCR-RFLP analysis. RESULTS: The prevalence of G6PD deficiency among the study participants was 11.2%. However, the prevalence of G6PD deficiency in hemizygous males (8.5%) was significantly higher than that in homozygous females (2.7%) (p = 0.005). The prevalence rates of sickle cell traits (HbAS and HbSC) and sickle cell disorder (HbSS) were 17.5% and 0.5%, respectively. Blood group O was dominant (41.4%), followed by blood group A (29.6%) and blood group B (23.3%), while blood group AB (5.7%) had the least frequency among the study participants. We observed that children on an iron supplement with HbAS had significantly moderate anaemia at the endline (EL) compared to the baseline level (BL) (p = 0.004). However, subjects with HbAS and HbAC and blood groups A and O in the iron group had a significantly increased number of malaria episodes at EL than at BL (p < 0.05). Furthermore, children in the iron group with HbSS (p < 0.001) and the noniron group with HbCC (p = 0.010) were significantly less likely to develop malaria. CONCLUSIONS: Iron supplementation increased anaemia in children with HbAS genotypes and provided less protection against malaria in children with HbAC and AS and blood groups A and O. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01001871 . Registered 27/10/2009. REGISTRATION NUMBER: https://clinicaltrials.gov/ct2/show/record/NCT01001871 .

"I don't want to have anything to do with someone suspected of COVID-19": a genuine infection avoidance interest or inappropriate concerns related to stigma?

Background: Human existence is being challenged by an outbreak of coronavirus disease 2019 (COVID-19) caused by the virus SARS-CoV-2 that began in Wuhan, China in December 2019. Efforts to avoid the spread of COVID-19 are undermined by the appearance of disease-associated avoidance of infected persons due to reasons such as social stigma and discrimination. Objective: This study seeks to investigate avoidance and discrimination against persons suspected of COVID-19 to help fight the pandemic in a predominantly rural setting in Ghana. Materials and Methods: The study is a cross sectional survey. A random sample of 517 individuals drawn from a health and demographic surveillance system database was used for this study. Participants resided in six contiguous districts and municipalities of predominantly rural setting in the Bono East Region of Ghana. Results: The findings showed that majority (60%) of the respondents agreed that they won't have anything to do with someone suspected of COVID-19. However, 67% of them were willing to accommodate persons that recovered from the infection. The majority (91%) of respondents agreed that there is a need to adopt tolerant attitude towards persons who recovered from the infection, whilst another 98% also reported the need to show compassion towards persons who recovered from COVID-19. Conclusions: There is the need to pay special attention to avoidance of suspected infected persons due to stigma or any other reason since it is a threat to the fight against the pandemic.

Malaria amongst children under five in sub-Saharan Africa: a scoping review of prevalence, risk factors and preventive interventions.

INTRODUCTION: Africa has a higher burden of malaria-related cases and deaths globally. Children under five accounted for over two-thirds of all malaria deaths in sub-Saharan Africa (SSA). This scoping review aims to map evidence of the prevalence, contextual factors and health education interventions of malaria amongst children under 5 years (UN5) in SSA. METHOD: Four main databases (PubMed, Central, Dimensions and JSTOR) produced 27,841 records of literature. Additional searches in Google, Google Scholar and institutional repositories produced 37 records. Finally, 255 full-text records were further screened, and 100 records were used for this review. RESULTS: Low or no formal education, poverty or low income and rural areas are risk factors for malaria amongst UN5. Evidence on age and malnutrition as risk factors for malaria in UN5 is inconsistent and inconclusive. Furthermore, the poor housing system in SSA and the unavailability of electricity in rural areas and unclean water make UN5 more susceptible to malaria. Health education and promotion interventions have significantly reduced the malaria burden on UN5 in SSA. CONCLUSION: Well-planned and resourced health education and promotion interventions that focus on prevention, testing and treatment of malaria could reduce malaria burden amongst UN5 in SSA.

Prevalence and factors associated with serious injuries and aggressive behaviours among in-school adolescents in Panama.

Introduction: Injuries during adolescence cause lifelong harm and death. Our study used a nationally representative sample to examine the prevalence and risk factors associated with serious injuries among in-school adolescents in Panama. Methods: We analysed Panama's 2018 Global School-Based Student Health Survey data using SPSS. Percentages were used to summarise the results of the prevalence of serious injuries. Binomial logistic regression analysis was performed to examine the risk factors of serious injuries. The results were presented as an adjusted odds ratio (AOR) at a 95% confidence interval (CI). Results: The prevalence of serious injury among in-school adolescents in Panama is 45%. Furthermore, the study found that males (AOR= 1.495, CI=1.272--1.756), truancy (AOR=1.493, CI=1.249--1.785), overweight (AOR= 1.246, 95% CI=11.057--1.469), drinking alcohol (AOR= 1.397, CI=1.151--1.695), experiencing physical attack (AOR= 2.100, CI=11.646--2.681), engaging in a physical fight (AOR=1.586, CI=1.289--1.952) and bullied outside school (AOR=1.276, CI=1.005--1.621) significantly predict serious injuries among adolescents in Panama. Conclusion: Multidisciplinary approaches targeting the correlates observed will help reduce the high prevalence of serious injuries among in-school adolescents in Panama.

Challenges and lessons learned during the planning and early implementation of the RTS,S/AS01E malaria vaccine in three regions of Ghana: a qualitative study.

BACKGROUND: In 2019, the RTS,S/AS01E malaria vaccine was introduced on a pilot basis in six regions of Ghana by the Ministry of Health/Ghana Health Service as part of the WHO-coordinated Malaria Vaccine Implementation Programme (MVIP). This is the first time a malaria vaccination programme has been implemented in any country. This paper describes the challenges faced, and lessons learned, during the planning and early implementation of the RTS,S/AS01E vaccine in three out of the six regions that implemented the programme in Ghana. METHODS: Twenty-one in-depth interviews were conducted with regional and district health service managers and frontline health workers three months after the start of MVIP in May 2019. Data were coded using NVivo software version 12 and a coding framework was developed to support thematic analysis to identify the challenges and lessons learned during the RTS,S/AS01E implementation pilot, which were also categorized into the Consolidated Framework for Implementation Research (CFIR). RESULTS: Participants reported challenges related to the characteristics of the intervention, such as issues with the vaccine schedule and eligibility criteria, and challenges related to how it was implemented as a pilot programme. Additionally, major challenges were faced due to the spread of rumours leading to vaccine refusals; thus, the outer setting of the CFIR was adapted to accommodate rumours within the community context. Health service managers and frontline health workers also experienced challenges with the process of implementing RTS,S/AS01E, including inadequate sensitization and training, as well as issues with the timeline. They also experienced challenges associated with the features of the systems within which the vaccine was being implemented, including inadequate resources for cold-chain at the health facility level and transportation at the district and health facility levels. This study identified the need for a longer, more intensive and sustained delivery of contextually-appropriate sensitization prior to implementation of a programme such as MVIP. CONCLUSIONS: This study identified 12 main challenges and lessons learned by health service managers and health workers during the planning and early implementation phases of the RTS,S/AS01E pilot introduction in Ghana. These findings are highly relevant to the likely scale-up of RTS,S/AS01E within Ghana and possible implementation in other African countries, as well as to other future introductions of novel vaccines.

Impact of IgG response to malaria-specific antigens and immunity against malaria in pre-school children in Ghana. A cluster randomized, placebo-controlled trial.

BACKGROUND: Iron fortification and micronutrient initiatives, specifically, vitamin A, and zinc supplementation are the most cost-effective developmental strategies against malnutrition and health emergencies in pre-school children. Iron-deficiency among pre-school children have been documented, however, studies evaluating the impact of immunoglobulin G (IgG) isotype responses among iron-fortified pre-school children in malaria endemic communities has not been assessed. We evaluated the impact of iron fortification on the IgG responses to GLURP R0, GLURP R2 and MSP3 FVO malaria-specific antigens among pre-school children in malaria endemic areas. METHODS: This community-based, placebo-controlled, double-blinded, cluster-randomized trial study was conducted in Wenchi Municipal and Tain District of Bono Region. The trial was registered at ClinicalTrials.gov-registered trial (Identifier: NCT01001871). Ethical approval was obtained and informed consent were sought from each participant parents/guardian. For the current objective, 871 children aged 6-35 months were screened, from which 435 children received semi-liquid home-made meals mixed with 12.5 mg of iron daily (intervention group), and 436 received micronutrient powder without iron (placebo group) for 5 months. Standardized clinical and epidemiological questionnaires were administered and blood samples taken to measure IgG responses to GLURP R0, GLURP R2 and MSP3 FVO recombinant antigens using the Afro Immunoassay (AIA) protocol. RESULTS: Baseline anthropometry, malaria diagnosis, anaemia and iron status, demographic features and dietary intake were identical among the groups (p > 0.05). After the intervention, there was no significant difference in the IgG response against GLUP R0, GLUP R2 and MSP3 FVO between the iron-containing micronutrient and placebo groups (p > 0.05). The iron-containing micronutrient powder group who were iron-sufficient or iron replete had significantly higher IgG response to GLURP R0 and GLURP R2 compared to iron-deficient and iron-deficiency anaemia in the same group (p < 0.05). The IgG responses to all the three malaria specific antigens were low among children without malaria episode but high among those with two and four episodes due to exposure differences. CONCLUSION: Iron fortification did not influence antibody response against endogenous malaria specific antigens among pre-school children in malaria endemic areas, however, IgG response to malaria specific antigens were high among children with sufficient iron status.

Impact of iron fortification on anaemia and iron deficiency among pre-school children living in Rural Ghana.

Anaemia in young sub-Saharan African children may be due to the double burden of malaria and iron deficiency. Primary analysis of a double-blind, cluster randomized trial of iron containing micronutrient powder supplementation in Ghanaian children aged 6 to 35 months found no difference in malaria risk between intervention and placebo groups. Here, we performed a secondary analysis of the trial data to assess the impact of long-term prophylactic iron fortificant on the risk of iron deficiency and anaemia in trial subjects. This population-based randomized-cluster trial involved 1958 children aged between 6 to 35 months, identified at home and able to eat semi-solid foods. The intervention group (n = 967) received a daily dose containing 12.5 mg elemental iron (as ferrous fumarate), vitamin A (400 µg), ascorbic acid (30 mg) and zinc (5 mg). The placebo group (n = 991) received a similar micronutrient powder but without iron. Micronutrient powder was provided daily to both groups for 5 months. At baseline and endline, health assessment questionnaires were administered and blood samples collected for analysis. The two groups had similar baseline anthropometry, anaemia, iron status, demographic characteristics, and dietary intakes (p > 0.05). Of the 1904 (97.2%) children who remained at the end of the intervention, the intervention group had significantly higher haemoglobin (p = 0.0001) and serum ferritin (p = 0.0002) levels than the placebo group. Soluble transferrin receptor levels were more saturated among children from the iron group compared to non-iron group (p = 0.012). Anaemia status in the iron group improved compared to the placebo group (p = 0.03). Continued long-term routine use of micronutrient powder containing prophylactic iron reduced anaemia, iron deficiency and iron deficiency anaemia among pre-school children living in rural Ghana's malaria endemic area.

Health service provider education and/or training in infant male circumcision to improve short- and long-term morbidity outcomes: A systematic review.

AIM: To systematically review the effectiveness of education and/or training for traditional (informal) and formal health service providers in infant male circumcision on morbidity or mortality outcomes. METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Global Health, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects and clinical trial registries in all languages from January 1985 to June 2018. Our primary outcomes were all-cause morbidity and all-cause mortality. RESULTS: We identified 1399 publications. Only four non-controlled before and after studies from the USA and Uganda satisfied our criteria, all of which examined the effect of training on the skills and knowledge of medical doctors, midwives and clinical officers. No study involved informal traditional circumcision providers. All included studies were low quality. CONCLUSIONS: High-quality studies of simple training packages to improve education and training of circumcision providers, especially informal non-medical providers in low income countries are needed.

Effectiveness of population based risk reduction programs for risky sexual behavior among young people in low- and middle-income countries: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this review is to synthesize the best available evidence on the effectiveness of population based (public health) risk reduction interventions (programs and services) on sexual risk taking among young people (aged 10 to 24 years old) in low- and middle-income countries (LMICs).The specific review questions are.

Healthcare seeking patterns of families of infants with circumcision-related morbidities from two population-based cohort studies in Ghana.

OBJECTIVE: This study assessed healthcare seeking patterns of families of infants with circumcision-related morbidities and families of infants with acute illnesses in rural Ghana. DESIGN: Two population-based cohort studies. SETTING: Brong Ahafo Region of central rural Ghana. PARTICIPANTS: A total of 22 955 infants enrolled in a large population-based trial (Neovita trial) from 16 August 2010 to 7 November 2011 and 3141 infants in a circumcision study from 21 May 2012 to 31 December 2012. PRIMARY OUTCOME: Care seeking for circumcision-related morbidities and acute illnesses unrelated to circumcision. RESULTS: Two hundred and thirty (8.1%) infants from the circumcision study had circumcision-related morbidities and 6265 (27.3%) infants from the Neovita study had acute illnesses unrelated to circumcision. A much lower proportion (35, 15.2%) of families of infants with circumcision-related morbidities sought healthcare compared with families of infants with acute illnesses in the Neovita study (5520, 88.1%). More families sought care from formal providers (24, 69%) compared with informal providers (11, 31%) for circumcision-related morbidities. There were no obvious determinants of care seeking for acute illnesses or circumcision-related morbidities in the population. CONCLUSIONS: Government and non-government organisations need to improve awareness about the complications and care seeking needed for circumcision-related morbidities.

The influence of socioeconomic factors on choice of infant male circumcision provider in rural Ghana; a community level population based study.

BACKGROUND: The influence of socio-economic determinants on choice of infant male circumcision provider is not known in areas with high population coverage such as rural Africa. The overall aim of this study was to determine the key socio-economic factors which influence the choice of infant male circumcision provider in rural Ghana. METHODS: The study investigated the effect of family income, distance to health facility, and cost of the circumcision on choice of infant male circumcision provider in rural Ghana. Data from 2847 circumcised infant males aged under 12 weeks and their families were analysed in a population-based cross-sectional study conducted from May to December 2012 in rural Ghana. Multivariable logistic regression models were adjusted for income status, distance to health facility, cost of circumcision, religion, maternal education, and maternal age. RESULTS: Infants from the lowest income households (325, 84.0%) were more likely to receive circumcision from an informal provider compared to infants from the highest income households (260, 42.4%) even after adjusting for religious affiliation (adjusted odds ratio [aOR] 4.42, 95% CI 3.12-6.27 p = <0.001). There appeared to be a dose response with increasing risk of receiving a circumcision from an informal provider as distance to a health facility increased (aOR 1.25, 95 CI 1.30-1.38 P = <0.001). Only 9.0% (34) of families in the lowest socio-economic quintile received free circumcision services compared to 27.9% (171) of the highest income families. CONCLUSIONS: The Government of Ghana and Non-Government Organisations should consider additional support to poor families so they can access high quality free infant male circumcision in rural Ghana.

Determinants of morbidity associated with infant male circumcision: community-level population-based study in rural Ghana.

OBJECTIVE: Male circumcision services have expanded throughout Africa as part of a long-term HIV prevention strategy. We assessed the effect of type of service provider (formal and informal) and hygiene practices on circumcision-related morbidities in rural Ghana. METHODS: Population-based, cross-sectional study conducted between May and December 2012 involving 2850 circumcised infant males aged under 12 weeks. Multivariable logistic regression models were adjusted for maternal age, maternal education, income, birthweight and site of circumcision. RESULTS: A total of 2850 (90.7%) infant males were circumcised. Overall, the risk of experiencing a morbidity (defined as complications occurring during or after the circumcision procedure as reported by the primary caregiver) was 8.1% (230). Risk was not significantly increased if the circumcision was performed by informal providers (121, 7.2%) vs. formal health service providers (109, 9.8%) [adjusted odds ratio (aOR) 1.11, 95% CI 0.80-1.47, P = 0.456]. Poor hygiene practices were associated with significantly increased risk of morbidity: no handwashing [148 (11.7%)] (aOR 1.78, 95% CI 1.27-2.52, P = 0.001); not cleaning circumcision instruments [174 (10.6%)] (aOR 1.80, 95% CI 1.27-2.54, P = 0.001); and uncleaned penile area [190 (10.0%)] (aOR 1.84, 95% CI 1.25-2.70, P = 0.002). CONCLUSION: The risk of morbidity after infant male circumcision in rural Ghana is high, chiefly due to poor hygiene practices. Governmental and non-governmental organisations need to improve training of circumcision providers in hygiene practices in sub-Saharan Africa.

Increasing access to care for sick newborns: evidence from the Ghana Newhints cluster-randomised controlled trial.

OBJECTIVES: To evaluate the impact of Newhints community-based surveillance volunteer (CBSV) assessments and referrals on access to care for sick newborns and on existing inequities in access. DESIGN: We evaluated a prospective cohort nested within the Newhints cluster-randomised controlled trial. SETTING: Community-based intervention involving more than 750 000, predominantly rural, population in seven contiguous districts in the Brong-Ahafo Region, Ghana. PARTICIPANTS: Participants were recently delivered women (from more than 120 000 women under surveillance) and their 16 168 liveborn babies. Qualitative in-depth interviews with referral narratives (IDIs) were conducted with 92 mothers, CBSVs and health facility front-desk and maternity/paediatrics ward staff. INTERVENTIONS: Newhints trained and effectively supervised 475 CBSVs (existing within the Ghana Health Service) in 49 of 98 supervisory zones (clusters) to assess and refer newborns with any of the 10-key-danger signs to health facilities within the first week after birth; promote independent care seeking for sick newborns and problem-solve around barriers between November 2008 and December 2009. PRIMARY OUTCOMES: The main evaluation outcomes were rates of compliance with referrals and independent care seeking for newborn illnesses. RESULTS: Of 4006 sampled, 2795 (69.8%) recently delivered women received CBSV assessment visits and 279 (10.0%) newborns were referred with danger signs. Compliance with referrals was unprecedentedly high (86.0%) with women in the poorest quintile (Q1) complying better than the least poor (Q5):87.5%(Q1) vs 69.7%(Q5); p=0.038. Three-quarters went to hospitals; 18% were admitted and 58% received outpatient treatment. Some (24%) mothers were turned away at facilities and follow-on IDIs showed that some of these untreated babies subsequently died. Independent care seeking for severe newborn illness increased from 55.4% in control to 77.3% in Newhints zones, especially among Q1 where care seeking almost doubled (95.0% vs 48.6%; RR=1.94 (1.32, 2.84); p=0.001). Rates were the highest among rural residents but urban residents complied quicker. CONCLUSIONS: Home visits are feasible and a potentially pro-poor approach to link sick newborns to facilities. Its effectiveness in improving survival hinges on matched improvement in facility quality of care. TRIAL REGISTRATION NUMBER: NCT00623337.

Health service provider education and/or training in infant male circumcision to improve short- and long-term morbidity outcomes: protocol for systematic review.

BACKGROUND: There has been an expansion of circumcision services in Africa as part of a long-term HIV prevention strategy. However, the effect of infant male circumcision on morbidity and mortality still remains unclear. Acute morbidities associated with circumcision include pain, bleeding, swelling, infection, tetanus or inadequate skin removal. Scale-up of circumcision services could lead to a rise in these associated morbidities that could have significant impact on health service delivery and the safety of infants. Multidisciplinary training programmes have been developed to improve skills of health service providers, but very little is known about the effectiveness of health service provider education and/or training for infant male circumcision on short- and long-term morbidity outcomes. This review aims to evaluate the effectiveness of health service provider education and/or training for infant male circumcision on short- and long-term morbidity outcomes. METHODS/DESIGN: The review will include studies comparing health service providers who have received education and/or training to improve their skills for infant male circumcision with those who have not received education and/or training. Randomised controlled trials (RCTs) and cluster RCTs will be included. The outcomes of interest are short-term morbidities of the male infant including pain, infection, tetanus, bleeding, excess skin removal, glans amputation and fistula. Long-term morbidities include urinary tract infection (UTI), HIV infection and abnormalities of urination. Databases such as MEDLINE (OVID), PsycINFO (OVID), EMBASE (OVID), CINAHL, Cochrane Library (including CENTRAL and DARE), WHO databases and reference list of papers will be searched for relevant articles. Study selection, data extraction and synthesis and risk of bias assessment using the Cochrane risk of bias assessment tool will be conducted. We will calculate the pooled estimates of the difference in means and risk ratios using random effects models. If insufficient data are available, we will present results descriptively. DISCUSSION: This review appears to be the first to be conducted in this area. The findings will have important implications for infant male circumcision programmes and policy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015029345.

Evaluating the implementation of community volunteer assessment and referral of sick babies: lessons learned from the Ghana Newhints home visits cluster randomized controlled trial.

A World Health Organization (WHO)/United Nations Children's Fund (UNICEF) (2009) joint statement recommended home visits by community-based agents as a strategy to improve newborn survival, based on promising results from Asia. This article presents detailed evaluation of community volunteer assessment and referral implemented within the Ghana Newhints home visits cluster-Randomized Controlled Trial (RCT). It highlights the lessons learned to inform implementation/scale-up of this model in similar settings. The evaluation used a conceptual framework adopted for increasing access to care for sick newborns and involves three main steps, each with a specific goal and key requirements to achieving this. These steps are: sick newborns are identified within communities and referred; families comply with referrals and referred babies receive appropriate management at health facilities. Evaluation data included interviews with 4006 recently delivered mothers; records on 759 directly observed volunteer assessments and 52 validation of supervisors' assessments; newborn care quality assessment in 86 health facilities and in-depth interviews (IDIs) with 55 mothers, 21 volunteers and 15 health professionals. Assessment accuracy of volunteers against supervisors and physician was assessed using Kappa (agreement coefficient). IDIs were analysed by generating and indexing into themes, and exploring relationships between themes and their contextual interpretations. This evaluation demonstrated that identifying, understanding and implementing the key requirements for success in each step of volunteer assessment and referrals was pivotal to success. In Newhints, volunteers (CBSVs) were trusted by families, their visits were acceptable and they engaged mothers/families in decisions, resulting in unprecedented 86% referral compliance and increased (55-77%) care seeking for sick newborns. Poor facility care quality, characterized by poor health worker attitudes, limited the mortality reduction. The important implication for future implementation of home visits in similar settings is that, with 100% specificity but 80% sensitivity of referral decisions, volunteers might miss some danger signs but if successful implementation must translate into mortality reductions, concurrent improvement in facility newborn care quality is imperative.

Effect of the Newhints home-visits intervention on neonatal mortality rate and care practices in Ghana: a cluster randomised controlled trial.

BACKGROUND: In 2009, on the basis of promising evidence from trials in south Asia, WHO and UNICEF issued a joint statement about home visits as a strategy to improve newborn survival. In the Newhints trial, we aimed to test this home-visits strategy in sub-Saharan Africa by assessing the effect on all-cause neonatal mortality rate (NMR) and essential newborn-care practices. METHODS: The Newhints cluster randomised trial was undertaken in 98 zones in seven districts in the Brong Ahafo Region, Ghana. 49 zones were randomly assigned to the Newhints intervention and 49 to the control intervention by use of restricted randomisation with stratification to ensure comparability between interventions. Community-based surveillance volunteers (CBSVs) in Newhints zones were trained to identify pregnant women in their community and to make two home visits during pregnancy and three in the first week of life to promote essential newborn-care practices, weigh and assess babies for danger signs, and refer as necessary. Primary outcomes were NMR and coverage of key essential newborn-care practices. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00623337. FINDINGS: 16,168 (99%) of 16,329 deliveries between November, 2008, and December, 2009, were livebirths; the status at 1 month was known for 15,619 (97%) livebirths. 482 neonatal deaths were recorded. Coverage data were available from 6029 women in Newhints zones; of these 4358 (72%) reported having CBSV visits during pregnancy and 3815 (63%) reported having postnatal visits. This coverage increased substantially from June, 2009, after the introduction of new implementation strategies and reached almost 90% for pregnancy visits by the end of the trial and 75% for postnatal visits. The Newhints intervention significantly increased coverage of key essential newborn-care behaviours, except for four or more antenatal-care visits (5975 [76%] of 7859 vs 5988 [74%] of 8121, respectively; relative risk 1·02, 95% CI 0·96-1·09; p=0·52) and baby delivered in a facility (5373 [68%] vs 5539 [68%], respectively; 0·97, 0·81-1·14; p=0·69). The largest increase was for care-seeking, with 102 (77%) of 132 sick babies in Newhints zones taken to a hospital or clinic compared with 77 (55%) of 139 in control zones (1·43, 1·17-1·76; p=0·001). Increases were also noted in bednet use during pregnancy (5398 [69%] of 7859 vs 5135 [63%] of 8121, respectively; 1·12, 1·03-1·21; p=0·005), money saved for delivery or emergency (5730 [86%] of 6681 vs 5525 [80%] of 6941, respectively; 1·09, 1·05-1·12; p<0·0001), transport arranged in advance for facility (2496 [37%] vs 2061 [30%], respectively; 1·30, 1·12-1·49; p=0·0004), birth assistant for home delivery washed hands with soap (1853 [93%] of 1992 vs 1817 [87%] of 2091, respectively; 1·05, 1·02-1·09; p=0·001), initiation of breastfeeding in less than 1 h of birth (3743 [49%] of 7673 vs 3280 [41%] of 7921, respectively; 1·22, 1·07-1·40; p=0·004), skin to skin contact (3355 [44%] vs 1931 [24%], respectively; 2·30, 1·85-2·87; p=0·0002), first bath delayed for longer than 6 h (3131 [41%] vs 2269 [29%], respectively; 1·65, 1·27-2·13; p<0·0001), exclusive breastfeeding for 26-32 days (1217 [86%] of 1414 vs 1091 [80%] of 1371; 1·10, 1·04-1·16; p=0·001), and baby sleeping under bednet for 8-56 days (4548 [79%] of 5756 vs 4291 [73%] of 5846; 1·09, 1·03-1·15; p=0·002). There were 230 neonatal deaths in the Newhints zones compared with 252 in the control zones. The overall NMRs per 1000 livebirths were 29·8 and 31·9, respectively (0·92, 0·75-1·12; p=0·405). INTERPRETATION: The reduction in NMR with Newhints is consistent with the reductions achieved in three trials undertaken in programme settings in south Asia. Because there is no suggestion of any heterogeneity (p=0·850) between these trials and Newhints, the meta-analysis summary estimate of a reduction of 12% (95% CI 5-18) provides the best evidence for the likely effect of the home-visits strategy delivered within programmes in sub-Saharan Africa and in south Asia. Improvements in the quality of delivery and neonatal care in health facilities and development of innovative, effective strategies to increase coverage of home visits on the day of birth could lead to the achievement of more substantial reductions. FUNDING: WHO, Bill & Melinda Gates Foundation, and UK Department for International Development.

NEWHINTS cluster randomised trial to evaluate the impact on neonatal mortality in rural Ghana of routine home visits to provide a package of essential newborn care interventions in the third trimester of pregnancy and the first week of life: trial protocol.

BACKGROUND: Tackling neonatal mortality is essential for the achievement of the child survival millennium development goal. There are just under 4 million neonatal deaths, accounting for 38% of the 10.8 million deaths among children younger than 5 years of age taking place each year; 99% of these occur in low- and middle-income countries where a large proportion of births take place at home, and where postnatal care for mothers and neonates is either not available or is of poor quality. WHO and UNICEF have issued a joint statement calling for governments to implement "Home visits for the newborn child: a strategy to improve survival", following several studies in South Asia which achieved substantial reductions in neonatal mortality through community-based approaches. However, their feasibility and effectiveness have not yet been evaluated in Africa. The Newhints study aims to do this in Ghana and to develop a feasible and sustainable community-based approach to improve newborn care practices, and by so doing improve neonatal survival. METHODS: Newhints is an integrated intervention package based on extensive formative research, and developed in close collaboration with seven District Health Management Teams (DHMTs) in Brong Ahafo Region. The core component is training the existing community based surveillance volunteers (CBSVs) to identify pregnant women and to conduct two home visits during pregnancy and three in the first week of life to address essential care practices, and to assess and refer very low birth weight and sick babies. CBSVs are supported by a set of materials, regular supervisory visits, incentives, sensitisation activities with TBAs, health facility staff and communities, and providing training for essential newborn care in health facilities.Newhints is being evaluated through a cluster randomised controlled trial, and intention to treat analyses. The clusters are 98 supervisory zones; 49 have been randomised for implementation of the Newhints intervention, with the other 49 acting as controls. Data on neonatal mortality and care practices will be collected from approximately 15,000 babies through surveillance of women of child-bearing age in the 7 districts. Detailed process, cost and cost-effectiveness evaluations are also being carried out. TRIAL REGISTRATION: http://www.clinicaltrials.gov (identifier NCT00623337).