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.

Could less be more? Accounting for fractional-dose regimens and different number of vaccine doses when measuring the impact of the RTS, S/AS01E malaria vaccine.

BACKGROUND: The RTS, S/AS01E malaria vaccine (RTS, S) is recommended for children in moderate-to-high Plasmodium falciparum malaria transmission areas. This phase 2b trial (NCT03276962) evaluates RTS, S fractional- and full-dose regimens in Ghana and Kenya. METHODS: 1500 children aged 5-17 months were randomised (1:1:1:1:1) to receive RTS, S or rabies control vaccine. RTS, S groups received two full RTS, S doses at month (M)0/M1 followed by either full (groups R012-20, R012-14-26) or fractional (1/5) doses (groups Fx012-14-26, Fx017-20-32). RESULTS: At M32 post-first dose, vaccine efficacy (VE) against clinical malaria (all episodes) ranged from 38% (R012-20; 95%CI: 24-49) to 53% (R012-14-26; 95%CI: 42-62). Vaccine impact estimates (cumulative number of malaria cases averted/1000 children vaccinated) were 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional- versus full-dose), in a post-hoc analysis, we also estimated cases averted/1000 RTS, S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), 880 (Fx017-20-32). CONCLUSIONS: VE against clinical malaria was similar in all RTS, S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If borne out through trial end (M50), these observations underscore the means to reduce cost per regimen with a goal of maximising impact and optimising supply.

Detection of naturally acquired, strain-transcending antibodies against rosetting Plasmodium falciparum strains in humans.

Strain-transcending antibodies against virulence-associated subsets of P. falciparum-infected erythrocyte surface antigens could protect children from severe malaria. However, the evidence supporting the existence of such antibodies is incomplete and inconsistent. One subset of surface antigens associated with severe malaria, rosette-mediating Plasmodium falciparum Erythrocyte Membrane Protein one (PfEMP1) variants, cause infected erythrocytes to bind to uninfected erythrocytes to form clusters of cells (rosettes) that contribute to microvascular obstruction and pathology. Here, we tested plasma from 80 individuals living in malaria-endemic regions for IgG recognition of the surface of four P. falciparum rosetting strains using flow cytometry. Broadly reactive plasma samples were then used in antibody elution experiments in which intact IgG was eluted from the surface of infected erythrocytes and transferred to heterologous rosetting strains to look for strain-transcending antibodies. We found that seroprevalence (percentage of positive plasma samples) against allopatric rosetting strains was high in adults (63%-93%) but lower in children (13%-48%). Strain-transcending antibodies were present in nine out of eleven eluted antibody experiments, with six of these recognizing multiple heterologous rosetting parasite strains. One eluate had rosette-disrupting activity against heterologous strains, suggesting PfEMP1 as the likely target of the strain-transcending antibodies. Naturally acquired strain-transcending antibodies to rosetting P. falciparum strains in humans have not been directly demonstrated previously. Their existence suggests that such antibodies could play a role in clinical protection and raises the possibility that conserved epitopes recognized by strain-transcending antibodies could be targeted therapeutically by monoclonal antibodies or vaccines.

Malaria.

Malaria is resurging in many African and South American countries, exacerbated by COVID-19-related health service disruption. In 2021, there were an estimated 247 million malaria cases and 619 000 deaths in 84 endemic countries. Plasmodium falciparum strains partly resistant to artemisinins are entrenched in the Greater Mekong region and have emerged in Africa, while Anopheles mosquito vectors continue to evolve physiological and behavioural resistance to insecticides. Elimination of Plasmodium vivax malaria is hindered by impractical and potentially toxic antirelapse regimens. Parasitological diagnosis and treatment with oral or parenteral artemisinin-based therapy is the mainstay of patient management. Timely blood transfusion, renal replacement therapy, and restrictive fluid therapy can improve survival in severe malaria. Rigorous use of intermittent preventive treatment in pregnancy and infancy and seasonal chemoprevention, potentially combined with pre-erythrocytic vaccines endorsed by WHO in 2021 and 2023, can substantially reduce malaria morbidity. Improved surveillance, better access to effective treatment, more labour-efficient vector control, continued drug development, targeted mass drug administration, and sustained political commitment are required to achieve targets for malaria reduction by the end of this decade.

Immediate "Kangaroo Mother Care" and Survival of Infants with Low Birth Weight.

BACKGROUND: "Kangaroo mother care," a type of newborn care involving skin-to-skin contact with the mother or other caregiver, reduces mortality in infants with low birth weight (<2.0 kg) when initiated after stabilization, but the majority of deaths occur before stabilization. The safety and efficacy of kangaroo mother care initiated soon after birth among infants with low birth weight are uncertain. METHODS: We conducted a randomized, controlled trial in five hospitals in Ghana, India, Malawi, Nigeria, and Tanzania involving infants with a birth weight between 1.0 and 1.799 kg who were assigned to receive immediate kangaroo mother care (intervention) or conventional care in an incubator or a radiant warmer until their condition stabilized and kangaroo mother care thereafter (control). The primary outcomes were death in the neonatal period (the first 28 days of life) and in the first 72 hours of life. RESULTS: A total of 3211 infants and their mothers were randomly assigned to the intervention group (1609 infants with their mothers) or the control group (1602 infants with their mothers). The median daily duration of skin-to-skin contact in the neonatal intensive care unit was 16.9 hours (interquartile range, 13.0 to 19.7) in the intervention group and 1.5 hours (interquartile range, 0.3 to 3.3) in the control group. Neonatal death occurred in the first 28 days in 191 infants in the intervention group (12.0%) and in 249 infants in the control group (15.7%) (relative risk of death, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P = 0.001); neonatal death in the first 72 hours of life occurred in 74 infants in the intervention group (4.6%) and in 92 infants in the control group (5.8%) (relative risk of death, 0.77; 95% CI, 0.58 to 1.04; P = 0.09). The trial was stopped early on the recommendation of the data and safety monitoring board owing to the finding of reduced mortality among infants receiving immediate kangaroo mother care. CONCLUSIONS: Among infants with a birth weight between 1.0 and 1.799 kg, those who received immediate kangaroo mother care had lower mortality at 28 days than those who received conventional care with kangaroo mother care initiated after stabilization; the between-group difference favoring immediate kangaroo mother care at 72 hours was not significant. (Funded by the Bill and Melinda Gates Foundation; Australian New Zealand Clinical Trials Registry number, ACTRN12618001880235; Clinical Trials Registry-India number, CTRI/2018/08/015369.).

Mosquito control exposures and breast cancer risk: analysis of 1071 cases and 2096 controls from the Ghana Breast Health Study.

Epidemiologic data on insecticide exposures and breast cancer risk are inconclusive and mostly from high-income countries. Using data from 1071 invasive pathologically confirmed breast cancer cases and 2096 controls from the Ghana Breast Health Study conducted from 2013 to 2015, we investigated associations with mosquito control products to reduce the spread of mosquito-borne diseases, such as malaria. These mosquito control products were insecticide-treated nets, mosquito coils, repellent room sprays, and skin creams for personal protection against mosquitos. Multivariable and polytomous logistic regression models were used to estimate odds ratios (ORadj) and 95% confidence intervals (CI) with breast cancer risk-adjusted for potential confounders and known risk factors. Among controls, the reported use of mosquito control products were mosquito coils (65%), followed by insecticide-treated nets (56%), repellent room sprays (53%), and repellent skin creams (15%). Compared to a referent group of participants unexposed to mosquito control products, there was no significant association between breast cancer risk and mosquito coils. There was an association in breast cancer risk with reported use of insecticide-treated nets; however, that association was weak and not statistically significant. Participants who reported using repellent sprays were at elevated risks compared to women who did not use any mosquito control products, even after adjustment for all other mosquito control products (OR = 1.42, 95% CI=1.15-1.75). We had limited power to detect an association with repellent skin creams. Although only a few participants reported using repellent room sprays weekly/daily or < month-monthly, no trends were evident with increased frequency of use of repellent sprays, and there was no statistical evidence of heterogeneity by estrogen receptor (ER) status (p-het > 0.25). Our analysis was limited when determining if an association existed with repellent skin creams; therefore, we cannot conclude an association. We found limited evidence of risk associations with widely used mosquito coils and insecticide-treated nets, which are reassuring given their importance for malaria prevention. Our findings regarding specific breast cancer risk associations, specifically those observed between repellent sprays, require further study.

Review of the establishment of trauma network of Ghana (TRANET): one-year review and implementation experience in a lower middle-income country.

INTRODUCTION: Globally, injuries account for about 5 million deaths every year out of which 90% occur in low- and middle-income countries. Injuries, particularly trauma, place a lifelong burden on affected individuals, families and society. In Ghana and most African countries particularly in sub-Saharan Africa, there is no effective surveillance system or registry of trauma. Where they exist, they are often poorly developed and incomplete. OBJECTIVE: The study was set out to document long bone fracture injuries which will be used for research, education, policy and public health prevention programmes as well as documenting the experience in setting up trauma registries in a LMIC. METHODS: The study is being conducted at the four Teaching Hospitals in Ghana which are situated in Cape Coast, Kumasi, Accra and Tamale. Persons of any age (from birth) who reports to any of the sentinel sites with an incident of trauma to long bones are eligible for recruitment into the surveillance data collection. Data were captured using the Research Electronic Data Capture (REDCap), cleaned and exported to Stata for analysis. RESULTS: Cumulatively, the sites had enrolled 3493 cases at one year of implementation. A total of 678 (19.41%) paediatric and 2815 (80.59%) adult cases were recorded over the period. In the establishment of the TRANET, we identified challenges in the planning, during data collection, data entry, follow-ups, support from local health authorities, and administrative issues. Quality improvement interventions were put in place, and it resulted in improved data quality. CONCLUSION: The established trauma registry of Ghana is assuring as it offers a timely, accurate, and comprehensive data source which will be useful for continuous monitoring of trauma care in Ghana. This first-year review information/findings will serve as a relevant information for stakeholders working to strengthen the health system.

Measured body size and serum estrogen metabolism in postmenopausal women: the Ghana Breast Health Study.

BACKGROUND: Several anthropometric measures have been associated with hormone-related cancers, and it has been shown that estrogen metabolism in postmenopausal women plays an important role in these relationships. However, little is known about circulating estrogen levels in African women, and the relevance to breast cancer or breast cancer risk factors. To shed further light on the relationship of anthropometric factors and estrogen levels in African women, we examined whether measured body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported body size were associated with serum estrogens/estrogen metabolites in a cross-sectional analysis among postmenopausal population-based controls of the Ghana Breast Health Study. METHODS: Fifteen estrogens/estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry in serum samples collected from postmenopausal female controls enrolled in the Ghana Breast Health Study, a population-based case-control study conducted in Accra and Kumasi. Geometric means (GMs) of estrogens/estrogen metabolites were estimated using linear regression, adjusting for potential confounders. RESULTS: Measured BMI (≥ 30 vs. 18.5-24.9 kg/m2) was positively associated with parent estrogens (multivariable adjusted GM for unconjugated estrone: 78.90 (66.57-93.53) vs. 50.89 (43.47-59.59), p-value < 0.0001; and unconjugated estradiol: 27.83 (21.47-36.07) vs. 13.26 (10.37-16.95), p-value < 0.0001). Independent of unconjugated estradiol, measured BMI was associated with lower levels of 2-pathway metabolites and higher levels of 16-ketoestradriol. Similar patterns of association were found with WHR; however, the associations were not entirely independent of BMI. Height was not associated with postmenopausal estrogens/estrogen metabolite levels in African women. CONCLUSIONS: We observed strong associations between measured BMI and parent estrogens and estrogen metabolite patterns that largely mirrored relations that have previously been associated with higher breast cancer risk in postmenopausal White women. The consistency of the BMI-estrogen metabolism associations in our study with those previously noted among White women suggests that estrogens likely explain part of the BMI-postmenopausal breast cancer risk in both groups. These findings merit evaluation in Black women, including prospective studies.

The oral microbiome and breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in the Ghana Breast Health Study.

The oral microbiome, like the fecal microbiome, may be related to breast cancer risk. Therefore, we investigated whether the oral microbiome was associated with breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in a case-control study in Ghana. A total of 881 women were included (369 breast cancers, 93 nonmalignant cases and 419 population-based controls). The V4 region of the 16S rRNA gene was sequenced from oral and fecal samples. Alpha-diversity (observed amplicon sequence variants [ASVs], Shannon index and Faith's Phylogenetic Diversity) and beta-diversity (Bray-Curtis, Jaccard and weighted and unweighted UniFrac) metrics were computed. MiRKAT and logistic regression models were used to investigate the case-control associations. Oral sample alpha-diversity was inversely associated with breast cancer and nonmalignant breast disease with odds ratios (95% CIs) per every 10 observed ASVs of 0.86 (0.83-0.89) and 0.79 (0.73-0.85), respectively, compared to controls. Beta-diversity was also associated with breast cancer and nonmalignant breast disease compared to controls (P ≤ .001). The relative abundances of Porphyromonas and Fusobacterium were lower for breast cancer cases compared to controls. Alpha-diversity and presence/relative abundance of specific genera from the oral and fecal microbiome were strongly correlated among breast cancer cases, but weakly correlated among controls. Particularly, the relative abundance of oral Porphyromonas was strongly, inversely correlated with fecal Bacteroides among breast cancer cases (r = -.37, P ≤ .001). Many oral microbial metrics were strongly associated with breast cancer and nonmalignant breast disease, and strongly correlated with fecal microbiome among breast cancer cases, but not controls.

Human genetic variant E756del in the ion channel PIEZO1 not associated with protection from severe malaria in a large Ghanaian study.

Recently, a common genetic variant E756del in the human gene PIEZO1 was associated with protection from severe malaria. Here, we performed a genetic association study of this gain-of-function variant in a large case-control study including 4149 children from the Ashanti Region in Ghana, West Africa. The statistical analysis did not indicate an association with protection from severe malaria and, thus, providing evidence against a strong protective effect of the PIEZO1 E756del variant on severe malaria susceptibility.

Associations of fecal microbial profiles with breast cancer and nonmalignant breast disease in the Ghana Breast Health Study.

The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and nonmalignant breast disease in a case-control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population-based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray-Curtis and unweighted/weighted UniFrac distance), and the presence and relative abundance of select taxa with breast cancer and nonmalignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest relative to lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13-0.36; Ptrend < .001). Alpha diversity associations were similar for nonmalignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen-conjugating and immune-related functions were strongly associated with breast cancer (all Ps < .001). There were no statistically significant differences between breast cancer and nonmalignant breast disease cases in any microbiota metric. In conclusion, fecal bacterial characteristics were strongly and similarly associated with breast cancer and nonmalignant breast disease. Our findings provide novel insight into potential microbially-mediated mechanisms of breast disease.

Evaluation of Intussusception after Monovalent Rotavirus Vaccination in Africa.

BACKGROUND: Postlicensure evaluations have identified an association between rotavirus vaccination and intussusception in several high- and middle-income countries. We assessed the association between monovalent human rotavirus vaccine and intussusception in lower-income sub-Saharan African countries. METHODS: Using active surveillance, we enrolled patients from seven countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) who had intussusception that met international (Brighton Collaboration level 1) criteria. Rotavirus vaccination status was confirmed by review of the vaccine card or clinic records. The risk of intussusception within 1 to 7 days and 8 to 21 days after vaccination among infants 28 to 245 days of age was assessed by means of the self-controlled case-series method. RESULTS: Data on 717 infants who had intussusception and confirmed vaccination status were analyzed. One case occurred in the 1 to 7 days after dose 1, and 6 cases occurred in the 8 to 21 days after dose 1. Five cases and 16 cases occurred in the 1 to 7 days and 8 to 21 days, respectively, after dose 2. The risk of intussusception in the 1 to 7 days after dose 1 was not higher than the background risk of intussusception (relative incidence [i.e., the incidence during the risk window vs. all other times], 0.25; 95% confidence interval [CI], <0.001 to 1.16); findings were similar for the 1 to 7 days after dose 2 (relative incidence, 0.76; 95% CI, 0.16 to 1.87). In addition, the risk of intussusception in the 8 to 21 days or 1 to 21 days after either dose was not found to be higher than the background risk. CONCLUSIONS: The risk of intussusception after administration of monovalent human rotavirus vaccine was not higher than the background risk of intussusception in seven lower-income sub-Saharan African countries. (Funded by the GAVI Alliance through the CDC Foundation.).

Decreased Mortality After Establishing a Pediatric Emergency Unit at an Urban Referral Hospital in Ghana.

ABSTRACT: Emergently ill infants and children are often inadequately recognized and stabilized by health care facilities in low- and middle-income countries. Limited reports have shown that process improvements and prioritization of emergency care for children presenting to the hospital can improve pediatric hospital mortality.A dedicated pediatric emergency unit (PEU) was established for nontrauma emergencies at a busy teaching and referral hospital in Kumasi, Ghana, in response to high inpatient mortality early during hospitalization. The PEU was designed to identify and separate critically ill children from more stable children on admission. Locally available hospital resources were reallocated from other areas of the hospital to prioritize staffing and supplies for the PEU.A multiyear data set of nonnewborn inpatient mortality was analyzed with a change point model to find the point at which mortality changed the most within the Department of Child Health or the maximum likelihood estimate. Relative risk of mortality for the periods 1 and 2 years immediately before and after the implementation of the PEU and each individual year compared with its preceding year was analyzed to further establish a temporal correlation of changes in mortality rates to the PEU implementation. Individual years were also analyzed against preimplementation data to establish the durability of mortality improvements.Patient mortality decreased over the analyzed period with the maximum change point strongly associated with implementation of the PEU. Relative risk values of mortality 1 year and 2 years immediately before and after implementation of the PEU were 0.70 (0.62-0.78) and 0.69 (0.64-0.74) respectively, representing a one-third reduction in mortality. The only other mortality improvements seen in the year-to-year analysis were between July 2004-June 2005 compared with July 2005-June 2006 with a relative risk of 0.86 (0.77-0.96).Prioritizing and redirecting limited resources toward pediatric emergency care in low- and middle-income country hospitals is associated with reductions in inpatient mortality that are both immediate and sustained.

Reproductive factors and risk of breast cancer by tumor subtypes among Ghanaian women: A population-based case-control study.

Higher proportions of early-onset and estrogen receptor (ER) negative cancers are observed in women of African ancestry than in women of European ancestry. Differences in risk factor distributions and associations by age at diagnosis and ER status may explain this disparity. We analyzed data from 1,126 cases (aged 18-74 years) with invasive breast cancer and 2,106 controls recruited from a population-based case-control study in Ghana. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for menstrual and reproductive factors using polytomous logistic regression models adjusted for potential confounders. Among controls, medians for age at menarche, parity, age at first birth, and breastfeeding/pregnancy were 15 years, 4 births, 20 years and 18 months, respectively. For women ≥50 years, parity and extended breastfeeding were associated with decreased risks: >5 births vs. nulliparous, OR 0.40 (95% CI 0.20-0.83) and 0.71 (95% CI 0.51-0.98) for ≥19 vs. <13 breastfeeding months/pregnancy, which did not differ by ER. In contrast, for earlier onset cases (<50 years) parity was associated with increased risk for ER-negative tumors (p-heterogeneity by ER = 0.02), which was offset by extended breastfeeding. Similar associations were observed by intrinsic-like subtypes. Less consistent relationships were observed with ages at menarche and first birth. Reproductive risk factor distributions are different from European populations but exhibited etiologic heterogeneity by age at diagnosis and ER status similar to other populations. Differences in reproductive patterns and subtype heterogeneity are consistent with racial disparities in subtype distributions.

Abortion in rural Ghana: Cultural norms, knowledge and attitudes.

Using qualitative methodology, semi-structured questionnaires were administered to participants in the Barakese subdistrict of Ghana in order to understand the extent to which men and women have knowledge of family planning services and in what ways cultural norms, practices, and attitudes toward abortion affect the decision to abort. Women in the community pursue abortion using unsafe methods, despite fear of shame, bleeding, infection, or death, as the perceived cost of maintaining the pregnancy is greater. Protective factors that were reported to dissuade women from pursuing unsafe abortion include fear of social disgrace, divine retribution, and death. Women reported the inability to control the timing of their pregnancies, despite harboring knowledge of family planning. Concerned about perceived side effects of modern family planning methods, respondents chose to use fertility awareness methods or to use no contraception. There remains a gap between knowledge of the benefits of and the actual use of family planning methods, leading to unwanted pregnancy and seeking unsafe abortion. Intensified health promotion and education regarding side effects to combat misconceptions related to contraception, as well as expanding alternative contraceptive options to all regions of Ghana, are critical to improve uptake.

Hospital-based Surveillance for Pediatric Bacterial Meningitis in the Era of the 13-Valent Pneumococcal Conjugate Vaccine in Ghana.

BACKGROUND: Global surveillance for vaccine preventable invasive bacterial diseases has been set up by the World Health Organization to provide disease burden data to support decisions on introducing pneumococcal conjugate vaccine (PCV). We present data from 2010 to 2016 collected at the 2 sentinel sites in Ghana. METHODS: Data were collected from children <5 years of age presenting at the 2 major teaching hospitals with clinical signs of meningitis. Cerebrospinal fluid specimens were collected and tested first at the sentinel site laboratory with conventional microbiology methods and subsequently with molecular analysis, at the World Health Organization Regional Reference Laboratory housed at the Medical Research Council Unit The Gambia, for identification of Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, the 3 most common bacteria causing meningitis. RESULTS: There were 4008 suspected cases of meningitis during the surveillance period, of which 31 (0.8%) were laboratory confirmed. Suspected meningitis cases decreased from 923 in 2010 to 219 in 2016. Of 3817 patients with available outcome data, 226 (5.9%) died. S. pneumoniae was the most common bacterial pathogen, accounting for 68.5% of confirmed cases (50 of 73). H. influenzae and N. meningitidis accounted for 6.8% (5 of 73) and 21.9% (16 of 73), respectively. The proportion of pneumococcal vaccine serotypes causing meningitis decreased from 81.3% (13 of 16) before the introduction of 13-valent PCV (2010-2012) to 40.0% (8 of 20) after its introduction (2013-2016). CONCLUSIONS: Cases of suspected meningitis decreased among children <5 years of age between 2010 and 2016, with declines in the proportion of vaccine-type pneumococcal meningitis after the introduction of 13-valent PCV in Ghana.

Determinants of paying national health insurance premium with mobile phone in Ghana: a cross-sectional prospective study.

INTRODUCTION: In an effort to increase Ghana's National Health Insurance Scheme (NHIS) enrollment and retention rates, the NHIS introduced membership renewal and premium payment by mobile phone. The success of such an innovation dependents on many factors including personal and community characteristics of members. OBJECTIVE: The objective of the study is to investigate the determinants of renewing membership and paying the NHIS premium through a mobile phone. METHODOLOGY: The prospective cross-sectional survey was used to solicit the required information from about 1192 respondents living in Kumasi Metropolis, Atwima Nwabiaya and Sekyere Central Districts of Ghana. Logistic regression model was employed to estimate the determinants of paying the NHIS premium with the mobile phone. RESULTS: The study found that factors including residing in an urban area (Kumasi metropolis), senior high education, tertiary education and informal employees are the determinants of paying the NHIS premium with the mobile phone. CONCLUSION: It is recommended that the NHIS consider making the mobile payment as simple as possible for the less educated and the rural members to access it.

Skin lighteners and hair relaxers as risk factors for breast cancer: results from the Ghana breast health study.

Skin lighteners and hair relaxers, both common among women of African descent, have been suggested as possibly affecting breast cancer risk. In Accra and Kumasi, Ghana, we collected detailed information on usage patterns of both exposures among 1131 invasive breast cancer cases and 2106 population controls. Multivariate analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for breast cancer risk factors. Control usage was 25.8% for ever use of skin lighteners and 90.0% for use of hair relaxers for >1 year. The OR for skin lighteners was 1.10 (95% CI 0.93-1.32), with higher risks for former (1.21, 0.98-1.50) than current (0.96, 0.74-1.24) users. No significant dose-response relations were seen by duration, age at first use or frequency of use. In contrast, an OR of 1.58 (95% CI 1.15-2.18) was associated with use of hair relaxers, with higher risks for former (2.22, 1.56-3.16) than current (1.39, 1.00-1.93) users. Although numbers of burns were inconsistently related to risk, associations increased with duration of use, restricted to women who predominately used non-lye products (P for trend < 0.01). This was most pronounced among women with few children and those with smaller tumors, suggesting a possible role for other unmeasured lifestyle factors. This study does not implicate a substantial role for skin lighteners as breast cancer risk factors, but the findings regarding hair relaxers were less reassuring. The effects of skin lighteners and hair relaxers on breast cancer should continue to be monitored, especially given some biologic plausibility for their affecting risk.

Genome-wide association study indicates two novel resistance loci for severe malaria.

Malaria causes approximately one million fatalities per year, mostly among African children. Although highlighted by the strong protective effect of the sickle-cell trait, the full impact of human genetics on resistance to the disease remains largely unexplored. Genome-wide association (GWA) studies are designed to unravel relevant genetic variants comprehensively; however, in malaria, as in other infectious diseases, these studies have been only partly successful. Here we identify two previously unknown loci associated with severe falciparum malaria in patients and controls from Ghana, West Africa. We applied the GWA approach to the diverse clinical syndromes of severe falciparum malaria, thereby targeting human genetic variants influencing any step in the complex pathogenesis of the disease. One of the loci was identified on chromosome 1q32 within the ATP2B4 gene, which encodes the main calcium pump of erythrocytes, the host cells of the pathogenic stage of malaria parasites. The second was indicated by an intergenic single nucleotide polymorphism on chromosome 16q22.2, possibly linked to a neighbouring gene encoding the tight-junction protein MARVELD3. The protein is expressed on endothelial cells and might therefore have a role in microvascular damage caused by endothelial adherence of parasitized erythrocytes. We also confirmed previous reports on protective effects of the sickle-cell trait and blood group O. Our findings underline the potential of the GWA approach to provide candidates for the development of control measures against infectious diseases in humans.

Design considerations for identifying breast cancer risk factors in a population-based study in Africa.

Although breast cancer is becoming more prevalent in Africa, few epidemiologic studies have been undertaken and appropriate methodologic approaches remain uncertain. We therefore conducted a population-based case-control study in Accra and Kumasi, Ghana, enrolling 2,202 women with lesions suspicious for breast cancer and 2,161 population controls. Biopsy tissue for cases prior to neoadjuvant therapy (if given), blood, saliva and fecal samples were sought for study subjects. Response rates, risk factor prevalences and odds ratios for established breast cancer risk factors were calculated. A total of 54.5% of the recruited cases were diagnosed with malignancies, 36.0% with benign conditions and 9.5% with indeterminate diagnoses. Response rates to interviews were 99.2% in cases and 91.9% in controls, with the vast majority of interviewed subjects providing saliva (97.9% in cases vs. 98.8% in controls) and blood (91.8% vs. 82.5%) samples; lower proportions (58.1% vs. 46.1%) provided fecal samples. While risk factor prevalences were unique as compared to women in other countries (e.g., less education, higher parity), cancer risk factors resembled patterns identified elsewhere (elevated risks associated with higher levels of education, familial histories of breast cancer, low parity and larger body sizes). Subjects with benign conditions were younger and exhibited higher socioeconomic profiles (e.g., higher education and lower parity) than those with malignancies, suggesting selective referral influences. While further defining breast cancer risk factors in Africa, this study showed that successful population-based interdisciplinary studies of cancer in Africa are possible but require close attention to diagnostic referral biases and standardized and documented approaches for high-quality data collection, including biospecimens.