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To investigate potential risk factors for acquisition in seven countries of the meningitis belt.Households were followed up every 2 weeks for 2 months, then monthly for a further 4 months. Pharyngeal swabs were collected from all available household members at each visit and questionnaires completed. Risks of acquisition over the whole study period and for each visit were analysed by a series of logistic regressions.Over the course of the study, acquisition was higher in: (i) 5-to 14-year olds, as compared with those 30 years or older (OR 3.6, 95% CI 1.4-9.9); (ii) smokers (OR 3.6, 95% CI 0.98-13); and (iii) those exposed to wood smoke at home (OR 2.6 95% CI 1.3-5.6). The risk of acquisition from one visit to the next was higher in those reporting a sore throat during the dry season (OR 3.7, 95% CI 2.0-6.7) and lower in those reporting antibiotic use (OR 0.17, 95% CI 0.03-0.56).Acquisition of meningococcal carriage peaked in school age children. Recent symptoms of sore throat during the dry season, but not during the rainy season, were associated with a higher risk of acquisition. Upper respiratory tract infections may be an important driver of epidemics in the meningitis belt.Investiguer les facteurs de risque potentiels d'acquisition dans sept pays de la ceinture de la méningite. MÉTHODES: Des ménages ont été suivis toutes les deux semaines pendant deux mois, puis tous les mois pendant quatre mois. Des prélèvements pharyngés sur écouvillons ont été collectés auprès de tous les membres disponibles du ménage à chaque visite et des questionnaires ont été remplis. Les risques d'acquisition sur l'ensemble de la période d’étude et pour chaque visite ont été analysés par une série de régressions logistiques. RÉSULTATS: Au cours de l’étude, l'acquisition a été plus élevée chez: (i) les 5-14 ans, par rapport à ceux âgés de 30 ans ou plus (OR = 3,6; IC95%: 1,4-9,9); (ii) les fumeurs (OR = 3,6; IC95%: 0,98-13); et (iii) les personnes exposées à la fumée de bois à la maison (OR = 2,6; IC95%: 1,3-5,6). Le risque d'acquisition d'une visite à l'autre était plus élevé chez les personnes signalant un mal de gorge pendant la saison sèche (OR = 3,7; IC95%: 2,0-6,7) et plus faible chez celles signalant une utilisation d'antibiotique (OR = 0,17; IC95%: 0,03-0,56).L'acquisition du portage du méningocoque a culminé chez les enfants d’âge scolaire. Les symptômes récents de maux de gorge pendant la saison sèche, mais pas pendant la saison des pluies, étaient associés à un risque d'acquisition plus élevé. Les infections des voies respiratoires supérieures pourraient être un facteur important d’épidémies dans la ceinture de la méningite.

Background Accurate measurement of anti-malarial drug concentrations in therapeutic efficacy studies is essential to distinguish between inadequate drug exposure and anti-malarial drug resistance, and to inform optimal anti-malarial dosing in key target population groups. Methods A sensitive and selective LC–MS/MS method was developed and validated for the simultaneous determination of amodiaquine and its active metabolite, desethylamodiaquine, and used to describe their pharmacokinetic parameters in Ghanaian patients with uncomplicated falciparum malaria treated with the fixed-dose combination, artesunate-amodiaquine. Results The day-28 genotype-adjusted adequate clinical and parasitological response rate in 308 patients studied was > 97% by both intention-to-treat and per-protocol analysis. After excluding 64 patients with quantifiable amodiaquine concentrations pre-treatment and 17 with too few quantifiable concentrations, the pharmacokinetic analysis included 227 patients (9 infants, 127 aged 1–4 years, 91 aged ≥ 5 years). Increased median day-3 amodiaquine concentrations were associated with a lower risk of treatment failure [HR 0.87 (95% CI 0.78–0.98), p = 0.021]. Amodiaquine exposure (median AUC0-∞) was significantly higher in infants (4201 ng h/mL) and children aged 1–5 years (1994 ng h/mL) compared to older children and adults (875 ng h/mL, p = 0.001), even though infants received a lower mg/kg amodiaquine dose (median 25.3 versus 33.8 mg/kg in older patients). Desethylamodiaquine AUC0-∞ was not significantly associated with age. No significant safety concerns were identified. Conclusions Efficacy of artesunate-amodiaquine at currently recommended dosage regimens was high across all age groups. Reassuringly, amodiaquine and desethylamodiaquine exposure was not reduced in underweight-for-age young children or those with high parasitaemia, two of the most vulnerable target populations. A larger pharmacokinetic study with close monitoring of safety, including full blood counts and liver function tests, is needed to confirm the higher amodiaquine exposure in infants, understand any safety implications and assess whether dose optimization in this vulnerable, understudied population is needed.

Background Studies suggest that diphtheria-tetanus-pertussis (DTP) vaccine administered simultaneously with measles vaccine (MV) or DTP administered after MV are associated with higher child mortality than having MV-after-DTP3 as most recent vaccination. We tested this in Northern Ghana where the prevalence of such out-of-sequence vaccinations has declined. Methods Using annual cohort data of children aged 12–23 months from 1996 to 2012 and Cox proportional hazards models, we assessed survival in relation to the most recent vaccination status within the next 12 months and until five years of age. We assessed whether mortality in children aged 12–59 months was higher when the most recent vaccine was non-live (DTP) rather than live (MV or OPV). Results Out-of-sequence vaccinations with DTP-containing vaccines and MV declined from 86% in 1989 to 24% in 1996 and 0.7% in 2012. Between 1996 and 2012, 38 070 children had their vaccinations status assessed: the adjusted hazard ratio (HR) for out-of-sequence vaccinations (DTP >= MV) compared with the recommended sequence of MV-after-DTP3 was 1.42(1.06–1.90) during the first 12 months after assessment of vaccination status and 1.29(1.03–1.60) with follow-up to five years of age; the HR was 2.58(1.14–5.84) before OPV or MV campaigns and 1.37(1.02–1.85) after the campaigns. Conclusion Out-of-sequence vaccinations with DTP and MV are associated with higher mortality than MV as most recent vaccination; the effect is unlikely to be due to confounding. Hence, the reduction in out-of-sequence vaccinations may have lowered child mortality. It is recommended not to give DTP with MV or DTP after MV.

Neisseria meningitidis is the leading cause of epidemic meningitis in the “meningitis belt” of Africa, where clonal waves of colonization and disease are observed. Point mutations and horizontal gene exchange lead to constant diversification of meningococcal populations during clonal spread. Maintaining a high genomic diversity may be an evolutionary strategy of meningococci that increases chances of fixing occasionally new highly successful “fit genotypes”. We have performed a longitudinal study of meningococcal carriage and disease in northern Ghana by analyzing cerebrospinal fluid samples from all suspected meningitis cases and monitoring carriage of meningococci by twice yearly colonization surveys. In the framework of this study, we observed complete replacement of an A: sequence types (ST)-2859 clone by a W: ST-2881 clone. However, after a gap of 1 year, A: ST-2859 meningococci re-emerged both as colonizer and meningitis causing agent. Our whole genome sequencing analyses compared the A population isolated prior to the W colonization and disease wave with the re-emerging A meningococci. This analysis revealed expansion of one clone differing in only one nonsynonymous SNP from several isolates already present in the original A: ST-2859 population. The colonization bottleneck caused by the competing W meningococci thus resulted in a profound reduction in genomic diversity of the A meningococcal population.

Background: The umbilical cord is a major route of infection among newborns. In Ghana, infections among neonates accounts for majority of under-five deaths. This study sought to investigate what mothers apply to the umbilical cord of their newborns and what motivates them to put such applications on the cord. Methods: This was a descriptive cross-sectional study of neonatal cord care practices among mothers and caregivers in the Nkwanta South District of the Volta region of Ghana. Quantitative and qualitative methods were used. Results: Majority of the mothers/caregivers used substances that have not been recommended for umbilical cord dressing (64.3%). Factors such as level of education [?2=8.2, p=0.02], place of delivery [?2 = 40.1, p

Background: The World Health Organization recommends use of a single yellow fever (YF) vaccine dose for life and fractional doses in outbreaks when there are limited vaccine stocks. In endemic regions, this vaccine is given as part of routine infant immunization programs around 9 months of age. There is a need to better understand immune responses when vaccinating infants particularly in contexts where the child may be malnourished. Methods: Data from 393 Malian and Ghanaian infants who concomitantly received measles and YF vaccines at 9 to 11 months of age were retrospectively analyzed. Response to YF vaccine was examined for association with nutritional status at time of vaccination, sex, age, pre-vaccination titers and season of vaccination. Results: Neutralizing antibodies following vaccination were unaffected by season of vaccination, sex, pre-vaccination titers or nutritional status, though there was a trend to higher titers in males and children with higher height for age z-scores. Seroconversion rates differed significantly between countries (63.5 in Ghana vs. 91.0% in Mali). Conclusion: Longitudinal, prospective studies are needed to optimize the use of YF vaccine in infants in endemic settings. There may be a need for booster vaccinations and to compare various vaccine preparations to optimize the use of available vaccines.

ObjectiveTo examine the association between early Bacille Calmette-Guerin (BCG) vaccination and neonatal mortality in northern Ghana.MethodsThis ecological study used vaccination and mortality data from the Navrongo Health and Demographic Surveillance System. First, we assessed and compared changes in neonatal mortality rates (NMRs) and median BCG vaccination age from 1996 to 2012. Second, we compared the changes in NMR and median BCG vaccination age from 2002 to 2012 by delivery place when data on delivery place were available.ResultsNeonatal mortality rates declined from 46 to 12 per 1000 live births between 1996 and 2012 (trend test: pConclusionThe data support the hypothesis that early BCG vaccination may be associated with a decrease in neonatal mortality. However, as suggested by WHO, randomised control trials are required to address the question of whether there is indeed a causal association between early BCG vaccination and neonatal mortality.

Accurate measurement of anti-malarial drug concentrations in therapeutic efficacy studies is essential to distinguish between inadequate drug exposure and anti-malarial drug resistance, and to inform optimal anti-malarial dosing in key target population groups. A sensitive and selective LC–MS/MS method was developed and validated for the simultaneous determination of amodiaquine and its active metabolite, desethylamodiaquine, and used to describe their pharmacokinetic parameters in Ghanaian patients with uncomplicated falciparum malaria treated with the fixed-dose combination, artesunate-amodiaquine. The day-28 genotype-adjusted adequate clinical and parasitological response rate in 308 patients studied was > 97% by both intention-to-treat and per-protocol analysis. After excluding 64 patients with quantifiable amodiaquine concentrations pre-treatment and 17 with too few quantifiable concentrations, the pharmacokinetic analysis included 227 patients (9 infants, 127 aged 1–4 years, 91 aged ≥ 5 years). Increased median day-3 amodiaquine concentrations were associated with a lower risk of treatment failure [HR 0.87 (95% CI 0.78–0.98), p = 0.021]. Amodiaquine exposure (median AUC0-∞) was significantly higher in infants (4201 ng h/mL) and children aged 1–5 years (1994 ng h/mL) compared to older children and adults (875 ng h/mL, p = 0.001), even though infants received a lower mg/kg amodiaquine dose (median 25.3 versus 33.8 mg/kg in older patients). Desethylamodiaquine AUC0-∞ was not significantly associated with age. No significant safety concerns were identified. Efficacy of artesunate-amodiaquine at currently recommended dosage regimens was high across all age groups. Reassuringly, amodiaquine and desethylamodiaquine exposure was not reduced in underweight-for-age young children or those with high parasitaemia, two of the most vulnerable target populations. A larger pharmacokinetic study with close monitoring of safety, including full blood counts and liver function tests, is needed to confirm the higher amodiaquine exposure in infants, understand any safety implications and assess whether dose optimization in this vulnerable, understudied population is needed.

IntroductionThe continuum of care has recently received attention in maternal, newborn and child health. It can be an effective policy framework to ensure that every woman and child receives timely and appropriate services throughout the continuum. However, a commonly used measurement does not evaluate if a pair of woman and child complies with the continuum of care. This study assessed the continuum of care based on two measurements: continuous visits to health facilities (measurement 1) and receiving key components of services (measurement 2). It also explored individual-level and area-level factors associated with the continuum of care achievement and then investigated how the continuum of care differed across areas.MethodsIn this cross-sectional study in Ghana in 2013, the continuum of care achievement and other characteristics of 1401 pairs of randomly selected women and children were collected. Multilevel logistic regression was used to estimate the factors associated with the continuum of care and its divergence across 22 areas.ResultsThroughout the pregnancy, delivery and post-delivery stages, 7.9% of women and children achieved the continuum of care through continuous visits to health facilities (measurement 1). Meanwhile, 10.3% achieved the continuum of care by receiving all key components of maternal, newborn and child health services (measurement 2). Only 1.8% of them achieved it under both measurements. Women and children from wealthier households were more likely to achieve the continuum of care under both measurements. Women’s education and complications were associated with higher continuum of care services-based achievement. Variance of a random intercept was larger in the continuum of care services-based model than the visit-based model.ConclusionsMost women and children failed to achieve the continuum of care in maternal, newborn and child health. Those who consistently visited health facilities did not necessarily receive key components of services.

Background: Disability and quality of life are key outcomes for older people. Little is known about how these measures vary with age and gender across lower income and middle-income countries; such information is necessary to tailor health and social care policy to promote healthy ageing and minimise disability. Methods: We analysed data from participants aged 50 years and over from health and demographic surveillance system sites of the International Network for the Demographic Evaluation of Populations and their Health Network in Ghana, Kenya, Tanzania, South Africa, Vietnam, India, Indonesia and Bangladesh, using an abbreviated version of the WHO Study on global AGEing survey instrument. We used the eight-item WHO Quality of Life (WHOQoL) tool to measure quality of life and theWHO Disability Assessment Schedule, version 2 (WHODAS-II) tool to measure disability. We collected selected health status measures via the survey instrument and collected demographic and socioeconomic data from linked surveillance site information. We performed regression analyses to quantify differences between countries in the relationship between age, gender and both quality of life and disability, and we used anchoring vignettes to account for differences in interpretation of disability severity. Results: We included 43 935 individuals in the analysis. Mean age was 63.7 years (SD 9.7) and 24 434 (55.6%) were women. In unadjusted analyses across all countries, WHOQoL scores worsened by 0.13 points (95% CI 0.12 to 0.14) per year increase in age and WHODAS scores worsened by 0.60 points (95% CI 0.57 to 0.64). WHODAS-II and WHOQoL scores varied markedly between countries, as did the gradient of scores with increasing age. In regression analyses, differences were not fully explained by age, socioeconomic status, marital status, education or health factors. Differences in disability scores between countries were not explained by differences in anchoring vignette responses. Conclusions: The relationship between age, sex and both disability and quality of life varies between countries. The findings may guide tailoring of interventions to individual country needs, although these associations require further study.

Background. The Meningitis Vaccine Project (MVP) was established to address epidemic meningitis as a public health problem in sub-Saharan Africa and, to that end, worked to develop a group A meningococcal conjugate vaccine, PsA-TT. Methods. Experiences in 4 clinical trial sites are described. Culturally sensitive collaborative strategies were adopted to manage acceptable communication methods, peculiarities with the consent process, participant medical issues, community care, and death. Results. The clinical trials were completed successfully through community acceptance and active community collaboration. The trials also strengthened the capacities in the participating communities, and actively worked to resolve community problems. Conclusions. The understanding and integration of sociocultural realities of communities were major assets in the conduct and acceptance of these trials. MVP succeeded in these sites and provided a sound example for future clinical studies in Africa. Clinical Trials Registration. ISRTCN78147026 (PsA-TT 002); ISRCTN87739946 (PsA-TT 003); ISRCTN82484612 (PsA-TT 004); PACTR ATMR2010030001913177 (PsA-TT 006); and PACTR201110000328305 (PsA-TT 007).

Background. Yellow fever (YF) is still a major public health problem in endemic regions of Africa and South America. In Africa, one of the main control strategies is routine vaccination within the Expanded Programme on Immunization (EPI). A new meningococcal A conjugate vaccine (PsA-TT) is about to be introduced in the EPI of countries in the African meningitis belt, and this study reports on the immunogenicity of the YF-17D vaccines in infants when administered concomitantly with measles vaccine and PsA-TT. Methods. Two clinical studies were conducted in Ghana and in Mali among infants who received PsA-TT concomitantly with measles and YF vaccines at 9 months of age. YF neutralizing antibody titers were measured using a microneutralization assay. Results. In both studies, the PsA-TT did not adversely affect the immune response to the concomitantly administered YF vaccine at the age of 9 months. The magnitude of the immune response was different between the 2 studies, with higher seroconversion and seroprotection rates found in Mali vs Ghana. Conclusions. Immunogenicity to YF vaccine is unaffected when coadministered with PsA-TT at 9 months of age. Further studies are warranted to better understand the determinants of the immune response to YF vaccine in infancy. Clinical Trials Registration. ISRCTN82484612 (PsA-TT-004); PACTR201110000328305 (PsA-TT-007).

Background: Obtaining informed consent is part of the expression of the principle of participant autonomy during clinical trials. It is critical that participants understand the content of informed consent forms and remain in a position to seek independent advice on its content. We conducted a survey among past participants of a clinical trial in the Kassena-Nankana Districts of rural northern Ghana about the usefulness of informed consent forms that are written in the local dialects. The written forms of local dialects are largely undeveloped. Method: We contacted a randomly selected sample of caregivers whose children were enrolled in a completed clinical trial and interviewed them using a structured questionnaire. Analysis sought to determine participants’ preference and whether or not they were likely to find confidants who will be able to read, understand and give advice on the content of the informed consent form to them when they take the informed consent forms home. Results: We interviewed 394 caregivers, 88.6% of whom were women. About half (54%) of the respondents wanted the informed consent forms to be in the English language. Caregivers with higher than primary level education were more likely to prefer the informed consent form to be in English than those with no formal education (74% versus 26%, p = 0.04). The majority (85%) indicated that they would be able to find close confidants who would be able to read and explain it to them if it is in English. In contrast, only 8% thought they would be able to do the same if the informed consent form was written in the local language. Respondents were more likely to find close confidants to read and explain the informed consent form if it were written in English than if it were written in the local language (94% versus 19%, p value Conclusion: The practice of translating informed consent forms into undeveloped local dialects and giving such copies to trial participants to send home needs to be re-evaluated. In populations where the written forms of local dialects are undeveloped and literacy is low, the use of local dialect versions of informed consent forms could ironically enhance the vulnerability of trial participants.

Previous research suggests that care-seeking in rural northern Ghana is often governed by a woman's husband or compound head. This study was designed to explore the role grandmothers (typically a woman's mother-in-law) play in influencing maternal and newborn healthcare decisions. In-depth interviews were conducted with 35 mothers of newborns, 8 traditional birth attendants and local healers, 16 community leaders and 13 healthcare practitioners. An additional 18 focus groups were conducted with stakeholders such as household heads, compound leaders and grandmothers. In this region, grandmothers play many roles. They may act as primary support providers to pregnant mothers, care for newborns following delivery, preserve cultural traditions and serve as repositories of knowledge on local medicine. Grandmothers may also serve as gatekeepers for health-seeking behaviour, especially with regard to their daughters and daughters-in-law. This research also sheds light on the potential gap between health education campaigns that target mothers as autonomous decision-makers, and the reality of a more collectivist community structure in which mothers rarely make such decisions without the support of other community members.

Understanding and acting on the link between weather and meningitis in the Sahel could help improve vaccine distribution and save lives. People living there know that meningitis epidemics occur in the dry season and end after the start of the rainy season. Integrating and analyzing newly available epidemiological and meteorological data quantified this relationship, showing that that the risk of meningitis epidemics climbed from a background level of 2% to a maximum risk of 25% during the dry season. These data also suggested that, of all meteorological variables, relative humidity has the strongest correlation to cases of meningitis. Weather acts alongside a complex set of environmental, social, and economic drivers, and a complementary investigation of local and regional knowledge, attitudes, and practices suggested several additional interventions to manage meningitis. These include improved awareness of early meningitis symptoms and vaccinations for farmworkers who migrate seasonally. An economic survey showed that the cost of a single case of meningitis is 3 times the average annual household income, underscoring the need for improved vaccination strategy. Using these insights, meteorologists and public health workers developed a tool to guide vaccination decisions. Iterative development allowed a multinational team of public health officials to use the tool while guiding its refinement and directed research toward maximum practical use. That meant focusing on predicting areas where high humidity would naturally end epidemics so vaccines could be moved elsewhere. Using this tool and this approach could have prevented an estimated 24,000 cases of meningitis over a 3-yr period.

Background: Measles vaccine (MV) administered as the last vaccine after the third dose of diphtheria-tetanus-pertussis (DTP) may be associated with better child survival unrelated to prevention of measles infection. Other studies have shown that MV administered after DTP was more beneficial and was associated with lower mortality compared with DTP administered after MV or DTP administered simultaneously with MV. We compared the difference in mortality between measles vaccinated after DTP3 and measles-unvaccinated children in Navrongo, Ghana. Methods: This was a follow-up study involving annual cohort of children aged 9-23 months from 1996 to 2012. We assessed survival in relation to the measles vaccination status within the first 12 months from interview date and until 5 years of age using Cox proportional hazards models. Results: In all, 38,333 children were included in the study. The proportion of children vaccinated with MV-after-DTP3 increased from 45% in 1996 to 95% in 2012. The adjusted hazard ratio (HR) for measles unvaccinated compared with MV-after-DTP3 vaccinated children was 1.38 (1.15-1.66) in the first 12 months after assessment of vaccination status and 1.22 (1.05-1.41) with follow-up to 5 years of age. The national immunization days campaigns with oral polio vaccine or MV might have reduced the effect of being MV-after-DTP3 vaccinated vs MV-unvaccinated. For 12 months of follow-up, the HR before a campaign for MV-unvaccinated children was 1.63 (1.23-2.17) compared to those who received MV-after-DTP3. After the campaign, the HR reduced to 1.23 (0.97-1.54). Stratifying the analysis by sex, measles-unvaccinated boys had a HR of 1.69 (1.33-2.61) compared to measles-unvaccinated girls who had a HR 1.06 (0.79-1.40) during 1-year follow-up. In 1989, only 7% of children in the area had received MV-after-DTP3; the increase in MV-after-DTP3 coverage from 1989 to 2012 may have lowered mortality rate among children aged 9 months to 3 years by 24 Conclusion: Though an observational study, our findings suggest that measles vaccination, administered in the recommended sequence, is associated with improved child survival and may have contributed importantly to the mortality decline toward the achievement of Millennium Development Goal 4. Background: Measles vaccine (MV) administered as the last vaccine after the third dose of diphtheria-tetanus-pertussis (DTP) may be associated with better child survival unrelated to prevention of measles infection. Other studies have shown that MV administered after DTP was more beneficial and was associated with lower mortality compared with DTP administered after MV or DTP administered simultaneously with MV. We compared the difference in mortality between measles vaccinated after DTP3 and measles-unvaccinated children in Navrongo, Ghana. Methods: This was a follow-up study involving annual cohort of children aged 9-23 months from 1996 to 2012. We assessed survival in relation to the measles vaccination status within the first 12 months from interview date and until 5 years of age using Cox proportional hazards models. Results: In all, 38,333 children were included in the study. The proportion of children vaccinated with MV-after-DTP3 increased from 45% in 1996 to 95% in 2012. The adjusted hazard ratio (HR) for measles unvaccinated compared with MV-after-DTP3 vaccinated children was 1.38 (1.15-1.66) in the first 12 months after assessment of vaccination status and 1.22 (1.05-1.41) with follow-up to 5 years of age. The national immunization days campaigns with oral polio vaccine or MV might have reduced the effect of being MV-after-DTP3 vaccinated vs MV-unvaccinated. For 12 months of follow-up, the HR before a campaign for MV-unvaccinated children was 1.63 (1.23-2.17) compared to those who received MV-after-DTP3. After the campaign, the HR reduced to 1.23 (0.97-1.54). Stratifying the analysis by sex, measles-unvaccinated boys had a HR of 1.69 (1.33-2.61) compared to measles-unvaccinated girls who had a HR 1.06 (0.79-1.40) during 1-year follow-up. In 1989, only 7% of children in the area had received MV-after-DTP3; the increase in MV-after-DTP3 coverage from 1989 to 2012 may have lowered mortality rate among children aged 9 months to 3 years by 24 Conclusion: Though an observational study, our findings suggest that measles vaccination, administered in the recommended sequence, is associated with improved child survival and may have contributed importantly to the mortality decline toward the achievement of Millennium Development Goal 4.

Background Meningococcal meningitis epidemics are frequent in the Sahel zone of Africa but there is little information on the frequency of long-term sequelae. We analysed excess mortality in the two years following the 1997 epidemic in northern Ghana and carried out a case-control study to assess sequelae in the survivors. Methods Two-year survival of 696 meningitis cases recorded at the War Memorial Hospital, Navrongo, was analysed using data from a demographic surveillance system. A structured questionnaire on disability and on psychiatric, neuropsychological and behavioural problems was administered to 505 of the survivors and 505 age- sex- and location-matched controls as well as to their respective relatives. Cases and controls underwent full neurological and neuropsychological examination and were evaluated for hearing impairment by audiometry. Results Survival rates after the first month following the attack were similar in cases and controls. Hearing impairment was the major sequela, and was reported in 6 per cent of cases and 2 per cent of controls (odds ratio [OR] = 3.10; 95% CI : 1.48-7.09). Audiometry detected severe and profound hearing loss in the worse affected ear (≥70 db) in 8/496 (1.6%) survivors but in only one control. Survivors of meningitis were more likely to suffer from feelings of tiredness (OR = 1.47; 95% CI : 1.03-2.11) and were more often reported by relatives to have insomnia (OR = 2.31; 95% CI : 1.17-4.82) and daily alcohol consumption. Interpretation Meningococcal meningitis annually causes approximately 10 000 cases of deafness in sub-Saharan Africa; there is a need for early detection of affected survivors and promotion of simple hearing devices. There is a sizeable burden of depressive disorders secondary to meningitis which should be identified and looked after appropriately

Countries of the African 'meningitis belt' are susceptible to meningococcal meningitis outbreaks. While in the past major epidemics have been primarily caused by serogroup A meningococci, W strains are currently responsible for most of the cases. After an epidemic in Mecca in 2000, W:ST-11 strains have caused many outbreaks worldwide. An unrelated W:ST-2881 clone was described for the first time in 2002, with the first meningitis cases caused by these bacteria reported in 2003. Here we describe results of a comparative whole-genome analysis of 74 W:ST-2881 strains isolated within the framework of two longitudinal colonization and disease studies conducted in Ghana and Burkina Faso. Genomic data indicate that the W:ST-2881 clone has emerged from Y:ST-175(CC175) bacteria by capsule switching. The circulating W:ST-2881 populations were composed of a variety of closely related but distinct genomic variants with no systematic differences between colonization and disease isolates. Two distinct and geographically clustered phylogenetic clonal variants were identified in Burkina Faso and a third in Ghana. On the basis of the presence or absence of 17 recombination fragments, the Ghanaian variant could be differentiated into five clusters. All 25 Ghanaian disease isolates clustered together with 23 out of 40 Ghanaian isolates associated with carriage within one cluster, indicating that W:ST-2881 clusters differ in virulence. More than half of the genes affected by horizontal gene transfer encoded proteins of the 'cell envelope' and the 'transport/binding protein' categories, which indicates that exchange of non-capsular antigens plays an important role in immune evasion.

Objective To evaluate the impact of a district hospital intervention focused on enhancing healthcare provider capacity to address leading causes of neonatal death: birth asphyxia, infection and prematurity. Methods The neonatal quality improvement initiative was launched at two intervention referral district hospitals in Ghana. Local Health and Demographic Surveillance Systems were enlisted to enhance recording of neonatal and infant deaths in the community and at the facility. After baseline site assessments, a team of local paediatric experts conducted three clinical trainings on-site at each intervention hospital. Assessments were conducted to evaluate participant knowledge before and after participation in training modules. Monthly mentorship visits provided additional training to support the adoption of essential early neonatal care practices. Results In the first year of implementation, the initiative provided focused clinical training to 278 participants. A comparison of pre- and post-training test results demonstrates significant improvement in provider knowledge (73% vs. 89% correct, P

Objective: to explore community and health-care provider attitudes towards maltreatment during delivery in rural northern Ghana, and compare findings against The White Ribbon Alliance's seven fundamental rights of childbearing women. Design: a cross-sectional qualitative study using in-depth interviews and focus groups. Setting: the Kassena-Nankana District of rural northern Ghana between July and October 2010. Participants: 128 community members, including mothers with newborn infants, grandmothers, household heads, compound heads, traditional healers, traditional birth attendants, and community leaders, as well as 13 formally trained health-care providers. Measurements and findings: 7 focus groups and 43 individual interviews were conducted with community members, and 13 individual interviews were conducted with health-care providers. All interviews were transcribed verbatim and entered into NVivo 9.0 for analysis. Despite the majority of respondents reporting positive experiences, unprompted, maltreatment was brought up in 6 of 7 community focus groups, 14 of 43 community interviews, and 8 of 13 interviews with health-care providers. Respondents reported physical abuse, verbal abuse, neglect, and discrimination. One additional category of maltreatment identified was denial of traditional practices. Key conclusions: maltreatment was spontaneously described by all types of interview respondents in this community, suggesting that the problem is not uncommon and may dissuade some women from seeking facility delivery. Implications for practice: provider outreach in rural northern Ghana is necessary to address and correct the problem, ensuring that all women who arrive at a facility receive timely, professional, nonjudgmental, high-quality delivery care.

ObjectiveTo evaluate the effect of a continuum-of-care intervention package on adequate contacts of women and newborn with healthcare providers and their reception of high-quality care.DesignCluster randomised controlled trial.Setting32 subdistricts in 3 rural sites in Ghana.ParticipantsThe baseline survey involved 1480 women who delivered before the trial, and the follow-up survey involved 1490 women who received maternal and newborn care during the trial.InterventionsThe intervention package included training healthcare providers, using an educational and recording tool named ‘continuum-of-care card’, providing the first postnatal care (PNC) by retaining women and newborns at healthcare facility or home visit by healthcare providers.Outcome measuresAdequate contacts were defined as at least four contacts during pregnancy, delivery with assistance of skilled healthcare providers at a healthcare facility and three timely contacts within 6 weeks postpartum. High-quality care was defined as receiving 6 care items for antenatal care (ANC), 3 for peripartum care (PPC) and 14 for PNC.ResultsThe difference-in-difference method was used to assess the effects of the intervention on the study outcome. The percentage of adequate contacts with high-quality care in the intervention group in the follow-up survey and the adjusted difference-in-difference estimators were 12.6% and 2.2 (p=0.61) at ANC, 31.5% and 1.9 (p=0.73) at PPC and 33.7% and 12.3 (p=0.13) at PNC in the intention-to-treat design, whereas 13.0% and 2.8 (p=0.54) at ANC, 34.2% and 2.7 (p=0.66) at PPC and 38.1% and 18.1 (p=0.02) at PNC in the per-protocol design that assigned the study sample by possession of the continuum-of-care card.ConclusionsThe interventions improved contacts with healthcare providers and quality of care during PNC. However, having adequate contact did not guarantee high-quality care. Maternal and newborn care in Ghana needs to improve its continuity and quality.Trial registration numberNCT90618993.

To explore community understanding of perinatal illness in northern Ghana.A cross-sectional descriptive study design.253 community members participated in in-depth interviews and focus group discussions, including women with newborn infants, grandmothers and health care providers. Four overarching themes emerged: (1) Local understanding of illness affects treatment practices. Respondents recognized danger signs of illness spanning antenatal to early neonatal periods. Understanding of causation often had a distinctly local flavor, and thus treatment sometimes differed from mainstream recommendations; (2) Mothers are frequently blamed for their infant's illness; (3) Healthcare decisions regarding infant care are often influenced by community members aside from the infant's mother and (4) Confidence in healthcare providers is issue-specific, and many households use a blended approach to meet their health needs.Despite widespread recognition of danger signs and reported intentions to treat ill infants through the formal health care system, traditional approaches to perinatal illness remain common. Interventions need to be aligned with community perceptions if they are to succeed.

Background: The benefits of integrated control of malaria, schistosomiasis, and soil-transmitted helminth infections have not been fully explored in Ghanaian schoolchildren.Objective: To assess the impact of co-administered artemether-lumefantrine plus albendazole, and artemether-lumefantrine plus albendazole plus praziquantel compared to albendazole plus praziquantel on anaemia, sustained attention, and recall in schoolchildren.Design: This three-arm, open-label intervention study was carried out in Ghana among class three schoolchildren. Artemether-lumefantrine and albendazole were co-administered to 131 schoolchildren in Study Arm 1; artemether-lumefantrine, albendazole, and praziquantel to 90 children in Study Arm 2 versus albendazole and praziquantel to 127 children in Control Arm 3. Medicines were administered to all children at least 30 min after a meal. A HemoCue® photometer was used to measure haemoglobin (Hb), while the code transmission test (CTT), adapted from the Test of Everyday Attention for Children (TEA-Ch), was used to measure sustained attention and recall before-and-after interventions in June 2011 and June 2012.Results: We observed significant malaria parasite prevalence reductions of 62.8 and 59.2% in Study Arm 1 from 24.2 to 9.0%, p0.05). Meanwhile, anaemia prevalence reduced significantly (p

BACKGROUND: Haemoglobin S (HbS) and C (HbC) are variants of the HBB gene which both protect against malaria. It is not clear, however, how these two alleles have evolved in the West African countries where they co-exist at high frequencies. Here we use haplotypic signatures of selection to investigate the evolutionary history of the malaria-protective alleles HbS and HbC in the Kassena-Nankana District (KND) of Ghana. METHODOLOGY/PRINCIPAL FINDINGS: The haplotypic structure of HbS and HbC alleles was investigated, by genotyping 56 SNPs around the HBB locus. We found that, in the KND population, both alleles reside on extended haplotypes (approximately 1.5 Mb for HbS and 650 Kb for HbC) that are significantly less diverse than those of the ancestral HbA allele. The extended haplotypes span a recombination hotspot that is known to exist in this region of the genome SIGNIFICANCE: Our findings show strong support for recent positive selection of both the HbS and HbC alleles and provide insights into how these two alleles have both evolved in the population of northern Ghana.

This paper contributes evidence documenting the continued decline in all-cause mortality and changes in the cause of death distribution over time in four developing country populations in Africa and Asia. We present levels and trends in age-specific mortality (all-cause and cause-specific) from four demographic surveillance sites: Agincourt (South Africa), Navrongo (Ghana) in Africa; Filabavi (Vietnam), Matlab (Bangladesh) in Asia. We model mortality using discrete time event history analysis. This study illustrates how data from INDEPTH Network centers can provide a comparative, longitudinal examination of mortality patterns and the epidemiological transition. Health care systems need to be reconfigured to deal simultaneously with continuing challenges of communicable disease and increasing incidence of non-communicable diseases that require long-term care. In populations with endemic HIV, long-term care of HIV patients on ART will add to the chronic care needs of the community.

Although the past decade has brought global reductions in maternal, infant and child mortality, many low-resource settings have failed to make significant gains relative to their high-income counterparts. In Ghana, nearly 50% of under-five mortality in 2014 could be attributed to deaths during the first 28 days after birth. This article analyses the data across a mixed-methods study of the factors impacting maternal and neonatal care in northern Ghana. The stillbirth and neonatal death study (SANDS) was conducted in 2010 and included both quantitative (N = 20 497) and qualitative data collection (N = 253) to explore the issues associated with the continuum of reproductive health care. Findings were compared against an adaptation of the WHO/UNICEF framework for integrated maternal and newborn care and used to generate concrete recommendations for clinicians, policymakers and programmers across the continuum of care, from pregnancy through delivery and postnatal care. SANDS elucidated epidemiological trends: 40% of neonatal deaths occurred on the first day after birth, and the leading causes of early neonatal mortality were birth asphyxia/injury, infection and complications of prematurity. Qualitative data reflect findings along two axes-community to facility-based care, and pre-pregnancy through the postnatal period. Resulting recommendations include the need to improving clinicians' understanding of and sensitization to local traditional practices, the need for policies to better address quality of care and coordination of training efforts, and the need for comprehensive, integrated programmes that ensure continuity of care from pre-pregnancy through the post-partum period. SANDS illustrates complex medical-social-cultural knowledge, attitudes and practices that span the reproductive period in rural northern Ghana. Data illustrate that not only are the first few days of life critical in infant survival but also there are significant social and cultural barriers to ensuring that mothers and their newborns are cared for in a timely, evidence-based manner.

Fil: Heymann, David L. London School of Hygiene & Tropical Medicine; Reino Unido. The Royal Institute of International Affairs; Reino Unido Fil: Hodgson, Abraham. Ghana Health Service; Ghana Fil: Sall, Amadou Alpha. Senegal Institut Pasteur de Dakar; Senegal Fil: Freedman, David O. University of Alabama at Birmingahm; Estados Unidos Fil: Staples, J Erin. Centers for Disease Control and Prevention; Estados Unidos Fil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Baruah, Kalpana. Ministry of Health and Family Welfare; India Fil: Mahmud, Ghazala. Quaid i Azam University; Pakistán Fil: Kandun, Nyoman. Ministry of Health; Indonesia Fil: Vasconcelos, Pedro F C. Evandro Chagas Institute; Brasil Fil: Bino, Silvia. Institute of Public Health; Albania Fil: Menon, K U. Ministry of Communications and Information; Singapur

The pattern of epidemic meningococcal disease in the African meningitis belt may be influenced by the background level of population immunity but this has been measured infrequently. A standardised enzyme-linked immunosorbent assay (ELISA) for measuring meningococcal serogroup A IgG antibodies was established at five centres within the meningitis belt. Antibody concentrations were then measured in 3930 individuals stratified by age and residence from six countries. Seroprevalence by age was used in a catalytic model to determine the force of infection. Meningococcal serogroup A IgG antibody concentrations were high in each country but showed heterogeneity across the meningitis belt. The geometric mean concentration (GMC) was highest in Ghana (9.09 μg/mL [95% CI 8.29, 9.97]) and lowest in Ethiopia (1.43 μg/mL [95% CI 1.31, 1.57]) on the margins of the belt. The force of infection was lowest in Ethiopia (λ = 0.028). Variables associated with a concentration above the putative protective level of 2 μg/mL were age, urban residence and a history of recent vaccination with a meningococcal vaccine. Prior to vaccination with the serogroup A meningococcal conjugate vaccine, meningococcal serogroup A IgG antibody concentrations were high across the African meningitis belt and yet the region remained susceptible to epidemics.

In particular in the 'meningitis belt' of sub-Saharan Africa, epidemic meningococcal meningitis is a severe public health problem. In the past decades, serogroup A lineages have been the dominant etiologic agents, but also other serogroups have caused outbreaks. A comprehensive vaccine based on subcapsular outer membrane proteins (OMPs) is not available. Here, we have investigated whether meningococcal populations overcome herd immunity by changing antigenic properties of their OMPs. Meningococcal isolates were collected in the context of longitudinal studies in Ghana between 2002 and 2008 and in Burkina Faso between 2006 and 2007. Serogroup A strains isolated during two clonal waves of colonization and disease showed no diversification in the genes encoding their PorA, PorB, and FetA proteins. However, we detected occasional allelic exchange of opa genes, as well as wide variation in the number of intragenic tandem repeats, showing that phase variation of Opa protein expression is a frequent event. Altogether we observed a remarkable antigenic stability of the PorA, PorB and FetA proteins over years. Our results indicate that while herd immunity may be responsible for the disappearance of meningococcal clones over time, it is not a strong driving force for antigenic diversification of the major OMPs analyzed here.

Bacterial (meningococcal) meningitis is a devastating infectious disease with outbreaks occurring annually during the dry season in locations within the ‘Meningitis Belt’, a region in sub-Saharan Africa stretching from Ethiopia to Senegal. Meningococcal meningitis occurs from December to May in the Sahel with large epidemics every 5–10 years and attack rates of up to 1000 infections per 100,000 people. High temperatures coupled with low humidity may favor the conversion of carriage to disease as the meningococcal bacteria in the nose and throat are better able to cross the mucosal membranes into the blood stream. Similarly, respiratory diseases such as influenza and pneumonia might weaken the immune defenses and add to the mucosa damage. Although the transmission dynamics are poorly understood, outbreaks regularly end with the onset of the rainy season and may begin anew with the following dry season. In this paper, we employ a generalized additive modeling approach to assess the association between number of reported meningitis cases and a set of weather variables (relative humidity, rain, wind, sunshine, maximum and minimum temperature). The association is adjusted for air quality (dust, carbon monoxide), as well as varying degrees of unobserved time-varying confounding processes that co-vary with both the disease incidence and weather. We present the analysis of monthly reported meningitis counts in Navrongo, Ghana, from 1998–2008.

Summary Objectives To compare (i) side effects associated with the simultaneous adminstration of praziquantel, albendazole and ivermectin with side affects associated with albendazole and ivermectin only and (ii) coverage by volunteers distributing three or two drugs. Methods Two-arm comparative study in northern Ghana integrated praziquantel distribution into an existing lymphatic filariasis and onchocerciasis control programme using Community Directed Distributors. The control arm continued to distribute only ivermectin and albendazole. Dosages of ivermectin and praziquantel were based on height. Treatment was directly observed, and all two/three drugs were co-administered. Adverse effects were recorded based on passive surveillance. Parasitological, anthropometric and haematological data were collected at baseline. Results Prevalence of Schistosoma haematobium infection among 1001 (boys: 47.9% girls: 52.1%) school-age children (6–15 years) [intervention: 30.0% (CI: 23.1–34.2); control: 23.0% (CI: 18.9–27.0)], mean haemoglobin, weight and age were similar among the intervention and control groups. While 1676 (99.1%) compounds in the control area were visited and 15 020 (96.58%) people were treated, only 1375 (88.5%) compounds in the intervention area were visited and 8454 (80.97%) people treated (P

Summary Background Rotavirus vaccine has proved effective for prevention of severe rotavirus gastroenteritis in infants in developed countries, but no efficacy studies have been done in developing countries in Asia. We assessed the clinical efficacy of live oral pentavalent rotavirus vaccine for prevention of severe rotavirus gastroenteritis in infants in Bangladesh and Vietnam. Methods In this multicentre, double-blind, placebo-controlled trial, undertaken in rural Matlab, Bangladesh, and urban and periurban Nha Trang, Vietnam, infants aged 4–12 weeks without symptoms of gastrointestinal disorders were randomly assigned (1:1) to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age, in conjunction with routine infant vaccines including oral poliovirus vaccine. Randomisation was done by computer-generated randomisation sequence in blocks of six. Episodes of gastroenteritis in infants who presented to study medical facilities were reported by clinical staff and from parent recollection. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score ≥11) arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648. Findings 2036 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=1018) or placebo (n=1018). 991 infants assigned to pentavalent rotavirus vaccine and 978 assigned to placebo were included in the per-protocol analysis. Median follow up from 14 days after the third dose of placebo or vaccine until final disposition was 498 days (IQR 480–575). 38 cases of severe rotavirus gastroenteritis (Vesikari score ≥11) were reported during more than 1197 person-years of follow up in the vaccine group, compared with 71 cases in more than 1156 person years in the placebo group, resulting in a vaccine efficacy of 48·3% (95% CI 22·3–66·1) against severe disease (p=0·0005 for efficacy >0%) during nearly 2 years of follow-up. 25 (2·5%) of 1017 infants assigned to receive vaccine and 20 (2·0%) of 1018 assigned to receive placebo had a serious adverse event within 14 days of any dose. The most frequent serious adverse event was pneumonia (vaccine 12 [1·2%]; placebo 15 [1·5%]). Interpretation In infants in developing countries in Asia, pentavalent rotavirus vaccine is safe and efficacious against severe rotavirus gastroenteritis, and our results support expanded WHO recommendations to promote its global use. Funding PATH (GAVI Alliance grant) and Merck.

In the Kassena-Nankana District of Ghana, researchers and health interventionists describe a phenomenon wherein some children are subject to infanticide because they are regarded as spirit children sent "from the bush" to cause misfortune and destroy the family. This phenomenon remains largely misunderstood and misrepresented. Based upon both ethnographic research and verbal autopsy data from 2006 to 2007 and 2009, this paper clarifies the characteristics of and circumstances surrounding the spirit child phenomenon, the role it plays within community understandings of childhood illness and mortality, and the variations present within the discourse and practice. The spirit child is a complex explanatory model closely connected to the Nankani sociocultural world and understandings surrounding causes of illness, disability, and misfortune, and is best understood within the context of the larger economic, social, and health concerns within the region. The identification of a child as a spirit child does not necessarily indicate that the child was a victim of infanticide. The spirit child best describes why a child died, rather than how the death occurred. In addition to shaping maternal and child health interventions, these findings have implications for verbal autopsy assessments and the accuracy of demographic data concerning the causes of child mortality.

Several associations between specific HLA alleles and susceptibility or resistance to Plasmodium falciparum malaria have been previously reported, but no associations have been confirmed in multiple populations. We studied associations between HLA-A, -B, and DRB1 alleles and severe malaria in northern Ghana. We analyzed HLA-DRB1*04 in 4,032 subjects from a severe malaria case-control study, 790 severe malaria cases, 1,611 mild malaria controls, and 1631 asymptomatic controls. The presence of HLA-DRB1*04 was associated with severe malaria (OR = 2.42, 95% CI = 1.64, 3.58). The allele frequency of DRB1*04 was similar in the two major ethnic groups in the study population, Kassem (4.4%) and Nankam (4.7%), and the OR for the association between DRB1*04 and severe malaria was similar in both ethnic groups. These findings are consistent with results from Gabon suggesting that DRB1*04 is a risk factor for severe malaria.

OBJECTIVES: To assess the factors associated with the use of health professionals for delivery following the implementation of a free obstetric care policy in the poorest regions of Ghana. METHODS: All 4,070 women identified in the Navrongo demographic surveillance system with pregnancy outcomes in the Kassena-Nankana district between January 1 and December 31, 2004 were eligible for the study. Three thousand four hundred and thirty three women completed interviews on socio-demographic and pregnancy related factors. Information on 259 communities including travel distance to the nearest health facility was also obtained. Multilevel logistic regression analyses were conducted. RESULTS: ninety eight percent of women received antenatal care but only 38% delivered with the assistance of health professionals. In a multilevel logistic model, physical access factors {such as availability of public transport, odds ratio (OR) = 1.50 (1.15-1.94), travel distance to the district hospital [for 20+ km, OR = 0.31 (0.23-0.43)] as well as community perception of access to the nearest health facility [for highest quintile, OR = 4.44 (2.88-6.84)]} showed statistically significant associations with use of health professionals at last delivery. Women who knew that delivery care was free of charge were 4.6 times more likely to use health professionals. Higher parity was strongly negatively associated with use of health professionals [OR = 0.37 (0.29-0.48) for parity > or = 4 compared to parity 0-1]. However, community perception of quality of care was not associated with use of health professionals for delivery. CONCLUSION: Physical access factors remain strong determinants of use of professional delivery care in rural northern Ghana.

The immunogenicity and safety of a meningococcal trivalent A/C/W135 polysaccharide vaccine was compared with that of a tetravalent A/C/Y/W135 polysaccharide vaccine in a randomised, double blind trial. The study included 360 adults, who received either a trivalent or tetravalent polysaccharide meningococcal vaccine. Antibody responses were determined by serum bactericidal antibody (rSBA) assays prior to vaccination and on day 28 and month 11 after vaccination. The percentage of participants in the trivalent vaccine group who had rSBA titres >or=8 on day 28 post-vaccination against serogroups A, C and W135 meningococci were 99, 98 and 91%, respectively. The corresponding figures in the tetravalent vaccine group were 99, 99 and 90%. The percentage of participants with various cut off levels of rSBA against serogroups A, W135 and C meningococci on day 28 and 11-month post-vaccination and the incidence of adverse events did not differ significantly between the two groups.

The objective was to determine the impact of deploying nurses and volunteers to village locations on demographic and health outcomes. We implemented an experimental design that emphasizes the value of aligning community health services with traditional social institutions that organize village life. Data for this analysis come from the Navrongo demographic surveillance system a longitudinal database that tracks fertility mortality and migration events over time. The experiment uses conventional demographic methods for estimating mortality rates from longitudinal demographic surveillance registers. Posting nurses to community locations reduced childhood mortality rates by over half in 3 years and accelerated attainment of the childhood-survival millennium development goal (MDG) in the study areas relative to trends observed in comparison areas. Results from the Navrongo experiment demonstrate that community health and family planning programmes can have an impact on childhood mortality. Posting nurses to communities can dramatically accelerate the pace of progress in achieving the childhood-survival MDGs. Community-volunteer approaches however have no additional impact a finding that challenges the child survival value of international investment in volunteer-based health programmes. The total cost of the intensive arm of the project is less than $10 per capita per year. Navrongo research thus demonstrates affordable means of attaining the child survival MDG agenda with existing technologies. (authors)

SummaryAccess to voluntary counselling and HIV testing (VCT) remains limited in most parts of Ghana with rural populations being the least served. Services remain facility-based and employ the use of an ever-dwindling number of health workers as counsellors. This study assessed approval for the use of lay counsellors to promote community-based voluntary counselling and testing for HIV and the extent of HIV/AIDS-related stigma in the Kassena-Nankana district of rural northern Ghana. A cross-sectional questionnaire survey was conducted. Logistic regression was used to identify predictors of the tendency to stigmatize people living with HIV/AIDS (PLWHAs). Focus group discussions were held and analytical coding of the data performed. The majority (91·1%) of the 403 respondents indicated a desire to know their HIV status. Most (88·1%) respondents considered locations outside of the health facility as preferred places for VCT. The majority (98·7%) of respondents approved the use of lay counsellors. About a quarter (24%) of respondents believed that it was possible to acquire HIV through sharing a drinking cup with a PLWHA. About half (52·1%) of the respondents considered that a teacher with HIV/AIDS should not be allowed to teach, while 77·2% would not buy vegetables from a PLWHA. Respondents who believed that sharing a drinking cup with a PLWHA could transmit HIV infection (OR 2·50, 95%CI 1·52–4·11) and respondents without formal education (OR 2·94, 95%CI 1·38–6·27) were more likely to stigmatize PLWHAs. In contrast, respondents with knowledge of the availability of antiretroviral (ARV) drugs were less likely to do so (OR 0·40, 95%CI 0·22–0·73). Findings from the thirteen focus group discussions reinforced approval for community-based VCT and lay counsellors but revealed concerns about stigma and confidentiality. In conclusion, community-based VCT and the use of lay counsellors may be acceptable options for promoting access. Interventional studies are required to assess feasibility and cost-effectiveness.

Background. The group A meningococcal vaccine (PsA-TT) clinical development plan included clinical trials in India and in the West African region between 2005 and 2013. During this period, the Meningitis Vaccine Project (MVP) accumulated substantial experience in the ethical conduct of research to the highest standards. Methods. Because of the public–private nature of the sponsorship of these trials and the extensive international collaboration with partners from a diverse setting of countries, the ethical review process was complex and required strategic, timely, and attentive communication to ensure the smooth review and approval for the clinical studies. Investigators and their site teams fostered strong community relationships prior to, during, and after the studies to ensure the involvement and the ownership of the research by the participating populations. As the clinical work proceeded, investigators and sponsors responded to specific questions of informed consent, pregnancy testing, healthcare, disease prevention, and posttrial access. Results. Key factors that led to success included (1) constant dialogue between partners to explore and answer all ethical questions; (2) alertness and preparedness for emerging ethical questions during the research and in the context of evolving international ethics standards; and (3) care to assure that approaches were acceptable in the diverse community contexts. Conclusions. Many of the ethical issues encountered during the PsA-TT clinical development are familiar to groups conducting field trials in different cultural settings. The successful approaches used by the MVP clinical team offer useful examples of how these problems were resolved. Clinical Trials Registration. ISRCTN17662153 (PsA-TT-001); ISRTCN78147026 (PsA-TT-002); ISRCTN87739946 (PsA-TT-003); ISRCTN46335400 (PsA-TT-003a); ISRCTN82484612 (PsA-TT-004); CTRI/2009/091/000368 (PsA-TT-005); PACTR ATMR2010030001913177 (PsA-TT-006); PACTR201110000328305 (PsA-TT-007).

Background Health worker shortage in rural areas is one of the biggest problems of the health sector in Ghana and many developing countries. This may be due to fewer incentives and support systems available to attract and retain health workers at the rural level. This study explored the willingness of community health officers (CHOs) to accept and hold rural and community job postings in Ghana. Methods A discrete choice experiment was used to estimate the motivation and incentive preferences of CHOs in Ghana. All CHOs working in three Health and Demographic Surveillance System sites in Ghana, 200 in total, were interviewed between December 2012 and January 2013. Respondents were asked to choose from choice sets of job preferences. Four mixed logit models were used for the estimation. The first model considered (a) only the main effect. The other models included interaction terms for (b) gender, (c) number of children under 5 in the household, and (d) years worked at the same community. Moreover, a choice probability simulation was performed. Results Mixed logit analyses of the data project a shorter time frame before study leave as the most important motivation for most CHOs (β 2.03; 95 % CI 1.69 to 2.36). This is also confirmed by the largest simulated choice probability (29.1 %). The interaction effect of the number of children was significant for education allowance for children (β 0.58; 95 % CI 0.24 to 0.93), salary increase (β 0.35; 95 % CI 0.03 to 0.67), and housing provision (β 0.16; 95 % CI −0.02 to 0.60). Male CHOs had a high affinity for early opportunity to go on study leave (β 0.78; 95 % CI −0.06 to 1.62). CHOs who had worked at the same place for a long time greatly valued salary increase (β 0.28; 95 % CI 0.09 to 0.47). Conclusions To reduce health worker shortage in rural settings, policymakers could provide “needs-specific” motivational packages. They should include career development opportunities such as shorter period of work before study leave and financial policy in the form of salary increase to recruit and retain them.

Background While many Ghanaian adolescents encounter sexual and reproductive health problems, their usage of services remains low. A social learning intervention, incorporating environment, motivation, education, and self-efficacy to change behaviour, was implemented in a low-income district of northern Ghana to increase adolescent services usage. This study aimed to assess the impact of this intervention on usage of sexual and reproductive health services by young people. Methods Twenty-six communities were randomly allocated to (i) an intervention consisting of school-based curriculum, out-of-school outreach, community mobilisation, and health-worker training in youth-friendly health services, or (ii) comparison consisting of community mobilisation and youth-friendly health services training only. Outcome measures were usage of sexually-transmitted infections (STIs) management, HIV counselling and testing, antenatal care or perinatal services in the past year and reported service satisfaction. Data was collected, at baseline and three years after, from a cohort of 2,664 adolescents aged 15–17 at baseline. Results Exposure was associated with over twice the odds of using STI services (AOR 2.47; 95%CI 1.78–3.42), 89% greater odds of using perinatal services (AOR 1.89; 95%CI 1.37–2.60) and 56% greater odds of using antenatal services (AOR 1.56; 95%CI 1.10–2.20) among participants in intervention versus comparison communities, after adjustment for baseline differences. Conclusions The addition of targeted school-based and outreach activities increased service usage by young people more than community mobilisation and training providers in youth-friendly services provision alone.

Background Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. Methods and Findings Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. Conclusions There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger study is required to confirm consistency of findings.

Summary objectives To describe the trend and causes of neonatal deaths in a rural district in northern Ghana.methods Descriptive analysis of data collected from the Navrongo Demographic Surveillance Systemand verbal autopsies conducted on all neonatal deaths from 1995–2002.results Of 1118 recorded neonatal deaths 1068 (95.5%) could be analysed. Only 13.2% of deathsoccurred at the health facility; 62.7% occurred in the early neonatal period, with prematurity (38%) andbirth injuries (19%) as leading causes. Infectious causes (66%) were the major contributors to lateneonatal deaths. Infanticide accounted for 4.9% of all neonatal deaths. The cause-specific mortality ratefor neonatal tetanus remained under 2.5% throughout the 8-year period. Overall, the neonatal mortalityrate declined at an average of 2.5 per 1000 live births per year: Down by nearly 50% from 40.9(95%C.I. 34.1–46.8) in 1995 to 20.5 (95%C.I.17.3–22.7) in 2002.conclusion The various health interventions undertaken in this district have had the collateral effectof causing decline in neonatal mortality. Neonatal mortality could be further reduced by preventing andtreating neonatal infections, having skilled attendance at delivery and the elimination of infanticide.Data from demographic surveillance sites may be useful in monitoring trends in child mortality.keywords neonatal, mortality, demographic, surveillance, Kassena–Nankana, GhanaIntroductionAchieving the millennium development goal of reducingunder-five mortality by two-thirds between 1990 and 2015would only be possible through significant reduction inneonatal deaths in sub-Saharan Africa. Four millionchildren die within the first 28 days of life, and almost two-thirds die in the first week. Neonatal deaths in sub-SaharanAfrica account for approximately one quarter of all deathsin children aged 1–3 months (Lawn et al. 2005; Zupan A Child Health Research Project 1999;Yu 2003; Lawn et al. 2005). The result of this tragic stateof affairs is a near absence of interventions specificallyaimed at reducing neonatal mortality. So acute is theproblem that many agencies do not mention any causes ofneonatal death on the list of major ‘child killers’. Bymaking available the epidemiological information regard-ing the time, place and causes of neonatal deaths, it ishoped that greater visibility will be given to neonataldeaths in policies and programme planning (Lawn et al.2004).Vital registrations systems in the developing world areunlikely to see dramatic improvements in the near future.The verbal autopsy (VA) technique, which involves ques-tioning the family of a dead infant about the features of thechild’s final illness and supplementing this account withany clinic or hospital records that are available providesthe only means of obtaining information on the cause ofdeath (COD) (Snow et al. 1992; Taylor 1992; Greenwood2003). VA continues to be used extensively in large-scaledemographic and health surveys, community-based sur-veillance and community intervention trials. Most sitesthat maintain demographic surveillance system (DSSs)routinely conduct VA. By definition they also routinelycollect data on vital events such as pregnancies, deliveriesand deaths. Potentially therefore, these sites could provide

Reported efficacies from vaccine trials may depend heavily on the clinical case definition used in the trial. The dependence may be particularly striking for diseases such as malaria, in which no single case definition is appropriate. We used logistic regression modeling of the relationship between parasitemia and fever in data sets from Ghanaian children to determine the fraction of fevers attributable to malaria and to model how the choice of a threshold parasitemia in the clinical case definition affects the measured efficacy of malaria vaccines. Calculated clinical attack rates varied 10-fold as a function of the threshold parasitemia. Strikingly, measured vaccine efficacies in reducing clinical malaria depended heavily on the threshold parasitemia, varying between 20% and 80% as the threshold varied between 1 and 5000 parasites/ microL. We suggest that clinical case definitions of malaria that incorporate a threshold parasitemia are arbitrary and do not yield stable estimates of vaccine trial end points.

Background Cooking over open fires using solid fuels is both common practice throughout much of the world and widely recognized to contribute to human health, environmental, and social problems. The public health burden of household air pollution includes an estimated four million premature deaths each year. To be effective and generate useful insight into potential solutions, cookstove intervention studies must select cooking technologies that are appropriate for local socioeconomic conditions and cooking culture, and include interdisciplinary measurement strategies along a continuum of outcomes. Methods/Design REACCTING (Research on Emissions, Air quality, Climate, and Cooking Technologies in Northern Ghana) is an ongoing interdisciplinary randomized cookstove intervention study in the Kassena-Nankana District of Northern Ghana. The study tests two types of biomass burning stoves that have the potential to meet local cooking needs and represent different “rungs” in the cookstove technology ladder: a locally-made low-tech rocket stove and the imported, highly efficient Philips gasifier stove. Intervention households were randomized into four different groups, three of which received different combinations of two improved stoves, while the fourth group serves as a control for the duration of the study. Diverse measurements assess different points along the causal chain linking the intervention to final outcomes of interest. We assess stove use and cooking behavior, cooking emissions, household air pollution and personal exposure, health burden, and local to regional air quality. Integrated analysis and modeling will tackle a range of interdisciplinary science questions, including examining ambient exposures among the regional population, assessing how those exposures might change with different technologies and behaviors, and estimating the comparative impact of local behavior and technological changes versus regional climate variability and change on local air quality and health outcomes. Discussion REACCTING is well-poised to generate useful data on the impact of a cookstove intervention on a wide range of outcomes. By comparing different technologies side by side and employing an interdisciplinary approach to study this issue from multiple perspectives, this study may help to inform future efforts to improve health and quality of life for populations currently relying on open fires for their cooking needs.

Improving community members' knowledge of obstetric danger signs is one strategy for increasing the use of skilled care during pregnancy and the puerperium. This study explored knowledge of obstetric danger signs among a range of community members, examined the sources of their information, and the perceived factors that affect health seeking behaviour in rural northern Ghana. We conducted 72 in-depth interviews and 18 focus groups with community members. All interactions were audio taped, transcribed verbatim and analysed using NVivo 9.0. Community members demonstrated knowledge of a wide range of obstetric danger signs, including excessive bleeding, stomach aches, waist pains, vomiting and fever. Pregnant women learn about danger signs from a range of providers, and regular contact with formal providers typically coincided with increased knowledge of danger signs. Traditional remedies for problems in obstetrics are plentiful and cultural beliefs often restrict the use of allopathic medicine. Increasing knowledge of obstetric danger signs is necessary but not sufficient to overcome cultural preferences for traditional treatments for pregnancy danger signs.

Neisseria meningitidis serogroup W135, well known for a long time as a cause of isolated cases of meningococcal meningitis, has recently increasingly been associated with disease outbreaks of considerable magnitude. Burkina Faso was hit by W135 epidemics in the dry seasons of 2002-2004, but only four W135 meningitis cases were recorded between February 2003 and March 2004 in adjoining Ghana. This reconfirms previous findings that bottlenecks exist in the spreading of new epidemic N. meningitidis clones within the meningitis belt of sub-Saharan Africa. Of the four Ghanaian W135 meningitis patients one died and three survived, of whom one had profound neurosensory hearing loss and speech impairment. All four disease isolates were sensitive to penicillin G, chloramphenicol, ciprofloxacin and cefotaxime and had the multi-locus sequence type (ST) 11, which is the major ST of the ET-37 clonal complex. Pulsed-field gel electrophoresis (PFGE) profiles of the Ghanaian disease isolates and recent epidemic isolates from Burkina Faso were largely identical. We conducted meningococcal colonization surveys in the home communities of three of the patients and in the Kassena Nankana District located at the border to Burkina Faso. W135 carriage rates ranged between 0% and 17.5%. When three consecutive surveys were conducted in the patient community with the highest carrier rate, persistence of W135 colonization over a period of 1 year was observed. Differences in PFGE profiles of carrier isolates taken at different times in the same patient community were indicative of rapid microevolution of the W135 bacteria, emphasizing the need for innovative fine typing methods to reveal the relationship between W135 isolates.

The Kassena-Nankana District (KND) of northern Ghana lies in the African meningitis belt, where epidemics of bacterial meningitis have been reoccurring every 8-12 years. These epidemics are generally caused by Neisseria meningitidis, an organism that is considered to be uniquely capable of causing meningitis epidemics.; We recruited all patients with suspected meningitis in the KND between 1998 and 2003. Cerebrospinal fluid samples were collected and analyzed by standard microbiological techniques. Bacterial isolates were subjected to serotyping, multilocus sequence typing (MLST), and antibiotic-resistance testing.; A continual increase in the incidence of pneumococcal meningitis was observed from 2000 to 2003. This outbreak exhibited strong seasonality, a broad host age range, and clonal dominance, all of which are characteristic of meningococcal meningitis epidemics in the African meningitis belt. The case-fatality rate for pneumococcal meningitis was 44.4%; the majority of pneumococcal isolates were antibiotic sensitive and expressed the serotype 1 capsule. MLST revealed that these isolates belonged to a clonal complex dominated by sequence type (ST) 217 and its 2 single-locus variants, ST303 and ST612.; The S. pneumoniae ST217 clonal complex represents a hypervirulent lineage with a high propensity to cause meningitis, and our results suggest that this lineage might have the potential to cause an epidemic. Serotype 1 is not included in the currently licensed pediatric heptavalent pneumococcal vaccine. Mass vaccination with a less complex conjugate vaccine that targets hypervirulent serotypes should, therefore, be considered.

We conducted all-age point prevalence surveys to profile the severity and seasonality of malaria and anaemia in Kassena-Nankana District of northern Ghana. Random cross-sectional surveys were timed to coincide with the end of low (May 2001) and high (November 2001) malaria transmission seasons and to yield information as to the potential value of haemoglobin (Hb) levels and parasitaemia as markers of malaria morbidity and/or malaria vaccine effect. Parasitaemia was found in 22% (515 of 2286) screened in May (dry-low transmission), and in 61% of the general population (1026 of 1676) screened in November (wet-high transmission). Malaria prevalence in May ranged from 4% (infants

Although many cross-sectional social surveys have included questions about female genital cutting status and correlated personal characteristics, no longitudinal studies have been launched that permit investigation of response biases associated with such surveys. This study draws upon the findings of a longitudinal study of women aged 15 to 49 in rural northern Ghana. The self-reported circumcision status of women interviewed in 1995 was compared with the status they reported when they were interviewed again in 2000 after the government began enforcing a law banning the practice and public information campaigns against it were launched. In all, 13 percent of respondents who reported in 1995 that they had been circumcised stated that they had not been circumcised in the 2000 reinterview; this inconsistency reached 50 percent for the youngest age group. Analysis shows that women who said they had not been circumcised are significantly younger, more likely to be educated, and less likely to practice traditional religion than are women who reported that they were circumcised. Factors that may explain these correlates of denial are discussed, and implications for research are reviewed.