Estimating malaria parasite density: assumed white blood cell count of 10,000/μl of blood is appropriate measure in Central Ghana.

BACKGROUND: White blood cells count (WBCc) is a bedrock in the estimation of malaria parasite density in malaria field trials, interventions and patient management. White blood cells are indirectly and relatively used in microscopy to estimate the density of malaria parasite infections. Due to frequent lack of facilities in some malaria-endemic countries, in order to quantify WBCc of patients, an assumed WBCc of 8.0 X 10(9)/L has been set by the World Health Organization to help in estimating malaria parasite densities. METHODS: This comparative analysis study, in Central Ghana, compiled laboratory data of 5,902 Plasmodium falciparum malaria parasite positive samples. Samples were obtained from consented participants of age groups less than five years. Full blood counts (FBC) of participants' samples were analysed using the ABX Micros 60 Haematology Analyzer. Blood slides were read by two competent microscopists to produce concordant results. All internal and external quality control measures were carried out appropriately. Parasite densities were calculated using participants' absolute WBCc and assumed WBCc of 5,000 to 10,000 per microlitre of blood. RESULTS: From the 5,902 Pf malaria positive samples, the mean (SD) WBCc and geometric mean parasite density were 10.4 (4.6) × 10(9)/L and 7,557/μL (95% CI 7,144/μL to 7,994/μL) respectively. The difference in the geometric mean parasite densities calculated using absolute WBCs and compared to densities with assumed WBCs counts were significantly lower for 5.0 × 10(9)/L; 3,937/μL, 6.0 × 10(9)/L; 4,725/μL and 8.0 × 10(9)/L; 6,300/μL. However, the difference in geometric mean parasite density, 7,874/μL (95 % CI, 7,445/μL to 8,328/μL), with assumed WBCc of 10.0 × 10(9)/L was not significant. CONCLUSION: Using the assumed WBCc of 8.0 X 10(9)/L or lower to estimate malaria parasite densities in Pf infected children less than five years old could result in significant underestimation of parasite burden. Assumed WBCc of 10.0 × 10(9)/L at 95 % CI of geometric mean of parasite density statistically agreed with the parasite densities produce by the absolute WBCc of participants. The study suggests where resources are limited, use of assumed WBCc of 10.0 × 10(9)/L of blood to estimate malaria parasite density in central Ghana. Preferably, absolute WBCc should be used in drug efficacy and vaccine trials

Adherence to Artesunate-Amodiaquine Therapy for Uncomplicated Malaria in Rural Ghana: A Randomised Trial of Supervised versus Unsupervised Drug Administration

Introduction. To enhance effective treatment, african nations including Ghana changed its malaria treatment policy from monotherapy to combination treatment with artesunate-amodiaquine (AS+AQ). The major challenge to its use in loose form is adherence. Objective. The objectives of this study were to investigate adherence and treatment outcome among patients treated with AS+AQ combination therapy for acute uncomplicated malaria. Methodology. The study was conducted in two rural districts located in the middle belt of Ghana using quantitative methods. Patients diagnosed with acute uncomplicated malaria as per the Ghana Ministry of Health malaria case definitions were randomly allocated to one of two groups. All patients in both groups were educated about the dose regimen of AS+AQ therapy and the need for adherence. Treatment with AS+AQ was supervised in one group while the other group was not supervised. Adherence was assessed by direct observation of the blister package of AS+AQ left on day 2. Results. 401 participants were randomized into the supervised (211) and unsupervised (190) groups. Compliance in both supervised (95.7%) and unsupervised (92.6%) groups were similar (P = .18). The commonest side-effects reported on day 2 among both groups were headaches, and body weakness. Parasite clearance by day 28 was >95% in both groups. Discussion/Conclusions. Administration of AS-AQ in both groups resulted in high levels of adherence to treatment regimen among adolescent and adult population in central Ghana. It appears that high level of adherence to AS-AQ is achievable through a rigorous education programme during routine clinic visits

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

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

An evaluation of the clinical assessments of under-five febrile children presenting to primary health facilities in rural Ghana.

BACKGROUND: The shift to test-based management of malaria represents an important departure from established practice under the Integrated Management of Childhood Illnesses (IMCI). The possibility of false results of tests for malaria and co-morbidity, however, make it important that guidelines in IMCI case assessment are still followed. METHODS AND FINDINGS: We conducted a cross-sectional observational study to evaluate current practices in IMCI-based assessment of febrile children in 10 health centres and 5 district hospitals, with follow up of a subset of children to determine day 7-10 post-treatment clinical outcome. Clinical consultation, examination and prescribing practices were recorded using a checklist by trained non-medical observers. The facility case management of 1,983 under-five years old febrile children was observed and 593 followed up at home on days 5-10. The mean number of tasks performed from the 11 tasks expected to be done by the IMCI guidelines was 6 (SD 1.6). More than 6 tasks were performed in only 35% of children and this varied substantially between health facilities (range 3-85%). All 11 tasks were performed in only 1% of children. The most commonly performed tasks were temperature measurement (91%) and weighing (88%). Respiratory rate was checked in only 4% of children presenting with cough or difficulty in breathing. The likelihood of performing "better than average number of tasks" (>6) was higher when the consultation was done by medical assistants than doctors (O.R. = 3.16, 1.02-9.20). The number of tasks performed during assessment did not, however, influence clinical outcome (O.R. = 1.02, 0.83-1.24). CONCLUSION: Facility-tailored interventions are needed to improve adherence to IMCI guidelines incorporating test-based management of malaria. Studies are needed to re-evaluate the continued validity of tasks defined in IMCI case assessment guidelines

Two years post affordable medicines facility for malaria program: availability and prices of anti-malarial drugs in central Ghana.

BACKGROUND: The Affordable Medicines Facility for malaria (AMFm) Program was a subsidy aimed at artemisinin-based combination therapies (ACTs) in order to increase availability, affordability, and market share of ACTs in 8 malaria endemic countries in Africa. The WHO supervised the manufacture of the subsidized products, named them Quality Assured ACTs (QAACT) and printed a Green Leaf Logo on all QAACT packages. Ghana began to receive the subsidized QAACTs in 2010. METHODS: A cross-sectional stock survey was conducted at 63 licensed chemical shops (LCS) and private pharmacies in two districts of the Brong-Ahafo region of Ghana to determine the availability and price of all anti-malarial treatments. Drug outlets were visited over a 3-weeks period in October and November of 2014, about 2 years after the end of AMFm program. RESULTS: At least one QAACT was available in 88.9% (95% CI 80.9% - 96.8%) of all drug outlets with no difference between urban and rural locations. Non-Assured ACTs (NAACT) were significantly more available in urban drug outlets [75.0% availability (95% CI 59.1% - 90.9%)] than in rural drug outlets [16.1% availability (95% CI 2.4% - 29.9%)]. The top selling product was Artemether Lumefantrine with the Green Leaf Logo, a QAACT. There was a significant difference in the mean price of a QAACT [$1.04 USD (95$0.98 - $1.11)], and the mean price of a NAACT in both the urban and rural areas [$2.46 USD (95% CI $2.11 -$2.81)]. There was no significant difference in the price of any product that was available in urban and rural settings. CONCLUSION: About 2 years after the AMFm program, subsidized QAACTs in Ghana were widely available and more affordable than NAACTs in the Kintampo North District and Kintampo South Municipality of Ghana. The AMFm program appeared to have mostly succeeded in making QAACTs available and affordable

Maximizing community participation and engagement: lessons learned over 2 decades of field trials in rural Ghana

BACKGROUND: Successful implementation of community-based research is dominantly influenced by participation and engagement from the local community without which community members will not want to participate in research and important knowledge and potential health benefits will be missed. Therefore, maximising community participation and engagement is key for the effective conduct of community-based research. In this paper, we present lessons learnt over two decades of conducting research in 7 rural districts in the Brong Ahafo region of Ghana with an estimated population of around 600,000. The trials which were mainly in the area of Maternal, Neonatal and Child Health were conducted by the Kintampo Health Research Centre (KHRC) in collaboration with the London School of Hygiene and Tropical Medicine (LSHTM). METHODS: The four core strategies which were used were formative research methods, the formation of the Information, Education and Communication (IEC) team to serve as the main link between the research team and the community, recruitment of field workers from the communities within which they lived, and close collaboration with national and regional stakeholders. RESULTS: These measures allowed trust to be built between the community members and the research team and ensured that potential misconceptions which came up in the communities were promptly dealt with through the IEC team. The decision to place field workers in the communities from which they came and their knowledge of the local language created trust between the research team and the community. The close working relationship between the District health authorities and the Kintampo Health Research Centre supported the acceptance of the research in the communities as the District Health Authorities were respected and trusted. CONCLUSION: The successes achieved during the past 2 decades of collaboration between LSHTM and KHRC in conducting community-based field trials were based on involving the community in research projects. Community participation and engagement helped not only to identify the pertinent issues, but also enabled the communities and research team to contribute towards efforts to address challenges

Patterns and seasonality of malaria transmission in the forest-savannah transitional zones of Ghana

BACKGROUND: Knowledge of the local pattern of malaria transmission and the effect of season on transmission is essential for the planning and evaluation of malaria interventions. Therefore, entomological surveys were carried out in the forest-savannah transitional belt of Ghana (Kintampo) from November 2003 to November 2005 in preparation for drug and vaccine trials. RESULTS: A total of 23,406 mosquitoes were caught from 919 traps over the two-year period (November 2003 to November 2005): 54.3% were Culicines, 36.2% Anopheles funestus, and 9.4% Anopheles gambiae. Infection rates with Plasmodium falciparum were 4.7% and 1.5% for Anopheles gambiae and Anopheles funestus, respectively. Entomological inoculation rates (EIRs) were 269 infective bites per person per year in the first year (November 2003-October 2004) and 231 the following year (November 2004-November 2005). Polymerase Chain Reaction (PCR) analysis detected only Anopheles gambiae s.s. Nineteen mosquitoes were tested by PCR in the wet season; 16 were S-molecular form, 2 M-molecular form and 1 hybrid (S/M). In the dry season, sixteen mosquitoes were tested; 11 S-molecular form, 2 M-molecular form and 3 S/M hybrids. The frequency of knock down resistance (kdr) genotypes F(R) was 0.60. CONCLUSION: The dynamics and seasonal abundance of malaria vectors in the Kintampo area was influenced by micro-ecology, rainfall and temperature patterns. Transmission patterns did not differ significantly between the two years (2004 and 2005) and both Anopheles gambiae and Anopheles funestus were identified as effective vectors. EIR estimates in 2004/2005 were between 231 and 269 infective bites per person per year. The information provided by the study will help in planning intensified malaria control activities as well as evaluating the impact of malaria interventions in the middle belt of Ghana

Association between probable postnatal depression and increased infant mortality and morbidity: findings from the DON population-based cohort study in rural Ghana.

OBJECTIVES: To assess the impact of probable depression in the immediate postnatal period on subsequent infant mortality and morbidity. DESIGN: Cohort study nested within 4 weekly surveillance of all women of reproductive age to identify pregnancies and collect data on births and deaths. SETTING: Rural/periurban communities within the Kintampo Health Research Centre study area of the Brong-Ahafo Region of Ghana. PARTICIPANTS: 16,560 mothers who had a live singleton birth reported between 24 March 2008 and 11 July 2009, who were screened for probable postnatal depression (pPND) between 4 and 12 weeks post partum (some of whom had also had depression assessed at pregnancy), and whose infants survived to this point. PRIMARY/SECONDARY OUTCOME MEASURES: All-cause early infant mortality expressed per 1000 infant-months of follow-up from the time of postnatal assessment to 6 months of age. The secondary outcomes were (1) all-cause infant mortality from the time of postnatal assessment to 12 months of age and (2) reported infant morbidity from the time of the postnatal assessment to 12 months of age. RESULTS: 130 infant deaths were recorded and singletons were followed for 67,457.4 infant-months from the time of their mothers' postnatal depression assessment. pPND was associated with an almost threefold increased risk of mortality up to 6 months (adjusted rate ratio (RR), 2.86 (1.58 to 5.19); p=0.001). The RR up to 12 months was 1.88 (1.09 to 3.24; p=0.023). pPND was also associated with increased risk of infant morbidity. CONCLUSIONS: There is new evidence for the association between maternal pPND and infant mortality in low-income and middle-income countries. Implementation of the WHO's Mental Health Gap Action Programme (mhGAP) to scale up packages of care integrated with maternal health is encouraged as an important adjunct to child survival efforts

Testing the assumptions of an indicator of unmet need for obstetric surgery in Ghana: A cross-sectional study of linked hospital and population-based delivery data.

BACKGROUND: The Unmet Obstetric Need (UON) indicator has been widely used to estimate unmet need for life-saving surgery at birth; however, its assumptions have not been verified. The objective of this study was to test two UON assumptions: (a) Absolute maternal indications (AMIs) require surgery for survival and (b) 1%-2% of deliveries develop AMIs, implying that rates of surgeries for AMIs below this threshold indicate excess mortality from these complications. METHODS: We used linked hospital and population-based data in central Ghana. Among hospital deliveries, we calculated the percentage of deliveries with AMIs who received surgery, and mortality among AMIs who did not. At the population level, we assessed whether the percentage of deliveries with surgeries for AMIs was inversely associated with mortality from these complications, stratified by education. RESULTS: A total of 380 of 387 (98%) hospital deliveries with recorded AMIs received surgery; an additional eight women with no AMI diagnosis died of AMI-related causes. Among the 50 148 deliveries in the population, surgeries for AMIs increased from 0.6% among women with no education to 1.9% among women with post-secondary education (P < .001). However, there was no association between AMI-related mortality and education (P = .546). Estimated AMI prevalence was 0.84% (95% CI: 0.76%-0.92%), below the assumed 1% minimum threshold. DISCUSSION: Obstetric providers consider AMIs absolute indications for surgery. However, low rates of surgeries for AMIs among less educated women were not associated with higher mortality. The UON indicator should be used with caution in estimating the unmet need for life-saving obstetric surgery; innovative approaches are needed to identify unmet need in the context of rising cesarean rates

Association between probable postnatal depression and increased infant mortality and morbidity: findings from the DON population-based cohort study in rural Ghana.

OBJECTIVES: To assess the impact of probable depression in the immediate postnatal period on subsequent infant mortality and morbidity. DESIGN: Cohort study nested within 4 weekly surveillance of all women of reproductive age to identify pregnancies and collect data on births and deaths. SETTING: Rural/periurban communities within the Kintampo Health Research Centre study area of the Brong-Ahafo Region of Ghana. PARTICIPANTS: 16,560 mothers who had a live singleton birth reported between 24 March 2008 and 11 July 2009, who were screened for probable postnatal depression (pPND) between 4 and 12 weeks post partum (some of whom had also had depression assessed at pregnancy), and whose infants survived to this point. PRIMARY/SECONDARY OUTCOME MEASURES: All-cause early infant mortality expressed per 1000 infant-months of follow-up from the time of postnatal assessment to 6 months of age. The secondary outcomes were (1) all-cause infant mortality from the time of postnatal assessment to 12 months of age and (2) reported infant morbidity from the time of the postnatal assessment to 12 months of age. RESULTS: 130 infant deaths were recorded and singletons were followed for 67,457.4 infant-months from the time of their mothers' postnatal depression assessment. pPND was associated with an almost threefold increased risk of mortality up to 6 months (adjusted rate ratio (RR), 2.86 (1.58 to 5.19); p=0.001). The RR up to 12 months was 1.88 (1.09 to 3.24; p=0.023). pPND was also associated with increased risk of infant morbidity. CONCLUSIONS: There is new evidence for the association between maternal pPND and infant mortality in low-income and middle-income countries. Implementation of the WHO's Mental Health Gap Action Programme (mhGAP) to scale up packages of care integrated with maternal health is encouraged as an important adjunct to child survival efforts