Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.

BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).

The effect of opioids on field block for hernia repair: a study comparing pethidine with a placebo.

BACKGROUND: Intramuscular (IM) pethidine injection is used as pre-analgesia (pre-medication) in hernia repair under local anaesthesia in some district hospitals. We evaluated the relevance of this practice in a facility based study at one of the district hospitals in Ghana. METHOD: One hundred and twenty patients above 10 years of age with a mean age of approximately 49 years diagnosed as having inguinal hernias of different sizes were recruited into the study. Each group of 60 patients was randomly selected. A maximum of 50 ml 1% lignocaine plus 2 ml (100 mg) of pethidine was used in group A and 50 ml 1% lignocaine plus 2 ml of sterile water in group B. A score ranging from 0 to 3 was assigned at the end of each surgery depending on the degree of pain experienced. RESULTS: 33.3%, 33.3%, 21.7% and 11.7% of patients in group A scored 0, 1, 2, and 3 respectively in pain perception while 26.7%, 33.3%, 25% and 15.0% were the scores in group B. None of the patients in group B experienced an adverse effect to any of the agents used. 2% and 5% in group A experienced nausea and generalized pruritus respectively. Post-operation condition was satisfactory and all patients were discharged the same day.

Compression force variability in mammography in Ghana - A baseline study.

INTRODUCTION: Breast compression during mammographic examinations improves image quality and patient management. Several studies have been conducted to assess compression force variability among practitioners in order to establish compression guidelines. However, no such study has been conducted in Ghana. This study aims to investigate the compression force variability in mammography in Ghana. METHODS: This retrospective study used data gathered from 1071 screening and diagnostic mammography patients from January, 2018-December, 2019. Data were gathered by seven radiographers at three centers. Compression force, breast thickness and practitioners' years of work experience were recorded. Compression force variability among practitioners and the correlation between compression force and breast thickness were investigated. RESULTS: Mean compression force values recorded for craniocaudal (CC) (17.2 daN) and mediolateral oblique (MLO) (18.2 daN), were within the recommended values used by western countries. Most of the mammograms performed - 80% - were within the National Health Service Breast Screening Programme (NHSBSP) range. However, 65% were above the Norwegian Breast Cancer Screening Programme (NBCSP) range. Compression forces varied significantly (p = 0.0001) among practitioners. Compression forces increased significantly (p = 0.0001) with the years of work experience. A weak negative correlation (r = -0.144) and a weak positive correlation (r = 0.142) were established between compression force and breast thickness for CC and MLO projections respectively. CONCLUSION: This initial study confirmed that although wide variations in compression force exist among practitioners in Ghana, most practitioners used compression forces broadly within the range set by the NHSBSP. As no national guidelines for compression force currently exist in Ghana, provision of these may help to reduce the range of variations recorded. IMPLICATIONS FOR PRACTICE: Confirmation of variations in compression will guide future practice to minimize image quality disparities and improve quality of care.

Impact of early infant feeding practices on mortality in low birth weight infants from rural Ghana.

OBJECTIVE: To assess the impact of early infant feeding practices on low birth weight- (LBW) specific neonatal mortality in rural Ghana. STUDY DESIGN: A total of 11 787-breastfed babies were born between July 2003 and June 2004 and survived to day 2. Overall, 3411 (30.3%) infants had weight recorded within 48 h. Two hundred and ninety-six (8.7%) infants were <2.5 kg and 15 died in the neonatal period. Associations were examined using multivariate logistic regression. RESULT: Initiation of breastfeeding after day 1 was associated with a threefold increase in mortality risk (adjusted odds ratio (adjOR) 3.23, 95% confidence interval (95% CI) (1.07-9.82)) in infants aged 2 to 28 days. Prelacteal feeding was associated with a threefold significantly increased mortality risk (adjOR 3.12, 95% CI (1.19-8.22)) in infants aged 2 to 28 days but there was no statistically significant increase in risk associated with predominant breastfeeding (adjOR 1.91, 95% CI (0.60-6.09)). There were no modifications of these effects by birth weight. The sample size was insufficient to allow assessment of the impact of partial breastfeeding. CONCLUSION: Improving early infant feeding practices is an effective, feasible, low-cost intervention that could reduce early infant mortality in LBW infants in developing countries. These findings are especially relevant for sub-Saharan Africa where many LBW infants are born at home, never taken to a health facility and mortality rates are unacceptably high.

Building Capability for Clinical Pharmacology Research in Sub-Saharan Africa.

A strong scientific rationale exists for conducting clinical pharmacology studies in target populations because local factors such as genetics, environment, comorbidities, and diet can affect variability in drug responses. However, clinical pharmacology studies are not widely conducted in sub-Saharan Africa, in part due to limitations in technical expertise and infrastructure. Since 2012, a novel public-private partnership model involving research institutions and a pharmaceutical company has been applied to developing increased capability for clinical pharmacology research in multiple African countries.

Anopheles gambiae (Diptera: Culicidae) Susceptibility to Insecticides and Knockdown Resistance Genes Prior to Introduction of Indoor Residual Spraying in 11 Districts in Ghana.

BACKGROUND: An insecticide susceptibility study was carried out on Anopheles gambiae sensu lato vectors in 11 districts in Ghana between October 2012 and January 2013. METHODS: An. gambiae s.l. larvae were collected, bred under standard conditions, and 3-5 d postemerged females were used for bioassay. Between 22 and 25 female An. gambiae s.l. fed only 10% sugar were used for testing. Exposure was for 1 h (2 h for fenitrothion). An gambiae that were knocked down were recorded every 10 min and mortalities recorded 24 h posttest. Eleven insecticides from four chemical classes were used: organochlorines, organophosphates, carbamates, and pyrethroids. Subsamples of An gambiae were analyzed by polymerase chain reaction for species and knockdown resistance (kdr) allele determination. RESULTS: Malathion was effective in killing An. gambiae in seven districts, fenitrothion in three districts, and propoxur in one district. The organophosphate and carbamate insecticides were effective in killing An. gambiae compared to pyrethroids and organochlorines. Of the limited samples analyzed, An. gambiae sensu stricto (39/110), An. coluzzii (66/110), and An. arabiensis (5/110) were identified. Few kdr (11/110) susceptible mosquitoes were detected. Homozygous kdrRR (65/110) and heterozygous kdrRS (8/110) genotypes were identified. CONCLUSIONS: An organophosphate insecticide is considered appropriate for indoor residual spraying (IRS) in the 11 districts earmarked for the IRS program in Ghana.

Incidence of symptomatic and asymptomatic Plasmodium falciparum infection following curative therapy in adult residents of northern Ghana.

Adult residents of holoendemic malaria regions in Africa have a naturally acquired immunity (NAI) to malaria that renders them more resistant to new infections, limits parasitemia, and reduces the frequency and severity of illness. Given such attributes, it is not clear how one might evaluate drug or vaccine efficacy in adults without serious confounding. To determine symptomatic and asymptomatic malaria attack rates in adults of northern Ghana, 197 men and women underwent curative therapy for any pre-existing malaria infections at the start of the high transmission (wet) season. They were monitored for first parasitemia and first clinical episode of infection by Plasmodium falciparum over a 20-week period (May-October 1996). The cumulative incidence of primary infection by P. falciparum was 0.98 and incidence density of infection was calculated to be 7.0 cases/person-year. Symptoms were reported by 19.5% of the individuals at the time of first recurrent parasitemia. Incidence of infection, parasite density, and the frequency of symptoms were comparable in males and females. The results suggest that NAI did not provide these adults with significant defense against rapid re-infection and suggest that this population-infection design could serve to demonstrate the efficacy of a drug or vaccine in preventing parasitemia.

Severe anemia in young children after high and low malaria transmission seasons in the Kassena-Nankana district of northern Ghana.

Malaria and anemia accounted for 41% and 18% respectively of hospital deaths in the Kassena-Nankana district of northern Ghana during 1996. We measured hemoglobin (Hb), malaria prevalence, and anthropometric indices of 6--24-month-old infants and young children randomly selected from this community at the end of the high (May-October, n = 347) and low (November-April, n = 286) malaria transmission seasons. High transmission season is characterized by rainfall (the equivalent of 800-900 mm/yr.), while the remaining months receive less than 50 mm/yr. Severe anemia, defined as Hb < 6.0 g/dL, was 22.1% at the end of the high transmission season compared to 1.4% at the end of the low transmission season (Odds Ratio [OR] = 20.1; 95% CI: 7.1-55.3). Parasitemia was 71% and 54.3% at these time points (OR = 2.1; 95% CI: 1.5-2.9). Nutritional anemia appeared to have little impact upon this seasonal difference since anthropometric indices were comparable. Although the relative contributions of other causes of severe anemia were not assessed, repeated malaria infections may be a primary determinant of severe anemia among infants and young children during the high transmission season.

Seasonal malaria attack rates in infants and young children in northern Ghana.

The incidence density of infection and disease caused by Plasmodium falciparum in children aged six to 24 months living in the holoendemic Sahel of northern Ghana was measured during the wet and dry seasons of 1996 and 1997. At the beginning of each season, a cohort composed of 259 and 277 randomly selected children received supervised curative therapy with quinine and Fansidar and primaquine for those with normal glucose-6-phosphate dehydrogenase activity. The 20 weeks of post-therapy follow-up consisted of three home visits weekly and examination of Giemsa-stained blood films once every two weeks. Blood films were also taken from children brought to clinic with illness. The incidence density of parasitemia after radical cure was 4.7 infections/person-year during the dry season and 7.1 during the wet season (relative risk = 1.51, 95% confidence interval [CI] = 1.25-1.81; P = 0.00001). Although the mean parasitemia count at time of reinfection in the dry season (3,310/microl) roughly equaled that in the wet season (3,056/microl; P = 0.737), the risk ratio for parasitemia > 20,000/microl during the wet season was 1.71 (95% CI = 1.2-2.4; P = 0.0025). The risk ratio for parasitemia > 20,000/microl with fever during the wet season was 2.45 (95% CI = 1.5-4.1; P = 0.0002). The risk ratio for anemia (hemoglobin < 8 g/dl) at first post-radical cure parasitemia showed no difference between seasons (1.0; 95% CI = 0.73-1.4; P = 0.9915). We did not see seasonal differences in anemia known to exist in this region, probably because the longitudinal cohort design using first parasitemia as an end point prevented the subjects from developing the repeated or chronic infections required for anemia induction. These findings bear upon the design of malaria drug and vaccine trials in holoendemic areas.

Seasonal characteristics of malaria infection in under-five children of a rural community in southern Ghana.

In a quarterly survey of malaria infection in the under-five children conducted at Gomoa Onyadze/Otsew Jukwa, a rural community in the Central Region of Ghana from December, 1986 to September, 1987, crude parasite rates ranged from 19.6 to 33.5 per cent in the dry season (December and March) and 33.0 to 44.0 per cent in the wet season (June and September). P. falciparum was the predominant parasite species by parasite formula analysis with higher rates in the rainy season (94.2 to 95.8 per cent) compared to that of the dry season (51.4 to 78.8 per cent). P. malariae (20.4 per cent), P. ovale (2.7 per cent) and mixed infection rates were higher in the dry season (December and March). As high as 30.4 to 44.8 per cent of positive parasite slides had parasite density of above 3200 per microliter of blood (above class 6 degree of parasitaemia). Depending on the season 7.2-27.3 per cent of children had parasite density above 25,600 per microliter of blood (above class 10 degree of parasitaemia).

Shifting from presumptive to test-based management of malaria - technical basis and implications for malaria control in Ghana.

The presumptive approach was the World Health Organisation (WHO) recommended to the management of malaria for many years and this was incorporated into syndromic guidelines such as the Integrated Management of Childhood Illnesses (IMCI). In early 2010 however, WHO issued revised treatment guidelines that call for a shift from the presumptive to the test-based approach. Practically, this implies that in all suspected cases, the diagnosis of uncomplicated malaria should be confirmed using rapid test before treatment is initiated. This revision effectively brings to an end an era of clinical practice that span several years. Its implementation has important implications for the health systems in malaria-endemic countries. On the basis of research in Ghana and other countries, and evidence from program work, the Ghana National Malaria Control Program has issued revised national treatment guidelines that call for implementation of test-based management of malaria in all cases, and across all age groups. This article reviews the evidence and the technical basis for the shift to test-based management and examines the implications for malaria control in Ghana.

Willingness to undergo HIV testing in the Kintampo districts of Ghana.

BACKGROUND: HIV testing is currently a major prevention intervention and remains an entry point to early treatment, care and support. Uptake is however low and alternative approaches are currently being adopted. OBJECTIVE: An HIV module was incorporated into the routine survey of the Kintampo Health and Demographic Surveillance System (KHDSS) to assess the willingness of adults living in the Kintampo North and South districts to undergo HIV testing. DESIGN: The study was a descriptive cross-sectional household survey. Univariate and multivariate analysis were used to identify predictors of the willingness to undergo HIV testing. PARTICIPANTS: Respondents were community members aged 15 to 49 years and selected from randomly generated household listings from the KHDSS. RESULTS: A total of 11,604 respondents were interviewed, 10,982 (94.6%) of respondents had good general knowledge on HIV/AIDS. Among those with knowledge about HIV/AIDS, 10,819 (98.5%) indicated their willingness to get tested for HIV. Rural residents were more willing to undergo HIV testing than urban dwellers Odds ratio=1.42 (95% Confidence interval: 1.03, 1.96; P-value=0.031). Respondents with primary education were more likely to go for testing relative to those without any education OR=2.02 (95% CI: 0.87, 4.70; P-value=0.046). CONCLUSION: Expressed willingness to test for HIV is high in this population. Exploring community and population-based interventions to HIV testing and counseling could increase uptake of HIV testing services and should be considered. The underlying motivations need to be explored in order to translate willingness into actual testing.

Age and seasonal variation in the transition rates and detectability of Plasmodium falciparum malaria.

The effect of acquired immunity on the duration of Plasmodium falciparum infections is unclear, although this is an important term in models of malaria transmission. It is problematical to determine the duration of infections because of the difficulty of distinguishing persisting infections from new ones, and because parasite densities are often transiently below the limit of detection. We recently developed a dynamic model for infection incidence, clearance and detection of multiple genotype P. falciparum infections and fitted it to a panel dataset from a longitudinal study in Northern Ghana. We now extend this model to allow for seasonal and age variation in infection rates and also age dependence in clearance and in detectability of infections. These models indicate that there is seasonal variation in the infection rate, and age dependence in detectability. The best fitting models had no age dependence in infection or clearance rates, suggesting that acquired immunity mainly affects detectability.

Molecular epidemiology of Plasmodium falciparum infections among asymptomatic inhabitants of a holoendemic malarious area in northern Ghana.

Age dependence of malaria infection was assessed in an age-stratified cluster sample of 308 individuals from Kassena-Nankana District of northern Ghana during June and July 2000. Overall prevalence of Plasmodium falciparum by microscopy was 70%, with the maximum among 5-9 year olds. Parasite density was highest (geometric mean 1922/microl blood) in 1-2 year olds. Eighty-two per cent of samples were positive by polymerase chain reaction (PCR), and restriction fragment length polymorphism typing of the P. falciparum msp2 revealed a mean msp2 multiplicity of 3.4 (range: 1-8) genotypes per PCR positive sample. Multiplicity increased with age until 5-9 years and then started to reduce again into adulthood. About 49.3% of infections belonged to the msp2 FC27 allelic family and 50.7% to the 3D7 family. On the day of the survey, only 3.6% of the participants had fever (axillary temperature >or= 37.5 degrees C) and 2.3% had fever associated with parasitaemia. The correlation between parasite density and msp2 multiplicity was 0.42; highest among infants, and decreased with age to a minimum among 5-9 year olds. Contrasting with results from Tanzania, this correlation increased with age in adolescents and adults. Parasite multiplicity is very high in this community, and the patterns of age dependence are similar to those in other holoendemic sites in Africa, validating the use of the age-multiplicity relationship as an indicator of malaria endemicity.

A randomized, comparative study of two regimens of beta-artemether for the treatment of uncomplicated, Plasmodium falciparum malaria, in northern Ghana.

In Ghana, wide-spread resistance to chloroquine has necessitated the drug's replacement as the first-line treatment for malaria, both to increase the likelihood of cure and to reduce transmission. To see if beta-artemether could be a suitable alternative to chloroquine, 223 adults (aged > or = 15 years) with uncomplicated, Plasmodium falciparum malaria were each given a total dose of 480 mg beta-artemether over 4 or 5 days. The patients were randomly allocated to receive an initial, loading dose of 80 or 160 mg, and were checked on days 1, 2, 3, 4 (or 5), 7 and 14, for fever clearance and any adverse events. Blood samples collected on days 0, 4 (or 5), 7 and 14 were smeared so that levels of parasitaemia could be evaluated. Haemoglobin concentrations on days 0 and 14 were also determined. In terms of the clinical cure 'rates' estimated in the intention-to-treat analysis (92.5% v. 97.4%) and the evaluability analysis (98.9% v. 100%), and of the frequency of parasitological cure by day 14 (97.0% v. 96.5%), the patients given an initial dose of 80 mg were similar to those given 160 mg as the loading dose. The regimen with the 160-mg loading dose appears as safe and as effective as the regimen with an initial dose of 80 mg. Since the regimen with the higher loading dose is shorter and involves fewer treatments than the other regimen, it would probably be associated with better compliance.