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Background: Asymptomatic malaria infections can serve as potential reservoirs for malaria transmission. The density of parasites contained in these infections range from microscopic to submicroscopic densities, making the accurate detection of asymptomatic parasite carriage highly dependent on the sensitivity of the tools used for the diagnosis. This study sought to evaluate the sensitivities of a variety of molecular and serological diagnostic tools at determining the prevalence of asymptomatic Plasmodium falciparum parasite infections in two communities with varying malaria parasite prevalence. Methods: Whole blood was collected from 194 afebrile participants aged between 6 and 70 years old living in a high (Obom) and a low (Asutsuare) malaria transmission setting of Ghana. Thick and thin blood smears, HRP2 based malaria rapid diagnostic test (RDT) and filter paper dried blood spots (DBS) were prepared from each blood sample. Genomic DNA was extracted from the remaining blood and used in Plasmodium specific photo-induced electron transfer polymerase chain reaction (PET-PCR) and Nested PCR, whilst the HRP2 antigen content of the DBS was estimated using a bead immunoassay. A comparison of malaria parasite prevalence as determined by each method was performed. Results: Parasite prevalence in the high transmission site of Obom was estimated at 71.4%, 61.9%, 60%, 37.8% and 19.1% by Nested PCR, the HRP2 bead assay, PET-PCR, HRP2-RDT and microscopy respectively. Parasite prevalence in the low transmission site of Asutsuare was estimated at 50.1%, 11.2%, 5.6%, 0% and 2.2% by Nested PCR, the HRP2 bead assay, PET-PCR, RDT and microscopy, respectively. The diagnostic performance of Nested PCR, PET-PCR and the HRP2 bead assay was similar in Obom but in Asutsuare, Nested PCR had a significantly higher sensitivity than PET-PCR and the HRP2 bead assay, which had similar sensitivity. Conclusions: Nested PCR exhibited the highest sensitivity by identifying the highest prevalence of asymptomatic P. falciparum in both the high and low parasite prevalence settings. However, parasite prevalence estimated by the HRP2 bead assay and PET-PCR had the highest level of inter-rater agreement relative to all the other tools tested and have the advantage of requiring fewer processing steps relative to Nested PCR and producing quantitative results. [ABSTRACT FROM AUTHOR]

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

Background: The return of chloroquine-sensitive Plasmodium falciparum in sub-Saharan Africa countries offers the opportunity for the reintroduction of chloroquine (CQ) either in combination with other drugs or as a single therapy for the management of malaria. This study assesses the influence of individual study sites on the selection of CQ sensitive P. falciparum markers in the Central region of Ghana. Methods: Genomic DNA was extracted from an archived filter paper blood blot from Cape Coast, Elmina, Assin Fosu, and Twifo Praso using the Chelex DNA extraction method. The age metadata of the patients from whom the blood spots were taken was collected. The prevalence of CQ-sensitive markers of pfcrt K76 and pfmdr1 N86 was performed using nested PCR and RFLP. The data were analysed using Chi-square and Odd ratio. Results: The overall prevalence of CQ-sensitive P. falciparum markers, pfcrt K76 and pfmdr1 N86 in the Central Region of Ghana were 142 out of 184 (77.17%) and 180 out of 184 (97.83%), respectively. The distribution of pfcrt K76 was assessed among the age groups per the individual study sites. 12 out of 33 (36.36%), 8 out of 33 (24.24%) and 6 out of 33 (18.18%) of pfcrt K76 CQ-sensitive marker were isolated from age 0 to 5 years, 16 to 30 years and 31 to 45 years old respectively at Cape Coast. Assin Fosu and Twifo Praso had the highest pfcrt K76 prevalence in 0–5 years, followed by 16–30 years and 6–15 years of age. The results showed that there was a significant prevalence of pfcrt K76 in all study sites; Cape Coast (χ2 = 26.48, p < 0.0001), Assin Fosu (χ2 = 37.67, p < 0.0001), Twifo Praso (χ2 = 32.25, p < 0.0001) and Elmina (χ2 = 17.88, p < 0.0001). Again, the likelihood to detect pfcrt K76 (OR (95% CI) was 7.105 (3.118–17.14), p < 0.0001 and pfmdr1 (2.028 (1.065–3.790), p < 0.001) among P. falciparum isolates from Cape Coast to be seven times and two times, respectively. Conclusion: The study showed a significant selection and expansion of chloroquine-sensitive P. falciparum markers in all the selected study areas in the Central region. This finding has a significant implication for the future treatment, management, and control of P. falciparum malaria. [ABSTRACT FROM AUTHOR]

Background: The Alere™ Malaria Ag P.f Ultra-sensitive RDT (UsmRDT) kit is an HRP2-based malaria rapid diagnostic test (RDT) with enhanced sensitivity relative to the SD Bioline Malaria Ag P.f RDT (mRDT) kit. However, the diagnostic performance of the UsmRDT kit has not been evaluated in Ghana. Methods: A total of 740 afebrile participants aged between 3 and 88 years old were recruited from the Central and Greater Accra Regions of Ghana during the off-peak malaria season. Axillary body temperature was measured, and a volume of 1 ml venous blood was drawn from each participant. Prior to separating the blood into plasma and packed cell pellets via centrifugation, the blood was spotted onto one UsmRDT and one mRDT kit and also used to prepare thick and thin blood smears as well as filter paper blood spots. Plasmodium falciparum specific polymerase chain reaction (PCR) was performed on gDNA extracted from 100 µl of the whole blood. Results: The overall positivity rate for microscopy, PCR, UsmRDT and mRDT kit were 20.4%, 40.8%, 31.3% and 30.8%, respectively. Overall, the UsmRDT identified 9.3% (28/302) more PCR positive samples than the mRDT kits. All samples that were negative by the UsmRDT kit were also negative by the mRDT kit. Overall, the sensitivity and specificity of the UsmRDT was 73% (221/302) and 89% (388/436), respectively, while that for the mRDT kit was 58% and 90%, respectively. Conclusion: Although the UsmRDT kit was not as sensitive as PCR at detecting asymptomatic P. falciparum carriage, it correctly identified P. falciparum in 9.3% of the study participants that were not captured by the mRDT kit. In malaria endemic settings, the UsmRDT would provide an added advantage by identifying more asymptomatic P. falciparum carriers than the mRDT kit for targeted treatment interventions. [ABSTRACT FROM AUTHOR]

Background: Artemisinin-based combination therapy (ACT) has been effective in the supervised treatment of uncomplicated malaria in Ghana. Since ACT usage is primarily unsupervised, this study aimed to determine the effectiveness of artemether–lumefantrine (AL) for treating malaria patients in two transmission settings in Ghana. Methods: Eighty-four individuals with uncomplicated Plasmodium falciparum malaria were recruited from Lekma Hospital (LH) in Accra (low-transmission area; N = 28), southern Ghana, and King's Medical Centre (KMC) in Kumbungu (high-transmission area; N = 56), northern Ghana. Participants were followed up for 28 days after unsupervised treatment with AL. The presence of asexual parasites was determined by microscopic examination of Giemsa-stained blood smears. Plasmodium species identification was confirmed using species-specific primers targeting the 18S rRNA gene. Parasite recrudescence or reinfection was determined by genotyping the Pfmsp 1 and Pfmsp 2 genes. Results: After AL treatment, 3.6% (2/56) of the patients from KMC were parasitaemic on day 3 compared to none from the LH patients. One patient from KMC with delayed parasite clearance on day 3 remained parasite-positive by microscopy on day 7 but was parasite-free by day 14. While none of the patients from LH experienced parasite recurrence during the 28-day follow-up, three and two patients from KMC had recurrent parasitaemia on days 21 and 28, respectively. Percentage reduction in parasite densities from day 1, 2, and 3 for participants from the KMC was 63.2%, 89.5%, and 84.5%. Parasite densities for participants from the LH reduced from 98.2%, 99.8% on day 1, and 2 to 100% on day 3. The 28-day cumulative incidence rate of treatment failure for KMC was 12.8% (95% confidence interval: 1.9–23.7%), while the per-protocol effectiveness of AL in KMC was 89.47%. All recurrent cases were assigned to recrudescence after parasite genotyping by Pfmsp 1 and Pfmsp 2. Conclusion: While AL is efficacious in treating uncomplicated malaria in Ghana, when taken under unsupervised conditions, it showed an 89.4% PCR-corrected cure rate in northern Ghana, which is slightly below the WHO-defined threshold. [ABSTRACT FROM AUTHOR]

Background: Clothianidin, an insecticide with a novel mode of action, has been deployed in the annual indoor residual spraying programme in northern Ghana since March 2021. To inform pragmatic management strategies and guide future studies, baseline data on local Anopheles gambiae sensu lato (s.l.) susceptibility to the clothianidin insecticide were collected in Kpalsogu, a village in the Northern region, Ghana. Methods: Phenotypic susceptibility of An. gambiae mosquitoes to clothianidin was assessed using the World Health Organization (WHO) insecticide resistance monitoring bioassay. The WHO cone bioassays were conducted on mud and cement walls sprayed with Sumishield 50 wettable granules (WG) (with clothianidin active ingredient). Daily mortalities were recorded for up to 7 days to observe for delayed mortalities. Polymerase chain reaction (PCR) technique was used to differentiate the sibling species of the An. gambiae complex and also for the detection of knock down resistance genes (kdr) and the insensitive acetylcholinesterase mutation (ace-1). Results: The WHO susceptibility bioassay revealed a delayed killing effect of clothianidin. Mosquitoes exposed to the cone bioassays for 5 min died 120 h after exposure. Slightly higher mortalities were observed in mosquitoes exposed to clothianidin-treated cement wall surfaces than mosquitoes exposed to mud wall surfaces. The kdr target-site mutation L1014F occurred at very high frequencies (0.89–0.94) across all vector species identified whereas the ace-1 mutation occurred at moderate levels (0.32–0.44). Anopheles gambiae sensu stricto was the most abundant species observed at 63%, whereas Anopheles arabiensis was the least observed at 9%. Conclusions: Anopheles gambiae s.l. mosquitoes in northern Ghana were susceptible to clothianidin. They harboured kdr mutations at high frequencies. The ace-1 mutation occurred in moderation. The results of this study confirm that clothianidin is an effective active ingredient and should be utilized in malaria vector control interventions. [ABSTRACT FROM AUTHOR]

Background: The routine surveillance of asymptomatic malaria using nucleic acid-based amplification tests is essential in obtaining reliable data that would inform malaria policy formulation and the implementation of appropriate control measures. Methods: In this study, the prevalence rate and the dynamics of Plasmodium species among asymptomatic children (n = 1697) under 5 years from 30 communities within the Hohoe municipality in Ghana were determined. Results and discussion: The observed prevalence of Plasmodium parasite infection by polymerase chain reaction (PCR) was 33.6% (571/1697), which was significantly higher compared to that obtained by microscopy [26.6% (451/1697)] (P < 0.0001). Based on species-specific analysis by nested PCR, Plasmodium falciparum infection [33.6% (570/1697)] was dominant, with Plasmodium malariae, Plasmodium ovale and Plasmodium vivax infections accounting for 0.1% (1/1697), 0.0% (0/1697), and 0.0% (0/1697), respectively. The prevalence of P. falciparum infection among the 30 communities ranged from 0.0 to 82.5%. Following artesunate-amodiaquine (AS + AQ, 25 mg/kg) treatment of a sub-population of the participants (n = 184), there was a substantial reduction in Plasmodium parasite prevalence by 100% and 79.2% on day 7 based on microscopy and nested PCR analysis, respectively. However, there was an increase in parasite prevalence from day 14 to day 42, with a subsequent decline on day 70 by both microscopy and nested PCR. For parasite clearance rate analysis, we found a significant proportion of the participants harbouring residual Plasmodium parasites or parasite genomic DNA on day 1 [65.0% (13/20)], day 2 [65.0% (13/20)] and day 3 [60.0% (12/20)] after initiating treatment. Of note, gametocyte carriage among participants was low before and after treatment. Conclusion: Taken together, the results indicate that a significant number of individuals could harbour residual Plasmodium parasites or parasite genomic DNA after treatment. The study demonstrates the importance of routine surveillance of asymptomatic malaria using sensitive nucleic acid-based amplification techniques. [ABSTRACT FROM AUTHOR]

Background: Global efforts to reduce malaria burden include distribution of insecticide-treated mosquito nets through mass campaigns and routine channels. Ghana's National Malaria Elimination Programme (NMEP) distributes insecticide-treated bed nets (ITNs) through various channels, including to pregnant women at antenatal care (ANC) visits and children at vaccination visits through child welfare clinics (CWC). This study assessed historical ITN distribution throughout ANCs and CWCs across Ghana and the characteristics of high performing facilities. Methods: Monthly data on routine ITN distribution was provided from Ghana's national health information management system for the years 2016–2021. Analyses were conducted to assess the performance of ITN distribution at ANC and CWC across time, ecological zone, regions, districts, facility ownership, and facility type. Univariate and multivariate logistic regressions were performed to predict the odds of ANC and CWC issuing rates greater or equal to 80% for a given facility type or ownership. Results: In 2021, 93% of women who attended their first antenatal care visit and 92% of children under five who received their second dose of the measles-rubella vaccine (MR2) had received an ITN. At the regional level, 94% of regions (n = 15/16) maintained the NSP target issuing rate of 80% throughout 2020 and 2021. While there were no clear differences in issuing rates between ecological zones, district-level differences were present across the six years. All health facility types performed at or above 80% in 2021 for both ANC and CWC. Odds ratios demonstrated differences in the likelihood of meeting the 80% issuing rate goal among different facility types as well as private versus public ownership when comparing ANC and CWC. Conclusion: By 2021, Ghana had improved its ITN issuing rates since the initial year of analysis, surpassing the 80% target by issuing nets to over 90% of pregnant women and young children attending ANC and CWC. Future work can explore the reasons for national and subnational differences in issuing rates as well as help understand additional characteristics of high performing facilities. Additionally, it is necessary to identify and expand on the drivers for improved performance over the time period. [ABSTRACT FROM AUTHOR]

Background: Continuous distribution channels are effective methods to deliver malaria interventions such as insecticide treated nets (ITNs) to pregnant women attending antenatal care clinics and children under five attending immunization visits. Facility-based and provider-based checklists were used during supportive supervision visits to measure the quality of facility-based services and interventions. This study looks at ITN distributions at health facilities in Ghana, with the aim of providing insights on how quality can be measured and monitored. Methods: Various quality improvement approaches for malaria services occur in Ghana. Selected indicators were analysed to highlight the similarities and differences of how the approaches measured how well the channel was doing. Generally, the approaches assessed (1) service data management, (2) logistics data management, and (3) observation of service provision (ITN issuance, malaria education, ITN use and care education). Two approaches used a binary (Yes/No) scale, and one used a Likert scale. Results: Results showed that most data reported to the national HMIS is accurate. Logistics data management remained an issue at health facilities, as results showed scores below average across facility stores, antenatal care, and immunization. Though the supervision approaches differed, overall results indicated that almost all eligible clients received ITNs, data were recorded accurately and reported on-time, and logistics was the largest challenge to optimal distribution through health facilities. Conclusion: The supervision approaches provided valuable insights into the quality of facility-based ITN distribution. Ghana should continue to implement supportive supervision in their malaria agenda, with additional steps needed to improve reporting of collected data and increase the number of facilities visited for supportive supervision and the frequency. There were various supervision approaches used with no clear guidance on how to measure quality of facility-based ITN distribution, so there is also need for the global community to agree on standardized indicators and approaches to measuring quality of facility-based ITN distribution. Additionally, future studies can review the effect of multiple rounds of supervision visits on the quality of ITN distribution as well as understand the facilitators and barriers to scaling up supervision of facility-based ITN distribution. [ABSTRACT FROM AUTHOR]

Background After years of disuse of chloroquine (CQ) as first-line anti-malarial drug in Ghana, reports from molecular studies conducted in parts of the country indicate varying prevalence of T76 mutation in the pfcrt gene. This situation has several health implications, one being that mutations that confer resistance to CQ have been reported to show substantial cross-resistance to other anti-malarial drugs. It is important to identify some of the factors contributing to the continuous presence of CQ resistance markers in the country. This study determined the prevalence of T76 mutation in pfcrt gene of Plasmodium falciparum isolates collected from selected areas of the Central region of Ghana and correlated with the level of CQ use in these areas. Methods Plasmodium falciparum DNA was extracted from collected blood-blot filter paper samples in the study sites. The prevalence of T76 point mutation in pfcrt gene was assessed using nested PCR followed by RFLP. CQ from pharmacy and chemical shops was obtained using mystery buying method. The extent of CQ use by the participants was determined by measuring the level of the drug in their urine samples using the Saker-Solomon method. Results Of the 214 P. falciparum isolates analysed, 71.9% were found to have T76 mutation of pfcrt gene. The study revealed that 14.49% of community pharmacies and chemical shops had stocks of CQ for sale while 16.9% of the participants had CQ in their urine samples. There is five times more risks of becoming infected with CQ resistant strain for staying in an area where CQ is stocked for sale [RR = 0.20, p < 0.0001] and thirteen times more risks of having CQ-resistant mutant from those who still use CQ than non-users [OR = 0.08, p < 0.0001]. Conclusion This study has shown that high variation in the prevalence of T76 mutations of P. falciparum is linked with the level of CQ stocking and usage within study area. [ABSTRACT FROM AUTHOR]

Background: Malaria remains a global public health problem responsible for 445,000 deaths in 2016. While microscopy remains the mainstay of malaria diagnosis, highly sensitive molecular methods for detection of low-grade sub-microscopic infections are needed for surveillance studies and identifying asymptomatic reservoirs of malaria transmission. Methods: The Plasmodium falciparum genome sequence was analysed to identify high copy number genes that improve P. falciparum parasite detection in blood by RT-PCR. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1)-specific primers were evaluated for P. falciparum detection in hospital-based microscopically positive dried blood spots and field-acquired whole blood from asymptomatic individuals from Ghana. Results: PfEMP1 outperformed the Pf18S sequence for amplification-based P. falciparum detection. PfEMP1 primers exhibited sevenfold higher sensitivity compared to Pf18S primers for parasite genomic DNA. Probit analysis established a 95% detection threshold of 9.3 parasites/mL for PfEMP1 compared to 98.2 parasites/mL for Pf18S primers. The PfEMP1 primers also demonstrated superior clinical sensitivity, identifying 100% (20/20) of dried blood spot samples and 70% (69/98) of asymptomatic individuals as positive versus 55% (11/20) and 54% (53/98), respectively, for Pf18S amplification. Conclusions: These results establish PfEMP1 as a novel amplification target for highly sensitive detection of both acute infections from filter paper samples and submicroscopic asymptomatic low-grade infections. [ABSTRACT FROM AUTHOR]

Background: Severe malaria (SM) is a fatal multi-system disease which accounted for an estimated 619,000 deaths in 2021. Less than 30% of children presenting with SM are diagnosed and treated promptly, resulting in increased mortality and neurologic impairments in survivors. Studies have identified cytokine profiles that differentiate the various clinical manifestations of malaria (severe and uncomplicated). However, the diagnostic capability of these cytokines in differentiating between the disease states in terms of cut-off values has not yet been determined. Methods: The plasma levels of 22 pro-inflammatory cytokines (Eotaxin/CCL 11, interferon-gamma (IFN-γ), interleukin (IL)- 2, IL-6, IL-1β, IL-12p40/p70, IL-17A, RANTES, MCP-1, IL-15, IL-5, IL-1RA, IL-2R, IFN-α, IP-10, TNF, MIG, MIP-1α, MIP-1β, IL-7, IL-8 and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), and 3 anti-inflammatory cytokines-(IL-4, IL-13 and IL-10) in patients with SM, uncomplicated malaria (UM) and other febrile conditions, were measured and compared using the Human Cytokine Magnetic 25-Plex Panel. The receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of these cytokines. Results: The level of the pro-inflammatory cytokine, IL-17A, was significantly higher in the SM group as compared to the UM group. Levels of the anti-inflammatory cytokines however did not differ significantly among the SM and UM groups. Only IL-1β and IL-17A showed good diagnostic potential after ROC curve analysis. Conclusion: The data show that levels of pro-inflammatory cytokines correlate with malaria disease severity. IL-1β and IL-17A showed good diagnostic potentials and can be considered for use in clinical practice to target treatment. [ABSTRACT FROM AUTHOR]

Background: Morbidities and mortalities due to malaria can be prevented by the use of insecticide-treated mosquito bed nets (ITN), which has been proven for malaria control and elimination. The purpose of this study was to assess the critical factors that predict the use of ITN among children under-fives in Ghana. Methods: The study utilized data from the 2019 Ghana Malaria Indicator Survey (GMIS). The outcome variable was mosquito bed net use among children under-fives. To determine critical factors that independently predict ITN use, multilevel multivariable logistic regression was employed using Stata version 16. Odds ratios and associated 95% confidence intervals and p-values were reported. A p < 0.05 was used to declare statistical significance. Results: The overall prevalence of ITN usage was 57.4%. Utilization of bed nets was 66.6% in the rural areas and 43.5% in the urban areas, was highest in the Upper West region (80.6%) even when stratified to rural (82.9%) and urban areas (70.3%) whilst Greater Accra region (30.5%, rural = 41.7%, urban = 28.9%) had the least. The community level multilevel analysis showed that bed net utilization was higher among children in rural areas [AOR = 1.99, 95% CI 1.32–3.01, p = 0.001] and in household with wooden wall materials [AOR = 3.29, 95% CI 1.15–9.40, p = 0.027]. Bed net utilization was however, less for households with 3 + children under-five [AOR = 0.29, 95% CI 0.19–0.46, p < 0.001), 4 years old (AOR = 0.66, 95% CI 00.48–00.92, p = 0.014], without universal access to bed net [AOR = 0.52, 95% CI 0.37–0.73, p < 0.001], those in the Greater Accra [AOR = 0.26, 95% CI 0.13–0.51, p < 0.001], Eastern [AOR = 0.47, 95% CI 0.23–0.95, p = 0.036], Northern [AOR = 0.42, 95% CI 0.20–0.88, p = 0.022], middle [AOR = 0.57, 95% CI 0.35–0.94, p = 0.026] and rich/richest [AOR = 0.51, 95% CI 0.29–0.92, p = 0.025] household wealth quintile. Substantial unobserved household and community level differences in bed net use were found. Conclusion: This study demonstrates the need to intensify promotion of ITN use to those in urban areas, Greater Accra, Eastern and Northern regions, houses without wooden wall materials, middle and rich/richest households. Interventions should be targeted at older children and households with more under-five children and to ensure full access and use of ITNs among all children under-fives in each household as part of the overall goal of achieving the health-related SDGs. [ABSTRACT FROM AUTHOR]

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 AUC 0-∞ ) 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 AUC 0-∞ 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: The World Health Organization recommends parasitological confirmation of all suspected malaria cases by microscopy or rapid diagnostic tests (RDTs) before treatment. These conventional tools are widely used for point-of-care diagnosis in spite of their poor sensitivity at low parasite density. Previous studies in Ghana have compared microscopy and RDT using standard 18S rRNA PCR as reference with varying outcomes. However, how these conventional tools compare with ultrasensitive varATS qPCR has not been studied. This study, therefore, sought to investigate the clinical performance of microscopy and RDT assuming highly sensitive varATS qPCR as gold standard. Methods: 1040 suspected malaria patients were recruited from two primary health care centers in the Ashanti Region of Ghana and tested for malaria by microscopy, RDT, and varATS qPCR. The sensitivity, specificity, and predictive values were assessed using varATS qPCR as gold standard. Results: Parasite prevalence was 17.5%, 24.5%, and 42.1% by microscopy, RDT, and varATS qPCR respectively. Using varATS qPCR as the standard, RDT was more sensitive (55.7% vs 39.3%), equally specific (98.2% vs 98.3%), and reported higher positive (95.7% vs 94.5%) and negative predictive values (75.3% vs 69.0%) than microscopy. Consequently, RDT recorded better diagnostic agreement (kappa = 0.571) with varATS qPCR than microscopy (kappa = 0.409) for clinical detection of malaria. Conclusions: RDT outperformed microscopy for the diagnosis of Plasmodium falciparum malaria in the study. However, both tests missed over 40% of infections that were detected by varATS qPCR. Novel tools are needed to ensure prompt diagnosis of all clinical malaria cases. [ABSTRACT FROM AUTHOR]

Background: This paper investigates the impact of malaria preventive interventions in Ghana and the prospects of achieving programme goals using mathematical models based on regionally diverse climatic zones of the country. Methods: Using data from the District Health Information Management System of the Ghana Health Service from 2008 to 2017, and historical intervention coverage levels, ordinary non-linear differential equations models were developed. These models incorporated transitions amongst various disease compartments for the three main ecological zones in Ghana. The Approximate Bayesian Computational sampling approach, with a distance based rejection criteria, was adopted for calibration. A leave-one-out approach was used to validate model parameters and the most sensitive parameters were evaluated using a multivariate regression analysis. The impact of insecticide-treated bed nets and their usage, and indoor residual spraying, as well as their protective efficacy on the incidence of malaria, was simulated at various levels of coverage and protective effectiveness in each ecological zone to investigate the prospects of achieving goals of the Ghana malaria control strategy for 2014–2020. Results: Increasing the coverage levels of both long-lasting insecticide-treated bed nets and indoor residual spraying activities, without a corresponding increase in their recommended utilization, does not impact highly on averting predicted incidence of malaria. Improving proper usage of long-lasting insecticide-treated bed nets could lead to substantial reductions in the predicted incidence of malaria. Similar results were obtained with indoor residual spraying across all ecological zones of Ghana. Conclusions: Projected goals set in the national strategic plan for malaria control 2014–2020, as well as World Health Organization targets for malaria pre-elimination by 2030, are only likely to be achieved if a substantial improvement in treated bed net usage is achieved, coupled with targeted deployment of indoor residual spraying with high community acceptability and efficacy. [ABSTRACT FROM AUTHOR]

Background: Under-five child malaria is one of the leading causes of morbidity and mortality globally, especially among sub-Saharan African countries like Ghana. In Ghana, malaria is responsible for about 20,000 deaths in children annually of which 25% are those aged < 5 years. To provide opportunities for efficient malaria surveillance and targeted control efforts amidst limited public health resources, the study produced high resolution interactive web-based spatial maps that characterized geographical differences in malaria risk and identified high burden communities. Methods: This modelling and web-based mapping study utilized data from the 2019 Malaria Indicators Survey (MIS) of the Demographic and Health Survey Program. A novel and advanced Bayesian geospatial modelling and mapping approaches were utilized to examine predictors and geographical differences in under-five malaria. The model was validated via a cross-validation approach. The study produced an interactive web-based visualization map of the malaria risk by mapping the predicted malaria prevalence at both sampled and unsampled locations. Results: In 2019, 718 (25%) of 2867 under-five children surveyed had malaria. Substantial geographical differences in under-five malaria risk were observed. ITN coverage (log-odds 4.5643, 95% credible interval = 2.4086–6.8874), travel time (log-odds 0.0057, 95% credible interval = 0.0017–0.0099) and aridity (log-odds = 0.0600, credible interval = 0.0079–0.1167) were predictive of under-five malaria in the spatial model. The overall predicted national malaria prevalence was 16.3% (standard error (SE) 8.9%) with a range of 0.7% to 51.4% in the spatial model with covariates and prevalence of 28.0% (SE 13.9%) with a range of 2.4 to 67.2% in the spatial model without covariates. Residing in parts of Central and Bono East regions was associated with the highest risk of under-five malaria after adjusting for the selected covariates. Conclusion: The high-resolution interactive web-based predictive maps can be used as an effective tool in the identification of communities that require urgent and targeted interventions by programme managers and implementers. This is key as part of an overall strategy in reducing the under-five malaria burden and its associated morbidity and mortality in a country with limited public health resources where universal intervention is practically impossible. [ABSTRACT FROM AUTHOR]

Background: Malaria remains the biggest public health challenge globally, and Ghana is among the 15 highest burden malaria countries in the world, with 2% of global malaria cases and 3% deaths in 2019. This study sought to assess the impact of mass LLIN distribution campaign on malaria morbidity using all health facilities outpatient data across 15 regions of Ghana. Methods: Data for this study was obtained from the DHIMS2 for health facilities providing OPD and malaria services in Ghana. This was an ecological study that employed the difference-in-difference approach to assess the change in proportion of uncomplicated confirmed malaria cases among OPDs in all types of health facilities in Ghana between 2015 and 2019 following the mass distribution campaign of LLINs in 2018. Malaria cases at the OPDs before and after the free LLIN mass distribution exercise were evaluated. Results: The trend of the proportion of OPD cases that were confirmed uncomplicated malaria cases increased from 14.8% in 2015 to 18.9% in 2019 at the national level. The average proportion of malaria cases among OPDs in Ghana in 2019 reduced against the expected by − 3.76% (95% CI − 4.69 to − 2.84], p<0.001) among all cases, − 4.52% (95% CI [− 5.70 to − 3.34], p<0.001) among children under-fives years, − 4.10% (95% CI − 5.3 to 2.9], p<0.001) among female children under-five and − 5.18% (95% CI [− 6.33 to − 4.02], p<0.001) among male children under-five. The reduction on the average proportion of malaria cases among OPDs varied significantly across regions and the type of health facilities. Conclusion: The mass distribution of LLINs across Ghana in 2018 can be associated with reduction in the proportion of malaria cases among OPDs across health facilities in Ghana. The study recommends the biannual mass distribution campaigns especially in the high-density regions. [ABSTRACT FROM AUTHOR]

Background: The Malaria Vaccine Implementation Programme (MVIP) coordinates the routine implementation of the RTS,S vaccine pilot in strategically selected locations in Malawi, Kenya, and Ghana. The pilot programme thoroughly assesses the programmatic feasibility of administering the four doses of the RTS,S vaccine. It will also assess the impact on malaria morbidity and mortality, as well as monitor and detect the vaccine's safety for routine usage. The malaria vaccine was introduced into Ghana's routine vaccination programme in May 2019 in seven regions, comprising 42 districts, including Kassena Nankana Municipal in the Upper East region of Ghana. Therefore, this study seeks to assess the predictors of the malaria vaccine uptake in children 6 to 24 months in the Kassena Nankana Municipal in Ghana. Methods: The survey used a cross-sectional study design and included 422 mothers/caregivers with children aged 6 to 24 months from the Kassena Nankana Municipality. WHO cluster survey questionnaire was altered for use in data gathering with caregivers as respondents. The Statistical Package for the Social Sciences (SPSS) version 25.0 (for descriptive statistics) and Stata version 13 (for calculating odds ratios) were used to analyse the data. Results: The findings depict that, the mean age of respondents for the study was 27 ± 5 years and average age of children was 15 ± 8 months. The study found that coverage uptake was high (94%). Chi-square and odds ratios testing revealed statistically significant associations between health service factors and vaccine uptake: education on malaria vaccine cOR(Cl); 9.69(3.496–25.425), (P < 0.001), giving caregivers the option to accept malaria vaccine cOR(Cl); 7.04 (2.759–17.476), (P < 0.001). Confidence in the efficiency of the vaccination was found to have a statistically significant association with malaria vaccine uptake (P < 0.005) and (p < 0.001) for 'somewhat confidence' and 'not confidence at all', respectively. Attitude of health workers was found to be significant predictor of malaria vaccine uptake (P < 0.003). Conclusion: Malaria vaccine uptake was high among the study population in the municipality; however, dose four uptake coverage by age two was low. This indicates that mothers/caregivers did not understand the notion of immunization throughout the second year of life. As a result, it is recommended that the municipality raise awareness about immunization services among mothers/caregivers beyond year one in order to improve performance and reduce the risk of disease outbreaks in the municipality. [ABSTRACT FROM AUTHOR]

Background: Despite several efforts at addressing the barriers to adherence to the WHO-supported test, treat and track (T3) malaria case management guideline in Ghana, adherence remains a challenge. This study explored the challenges of prescribers regarding adherence to the T3 guideline. Methods: This was an explorative study using key informant interviews amongst prescribers comprising medical doctors, physician assistants, nurses and a health extension worker from 16 health facilities in six districts in Ghana. The data was analysed using Nvivo 10 and organized into thematic areas. Results: Prescribers lauded the guideline on testing and treatment as it ensures the quality of malaria case management, but irregular supply of malaria rapid diagnostic test kits (RDT), mistrust of laboratory tests, and the reluctance of prescribers to change from presumptive treatment were key barriers to testing. Patients with malaria test negative results if not treated, revisiting the facility with severe malaria, the experience of prescribers, lack of regular training and supervision for old and new staff and the inability of prescribers to investigate non-malaria fever hindered adherence to results-based treatment. Conclusion: As malaria remains a significant cause of morbidity and mortality in Ghana, this study provides insights on gaps in adherence to the testing and treatment of malaria. While the diagnostic capacity for malaria case management is a challenge, the lack of training resulting in the inability of some prescribers to investigate non-malaria fever hinders adherence to the malaria case management guideline. Therefore, there is a need to train new prescribers, laboratory personnel, and other staff involved in malaria diagnosis and treatment on the malaria case management guideline before they assume duty. Equipping laboratory personnel and prescribers with the knowledge to investigate non-malaria fevers could improve adherence to the guideline for improved patient care. [ABSTRACT FROM AUTHOR]

Background: Malaria in pregnancy control interventions have been implemented through antenatal care services for more than 2 decades in Ghana. The uptake of these interventions has seen steady improvement over the years. This has occurred within the context of decreasing global trends of malaria infection confirmed by decreasing malaria in pregnancy prevalence in Ghana. However, not much is known about how these improvements in interventions uptake and reduction in malaria infection prevalence have impacted pregnancy outcomes in the country. This study aimed at describing trends of maternal anaemia and low birth weight prevalence and uptake of malaria in pregnancy control interventions over the last decade using data from Ghana's District Health Information Management System (DHIMS II). Methods: Data from Ghana's DHIMS II on variables of interest covering the period 2012 to 2021 was analysed descriptively using Microsoft Excel 365. Results were computed as averages and percentages and presented in tables and graphs. Results: The prevalence of maternal anaemia at booking and at term and low birth weight increased marginally from 31.0%, 25.5% and 8.5% in 2012 to 36.6%, 31.9% and 9.5% in 2021 respectively. Severe anaemia prevalence at booking and at term remained under 2% over the study period. Women making at least 4 ANC visits, receiving at least 3 doses of intermittent preventive treatment of malaria and an insecticide-treated net increased from 77.0%, 41.4% and 4.1% in 2012 to 82%, 55.0% and 93.3% in 2021, respectively. Malaria test positivity rate reduced from 54.0% to 34.3% between 2014 and 2021 while women receiving iron and folate supplementation for 3 and 6 months rose from 43.0% and 25.5% to 89.7% and 61.8%, respectively between 2017 and 2021. Conclusion: Maternal anaemia and low birth weight prevalence showed marginal upward trends over the last decade despite reduced malaria infection rate and improved uptake of malaria in pregnancy control interventions. There is room for improvement in current intervention implementation levels but the complex and multi-factorial aetiologies of maternal anaemia and low birth weight need urgent investigation and quantification to inform policy and practice. [ABSTRACT FROM AUTHOR]

Background: The growing need to capture data on health and health events using faster and efficient means to enable prompt evidence-based decision-making is making the use of mobile phones for health an alternative means to capture anti-malarial drug safety data. This paper examined the feasibility and cost of using mobile phones vis-à-vis home visit to monitor adverse events (AEs) related to artemisinin-based combination therapy (ACT) for treatment of uncomplicated malaria in peri-urban Ghana. Methods: A prospective, observational, cohort study conducted on 4270 patients prescribed ACT in 21 health facilities. The patients were actively followed by telephone or home visit to document AEs associated with anti-malarial drugs. Call duration and travel distances of each visit were recorded. Pre-paid call cards and fuel for motorbike travels were used to determine cost of conducting both follow-ups. Ms-Excel 2010 and STATA 11.2 were used for analysis. Results: Of the 4270 patients recruited, 4124 (96.6 %) were successfully followed up and analyzed. Of these, 1126/4124 (27.3 %) were children under 5 years. Most 3790/4124 (91.9 %) follow-ups were done within 7 days of ACT intake. Overall, follow up by phone (2671/4124—64.8 %) was almost two times the number done by home visits (1453/4124—35.2 %). Duration of telephone calls ranged from 38 s to 53 min, costing between GH¢0.26 (0.20USD) and GH¢41.70 (27.USD). On the average, the calls lasted 3 min 51 s (SD = 3 min, 21 s) costing GH¢2.70 (0.77USD). Distance travelled for home visit ranged from 0.65 to 62 km costing GH¢0.29 (0.20USD) and GH¢279.00 (79.70USD). Thirty-two per cent (1128/4124) of patients reported AEs. In total, 1831 AE were reported, 1016/1831(55.5 %) by telephone and 815/1831 (44.5 %) by home visits. Events such as nausea, dizziness, diarrhoea, and vomiting were commonly reported. Conclusion: Majority of patients was successfully followed up by telephone and reported the most AEs. The cost of telephone interviewing was almost two times less than the cost of home visit. Telephone follow up should be considered for monitoring drug adverse events in low resource settings. [ABSTRACT FROM AUTHOR]

Background: Although under-five mortality rate seems to be declining in Ghana, the northern part of the country has higher levels of under-five mortality vis-à-vis the national rates. This research examines the correlates of the high under-five mortality among children in the northern part of Ghana, with emphasis on the usage of insecticide-treated bed net (ITN), as recommended by the World Health Organization. Methods: A total of 3,839 under-five children sourced from the Ghana Demographic and Health Survey--was used for this study. Univariate descriptive statistics was employed to describe the variables used for the empirical estimation. The maximum likelihood estimation technique was used to estimate a logit model in other to determine the effect of insecticide treated bed net usage on under-five mortality. Results: Insecticide-treated bed net usage among children enhances their survival rates. Thus, under-five mortality among children who sleep under treated bed nets is about 18.8% lower than among children who do not sleep under treated bed nets. While health facility delivery was found to reduce to reduce under-five mortality, child bearing among older women is detrimental to the survival of the child. Conclusions: The study, therefore, recommends that policies targeting reduction in under-five mortality in northern Ghana should consider not mere availability of ITNs in the household, but advocate the usage of these treated nets. The study recommends to the Ministry of Health to extend their services to unreached rural communities to encourage health facility delivery to reduce under-five mortality. [ABSTRACT FROM AUTHOR]

Background: An estimated 1.5 billion malaria cases and 7.6 million malaria deaths have been averted globally since 2000; long-lasting insecticidal nets (LLINs) have contributed an estimated 68% of this reduction. Insufficient funding at the international and domestic levels poses a significant threat to future progress and there is growing emphasis on the need for enhanced domestic resource mobilization. The Private Sector Malaria Prevention (PSMP) project was a 3-year intervention to catalyse private sector investment in malaria prevention in Ghana. Methods: To assess value for money of the intervention, non-donor expenditure in the 5 years post-project catalysed by the initial donor investment was predicted. Non-donor expenditure catalysed by this investment included: workplace partner costs of malaria prevention activities; household costs in purchasing LLINs from retail outlets; domestic resource mobilization (public sector financing and private investors). Annual ratios of projected non-donor expenditure to annualized donor costs were calculated for the 5 years post-project. Alternative scenarios were constructed to explore uncertainty around future consequences of the intervention. Results: The total donor financial cost of the 3-year PSMP project was USD 4,418,996. The average annual economic donor cost per LLIN distributed through retail sector and workplace partners was USD 21.17 and USD 7.55, respectively. Taking a 5-year post-project time horizon, the annualized donor investment costs were USD 735,805. In the best-case scenario, each USD of annualized donor investment led to USD 4.82 in annual projected non-donor expenditure by the fifth-year post-project. With increasingly conservative assumptions around the project consequences, this ratio decreased to 3.58, 2.16, 1.07 and 0.93 in the "very good", "good", "poor" and "worst" case scenarios, respectively. This suggests that in all but the worst-case scenario, donor investment would be exceeded by the non-donor expenditure it catalysed. Conclusions: The unit cost per net delivered was high, reflecting considerable initial investment costs and relatively low volumes of LLINs sold during the short duration of the project. However, taking a longer time horizon and broader perspective on the consequences of this complex catalytic intervention suggests that considerable domestic resources for malaria control could be mobilized, exceeding the value of the initial donor investment. [ABSTRACT FROM AUTHOR]

Background: Malaria is a major cause of morbidity and mortality globally, especially in sub-Saharan Africa. Widespread resistance to pyrethroids threatens the gains achieved by vector control. To counter resistance to pyrethroids, third-generation indoor residual spraying (3GIRS) products have been developed. This study details the results of a multi-country cost and cost-effectiveness analysis of indoor residual spraying (IRS) programmes using Actellic®300CS, a 3GIRS product with pirimiphos-methyl, in sub-Saharan Africa in 2017 added to standard malaria control interventions including insecticide-treated bed nets versus standard malaria control interventions alone. Methods: An economic evaluation of 3GIRS using Actellic®300CS in a broad range of sub-Saharan African settings was conducted using a variety of primary data collection and evidence synthesis methods. Four IRS programmes in Ghana, Mali, Uganda, and Zambia were included in the effectiveness analysis. Cost data come from six IRS programmes: one in each of the four countries where effect was measured plus Mozambique and a separate programme conducted by AngloGold Ashanti Malaria Control in Ghana. Financial and economic costs were quantified and valued. The main indicator for the cost was cost per person targeted. Country-specific case incidence rate ratios (IRRs), estimated by comparing IRS study districts to adjacent non-IRS study districts or facilities, were used to calculate cases averted in each study area. A deterministic analysis and sensitivity analysis were conducted in each of the four countries for which effectiveness evaluations were available. Probabilistic sensitivity analysis was used to generate plausibility bounds around the incremental cost-effectiveness ratio estimates for adding IRS to other standard interventions in each study setting as well as jointly utilizing data on effect and cost across all settings. Results: Overall, IRRs from each country indicated that adding IRS with Actellic®300CS to the local standard intervention package was protective compared to the standard intervention package alone (IRR 0.67, [95% CI 0.50–0.91]). Results indicate that Actellic®300CS is expected to be a cost-effective (> 60% probability of being cost-effective in all settings) or highly cost-effective intervention across a range of transmission settings in sub-Saharan Africa. Discussion: Variations in the incremental costs and cost-effectiveness likely result from several sources including: variation in the sprayed wall surfaces and house size relative to household population, the underlying malaria burden in the communities sprayed, the effectiveness of 3GIRS in different settings, and insecticide price. Programmes should be aware that current recommendations to rotate can mean variation and uncertainty in budgets; programmes should consider this in their insecticide-resistance management strategies. Conclusions: The optimal combination of 3GIRS delivery with other malaria control interventions will be highly context specific. 3GIRS using Actellic®300CS is expected to deliver acceptable value for money in a broad range of sub-Saharan African malaria transmission settings. [ABSTRACT FROM AUTHOR]

Background: Following a 30-year development process, RTS,S/AS01E (GSK, Belgium) is the first malaria vaccine to reach Phase IV assessments. The World Health Organization-commissioned Malaria Vaccine Implementation Programme (MVIP) is coordinating the delivery of RTS,S/AS01E through routine national immunization programmes in areas of 3 countries in sub-Saharan Africa. The first doses were given in the participating MVIP areas in Malawi on 23 April, Ghana on 30 April, and Kenya on 13 September 2019. The countries participating in the MVIP have little or no baseline incidence data on rare diseases, some of which may be associated with immunization, a deficit that could compromise the interpretation of possible adverse events reported following the introduction of a new vaccine in the paediatric population. Further, effects of vaccination on malaria transmission, existing malaria control strategies, and possible vaccine-mediated selective pressure on Plasmodium falciparum variants, could also impact long-term malaria control. To address this data gap and as part of its post-approval commitments, GSK has developed a post-approval plan comprising of 4 complementary Phase IV studies that will evaluate safety, effectiveness and impact of RTS,S/AS01E through active participant follow-up in the context of its real-life implementation. Methods: EPI-MAL-002 (NCT02374450) is a pre-implementation safety surveillance study that is establishing the background incidence rates of protocol-defined adverse events of special interest. EPI-MAL-003 (NCT03855995) is an identically designed post-implementation safety and vaccine impact study. EPI-MAL-005 (NCT02251704) is a cross-sectional pre- and post-implementation study to measure malaria transmission intensity and monitor the use of other malaria control interventions in the study areas, and EPI-MAL-010 (EUPAS42948) will evaluate the P. falciparum genetic diversity in the periods before and after vaccine implementation. Conclusion: GSK's post-approval plan has been designed to address important knowledge gaps in RTS,S/AS01E vaccine safety, effectiveness and impact. The studies are currently being conducted in the MVIP areas. Their implementation has provided opportunities and posed challenges linked to conducting large studies in regions where healthcare infrastructure is limited. The results from these studies will support ongoing evaluation of RTS,S/AS01E's benefit-risk and inform decision-making for its potential wider implementation across sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic and its collateral damage severely impact health systems globally and risk to worsen the malaria situation in endemic countries. Malaria is a leading cause of morbidity and mortality in Ghana. This study aims to describe the potential effects of the COVID-19 pandemic on malaria cases observed in health facilities in the Northern Region of Ghana. Methods: Monthly routine data from the District Health Information Management System II (DHIMS2) of the Northern Region of Ghana were analysed. Overall outpatient department visits (OPD) and malaria case rates from the years 2015–2019 were compared to the corresponding data of the year 2020. Results: Compared to the corresponding periods of the years 2015–2019, overall visits and malaria cases in paediatric and adult OPDs in northern Ghana decreased in March and April 2020, when major movement and social restrictions were implemented in response to the pandemic. Cases slightly rebounded afterwards in 2020, but stayed below the average of the previous years. Malaria data from inpatient departments showed a similar but more pronounced trend when compared to OPDs. In pregnant women, however, malaria cases in OPDs increased after the first COVID-19 wave. Conclusions: The findings from this study show that the COVID-19 pandemic affects the malaria burden in health facilities of northern Ghana, with declines in inpatient and outpatient rates except for pregnant women. They may have experienced reduced access to insecticide-treated nets and intermittent preventive malaria treatment in pregnancy, resulting in subsequent higher malaria morbidity. Further data, particularly from community-based studies and ideally complemented by qualitative research, are needed to fully determine the impact of the pandemic on the malaria situation in Africa. [ABSTRACT FROM AUTHOR]

Background: Ghana has adopted and implemented intermittent preventive treatment using sulfadoxine-pyrimethamine (IPTp-SP) and insecticide-treated nets (ITNs) in an antenatal care (ANC) context to prevent malaria among pregnant women. However, the increased ANC attendance and its frequency facilitated by a free maternal health care policy in Ghana does not correspond with the uptake of IPTp-SP and ITN use among pregnant women. This study sought to elucidate the contextual health system factors influencing the delivery of IPTp-SP and ITN from a related quantitative study conducted in Ghana. Methods: This is the qualitative section of a mixed-methods study design, where audio recorded key informant interviews (KIIs) were conducted with health workers from across health facilities, districts, regional and national health directorates. The KIIs elicited information on health worker knowledge, perceptions, and rationale for the delivery practices of IPTp-SP and ITN revealed in the quantitative findings. The interviews were transcribed and imported into NVivo for analysis. Using the World Health Organization (WHO) Health Systems Framework as the theoretical basis, thematic analysis was conducted under broad themes of the building blocks. Findings are presented in narrative quotes, with a mindmap used to summarize the various health system factors and their interrelated relationship influencing the delivery of IPTp-SP and ITN. Results: Health system factors identified included health staff untrained on malaria delivery directives due to an ineffective trainer of trainer (ToT) system. Additionally, health worker confusion on when to commence SP (at quickening or ≥ 16 weeks) was found to result in delayed start of SP. Stock-outs in facilities due to procurement delays at the national level resulted in missed opportunities to deliver SP to eligible pregnant women at the ANC. Similarly, ITN stock outs led to eligible pregnant women not receiving one at ANC clinics. Conclusion: Poor health worker knowledge on policy directives, a consequence of ineffective training strategy led to delayed delivery of IPTp-SP to eligible pregnant women. Supply chain management challenges related to stock of SP and ITN resulted in missed opportunities to deliver the interventions to pregnant women attending ANC. [ABSTRACT FROM AUTHOR]

Background: The Global Fund alone contributed 56% of all international financing for malaria and has invested more than US$13.5 billion in malaria treatment, prevention, and control programmes by June 2021. These investments include interventions such as mosquito nets, indoor residual spraying, and preventive treatment for children and pregnant women. However, there is paucity of studies for assessment of such investments to a reduction in malaria prevalence. This study was aimed at quantifying the impact of household access to insecticide-treated nets (ITNs) and the indoor residual spraying (IRS) on self-reported malaria prevalence among women of reproductive age in Ghana. Methods: The study analysed the 2016 Ghana Malaria Indicator Survey (MIS) data. The MIS is a nationwide survey that included women aged 15-49 years. Poisson regression model with inverse probability to treatment weighting was used to determine average treatment effect estimate of the two malaria interventions on self-reported malaria prevalence among women of reproductive age in Ghana. Results: A total sample of 4861 women interviewed from the 2016 Ghana MIS was used for analysis. The prevalence of self-reported malaria in 2016 was 34.4% (95% CI [32.4%, 36.4%]). Approximately 80.0% of women lived in households with access to ITNs [Percentage (Pr) = 79.9%, (95% CI [78.0%, 81.7%])], 12.4% (95% CI [7.5%, 19.8%]) of the households had access to IRS and 11.4% (95% CI [7.0%, 18.0%]) of the households had access to both ITNs and IRS. Household access to only ITN contributed to 7.1 percentage point (pt) reduction in the self-reported malaria among women (95% CI [- 12.0%, - 2.1%], p = 0.005) whilst IRS at the households contributed to 6.8pt reduction in malaria prevalence (95% CI [- 12.0%, - 2.1%], p = 0.005). Households with access to both ITNs and IRS contributed to a 27.1pt reduction in self-reported malaria prevalence among women (95% CI [- 12.0%, - 2.1%], p = 0.005). Conclusion: Access to both ITNs and application of IRS at the household level contributed to a significant reduction in self-reported malaria prevalence among women of reproductive age in Ghana. This finding confirms the need for integration of malaria control interventions to facilitate attainment of malaria elimination in Ghana. [ABSTRACT FROM AUTHOR]

Background: Despite decades of prevention efforts, the burden of malaria in pregnancy (MiP) remains a great public health concern. Sulfadoxine-pyrimethamine (SP), used as intermittent preventive treatment in pregnancy (IPTp-SP) is an important component of the malaria prevention strategy implemented in Africa. However, IPTp-SP is under constant threat from parasite resistance, thus requires regular evaluation to inform decision-making bodies. Methods: In two malaria endemic communities in the Volta region (Adidome and Battor), a cross-sectional hospital-based study was conducted in pregnant women recruited at their first antenatal care (ANC) visit and at delivery. Basic clinical and demographic information were documented and their antenatal records were reviewed to confirm IPTp-SP adherence. Peripheral and placental blood were assayed for the presence of Plasmodium falciparum parasites by quantitative polymerase chain reaction (qPCR). One hundred and twenty (120) positive samples were genotyped for mutations associated with SP resistance. Results: At first ANC visit, P. falciparum prevalence was 28.8% in Adidome and 18.2% in Battor. At delivery, this decreased to 14.2% and 8.2%, respectively. At delivery, 66.2% of the women had taken at least the recommended 3 or more doses of IPTp-SP and there was no difference between the two communities. Taking at least 3 IPTp-SP doses was associated with an average birth weight increase of more than 360 g at both study sites compared to women who did not take treatment (p = 0.003). The Pfdhfr/Pfdhps quintuple mutant IRNI-A/FGKAA was the most prevalent (46.7%) haplotype found and the nonsynonymous Pfdhps mutation at codon A581G was higher at delivery among post-SP treatment isolates (40.6%) compared to those of first ANC (10.22%). There was also an increase in the A581G mutation in isolates from women who took 3 or more IPTp-SP. Conclusions: This study confirms a positive impact following the implementation of the new IPTp-SP policy in Ghana in increasing the birth weight of newborns. However, the selection pressure exerted by the recommended 3 or more doses of IPTp-SP results in the emergence of parasites carrying the non-synonymous mutation on codon A581G. This constant selective pressure calls into question the time remaining for the clinical utility of IPTp-SP treatment during pregnancy in Africa. [ABSTRACT FROM AUTHOR]

Background: Adults with diabetes mellitus (DM) in malaria-endemic areas might be more susceptible to Plasmodium infection than healthy individuals. Herein, the study was aimed at verifying the hypothesis that increased fasting blood glucose (FBG) promotes parasite growth as reflected by increased parasite density. Methods: Seven adults without DM were recruited in rural Ghana to determine the relationships between FBG and malaria parasite load. Socio-economic data were recorded in questionnaire-based interviews. Over a period of 6 weeks, FBG and Plasmodium sp. Infection were measured in peripheral blood samples photometrically and by polymerase chain reaction (PCR)-assays, respectively. Daily physical activity and weather data were documented via smartphone recording. For the complex natural systems of homeostatic glucose control and Plasmodium sp. life cycle, empirical dynamic modelling was applied. Results: At baseline, four men and three women (median age, 33 years; interquartile range, 30–48) showed a median FBG of 5.5 (5.1–6.0 mmol/L); one participant had an asymptomatic Plasmodium sp. infection (parasite density: 240/µL). In this participant, convergent cross mapping (CCM) for 34 consecutive days, showed that FBG was causally affected by parasite density (p < 0.02), while the reciprocal relationship was not discernible (p > 0.05). Additionally, daily ambient temperature affected parasite density (p < 0.01). Conclusion: In this study population living in a malaria-endemic area, time series analyses were successfully piloted for the relationships between FBG and Plasmodium sp. density. Longer observation periods and larger samples are required to confirm these findings and determine the direction of causality. [ABSTRACT FROM AUTHOR]

Background: Access to healthcare is important in controlling malaria burden and, as a result, distance or travel time to health facilities is often a significant predictor in modelling malaria prevalence. Adding new health facilities may reduce overall travel time to health facilities and may decrease malaria transmission. To help guide local decision-makers as they scale up community-based accessibility, the influence of the spatial allocation of new health facilities on malaria prevalence is evaluated in Bunkpurugu-Yunyoo district in northern Ghana. A location-allocation analysis is performed to find optimal locations of new health facilities by separately minimizing three district-wide objectives: malaria prevalence, malaria incidence, and average travel time to health facilities. Methods: Generalized additive models was used to estimate the relationship between malaria prevalence and travel time to the nearest health facility and other geospatial covariates. The model predictions are then used to calculate the optimisation criteria for the location-allocation analysis. This analysis was performed for two scenarios: adding new health facilities to the existing ones, and a hypothetical scenario in which the community-based healthcare facilities would be allocated anew. An interactive web application was created to facilitate efficient presentation of this analysis and allow users to experiment with their choice of health facility location and optimisation criteria. Results: Using malaria prevalence and travel time as optimisation criteria, two locations that would benefit from new health facilities were identified, regardless of scenarios. Due to the non-linear relationship between malaria incidence and prevalence, the optimal locations chosen based on the incidence criterion tended to be inequitable and was different from those based on the other optimisation criteria. Conclusions: This study findings underscore the importance of using multiple optimisation criteria in the decision-making process. This analysis and the interactive application can be repurposed for other regions and criteria, bridging the gap between science, models and decisions. [ABSTRACT FROM AUTHOR]

Background: Malaria eradication requires a combined effort involving all available control tools, and these efforts would be complemented by an effective vaccine. The antigen targets of immune responses may show polymorphisms that can undermine their recognition by immune effectors and hence render vaccines based on antigens from a single parasite variant ineffective against other variants. This study compared the influence of allelic polymorphisms in Plasmodium falciparum apical membrane antigen 1 (PfAMA1) peptide sequences from three strains of P. falciparum (3D7, 7G8 and FVO) on their function as immunodominant targets of T cell responses in high and low malaria transmission communities in Ghana. Methods: Peripheral blood mononuclear cells (PBMCs) from 10 subjects from a high transmission area (Obom) and 10 subjects from a low transmission area (Legon) were tested against 15 predicted CD8 + T cell minimal epitopes within the PfAMA1 antigen of multiple parasite strains using IFN-γ ELISpot assay. The peptides were also tested in similar assays against CD8 + enriched PBMC fractions from the same subjects in an effort to characterize the responding T cell subsets. Results: In assays using unfractionated PBMCs, two subjects from the high transmission area, Obom, responded positively to four (26.7%) of the 15 tested peptides. None of the Legon subject PBMCs yielded positive peptide responses using unfractionated PBMCs. In assays with CD8 + enriched PBMCs, three subjects from Obom made positive recall responses to six (40%) of the 15 tested peptides, while only one subject from Legon made a positive recall response to a single peptide. Overall, 5 of the 20 study subjects who had positive peptide-specific IFN-γ recall responses were from the high transmission area, Obom. Furthermore, while subjects from Obom responded to peptides in PfAMA1 from multiple parasite strains, one subject from Legon responded to a peptide from 3D7 strain only. Conclusions: The current data demonstrate the possibility of a real effect of PfAMA1 polymorphisms on the induction of T cell responses in malaria exposed subjects, and this effect may be more pronounced in communities with higher parasite exposure. [ABSTRACT FROM AUTHOR]

Background: Malaria continues to be a major disease of public health concern affecting several million people worldwide. The World Health Organization (WHO) started a pilot study on a malaria vaccine (RTS,S) in Ghana and two other countries in 2019. This study aimed at assessing the factors associated with uptake of the vaccine in the Sunyani Municipality of Ghana. Methods: The study was a cross-sectional study employing a quantitative approach. Stratified sampling technique was used to select respondents. A structured questionnaire was administered to parents/caregivers with children eligible to have taken the first three doses of the malaria vaccine by December 2019. The Child Welfare Clinic (CWC) cards of the eligible children were also inspected. Ordinal logistic regression analysis was done to determine the association between the independent variables and full vaccine uptake. Results: Uptake of RTS,S 1 was 94.1%. However, this figure reduced to 90.6% for RTS,S 2, and 78.1% for RTS,S 3. Children with a parent who had been educated up to the tertiary level had 4.72 (AOR: 4.72, 95% CI 1.27–17.55) increased odds of full uptake as compared to those who completed secondary education. Parents whose children had experienced fever as an adverse reaction were more likely to send their children for the malaria vaccine as compared to those whose children had ever suffered abscess as an adverse reaction (AOR: 2.27, 95% CI 1.13–5.10). Children with parents who thought vaccines were becoming too many for children had 71% (AOR: 0.29, 95% CI 0.14–0.61) reduced odds of full uptake as compared to those who thought otherwise. Conclusion: Uptake of RTS,S 1 and RTS,S 2 in Sunyani Municipality meets the WHO's target coverage for vaccines, however, RTS,S 3 uptake does not. Furthermore, there is a growing perception amongst parents/caregivers that vaccines are becoming too many for children which negatively affects uptake. [ABSTRACT FROM AUTHOR]

Background: The lack of background disease incidence rates in sub-Saharan countries where the RTS,S/AS01E malaria vaccine is being implemented may hamper the assessment of vaccine safety and effectiveness. This study aimed to document baseline incidence rates of meningitis, malaria, mortality, and other health outcomes prior to vaccine introduction through the Malaria Vaccine Implementation Programme. Methods: An ongoing disease surveillance study is combining prospective cohort event monitoring and hospital-based disease surveillance in three study sites in Ghana and Kenya. An interim analysis was performed on the prospective cohort in which children were enrolled in two age-groups (the 5 to 17 months or 6 to 12 weeks age-group), capturing data in the framework of routine medical practice before the introduction of the malaria vaccine. Incidence and mortality rates were computed with 95% confidential intervals (CI) using an exact method for a Poisson variable. Results: This analysis includes 14,329 children; 7248 (50.6%) in the 6 to 12 weeks age-group and 7081 (49.4%) in the 5 to 17 months age-group. In the 5 to 17 months age-group (where the malaria vaccine was planned to be subsequently rolled out) the meningitis, malaria, severe malaria and cerebral malaria incidences were 92 (95% CI 25–236), 47,824 (95% CI 45,411–50,333), 1919 (95% CI 1461–2476) and 33 (95% CI 1–181) per 100,000 person-years, respectively. The all-cause mortality was 969 (95% CI 699–1310) per 100,000 person-years. Conclusion: Incidence estimates of multiple health outcomes are being generated to allow before-after vaccine introduction comparisons that will further characterize the benefit-risk profile of the RTS,S/AS01E vaccine. Trial registration: clinicaltrials.gov NCT02374450. [ABSTRACT FROM AUTHOR]

Background: Understanding why some infants tolerate infections, remaining asymptomatic while others succumb to repeated symptomatic malaria is beneficial for studies of naturally acquired immunity and can guide control interventions. This study compared demographic, host and maternal factors associated with being either parasite negative or having asymptomatic infections versus developing symptomatic malaria in the first year of life. Methods: A birth cohort (n = 1264) was monitored longitudinally over two years for malaria infections in Kintampo, Ghana. Symptomatic and asymptomatic infections were detected actively through monthly home visits, complemented by passive case detection. Light microscopy was used to detect parasitaemia. Based on data from a minimum of eight monthly visits within the first year of life, infants were classified into one of four groups: "parasite negative", "only-asymptomatic", "only-symptomatic" or "alternating" i.e., sometimes symptomatic and other times asymptomatic. The host and maternal characteristics and demographic factors in relation to these four groups were compared. Results: The parasite negative group formed 36% of the cohort, whilst the only-symptomatic were 35%. The alternating group were 22% and the only-asymptomatic were 7% of the cohort. There were significant associations between residence, socio-economic status (SES), parity, IPTp doses, delivery place of infant and having or not having malaria parasites. Maternal factors such as early commencement and frequency of ante-natal care (ANC) were significantly higher in the parasite negative group compared to all others. ITN use in pregnancy increased the odds of infant having only asymptomatic infections ("protected against disease"). Placental malaria was more common in the groups of infants with symptomatic malaria. Urban residence was significantly higher in the parasite negative group, while birth in the malaria transmission season were significantly more common in the alternating and parasite negative groups. Risk factors for infants with symptomatic malaria included low SES, birth in private maternity homes, sickle cell normal variant, lower MUAC, reported intake of anti-malarials and increased morbidity before the first microscopic infection was detected. Conclusion: Strengthening ANC by encouraging early and regular attendance, the use of IPTp, maternal bed nets and improving the nourishment of infants help reduce the frequency of symptomatic malaria over the first year of life. [ABSTRACT FROM AUTHOR]

Background: Recent studies from different malaria-endemic regions including western Africa have now shown that Plasmodium vivax can infect red blood cells (RBCs) and cause clinical disease in Duffy-negative people, though the Duffy-negative phenotype was thought to confer complete refractoriness against blood invasion with P. vivax. The actual prevalence of P. vivax in local populations in Ghana is unknown and little information is available about the distribution of Duffy genotypes. The aim of this study was to assess the prevalence of P. vivax in both asymptomatic and symptomatic outpatients and the distribution of Duffy genotypes in Ghana. Methods: DNA was extracted from dried blood spots (DBS) collected from 952 subjects (845 malaria patients and 107 asymptomatic persons) from nine locations in Ghana. Plasmodium species identification was carried out by nested polymerase chain reaction (PCR) amplification of the small-subunit (SSU) rRNA genes. For P. vivax detection, a second PCR of the central region of the Pvcsp gene was carried out. Duffy blood group genotyping was performed by allele-specific PCR to detect the presence of the FYES allele. Results: No cases of P. vivax were detected in any of the samples by both PCR methods used. Majority of infections (542, 94.8%) in the malaria patient samples were due to P. falciparum with only 1 infection (0.0017%) due to Plasmodium malariae, and 2 infections (0.0034%) due to Plasmodium ovale. No case of mixed infection was identified. Of the samples tested for the FYES allele from all the sites, 90.5% (862/952) had the FYES allele. All positive samples were genotyped as FY*B-33/FY*B-33 (Duffy-negative homozygous) and therefore classified as Fy(a−b−). Conclusions: No cases of P. vivax were detected by both PCRs and majority of the subjects tested carried the FYES allele. The lack of P. vivax infections observed can be attributed to the high frequency of the FYES allele that silences erythroid expression of the Duffy. These results provide insights on the host susceptibility for P. vivax infections that had not been investigated in Ghana before. [ABSTRACT FROM AUTHOR]

Background: In the absence of microscopy, Plasmodium falciparum histidine-rich proteins 2 (PfHRP2)-based rapid diagnostic tests (RDTs) are recommended for the diagnosis of falciparum malaria, particularly in endemic regions. However, genetic variability of the pfhrp2 gene threatens the usefulness of the test due to its impact on RDT sensitivity. This study aimed to investigate the diversity of pfhrp2 in malaria cases among children in Ghana. Methods: A cross-sectional study was conducted at the Adidome Government Hospital in the Volta Region of Ghana. A total of 50 children with mean age of 6.6 ± 3.5 years and diagnosed falciparum malaria were included. Blood samples were collected for complete blood count, malaria parasite identification and counting using auto analyzer and microscopy, respectively. DNA was isolated from blood-spotted Whatman filters, amplified and sequenced. Nucleotide sequences were translated in silico to corresponding amino acids and the deduced amino acids sequences were analyzed for diversity using Mega X. Results: The number of repeats and number of each repeat within PfHRP2 varied between isolates. Twelve rare PfHRP2 repeat types, two of which are previously unreported, were identified in this study. The HRP2 sequence obtained in this study shared high similarities with isolates from Kenya. Using Baker's regression model, Group B was the highest occurring type (58.0%). Screening of all sequences for epitopes recognized by PfHRP2-specific monoclonal antibodies (mAbs), the predominant motif was AHHAADAHH, which is recognized by the C1-13 mAbs. Conclusion: This study reports diversity of P. falciparum HRP2 in samples from Ghanaian children with symptomatic malaria. The findings of this study highlight the existence of extra amino acid repeat types which adds to the PfHRP2 antigenic variability. [ABSTRACT FROM AUTHOR]

Background: Artemisinin-based combination therapy (ACT) partner drugs, currently used in Ghana are lumefantrine, amodiaquine and piperaquine. Plasmodium falciparum isolates with reduced susceptibility to these partner drugs may affect treatment outcome. Mutations in pfmdr1 gene is linked to reduced parasite susceptibility to amodiaquine and lumefantrine. In addition, the potency of the partner drugs in vivo depends on the metabolism by the cytochrome P450 (CYP) enzyme in the host. Mutations in the CYP2C8 and CYP3A4 genes are linked to reduced metabolism of amodiaquine and lumefantrine in vitro, respectively. This study investigated the host and parasite genetic factors affecting the susceptibility of the malaria parasite to ACT partner drugs. Methods: Archived samples from 240 patients age ≤ 9 years participating in anti-malarial drug resistance survey in Ghana, and given artemether with lumefantrine (AL) or artesunate with amodiaquine (AA), were selected and analysed. Polymerase chain reaction (PCR) followed by Sanger sequencing was used to determine the polymorphisms in CYP2C8, CYP3A4 and pfmdr1 genes. Results: For CYP3A4, all had wild type alleles, suggesting that the hosts are good metabolizers of lumefantrine. For CYP2C8 60% had wild type alleles, 35% heterozygous and 5% homozygous recessive alleles suggesting efficient metabolism of amodiaquine by the hosts. For pfmdr1 gene, at codon 86, 95% were wild type (N86) and 5% mutant (Y86). For codon 184, 36% were wild type (Y184) and 64% mutant (F184) while for codons 1034, 1042 and 1246, 100% (all) were wild type. The high prevalence of N86-F184-D1246 haplotype (NFD) suggest presence of parasites with reduced susceptibility to lumefantrine and not amodiaquine. Delayed clearance was observed in individuals with mutations in the pfmdr1 gene and not cytochrome 450 gene. Both synonymous and non-synonymous mutations were observed in the pfmdr1 at low prevalence. Conclusion: The outcome of this study indicates that the parasite's genetic factors rather than the host's are likely to drive resistance to ACT in Ghana. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to determine the coverage of intermittent preventive treatment of malaria in pregnancy (IPTp) and its relationship with delivery outcomes among obstetric referral cases at the district level of healthcare. Methods: An implementation research within three districts of the Greater Accra region was conducted from May 2017 to February 2018, to assess the role of an enhanced inter-facility communication system on processes and outcomes of obstetric referrals. A cross-sectional analysis of the data on IPTp coverage as well as delivery outcomes for the period of study was conducted, for all the referrals ending up in deliveries. Primary outcomes were maternal and neonatal complications at delivery. IPTp coverage was determined as percentages and classified as adequate or inadequate. Associated factors were determined using Chi square. Odds ratios (OR, 95% CI) were estimated for predictors of adequate IPTp dose coverage for associations with delivery outcomes, with statistical significance set at p = 0.05. Results: From a total of 460 obstetric referrals from 16 lower level facilities who delivered at the three district hospitals, only 223 (48.5%) received adequate (at least 3) doses of IPTp. The district, type of facility where ANC is attended, insurance status, marital status and number of antenatal clinic visits significantly affected IPTp doses received. Adjusted ORs show that adequate IPTp coverage was significantly associated with new-born complication [0.80 (0.65–0.98); p = 0.03], low birth weight [0.51 (0.38–0.68); p < 0.01], preterm delivery [0.71 (0.55–0.90); p = 0.01] and malaria as indication for referral [0.70 (0.56–0.87); p < 0.01]. Positive association with maternal complication at delivery was seen but was not significant. Conclusion: IPTp coverage remains low in the study setting and is affected by type of health facility that ANC is received at, access to health insurance and number of times a woman attends ANC during pregnancy. This study also confirmed earlier findings that, as an intervention IPTp prevents bad outcomes of pregnancy, even among women with obstetric referrals. It is important to facilitate IPTp service delivery to pregnant women across the country, improve coverage of required doses and maximize the benefits to both mothers and newborns. [ABSTRACT FROM AUTHOR]

Background: The ABO and the Rhesus blood group systems, as well as various abnormal haemoglobin (Hb) variants (haemoglobinopathies) are known to influence malaria parasite carriage and disease severity in individuals living in malaria endemic areas. This study identified the blood group and Hb variant distribution and Plasmodium falciparum infection status of afebrile individuals living in southern Ghana. Methods: Afebrile participants were recruited from Obom (358) in the Greater Accra Region and Ewim (100) and Simiw (329) in the Central Region of Ghana. Venous blood (1 ml) was collected into EDTA vacutainer tubes. Three 20 μl drops of blood were used for blood group analysis using the tile method. Another 500 μl aliquot was used for the qualitative sickling test using sodium metabisulphite and haemoglobin electrophoresis. Genomic DNA was extracted from 100 μl of whole blood and used in P. falciparum species-specific PCR. Results: The most abundant blood group and abnormal haemoglobin variant in both sites was blood group O + (47.4%) and HbAS (15.8%). A total of 13 (1.7%) of the participants had full haemoglobinopathies (SS, SC and CC), whilst 196 (25.4%) were carriers (AS and AC). Although there was a significantly higher prevalence of sickling positive participants from the Central Region, genotyping identified a similar prevalence of each of the abnormal haemoglobin genes in both sites. Asymptomatic parasite carriage estimated by PCR was 40.9% in the Central Region and 41.8% in the Greater Accra Region. Conclusions: Asymptomatic carriage of P. falciparum parasite in the study population was not associated with any particular blood group variant or haemoglobin genotype. [ABSTRACT FROM AUTHOR]

Background: Ghana has made impressive progress against malaria, decreasing mortality and morbidity by over 50% between 2005 and 2015. These gains have been facilitated in part, due to increased financial commitment from government and donors. Total resources for malaria increased from less than USD 25 million in 2006 to over USD 100 million in 2011. However, the country still faces a high burden of disease and is at risk of declining external financing due to its strong economic growth and the consequential donor requirements for increased government contributions. The resulting financial gap will need to be met domestically. The purpose of this study was to provide economic evidence of the potential risks of withdrawing financing to shape an advocacy strategy for resource mobilization. Methods: A compartmental transmission model was developed to estimate the impact of a range of malaria interventions on the transmission of Plasmodium falciparum malaria between 2018 and 2030. The model projected scenarios of common interventions that allowed the attainment of elimination and those that predicted transmission if interventions were withheld. The outputs of this model were used to generate costs and economic benefits of each option. Results: Elimination was predicted using the package of interventions outlined in the national strategy, particularly increased net usage and improved case management. Malaria elimination in Ghana is predicted to cost USD 961 million between 2020 and 2029. Compared to the baseline, elimination is estimated to prevent 85.5 million cases, save 4468 lives, and avert USD 2.2 billion in health system expenditures. The economic gain was estimated at USD 32 billion in reduced health system expenditure, increased household prosperity and productivity gains. Through malaria elimination, Ghana can expect to see a 32-fold return on their investment. Reducing interventions, predicted an additional 38.2 clinical cases, 2500 deaths and additional economic losses of USD 14.1 billion. Conclusions: Malaria elimination provides robust epidemiological and economic benefits, however, sustained financing is need to accelerate the gains in Ghana. Although government financing has increased in the past decade, the amount is less than 25% of the total malaria financing. The evidence generated by this study can be used to develop a robust domestic strategy to overcome the financial barriers to achieving malaria elimination in Ghana. [ABSTRACT FROM AUTHOR]

Background: The Ministry of Health, Ghana, in accordance with global policy, recommends that all suspected malaria cases be confirmed parasitologically before treatment. Not all clinicians, however, base their treatment on test results. Patients also spend a lot of time at health facilities waiting to consult a clinician before being asked to go for testing and to see a clinician with test results. The purpose of the study was to determine if testing all children aged 6 to 59 months with fever reporting at an outpatients department (OPD) for malaria before consultation with a clinician (pre-consultation testing) will influence clinicians to adhere to test results and also reduce the time spent by such patients. Methods: A quasi-experimental study design was used involving two randomly selected government-owned hospitals in the Northern Volta, Ghana. In each hospital, 439 children were recruited between November 2018 and January 2019. The intervention hospital implemented pre-consultation testing. In the comparator arm, standard practices, which involved patients seeing the clinician before he/she decides whether to send the patient for testing or not, were maintained. Results: Out of 878 children screened the overall prevalence of malaria was 31.9% by malaria rapid diagnostic test (RDT) and 26.7% by microscopy. Clinicians in the intervention arm adhered more to the malaria test results than those in the comparator arm (93.2 vs. 84.3%; p < 0.001). The proportion of children who tested negative but were still diagnosed with malaria was significantly lower in the intervention arm compared to the comparator arm (8.4 vs. 21.2%: p < 0.001). Clinicians and mothers/caregivers in both arms preferred pre-consulting testing. Six out of every 10 mothers/caregivers in the comparator arm viewed the waiting time as 'too long" compared to 4 out of every 10 mothers in the intervention arm. On average, patient waiting time was significantly lower in the intervention arm (2.61 h) than in the comparator arm (3.42 h). Conclusion: Pre-consultation testing significantly improves clinicians' adherence to malaria test results, shortens patients' waiting time and leads to overall patient satisfaction. There is a need to establish RDT corners at OPDs of health facilities to implement pre-consultation testing. [ABSTRACT FROM AUTHOR]

Background: Insecticide-treated nets (ITNs) are one of the most cost-effective measures for preventing malaria. The World Health Organization recommends both large-scale mass distribution campaigns and continuous distributions (CD) as part of a multifaceted strategy to achieve and sustain universal access to ITNs. A combination of these strategies has been effective for scaling up ITN access. For policy makers to make informed decisions on how to efficiently implement CD or combined strategies, information on the costs and cost-effectiveness of these delivery systems is necessary, but relatively few published studies of the cost continuous distribution systems exist. Methods: To address the gap in continuous distribution cost data, four types of delivery systems—CD through antenatal care services (ANC) and the expanded programme on immunization (EPI) (Ghana, Mali, and mainland Tanzania), CD through schools (Ghana and mainland Tanzania), and a combined community/health facility-based distribution (Zanzibar, Tanzania), as well as mass distributions (Mali)—were costed. Data on costs were collected retrospectively from financial and operational records, stakeholder interviews, and resource use surveys. Results: Overall, from a full provider perspective, mass distributions and continuous systems delivered ITNs at overlapping economic costs per net distributed (mass distributions: 4.37–4.61 USD, CD channels: 3.56–9.90 USD), with two of the school-based systems and the mass distributions at the lower end of this range. From the perspective of international donors, the costs of the CD systems were, for the most part, less costly than the mass distributions (mass distributions: 4.34–4.55 USD, Ghana and Tanzania 2017 school-based: 3.30–3.69 USD, health facility-based: 3.90–4.55 USD, combined community/health facility 4.55 USD). The 2015 school-based distribution (7.30 USD) and 2016 health facility-based distribution (6.52 USD) programmes in Tanzania were an exception. Mass distributions were more heavily financed by donors, while CD relied more extensively on domestic resource contributions. Conclusions: These results suggest that CD strategies can continue to deliver nets at a comparable cost to mass distributions, especially from the perspective of the donor. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic carriage of Plasmodium falciparum is widespread in adults and children living in malaria-endemic countries. This study identified the prevalence of malaria parasites and the corresponding levels of naturally acquired anti-parasite antibody levels in afebrile adults living in two communities in the Greater Accra Region of Ghana. Methods: Two cross-sectional studies conducted in January and February 2016 and repeated in July and August 2016 recruited subjects aged between 6 and 75 years from high parasite prevalence (Obom) and low parasite prevalence (Asutsuare) communities. Whole blood (5 ml) was collected from each volunteer, plasma was aliquoted and frozen until needed. An aliquot (10 µl) of the blood was used to prepare thick and thin blood smears, 100 µl was preserved in Trizol and the rest was separated into plasma and blood cells and each stored at − 20 °C until needed. Anti-MSP3 and Pfs230 antibody levels were measured using ELISA. Results: Asexual parasite and gametocyte prevalence were higher in Obom than Asutsuare. Antibody (IgG, IgG1, IgG3, IgM) responses against the asexual parasite antigen MSP3 and gametocyte antigen Pfs230 were higher in Obom during the course of the study except for IgM responses against Pfs230, which was higher in Asutsuare than in Obom during the rainy season. Antibody responses in Asutsuare were more significantly associated with age than the responses measured in Obom. Conclusion: The pattern of antibody responses measured in people living in the high and low malaria transmission setting was similar. All antibody responses measured against the asexual antigen MSP3 increased, however, IgG and IgG1 responses against gametocyte antigen Pfs230 decreased in moving from the dry to the peak season in both sites. Whilst asexual and gametocyte prevalence was similar between the seasons in the low transmission setting, in the high transmission setting asexual parasite prevalence increased but gametocyte prevalence decreased in the rainy season relative to the dry season. [ABSTRACT FROM AUTHOR]

Background: Expanding access to long-lasting insecticidal nets (LLINs) is difficult if one is limited to government and donor financial resources. Private commercial markets could play a larger role in the continuous distribution of LLINs by offering differentiated LLINs to middle-class Ghanaians. This population segment has disposable income and may be willing to pay for LLINs that meet their preferences. Measuring the willingness-to-pay (WTP) for LLINs with specialty features that appeal to middle-class Ghanaians could help malaria control programmes understand what is the potential for private markets to work alongside fully subsidized LLIN distribution channels to assist in spreading this commodity. Methods: This study conducted a discrete choice experiment (DCE) including a real payment choice among a representative sample of 628 middle-income households living in Ashanti, Greater Accra, and Western regions in Ghana. The DCE presented 18 paired combinations of LLIN features and various prices. Respondents indicated which LLIN of each pair they preferred and whether they would purchase it. To validate stated willingness-to-pay, each participant was given a cash payment of $14.30 (GHS 65) that they could either keep or immediately spend on one of the LLIN products. Results: The households' average probability of purchasing a LLIN with specialty features was 43.8% (S.D. 0.07) and WTP was $7.48 (GHS34.0). The preferred LLIN features were conical or rectangular one-point-hang shape, queen size, and zipper entry. The average WTP for a LLIN with all the preferred features was $18.48 (GHS 84). In a scenario with the private LLIN market, the public sector outlay could be reduced by 39% and private LLIN sales would generate $8.1 million ($311 per every 100 households) in revenue in the study area that would support jobs for Ghanaian retailers, distributors, and importers of LLINs. Conclusion: Results support a scenario in which commercial markets for LLINs could play a significant role in improving access to LLINs for middle-income Ghanaians. Manufacturers interested could offer LLIN designs with features that are most highly valued among middle-income households in Ghana and maintain a retail price that could yield sufficient economic returns. [ABSTRACT FROM AUTHOR]

Background: Routine surveillance on the therapeutic efficacy of artemisinin-based combination therapy (ACT) has been ongoing in Ghana since 2005. The sixth round of surveillance was conducted between 2015 and 2017 to determine the therapeutic efficacy of artesunate–amodiaquine (AS–AQ) and artemether–lumefantrine (AL) in 10 sentinel sites across the country. Methods: The study was a one-arm, prospective, evaluation of the clinical, parasitological, and haematological responses to directly observed treatment with AS–AQ and AL among children 6 months to 9 years old with uncomplicated falciparum malaria. The WHO 2009 protocol on surveillance of anti-malaria drug efficacy was used for the study with primary outcomes as prevalence of day 3 parasitaemia and clinical and parasitological cure rates on day 28. Secondary outcomes assessed included patterns of fever and parasite clearance as well as changes in haemoglobin concentration. Results: Day 3 parasitaemia was absent in all sites following treatment with AS–AQ whilst only one person (0.2%) was parasitaemic on day 3 following treatment with AL. Day 28 PCR-corrected cure rates following treatment with AS–AQ ranged between 96.7% (95% CI 88.5–99.6) and 100%, yielding a national rate of 99.2% (95% CI 97.7–99.7). Day 28 PCR-corrected cure rates following treatment with AL ranged between 91.3% (95% CI 79.2–97.6) and 100%, yielding a national rate of 96% (95% CI 93.5–97.6). Prevalence of fever declined by 88.4 and 80.4% after first day of treatment with AS–AQ and AL, respectively, whilst prevalence of parasitaemia on day 2 was 2.1% for AS–AQ and 1.5% for AL. Gametocytaemia was maintained at low levels (< 5%) during the 3 days of treatment. Post-treatment mean haemoglobin concentration was significantly higher than pre-treatment concentration following treatment with either AS–AQ or AL. Conclusions: The therapeutic efficacy of AS–AQ and AL is over 90% in sentinel sites across Ghana. The two anti-malarial drugs therefore remain efficacious in the treatment of uncomplicated malaria in the country and continue to achieve rapid fever and parasite clearance as well as low gametocyte carriage rates and improved post-treatment mean haemoglobin concentration. [ABSTRACT FROM AUTHOR]

Background: Injectable artesunate (AS) is the World Health Organization (WHO) recommended medication for the treatment of severe malaria followed with an oral artemisinin-based combination therapy (ACT). There are few studies indicating how physicians prescribe injectable AS, injectable quinine (Q) or injectable artemether (AR) and ACT for severe malaria. This study was undertaken to evaluate prescription compliance to the WHO recommendation in 8 public health facilities in Ghana and Uganda. This was a modified cohort event monitoring study involving patients who were administered with injectable anti-malarial for treatment of presumed or confirmed severe malaria. Patients prescribed at least one dose of injectable artesunate, artemether or quinine qualified to enrol in the study. Patients were recruited at inpatient facilities and followed up in the hospital, by phone or at home. Following WHO recommendations, patients are to be prescribed 3 doses of injectable AS, Q or AR for at least 24 h followed with oral ACT. Compliance rate was estimated as the number of patient prescriptions that met the WHO recommendation for treatment of severe malaria divided by the total number of patients who completed the study by end of follow up. Log-binomial regression model was used to identify predictors for compliance. Based on the literature and limitations of available data from the patients' record, the diagnosis results, age, gender, weight, and country were considered as potential predictors of prescriber adherence to the WHO recommendations. Results: A total of 1191 patients completed the study, of which 93% were prescribed injectable AS, 3.1% (injectable AR or Q) with 32.5% prescribed follow-on oral ACT and 26% on concomitant antibiotics. 391 (32.8%) were in Ghana and 800 (67.2%) in Uganda. There were 582 (48.9%) women. The median age was 3.9 years (IQR = 2, 9) and median weight was 13 kg (IQR = 10, 20). Of the 1191 patients, 329 of the prescriptions complied with the WHO recommendation (compliance rate = 27.6%; 95% CI = [25.2, 30.2]). Diagnostic results (Adjusted prevalence ratio (aPR) = 4.56; 95% = [3.42, 6.08]; p < 0.0001) and weight (20 + kg vs < 10 kg: aPR = 0.65; 95% = [0.44, 0.96]; p = 0.015) were identified as factors independently associated with compliance. Conclusion: Injectable AS is the most commonly prescribed medicine in the management of severe malaria in Ghana and Uganda. However, adherence to the WHO recommendation of at least 3 doses of injectable anti-malarial in 24 h followed by a full course of ACT is low, at less than 30%. [ABSTRACT FROM AUTHOR]

Background: Recent global reports on malaria suggest significant decrease in disease severity and an increase in control interventions in many malaria endemic countries, including Ghana. However, a major driving force sustaining malaria transmission in recent times is the asymptomatic carriage of malaria parasites, which can enhance immune responses against parasite antigens. This study determined the prevalence and relative avidities of naturally induced antibodies to EBA175RIII-VLl in asymptomatic children living in two communities with varying malaria transmission patterns. Methods: An asexual stage Plasmodium falciparum antigen, EBA175RIII-VLl was expressed in Lactococcus lactis, purified and used in indirect ELISA to measure total and cytophilic IgG concentrations and avidities in children aged between 6 and 12 years. The children were selected from Obom and Abura, communities with perennial and seasonal malaria transmission, respectively. Venous blood samples were collected in July and October 2015 and again in January 2016. The multiplicity of infection and the genetic diversity of EBA175RIII circulating in both sites were also assessed using polymerase chain reaction. Results: Asymptomatic parasite carriage in the children from Obom decreased from July (peak season), through October and January, however parasite carriage in children from Abura was bimodal, with the lowest prevalence estimated in October. Antibody concentrations over the course of the study remained stable within each study site however, children living in Obom had significantly higher EBA175RIII-VLl antibody concentrations than children living in Abura (P < 0.05, Mann-Whitney test). Over the course of the study, the relative antibody avidities of EBA175RIII-VLl IgG antibodies were similar within and between the sites. Conclusion: Naturally acquired IgG concentrations but not relative antibody avidities to EBA175RIII-V were significantly higher in Obom where malaria transmission is perennial than in Abura, where malaria transmission is seasonal. [ABSTRACT FROM AUTHOR]

Background: In the past two decades, there has been a reported decline in malaria in Ghana and the rest of the world; yet it remains the number one cause of mortality and morbidity. Human immuno-deficiency virus (HIV) and sickle cell disease (SCD) share a common geographical space with malaria in sub-Saharan Africa and an interaction between these three conditions has been suggested. This study determined the Plasmodium falciparum and non-P. falciparum status of symptomatic and non-symptomatic residents of Mpraeso in the highlands of Kwahu-South district of Ghana based on evidence of current national decline. The influence of HIV and SCD on malaria was also determined. Methods: Participants were 354 symptomatic patients visiting the Kwahu Government Hospital and 360 asymptomatic residents of the district capital. This cross-sectional study was conducted during the minor rainy season (October--December 2014). Rapid diagnostic tests (RDT), blood film microscopy and real-time polymerase chain reaction assessment of blood were done. Participants who tested positive with RDT were treated with artemisininbased combination therapy; and assessment of venous blood was repeated 7 days after treatment. HIV screening and haemoglobin genotyping was done. Univariate and multivariate regression analysis was used to determine the influence of SCD and HIV. Results: Plasmodium falciparum was prevalent at 124/142 (87.3%). Plasmodium malariae was the only non-falciparum species detected at 18/142 (12.7%). HIV and SCD did not significantly increase odds of malaria infection. However, the use of ITN and recent anti-malarial intake significantly decreased the odds of being malaria infected by 0.45-fold and 0.46-fold respectively. Conclusion: Plasmodium falciparum and P. malariae infection are the prevailing species in the study area; albeit varying from the national average. HIV and SCD were not associated with the risk of having malaria. [ABSTRACT FROM AUTHOR]