Detection of Invasive Anopheles stephensi Mosquitoes through Molecular Surveillance, Ghana.

The invasive Anopheles stephensi mosquito has rapidly expanded in range in Africa over the past decade. Consistent with World Health Organization guidelines, routine entomologic surveillance of malaria vectors in Accra, Ghana, now includes morphologic and molecular surveillance of An. stephensi mosquitoes. We report detection of An. stephensi mosquitoes in Ghana.

Patterns and predictors of malaria among head porters: a mobile population in Ghana.

BACKGROUND: Head porters popularly known as 'Kayayeis in Ghana, face challenges in accessing essential health care services due to the mobile nature of their trade, low formal education, poor settlements, low-income among others. Kayayeis are predominantly females and form part of the mobile population who are at increased risk of malaria infection. Despite their increased risk of malaria, mobile populations are difficult to target for malaria interventions, hence serving as potential drivers of transmission even if malaria in the general population is controlled. The study, therefore, assessed the patterns and predictors of malaria among the Kayayei population in Ghana to inform policy decisions. METHODS: A mixed methods study was conducted among Head-porters and their leaders in the three main hubs of Head-porters in Ghana; namely Accra, Kumasi, and Tamale. Blood samples were collected from participants and tested for malaria parasites using Rapid Diagnostic Test (RDT). Additionally, data including socio-demographics, malaria knowledge, attitude and practice were collected using a semi-structured questionnaire. Associations between malaria status and participants characteristics were determined by logistic regression (p < 0.05). Thematic analysis was used to analyse transcripts from the key informant interviews. RESULTS: Out of 754 head porters studied, 10.48% (79) tested positive for malaria. The majority 43.10% (325/754) of the head porters were twenty years and below, and most 67.11% (506/754) had no formal education. Nearly half (50.4%) were not on any health insurance. Receiving malaria education in the past 6 months [AOR = 0.48, (0.26-0.88), p-value 0.02], and having poor knowledge of malaria [AOR = 2.23, (1.26-4.27), p < 0.02], were the factors significantly associated with malaria infection. CONCLUSION: The prevalence of malaria among 'Kayayei's was estimated at 10.46%. A majority of them sleeps outside and in structures without mosquito screens. Receiving malaria education in the past 6 months reduced the odds of malaria infection whilst poor knowledge of malaria increased the odds of malaria infection among the porters. The authors recommend that the National Malaria Elimination Programme and partners should provide long-lasting insecticidal nets (LLIN) and other outdoor interventions for use by this special group. Designated state institutions should arrange free National Health Insurance Scheme (NHIS) registration for 'Kayayeis' to narrow the health access gap.

Patient socio-demographics and clinical factors associated with malaria mortality: a case control study in the northern region of Ghana.

BACKGROUND: Ghana is a malaria-endemic country with the entire population at risk. The Northern region of the country recorded the highest malaria case fatality rate (CFR) for two consecutive years: 1.11% in 2013 and 1.07% in 2014. Even though the National Malaria Elimination Programme (NMEP) has achieved a reduction in malaria mortality, the existence of high case fatality in the Northern region was alarming. This study, therefore, aimed to determine the factors associated with malaria mortality in the northern region of Ghana to institute control measures. METHODS: An unmatched case control study was conducted from July 2015 to August 2015. The study population consisted of patients admitted to health facilities for severe malaria in the Northern region of Ghana. A case was defined as a patient diagnosed with severe malaria at an eligible health facility who died as a result of malaria. A control was a patient diagnosed with severe malaria admitted to an eligible health facility who did not die. Health facilities that recorded CFRs of 1.0% and above were randomly sampled for this study, after which, 10 cases and 20 controls were recruited from each health facility. Information on cases and controls was then abstracted from hospital records using an electronically deployed abstraction tool. Continuous variables were expressed as means and medians, and categorical variables as frequencies and proportions. Multivariable logistic regression was used to assess the strength of the association between malaria mortality and factors predictive of malaria mortality. A p-value of < 0.05 was considered statistically significant. RESULTS: In all, a total of 95 cases and 190 controls participated in this study. The median ages of cases and controls were 4.1 years (IQR = 21.6) and 5.7 years (IQR = 18.2), respectively. Fifty-four (56.8%) cases were females, while 93 (49.0%) of the controls were females. Factors associated with malaria mortality included: duration of hospital stay less than 24 h [aOR: 12.0, 95% CI (5.9-24.6)], severe pallor [aOR: 2.3, 95% CI (1.1-4.6)], children under 5 years [aOR: 2.8, 95% CI (1.4-5.6)], oral Artesunate/Amodiaquine administration [aOR: 0.4, 95% CI (0.2-0.9)] and sepsis as an additional diagnosis [aOR: 4.1, 95% CI (1.8-9.5)]. CONCLUSION: Predictors of malaria mortality in the Northern region include children under 5 years, severe pallor, sepsis as an additional diagnosis, and use of oral anti-malarial. Patients with severe pallor and sepsis as co-morbidities should receive proactive management. The NMEP and its partners should implement measures to strengthen the referral system, anaemia prevention and management, and retrain health workers on malaria case management. Malaria control interventions targeted at under five children in the region should be reviewed and enhanced.

Successful implementation of ITN distribution through health facilities in Ghana.

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.

Measuring quality of facility-based ITN distribution in Ghana.

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.

Cost of inappropriate prescriptions for uncomplicated malaria in Ghana.

BACKGROUND: Malaria remains a common course of morbidity in many sub-Saharan African countries. While treatment options have improved in recent times, inappropriate prescription seems conventional among providers, increasing the burden on patients and society. This study examined the cost of inappropriate prescriptions for uncomplicated malaria treatment in Ghana. METHODS: This study used retrospective data collected from January to December 2016 in 27 selected facilities, under different ownership in three regions of the country, mainly Volta, Upper East and Brong Ahafo. Stratified random sampling technique was used to extract 1625 outpatient folders of patients diagnosed and treated for malaria. Two physicians independently reviewed patient folders according to the stated diagnoses. Malaria prescriptions were described as inappropriate when they do not adhere to the standard treatment guidelines. The economic cost was mainly treatment cost which was sourced as medication cost. Total and average costs for country were calculated using sample estimates and the total number of uncomplicated malaria cases that received inappropriate prescriptions. RESULTS: The study revealed that patients received an average of two prescriptions per malaria episode. Artemether-lumefantrine (AL) was the major malaria medication (79.5%) prescribed to patients. Other medications usually antibiotics and vitamins and minerals were included in the prescription. More than 50% of prescribers did not follow the guidelines for prescribing medications to clients. By facility type, inappropriate prescription was high in the CHPS compounds (59.1%) and by ownership, government (58.3%), private (57.5%) and mission facilities (50.7%). Thus, about 55% of malaria prescriptions were evaluated as inappropriate during the review period, which translates into economic cost of approximately US$4.52 million for the entire country in 2016. The total cost of inappropriate prescription within the study sample was estimated at US$1,088.42 while the average cost was US$1.20. CONCLUSION: Inappropriate prescription for malaria is a major threat to malaria management in Ghana. It presents a huge economic burden to the health system. Training and strict enforcement of prescribers' adherence to the standard treatment guideline is highly recommended.

Incremental cost and cost-effectiveness of the addition of indoor residual spraying with pirimiphos-methyl in sub-Saharan Africa versus standard malaria control: results of data collection and analysis in the Next Generation Indoor Residual Sprays (NgenIRS) project, an economic-evaluation.

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.

Impact of malaria diagnostic refresher training programme on competencies and skills in malaria diagnosis among medical laboratory professionals: evidence from Ghana 2015-2019.

BACKGROUND: The quality of malaria test results is crucial for optimal patient treatment and care. The Ghana Health Service is successfully shifting from presumptive clinical diagnosis and treatment of malaria to the Test, Treat and Track (T3) initiative. In line with the initiative, the National Malaria Control Programme (NMCP) set out to improve the capacity of medical laboratory professionals in Ghana through a five-day Malaria Diagnostic Refresher Training (MDRT) to build competencies and skills in malaria diagnosis, especially in the three components of microscopy: parasite detection, species identification and parasite quantification. This study evaluates the impact of the training on malaria microscopy. METHODS: The training which was based on the World Health Organization basic malaria microscopy training guide employed presentations and practical approaches to malaria diagnosis. A total number of 765 medical laboratory professionals from various health facilities across the country were trained every other year from 2015 to 2019 and were included in this evaluation. Evaluation of this training was done using pre-test and post-test microscopy scores. The Negative Binomial fixed effect model was used in determining the overall effect of the training in improving the competencies of the participants on malaria microscopy. RESULTS: The ability of the medical laboratory professionals to correctly detect malaria parasites increased significantly from a median score of 64% prior to the training to 87% after the training (p < 0.001). The competencies of the medical laboratory scientists to correctly identify malaria parasite species and quantify the number of malaria parasites increased significantly from a median score of 17% and 20% pre-test to 78% and 50% post-test, respectively (p < 0.001). The results showed that participants' competency level and skill to perform malaria microscopy (species identification, parasite quantification and detection of malaria parasites) increased by approximately two folds after the training compared to the no-training scenario (adjusted rate ratio = 2.07, 95% CI 2.01-2.13, p < 0.001). CONCLUSION: The MDRT programme significantly improved participants' performance of malaria microscopy over a short period of time.

Evaluation of pilot implementation of seasonal malaria chemoprevention on morbidity in young children in Northern Sahelian Ghana.

BACKGROUND: In Sahelian Africa, the risk of malaria increases with the arrival of the rains, particularly in young children. Following successful trials, the World Health Organization (WHO) recommended the use of seasonal malaria chemoprevention (SMC) in areas with seasonal peak in malaria cases. This study evaluated the pilot implementation of SMC in Northern Ghana. METHODS: Fourteen communities each serving as clusters were selected randomly from Lawra District of Upper West Region as intervention area and West Mamprusi District in the Northern Region as the non-intervention area. The intervention was undertaken by the National Malaria Control Programme in collaboration with regional health directorates using sulfadoxine-pyrimethamine plus amodiaquine and standard WHO protocols. Before and after surveys for malaria parasitaemia and haemoglobin levels as well as monitoring for malaria morbidity and mortality were undertaken. RESULTS: At the end of the intervention, participant retention was 92.9% (697/731) and 89.5% (634/708) in the intervention and the non-intervention areas, respectively. The proportion of children with asexual parasites reduced by 19% (p = 0.000) in the intervention and increased by 12% (p = 0.000) in the non-intervention area. Incidence rates of severe malaria were 10 and 20 per 1000 person-years follow up in the intervention and comparison areas, respectively with P.E of 45% (p = 0.62). For mild malaria, it was 220 and 170 per 1000 person-years in intervention and comparison area, respectively with PE of - 25% (p = 0.31). The proportion of children with anaemia defined as Hb< 11.0 g/dl reduced from 14.2% (52.8-38.6%) in the intervention area as compared to an increase of 8.1% (54.5% to 62.6) the non-intervention arm, Mean Hb reduced by 0. 24 g/dl (p = 0.000) in the non-intervention area and increased of 0.39 g/dl (p = 000) in the intervention area. CONCLUSIONS: The feasibility and effectiveness of SMC introduction in Northern Ghana was demonstrated as evidenced by high study retention, reduction in malaria parasitaemia and anaemia during the wet season.

Trends and predictive factors for treatment failure following artemisinin-based combination therapy among children with uncomplicated malaria in Ghana: 2005-2018.

BACKGROUND: Since the introduction of artemisinin-based combination therapy (ACT) in Ghana in 2005 there has been a surveillance system by the National Malaria Control Programme (NMCP) and the University of Ghana Noguchi Memorial Institute for Medical Research (UG-NMIMR) to monitor the therapeutic efficacy of ACTs for the treatment of uncomplicated malaria in the country. We report trends and determinants of failure following treatment of Ghanaian children with artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) combinations. METHODS: Per protocol analyses as well as cumulative incidence of day 28 treatment failure from Kaplan Meier survival analyses were used to describe trends of failure over the surveillance period of 2005-2018. Univariable and multivariable cox regression analyses were used to assess the determinants of treatment failure over the period. RESULTS: Day 28 PCR-corrected failure, following treatment with ASAQ, significantly increased from 0.0% in 2005 to 2.0% (95% CI: 1.1-3.6) in 2015 (p = 0.013) but significantly decreased to 0.4% (95% CI: 0.1-1.6) in 2018 (p = 0.039). Failure, following treatment with AL, decreased from 4.5% (95% CI: 2.0-9.4) in 2010 to 2.7% (95% CI: 1.4-5.1) in 2018, though not statistically significant (p = 0.426). Risk of treatment failure, from multivariable cox regression analyses, was significantly lower among children receiving ASAQ compared with those receiving AL (HR = 0.24; 95% CI: 0.11-0.53; p < 0.001); lower among children with no parasitaemia on day 3 compared with those with parasitaemia on day 3 (HR = 0.02; 95% CI: 0.01-0.13; p < 0.001); and higher among children who received ASAQ and had axillary temperature ≥ 37.5 °C on day 1 compared with those with axillary temperature < 37.5 °C (HR = 3.96; 95% CI: 1.61-9.75; p = 0.003). CONCLUSIONS: Treatment failures for both ASAQ and AL have remained less than 5% (below WHO's threshold of 10%) in Ghana since 2005. Predictors of treatment failure that need to be considered in the management of uncomplicated malaria in the country should include type of ACT, day 3 parasitaemia, and day 1 axillary temperature of patients being treated.

Malaria parasitaemia and mRDT diagnostic performances among symptomatic individuals in selected health care facilities across Ghana.

BACKGROUND: Parasitological diagnosis generates data to assist malaria-endemic countries determine their status within the malaria elimination continuum and also inform the deployment of proven interventions to yield maximum impact. This study determined prevalence of malaria parasitaemia and mRDT performances among febrile patients in selected health care facilities across Ghana. METHODS: This study was a cross-sectional survey conducted in the previously 10 regions of Ghana from May to August 2018. Each patient suspected to have uncomplicated malaria was tested using microscopy and two malaria rapid diagnostic tests (mRDTs): routinely used CareStart™ Malaria HRP2 (Pf) and SD Bioline Malaria Ag Pf (HRP2/pLDH). Main outcome variables were malaria slide and CareStart™ Malaria HRP2 (Pf) positivity rates; and diagnostic accuracy of CareStart™ Malaria HRP2 (Pf) and SD Bioline Malaria Ag Pf (HRP2/pLDH) using microscopy as "gold standard". RESULTS: Overall parasite positivity rates were 32.3% (6266/19402) by mRDT and 16.0% (2984/18616) by microscopy, with Plasmodium falciparum mono-infection accounting for 98.0% of all infections. The odds of parasitaemia by microscopy was significantly lower among female patients compared with males (OR = 0.78; 95% CI: 0.66-0.91), and among patients with history of previous antimalarial intake compared with those with no such history (OR = 0.72; 95% CI: 0.54-0.95). Overall sensitivity of CareStart™ Malaria HRP2 (Pf) was statistically similar to that of the HRP2 band of SD Bioline Malaria Ag Pf (HRP2/pLDH) combo kit (95.4%; 95% CI: 94.6-96.1 vs 94.3%; 95% CI: 93.4-95.1; p = 0.065) but significantly higher than the pLDH band (89.3%; 95% CI: 88.1-90.4; p < 0.001). The same pattern was observed for negative predictive value. CONCLUSIONS: Malaria control interventions should be targeted at the general population, and history of antimalarial intake considered a key predictor of malaria slide negativity. Furthermore, HRP2-based mRDTs remain effective diagnostic tool in the management of suspected uncomplicated malaria in the country.

Estimating the risk of declining funding for malaria in Ghana: the case for continued investment in the malaria response.

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.

An observational analysis of the impact of indoor residual spraying in Northern, Upper East, and Upper West Regions of Ghana: 2014 through 2017.

BACKGROUND: Ghana has been implementing the indoor residual spraying (IRS) of insecticides since 2006, focusing operations in the north. Insecticide resistance concerns prompted a switch from pyrethroids to organophosphates, beginning gradually in 2011 and switching fully to the micro-encapsulated formulation of pirimiphosmethyl (PM CS), Actellic® 300CS, a third-generation indoor residual spraying (3GIRS) product, by 2014. Entomological surveillance studies have shown IRS to be a highly effective malaria control tool, but epidemiological evidence is needed as well. Countrywide prevalence surveys have shown that malaria parasite prevalence in children under 5 years of age in Northern, Upper East, and Upper West Regions had declined to less than 40% in each region by 2016. Similarly, malaria deaths in children under 5 years of age have also been declining nationally since 2009. Although IRS is suspected to have contributed to this decline, stronger evidence is needed to link the IRS interventions to the epidemiological impact. METHODS: To assess the epidemiological impact of Ghana's IRS programmatic activities, a retrospective, observational analysis using routine epidemiological data was conducted to compare malaria incidence rates from IRS and non-IRS districts in Northern, Upper East, and Upper West Regions. Routine epidemiological data consisted of passive malaria case surveillance data reported in the District Health Information System 2 (DHIS2); with cases representing patients with suspected malaria who had sought care in the public health system and had received a confirmatory diagnosis with a positive malaria RDT result. Final routine data were extracted in September 2018. All districts that had received IRS were included in the analysis and compared to all non-IRS districts within the same region. In the Northern Region, only PMI districts were included in the analysis, as they had similar historical data. RESULTS: District-level analysis from Northern Region from 2015 to 2017 of the aggregate malaria incidence reported from IRS districts relative to non-IRS comparator districts showed 39%, 26%, and 58% fewer confirmed malaria cases reported from IRS districts in 2015, 2016, and 2017, respectively. This translates to approximately 257,000 fewer cases than expected over the three years. In Upper East Region, the effect on reported malaria cases of withdrawing IRS from the region was striking; after spray operations were suspended in 2015, incidence increased an average of 485% per district (95% confidence interval: 330% to 640%) compared to 2014. CONCLUSIONS: The current observational analysis results are in line with the entomological studies in demonstrating the positive contribution of IRS with a 3GIRS product to malaria control programmes in northern Ghana and the value of using routine surveillance and implementation data to rapidly assess the impact of vector control interventions in operational settings, even in complex implementation environments.

Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine combinations for uncomplicated malaria in 10 sentinel sites across Ghana: 2015-2017.

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.

Probing the composition of Plasmodium species contained in malaria infections in the Eastern region of Ghana.

BACKGROUND: Asymptomatic falciparum and non-falciparum malaria infections are major challenges to malaria control interventions, as they remain a source of continual infection in the community. This becomes even more important as the debate moves towards elimination and eradication. This study sought to quantify the burden of Plasmodium malaria infection in seven communities in the Eastern Region of Ghana. METHODS: The cross-sectional study recruited 729 participants aged 85 years old and below from 7 closely linked communities. Finger pricked blood was used to prepare thick and thin blood smears as well as spot filter paper and an histidine rich protein 2 (HRP2) rapid diagnostic test kit (RDT). Genomic DNA was extracted from the filter paper dry blood spot (DBS) and used in PCR to amplify the Plasmodium 18S rRNA gene using species specific PCR. RESULTS: 96.6% of the participants were identified as afebrile, with axillary temperatures below 37.5 °C. PCR identified 66% of the participants to harbor malaria parasites, with 9 P. malariae and 7 P. ovale mono-infections accounting for 2.2% and P. falciparum combined with either 36 P. malariae or 25 P. ovale infections, accounting for 13.3%. Parasite prevalence by microscopy (32%) was similar to the RDT positivity rate (33%). False positive RDT results ranged from 64.6% in children aged between 5 and 9 years to 10% in adults aged 20 years and above. No significant differences were observed in falciparum and non-falciparum parasite carriage at the community level, however young adults aged between 15 and 19 years had the highest prevalence (34.8% (16/46)) of P. falciparum and P. malariae parasite carriage whilst children aged between 5 and 9 years had the highest level (11.4% (14/123)) of P. ovale carriage. CONCLUSION: The high rate of misidentification of non-falciparum parasites and the total absence of detection of P. ovale by microscopy suggests that more sensitive malaria diagnostic tools including molecular assays are required to accurately determine the prevalence of carriers of non-falciparum parasites and low density P. falciparum infections, especially during national surveillance exercises. Additionally, malaria control interventions targeting the non-falciparum species P. malariae and P. ovale parasites are needed.

Evaluation of piperonyl butoxide in enhancing the efficacy of pyrethroid insecticides against resistant Anopheles gambiae s.l. in Ghana.

BACKGROUND: Malaria vector control methods involving the use of pyrethroids remain the strategies being used against malaria vectors in Ghana. These methods include the use of long-lasting insecticidal nets and indoor residual spraying in many areas in Ghana. However, there is evidence that pyrethroid resistance is widespread in many areas in Ghana. Synergists have been shown to be useful in inhibiting the enzymes that are responsible for the development of resistance and hence enhance the insecticide susceptibility of Anopheles gambiae sensu lato (s.l.) in many areas. The present study investigated the effect of piperonyl butoxide (PBO) on the susceptibility status of An. gambiae s.l. across some sentinel sites in Ghana. METHODS: Three to five day old An. gambiae s.l. reared from larvae were used in WHO susceptibility tube assays. Batches of 20-25 female adult An. gambiae s.l. were exposed simultaneously to the insecticide alone and to the PBO + insecticide. The knock down rate after 60 min and mortality at 24 h were recorded. RESULTS: Deltamethrin and permethrin resistance of An. gambiae s.l. was observed in all the sites in 2015 and 2016. The mortality after 24 h post exposure for deltamethrin ranged from 16.3% in Weija to 82.3% in Kade, whereas that for permethrin ranged from 3.8% in Gomoa Obuasi to 91.3% in Prestea. A significant increase in susceptibility to deltamethrin and less to permethrin was observed during both 2015 and 2016 years in most of the sites when An. gambiae s.l. mosquitoes were pre-exposed to PBO. CONCLUSION: Findings from this study showed that the use of PBO significantly enhanced the susceptibility of An. gambiae s.l. mosquitoes in most of the sentinel sites. It is recommended that vector control strategies incorporating PBO as a synergist can be effective in killing mosquitoes in the presence of deltamethrin and permethrin resistance.

Effect of anti-malarial interventions on trends of malaria cases, hospital admissions and deaths, 2005-2015, Ghana.

BACKGROUND: Since 2005, the Government of Ghana and its partners, in concerted efforts to control malaria, scaled up the use of artemisinin-based combination therapy (ACT) and insecticide-treated nets (ITNs). Beginning in 2011, a mass campaign of long-lasting insecticidal nets (LLINs) was implemented, targeting all the population. The impact of these interventions on malaria cases, admissions and deaths was assessed using data from district hospitals. METHODS: Records of malaria cases and deaths and availability of ACT in 88 hospitals, as well as at district level, ITN distribution, and indoor residual spraying were reviewed. Annual proportion of the population potentially protected by ITNs was estimated with the assumption that each LLIN covered 1.8 persons for 3 years. Changes in trends of cases and deaths in 2015 were estimated by segmented log-linear regression, comparing trends in post-scale-up (2011-2015) with that of pre-scale-up (2005-2010) period. Trends of mortality in children under 5 years old from population-based household surveys were also compared with the trends observed in hospitals for the same time period. RESULTS: Among all ages, the number of outpatient malaria cases (confirmed and presumed) declined by 57% (95% confidence interval [CI], 47-66%) by first half of 2015 (during the post-scale-up) compared to the pre-scale-up (2005-2010) period. The number of microscopically confirmed cases decreased by 53% (28-69%) while microscopic testing was stable. Test positivity rate (TPR) decreased by 41% (19-57%). The change in malaria admissions was insignificant while malaria deaths fell significantly by 65% (52-75%). In children under 5 years old, total malaria outpatient cases, admissions and deaths decreased by 50% (32-63%), 46% (19-75%) and 70% (49-82%), respectively. The proportion of outpatient malaria cases, admissions and deaths of all-cause conditions in both all ages and children under five also fell significantly by >30%. Similar decreases in the main malaria indicators were observed in the three epidemiological strata (coastal, forest, savannah). All-cause admissions increased significantly in patients covered by the National Health Insurance Scheme (NHIS) compared to the non-insured. The non-malaria cases and non-malaria deaths increased or remained unchanged during the same period. All-cause mortality for children under 5 years old in household surveys, similar to those observed in the hospitals, declined by 43% between 2008 and 2014. CONCLUSIONS: The data provide compelling evidence of impact following LLIN mass campaigns targeting all ages since 2011, while maintaining other anti-malarial interventions. Malaria cases and deaths decreased by over 50 and 65%, respectively. The declines were stronger in children under five. Test positivity rate in all ages decreased by >40%. The decrease in malaria deaths was against a backdrop of increased admissions owing to free access to hospitalization through the NHIS. The study demonstrated that retrospective health facility-based data minimize reporting biases to assess effect of interventions. Malaria control in Ghana is dependent on sustained coverage of effective interventions and strengthened surveillance is vital to monitor progress of these investments.

Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine combinations in the treatment of uncomplicated malaria in two ecological zones in Ghana.

BACKGROUND: Case management based on prompt diagnosis and adequate treatment using artemisinin-based combination therapy (ACT) remains the main focus of malaria control in Ghana. As part of routine surveillance on the therapeutic efficacy of ACT in Ghana, the efficacy of amodiaquine-artesunate (AS-AQ) and artemether-lumefantrine (AL) were studied in six sentinel sites representing the forest and savannah zones of the country. METHODS: Three sites representing the two ecological zones studied AS-AQ whilst the other three sites studied AL. In each site, the study was a one-arm prospective evaluation of the clinical, parasitological, and haematological responses to directly observed therapy for uncomplicated malaria with either AS-AQ or AL among children aged 6 months and 9 years. The WHO 2009 protocol for monitoring anti-malarial drug efficacy was used for the study between July 2013 and March 2014. RESULTS: Per-protocol analyses on day 28 showed an overall PCR-corrected cure rate of 100% for AS-AQ and 97.6% (95% CI 93.1, 99.5) for AL: 97.2% (95% CI 92.0, 99.4) in the forest zone and 100% in the savannah zone. Kaplan-Meier survival analysis showed similar outcomes. Prevalence of fever decreased by about 75% after the first day of treatment with each ACT in the two ecological zones. No child studied was parasitaemic on day 3, and gametocytaemia was generally maintained at low levels (<5%). Post-treatment mean haemoglobin concentrations significantly increased in the two ecological zones. CONCLUSIONS: Therapeutic efficacy of AS-AQ and AL remains over 90% in the forest and savannah zones of Ghana. Additionally, post-treatment parasitaemia on day 3 is rare suggesting that artemisinin is still efficacious in Ghana.

Strengthening individual capacity in monitoring and evaluation of malaria control programmes to streamline M&E systems and enhance information use in malaria endemic countries.

BACKGROUND: Malaria control interventions in most endemic countries have intensified in recent years and so there is a need for a robust monitoring and evaluation (M&E) system to measure progress and achievements. Providing programme and M&E officers with the appropriate skills is a way to strengthen malaria's M&E systems and enhance information use for programmes' implementation. This paper describes a recent effort in capacity strengthening for malaria M&E in sub-Saharan Africa (SSA). METHODS: From 2010 to 2014, capacity-strengthening efforts consisted of organizing regional in-person workshops for M&E of malaria programmes for Anglophone and Francophone countries in SSA in collaboration with partners from Ghana and Burkina Faso. Open-sourced online courses were also available in English. A post-workshop assessment was conducted after 5 years to assess the effects of these regional workshops and identify gaps in capacity. RESULTS: The regional workshops trained 181 participants from 28 countries from 2010 to 2014. Trained participants were from ministries of health, national malaria control and elimination programmes, non-governmental organizations, and development partners. The average score (%) for participants' knowledge tests increased from pretest to posttest for Anglophone workshops (2011: 59 vs. 76, 2012: 41 vs. 63, 2013: 51 vs. 73; 2014: 50 vs. 74). Similarly, Francophone workshop posttest scores increased, but were lower than Anglophone due to higher scores at pretest. (2011: 70 vs. 76, 2012: 74 vs. 79, 2013: 61 vs. 68; 2014: 64 vs. 75). Results of the post-workshop assessment revealed that participants retained practical M&E knowledge and skills for malaria programs, but there is a need for a module on malaria surveillance adapted to the pre-elimination context. CONCLUSION: The workshops were successful because of the curriculum content, facilitation quality, and the engagement of partner institutions with training expertise. Results from the post-workshop assessment will guide the curriculum's development and restructuring for the next phase of workshops. Country-specific malaria M&E capacity needs assessments may also inform this process as countries reduce malaria burden.

Cost-effectiveness of seasonal malaria chemoprevention in upper west region of Ghana.

BACKGROUND: In Ghana, malaria is endemic and perennial (with significant seasonal variations in the three Northern Regions), accounting for 33 % of all deaths among children under 5 years old, with prevalence rates in children under-five ranging from 11 % in Greater Accra to 40 % in Northern Region. Ghana adopted the WHO-recommended Seasonal Malaria Chemoprevention (SMC) strategy with a trial in the Upper West Region in 2015. The objective of this study was to estimate the cost-effectiveness of seasonal malaria chemoprevention. METHODS: Costs were analysed from provider and societal perspectives and are reported in 2015 US$. Data on resource use (direct and indirect costs) of the SMC intervention were collected from intervention records and a survey in all districts and at regional level. Additional numbers of malaria cases and deaths averted by the intervention were estimated based on prevalence data obtained from an SMC effectiveness study in the region. Incremental cost-effectiveness ratios (ICERs) were estimated for the districts and region. Sensitivity analyses were conducted to test the robustness of the ICERs. RESULTS: The total financial cost of the intervention was US$1,142,040.80. The total economic cost was estimated to be US$7.96 million and US$2.66 million from the societal and provider perspectives, respectively. The additional numbers of cases estimated to be averted by the intervention were 24,881 and 808, respectively. The economic cost per child dosed was US$67.35 from societal perspective and US$22.53 from the provider perspective. The economic cost per additional case averted was US$107.06 from the provider perspective and US$319.96 from the societal perspective. The economic cost per additional child death averted by the intervention was US$3298.36 from the provider perspective and US$9858.02 from the societal perspective. The financial cost per the SMC intervention delivered to a child under-five was US$9.66. The ICERs were sensitive to mortality rate used. CONCLUSIONS: The SMC intervention is economically beneficial in reducing morbidity in children under-5 years and presents a viable approach to improving under-five health in Ghana.