Profiling the Plasmodium falciparum Erythrocyte Membrane Protein 1-Specific Immununoglobulin G Response Among Ghanaian Children With Hemoglobin S and C.

Members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are important targets for protective immunity. Abnormal display of PfEMP1 on the surfaces of infected erythrocytes (IEs) and reduced cytoadhesion have been demonstrated in hemoglobin (Hb) AS and HbAC, inherited blood disorders associated with protection against severe P. falciparum malaria. We found that Ghanaian children with HbAS had lower levels of immunoglobulin G against several PfEMP1 variants and that this reactivity increased more slowly with age than in their HbAA counterparts. Moreover, children with HbAS have lower total parasite biomass than those with HbAA at comparable peripheral parasitemias, suggesting impaired cytoadhesion of HbAS IEs in vivo and likely explaining the slower acquisition of PfEMP1-specific immunoglobulin G in this group. In contrast, the function of acquired antibodies was comparable among Hb groups and appears to be intact and sufficient to control parasitemia via opsonization and phagocytosis of IEs.

Impact of insecticide-treated nets and indoor residual spraying on self-reported malaria prevalence among women of reproductive age in Ghana: implication for malaria control and elimination.

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.

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.

Acute Phase Responses Vary Between Children of HbAS and HbAA Genotypes During Plasmodium falciparum Infection.

PURPOSE: Haemoglobin genotype S is known to offer protection against Plasmodium falciparum infections but the mechanism underlying this protection is not completely understood. Associated changes in acute phase proteins (APPs) during Plasmodium falciparum infections between Haemoglobin AA (HbAA) and Haemoglobin AS (HbAS) individuals also remain unclear. This study aimed to evaluate changes in three APPs and full blood count (FBC) indices of HbAA and HbAS children during Plasmodium falciparum infection. METHODS: Venous blood was collected from three hundred and twenty children (6 months to 15 years) in Begoro in Fanteakwa District of Ghana during a cross-sectional study. Full blood count (FBC) indices were measured and levels of previously investigated APPs in malaria patients; C-reactive protein (CRP), ferritin and transferrin measured using Enzyme-Linked Immunosorbent Assays. RESULTS: Among the HbAA and HbAS children, levels of CRP and ferritin were higher in malaria positive children as compared to those who did not have malaria. The mean CRP levels were significantly higher among HbAA children (p=0.2e-08) as compared to the HbAS children (p=0.43). Levels of transferrin reduced in both HbAA and HbAS children with malaria, but the difference was only significant among HbAA children (p=0.0038), as compared to the HbAS children. No significant differences were observed in ferritin levels between HbAA and HbAS children in both malaria negative (p=0.76) and positive (p=0.26) children. Of the full blood count indices measured, red blood cell count (p=0.044) and haemoglobin (Hb) levels (p=0.017) differed between HbAA and HbAS in those without malaria, with higher RBC counts and lower Hb levels found in HbAS children. In contrast, during malaria, lymphocyte and platelet counts were elevated, whilst granulocytes and Mean Cell Haematocrit counts were reduced among children of the HbAS genotypes. CONCLUSION: Significant changes in APPs were found in HbAA children during malaria as compared to HbAS children, possibly due to differences in malaria-induced inflammation levels. This suggests that the HbAS genotype is associated with better control of P. falciparum infection-induced inflammatory response than HbAA genotype.

Ex vivo Sensitivity Profile of Plasmodium falciparum Clinical Isolates to a Panel of Antimalarial Drugs in Ghana 13 Years After National Policy Change.

PURPOSE: Malaria continues to be a major health issue globally with almost 85% of the global burden and deaths borne by sub-Saharan Africa and India. Although the current artemisinin derived combination therapies in Ghana are still efficacious against the Plasmodium falciparum (Pf) parasite, compounding evidence of artemisinin and amodiaquine resistance establish the need for a full, up-to-date understanding and monitoring of antimalarial resistance to provide evidence for planning control strategies. MATERIALS AND METHODS: The study was cross-sectional and was conducted during the peak malaria transmission seasons of 2015, 2016, and 2017 in two ecological zones of Ghana. Study participants included children aged 6 months to 14 years. Using ex vivo 4,6-diamidino-2-phenylindole (DAPI) drug sensitivity assay, 330 Pf isolates were used to investigate susceptibility to five antimalarial drugs: chloroquine (CQ), amodiaquine (AMD) dihydroartemisinin (DHA), artesunate (ART) and mefloquine (MFQ). RESULTS: The pooled geometric mean IC50S (GMIC50) of the five drugs against the parasites from Cape Coast and Begoro were 15.5, 42.4, 18.9, 4.6 and 27.3nM for CQ, AMD, DHA, ART, and MFQ, respectively. The GMIC50 values for CQ (p<0.001), ART (p<0.011) and DHA (p<0.018) were significantly higher for Cape Coast isolates as compared to Begoro isolates. However, GMIC50 estimates for MFQ (p<0.022) were significantly higher for Begoro isolates. Positive correlations were found between each pair of drugs with the weakest found between MFQ and DHA (r = 0.34;p<0.001), and the strongest between ART and DHA (r =0.66; p<0.001). CONCLUSION: The parasites showed reduced sensitivities to three (AMD, DHA and MFQ) out of the five drugs assessed. The study also demonstrated the continual return of chloroquine-sensitive parasites after 13 years of its withdrawal as the first-line drug for the treatment of uncomplicated malaria in Ghana. The ex vivo DAPI assay is a reliable method for assessing antimalarial drug sensitivities of Pf field isolates under field settings.

Reference intervals for selected haematological and biochemical parameters among apparently healthy adults in different eco-geographical zones in Ghana.

BACKGROUND: Due to the influence of gender, race/genetics, age, lifestyle habits and geography on the references intervals (RIs), the Clinical and Laboratory Standards Institute (CLSI) recommends the determination of population-specific RIs. Ghana continues to depend on pre-established RIs from other countries which poses the risk of misdiagnoses and wrong treatment. This study presents the haemato-biochemical RIs from four eco-geographical zones in Ghana. METHODS: In this population-based cross-sectional study, a total of 1227 randomly selected healthy voluntary blood donors from the four eco-geographic zones (Coastal Savannah, Rain Forest, Savannah and Transitional) were enrolled and screened. Based on the CLSI Guidance Document C28A2992, the data of eligible participants were used to non-parametrically determine the RIs for the haemato-biochemical parameters at the 2.5th and 97.5th percentiles. Comparison of analytes by gender was done by Wilcoxon rank sum test and eco-geographic differences were assessed using the Kruskal-Wallis with the Dunn post hoc multiple comparison tests. RESULTS: There were statistically significant differences in most of the haematological parameters (RBC, Hb, HCT, MCV, PLT, WBC; p-values <0.0001 and MCH; p-value = 0.007), and biochemical analytes (Urea, Cr, Trig, HDL-C, AST, ALT, ALP, GGT, BID, BIT, Prot-T and Albumin; p-values <0.0001) based on gender. Significant inter eco-geographic (intra-population) variations and substantial differences between the established RI and the RIs accompanying the analyzers used were also observed. CONCLUSION: This study reports significant inter-sex and inter-geographical differences in haemato-biochemical RIs in Ghana as well as differences in RIs with both the RIs accompanying the analyzers and those of other countries. Determining RIs representative of populations and including them in the report systems of laboratories to ensure effective and efficient healthcare service delivery is thus recommended.