The prevalence of molecular markers of resistance to sulfadoxine-pyrimethamine among pregnant women at first antenatal clinic attendance and delivery in the forest-savannah area of Ghana.

Intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is used to prevent malaria and associated unfavorable maternal and foetal outcomes in pregnancy in moderate to high malaria transmission areas. Effectiveness of IPTp-SP is, however, threatened by mutations in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes which confer resistance to pyrimethamine and sulfadoxine, respectively. This study determined the prevalence of molecular markers of SP resistance among pregnant women in a high malaria transmission area in the forest-savannah area of Ghana. Genomic DNA was extracted from 286 P. falciparum-positive dried blood spots obtained from pregnant women aged ≥18 years (255 at first Antenatal Care (ANC) clinic visit and 31 at delivery from 2017 to 2019) using Chelex 100. Mutations in Pfdhfr and Pfdhps genes were detected using molecular inversion probes and next generation sequencing. In the Pfdhfr gene, single nucleotide polymorphisms (SNPs) were detected in 83.1% (157/189), 92.0% (173/188) and 91.0% (171/188) at codons 51, 59, and 108 respectively in samples collected at first ANC visit, while SNPs were detected in 96.6 (28/29), 96.6% (28/29) and 96.8% (30/31) in isolates collected at delivery. The Pfdhfr triple mutant N51I, C59R and S108N (IRN) was carried by 80.5% (128/159) and 96.5% (28/29) of the typed isolates collected at ANC visit and at delivery respectively. In the Pfdhps gene, SNPs were detected in 0.6% (1/174), 76.2% (138/181), 33.2% (60/181), 1.2% (2/174), 0% (0/183), and 16.6% (27/173) at codons 431, 436, 437, 540, 581 and 613 respectively in samples collected at ANC, and 0% (0/25), 72% (18/25), 40% (10/25), 3.6% (1/25), 0% (0/29) and 7.4% (2/27) in samples collected at delivery. Quadruple mutant Pfdhfr N51I, C59R, and S108N + Pfdhps A437G (IRN-GK) was present in 25.8% (33/128) and 34.8% (8/23) of isolates at ANC and at delivery respectively. Quintuple mutant alleles Pfdhfr N51I, C59R, and S108N + Pfdhps A437G and K540E (IRN-GE) were detected in 0.8% (1/128) and 4.4% (1/23) of samples collected at ANC and at delivery respectively. No mutations were identified at Pfdhfr codons 16 or 164 or Pfdhps 581. There is a high prevalence of Pfdhfr triple mutant P. falciparum infections among pregnant women in the study area. However, prevalence of the combined Pfdhfr/Pfdhps quadruple and quintuple mutants IRN-GK and IRN-GE respectively prior to commencement of IPTp-SP were low, and no Pfdhps A581G mutant was detected, indicating that SP is still likely to be efficacious for IPTp-SP in the forest-savannah area in the middle belt of Ghana.

Effectiveness of intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) in Ghana.

INTRODUCTION: Ghana adopted the revised WHO recommendation on intermittent preventive treatment in pregnancy using sulfadoxine-pyrimethamine (IPTp-SP) in 2012. This study has assessed the effectiveness and safety of this policy in Ghana. METHODS: A total of 1926 pregnant women enrolled at antenatal care (ANC) clinics were assessed for birth outcomes at delivery, and placental histology results for malaria infection were obtained from 1642 participants. Association of reduced placental or peripheral malaria, anaemia and low birth weight (LBW) in women who received ≥4 IPTp-SP doses compared with 3 or ≤2 doses was determined by logistic regression analysis. RESULTS: Among the 1926 participants, 5.3% (103), 19.2% (369), 33.2% (640) and 42.3% (817) of women had received ≤1, 2, 3 or ≥4 doses, respectively. There was no difference in risk of active placental malaria (PM) infection in women who received 3 doses compared with ≥4 doses (adjusted OR (aOR) 1.00, 95% CI 0.47 to 2.14). The risk of overall PM infection was 1.63 (95% CI 1.07 to 2.48) in 2 dose group and 1.06 (95% CI 0.72 to 1.57) in 3 dose group compared with ≥4 dose group. The risk of LBW was 1.55 (95% CI 0.97 to 2.47) and 1.06 (95% CI 0.68 to 1.65) for 2 and 3 dose groups, respectively, compared with the ≥4 dose group. Jaundice in babies was present in 0.16%, and 0% for women who received ≥4 doses of SP. CONCLUSION: There was no difference in the risk of PM, LBW or maternal anaemia among women receiving 3 doses compared with ≥4 doses. Receiving ≥3 IPTp-SP doses during pregnancy was associated with a lower risk of overall PM infection compared with 2 doses. As there are no safety concerns, monthly administration of IPTp-SP offers a more practical opportunity for pregnant women to receive ≥3 doses during pregnancy.

Epidemiology of malaria among pregnant women during their first antenatal clinic visit in the middle belt of Ghana: a cross sectional study.

BACKGROUND: Malaria during pregnancy may result in unfavourable outcomes in both mothers and their foetuses. This study sought to document the current burden and factors associated with malaria and anaemia among pregnant women attending their first antenatal clinic visit in an area of Ghana with perennial malaria transmission. METHODS: A total of 1655 pregnant women aged 18 years and above with a gestational age of 13-22 weeks, who attended an antenatal care (ANC) clinic for the first time, were consented and enrolled into the study. A structured questionnaire was used to collect socio-demographic and obstetric data and information on use of malaria preventive measures. Venous blood (2 mL) was collected before sulfadoxine-pyrimethamine administration. Malaria parasitaemia and haemoglobin concentration were determined using microscopy and an automated haematology analyser, respectively. Data analysis was carried out using Stata 14. RESULTS: Mean age (SD) and gestational age (SD) of women at enrolment were 27.4 (6.2) years and 16.7 (4.3) weeks, respectively. Overall malaria parasite prevalence was 20.4% (95% CI 18.5-22.4%). Geometric mean parasite density was 442 parasites/µL (95% CI 380-515). Among women with parasitaemia, the proportion of very low (1-199 parasites/µL), low (200-999 parasites/µL), medium (1000-9999 parasites/µL) and high (≥ 10,000 parasites/µL) parasite density were 31.1, 47.0, 18.9, and 3.0%, respectively. Age ≥ 25 years (OR 0.57, 95% CI 0.41-0.79), multigravid (OR 0.50, 95% CI 0.33-0.74), educated to high school level or above (OR 0.53, 95% CI 0.33-0.83) and in household with higher socio-economic status (OR 0.34, 95% CI 0.21-0.54) were associated with a lower risk of malaria parasitaemia. The prevalence of anaemia (< 11.0 g/dL) was 56.0%, and the mean haemoglobin concentration in women with or without parasitaemia was 9.9 g/dL or 10.9 g/dL, respectively. CONCLUSION: One out of five pregnant women attending their first ANC clinic visit in an area of perennial malaria transmission in the middle belt of Ghana had Plasmodium falciparum infection. Majority of the infections were below 1000 parasites/µL and with associated anaemia. There is a need to strengthen existing malaria prevention strategies to prevent unfavourable maternal and fetal birth outcomes in this population.

Prevalence of Hypertension in the Middle Belt of Ghana: A Community-Based Screening Study.

OBJECTIVE: Prevalence of hypertension is on the rise and can be attributed to aging populations and changing behavioral or lifestyle risk factors. The objectives of this study were to determine the prevalence, awareness, treatment, control, and risk factors of hypertension in the middle part of Ghana. METHODS: A total of 2,555 participants aged ≥18 years (mean age of 43 years; 60.5% female) were enrolled using a two-stage sampling method. The World Health Organization STEPwise approach to chronic disease risk factor Surveillance-Instrument v2.1 was used for data collection. Blood pressure and anthropometric measurements were assessed. Blood glucose and lipids were also measured using blood samples collected after an overnight fast. RESULTS: Prevalence of hypertension was 28.1% (95% CI: 26.3%-29.8%). Less than half, i.e., 45.9% (95% CI: 42.2%-49.6%), of the respondents were aware of their hypertensive status. Of those aware and had sought medical treatment, 41.3% (95% CI: 36.1-46.8) had their hypertension controlled. Risk factors associated with being hypertensive were current (p=0.053) and past tobacco usage (p < 0.001), prediabetes (p=0.042), high body mass index (p < 0.001), hyperglycaemia (p=0.083), and hypercholesterolaemia (p=0.010). Doing vigorous work and being active in sports were less associated with being hypertensive (p < 0.001). CONCLUSION: Our study showed that close to one-quarter of adults who were involved in the survey in the middle belt of Ghana were hypertensive with less than half being aware of their hypertensive status; nearly half of those on treatment had controlled hypertension. Healthcare systems need adequate resources that enable them to screen, educate, and refer identified hypertensive patients for appropriate management to prevent or minimize the development of hypertension-related complications.

Intermittent preventive treatment of pregnant women in Kintampo area of Ghana with sulphadoxine-pyrimethamine (SP): trends spanning 2011 and 2015.

OBJECTIVE: In Ghana, intermittent preventive treatment during pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) is recommended for the prevention of malaria-related adverse outcomes. This study demonstrates the coverage of IPTp-SP use among pregnant women over a period (2011-2015) and the impact of various sociodemographic groups on the uptake of IPTp-SP. DESIGN: Retrospective analysis using data from all pregnant women in the Kintampo Health and Demographic Surveillance System area on the uptake of IPTp-SP. SETTING: Kintampo North Municipality and Kintampo South District of Ghana. PARTICIPANTS: All pregnant women in the Kintampo Health and Demographic Surveillance System area. PRIMARY AND SECONDARY OUTCOME MEASURES: The number of doses of IPTp-SP taken by pregnant women were examined. Logistic regression was used to assess the determinant of uptake of IPTp-SP while adjusting for within-subject correlation from women with multiple pregnancies. RESULTS: Data from 2011 to 2015 with a total of 17 484 pregnant women were used. The coverage of the recommended three or more doses of IPTp-SP among all pregnant women was 40.6%, 44.0%, 45.9%, 20.9% and 32.4% in 2011, 2012, 2013, 2014 and 2015, respectively. In the adjusted analysis, age, household size, education, religion, number of antenatal care visits, ethnicity, marital status, wealth index and place of residence were significantly associated with the uptake of three or more doses of IPTp-SP. Having middle school education or higher, aged 20 years and above, visiting antenatal care five times or more (OR 2.83, 95% CI 2.64 to 3.03), being married (OR 1.10, 95% CI 1.02 to 1.19) and those in higher wealth quintiles were significantly more likely to take three or more doses of IPTp-SP. CONCLUSION: The uptake of the recommended three or more doses of IPTp-SP is low in the study area. We recommend a community-based approach to identify women during early pregnancy and to administer IPTp-SP.

Non-malaria fevers in a high malaria endemic area of Ghana.

BACKGROUND: The importance of fevers not due to malaria [non-malaria fevers, NMFs] in children in sub-Saharan Africa is increasingly being recognised. We have investigated the influence of exposure-related factors and placental malaria on the risk of non-malaria fevers among children in Kintampo, an area of Ghana with high malaria transmission. METHODS: Between 2008 and 2011, a cohort of 1855 newborns was enrolled and followed for at least 12 months. Episodes of illness were detected by passive case detection. The primary analysis covered the period from birth up to 12 months of age, with an exploratory analysis of a sub-group of children followed for up to 24 months. RESULTS: The incidence of all episodes of NMF in the first year of life (first and subsequent) was 1.60 per child-year (95 % CI 1.54, 1.66). The incidence of NMF was higher among infants with low birth weight [adjusted hazard ratio (aHR) 1.22 (95 % CI 1.04-1.42) p = 0.012], infants from households of poor socio-economic status [aHR 1.22 (95 % CI 1.02-1.46) p = 0.027] and infants living furthest from a health facility [aHR 1.20 (95 % CI 1.01-1.43) p = 0.037]. The incidence of all episodes of NMF was similar among infants born to mothers with or without placental malaria [aHR 0.97 (0.87, 1.08; p = 0.584)]. CONCLUSION: The incidence of NMF in infancy is high in the study area. The incidence of NMF is associated with low birth weight and poor socioeconomic status but not with placental malaria.

Placental malaria and the risk of malaria in infants in a high malaria transmission area in ghana: a prospective cohort study.

BACKGROUND: Whether the risk of malaria is increased in infants born to mothers who experience malaria during pregnancy is uncertain. METHODS: We investigated malaria incidence among an infant cohort born to 355 primigravidae and 1500 multigravidae with or without placental malaria (PM) in a high malaria transmission area of Ghana. PM was assessed using placental histology. RESULTS: The incidence of all episodes of malaria parasitemia or clinical malaria was very similar among 3 groups of infants: those born to multigravidae without PM, multigravidae with PM, and primigravidae with PM. Infants born to primigravidae without PM experienced a lower incidence of malaria parasitemia or clinical malaria than the other 3 groups: adjusted hazard ratio, 0.64 (95% confidence interval [CI], .48-.86, P < .01) and 0.60 (95% CI, .43-.84, P < .01), respectively. The incidence of malaria parasitemia or clinical malaria was about 2 times higher in most poor infants compared to least poor infants. CONCLUSIONS: There was no suggestion that exposure to PM directly increased incidence of malaria among infants of multigravidae. In our study area, absence of placental malaria in primigravidae is a marker of low exposure, and this probably explains the lower incidence of malaria-related outcomes among infants of PM-negative primigravidae.

The benefits or otherwise of managing malaria cases with or without laboratory diagnosis: the experience in a district hospital in Ghana.

BACKGROUND: This study was conducted at the Kintampo Municipal Hospital in Ghana to determine whether there was any benefit (or otherwise) in basing the management of cases of suspected malaria solely on laboratory confirmation (microscopy or by RDT) as compared with presumptive diagnosis. METHOD: Children under five years who reported at the Out-Patient Department of the Hospital with axillary temperature ≥37.5°C or with a 48 hr history of fever were enrolled and had malaria microscopy and RDT performed. The attending clinician was blinded from laboratory results unless a request for these tests had been made earlier. Diagnosis of malaria was based on three main methods: presumptive or microscopy and/or RDT. Cost implication for adopting laboratory diagnosis or not was determined to inform malaria control programmes. RESULTS: In total, 936 children were enrolled in the study. Proportions of malaria diagnosed presumptively, by RDT and microscopy were 73.6% (689/936), 66.0% (618/936) and 43.2% (404/936) respectively. Over 50% (170/318) of the children who were RDT negative and 60% (321/532) who were microscopy negative were treated for malaria when presumptive diagnoses were used. Comparing the methods of diagnoses, the cost of malaria treatment could have been reduced by 24% and 46% in the RDT and microscopy groups respectively; the reduction was greater in the dry season (43% vs. 50%) compared with the wet season (20% vs. 45%) for the RDT and microscopy confirmed cases respectively. DISCUSSION/CONCLUSION: Over-diagnosis of malaria was prevalent in Kintampo during the period of the study. Though the use of RDT for diagnosis of malaria might have improved the quality of care for children, it appeared not to have a cost saving effect on the management of children with suspected malaria. Further research may be needed to confirm this.

An open label, randomised trial of artesunate+amodiaquine, artesunate+chlorproguanil-dapsone and artemether-lumefantrine for the treatment of uncomplicated malaria.

BACKGROUND: Artesunate+amodiaquine (AS+AQ) and artemether-lumefantrine (AL) are now the most frequently recommended first line treatments for uncomplicated malaria in Africa. Artesunate+chlorproguanil-dapsone (AS+CD) was a potential alternative for treatment of uncomplicated malaria. A comparison of the efficacy and safety of these three drug combinations was necessary to make evidence based drug treatment policies. METHODS: Five hundred and thirty-four, glucose-6-phosphate dehydrogenase (G6PD) normal children were randomised in blocks of 15 to the AS+AQ, AL or AS+CD groups. Administration of study drugs was supervised by project staff and the children were followed up at r home on days 1,2,3,7,14 and 28 post treatment. Parasitological and clinical failures and adverse events were compared between the study groups. MAIN FINDINGS: In a per-protocol analysis, the parasitological and clinical failure rate at day 28 post treatment (PCF28) was lower in the AS+AQ group compared to the AL or AS+CD groups (corrected for re-infections: 6.6% vs 13.8% and 13.8% respectively, p = 0.08; uncorrected: 14.6% vs 27.6% and 28.1% respectively, p = 0.005). In the intention to treat analysis, the rate of early treatment failure was high in all three groups (AS+AQ 13.3%; AL 15.2%; and AS+CD 9.3%, p = 0.2) primarily due to vomiting. However, the PCF28 corrected for re-infection was lower, though not significantly, in the AS+AQ group compared to the AL or the AS+CD groups (AS+AQ 18.3%; AL 24.2%; AS+CD 20.8%, p = 0.4) The incidence of adverse events was comparable between the groups. CONCLUSIONS: AS+AQ is an appropriate first line treatment for uncomplicated malaria in Ghana and possibly in the neighbouring countries in West Africa. The effectiveness of AL in routine programme conditions needs to be studied further in West Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT00119145.