Pharmacokinetic profile of amodiaquine and its active metabolite desethylamodiaquine in Ghanaian patients with uncomplicated falciparum malaria.

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 AUC0-∞) 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 AUC0-∞ 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.

Adherence to Dihydroartemisinin-Piperaquine Treatment among Patients with Uncomplicated Malaria in Northern Ghana.

Treatment adherence has been described as the process whereby patients take medications, follow diet, and effect other lifestyle changes that relate to agreed recommendations from healthcare providers. The determinants of such treatment adherence include patient, the health condition, therapy type, socioeconomic conditions, and the healthcare system. The study examined adherence in malaria patients treated with dihydroartemisinin-piperaquine in routine clinical care in northern Ghana. The study was conducted in Navrongo Health Research Centre in the Kassena-Nankana district of northern Ghana. Patients confirmed with uncomplicated malaria were prescribed dihydroartemisinin-piperaquine in blister packs to be taken daily for three days. Follow-up visits were made on days 3 and 28 after diagnosis to collect data on adherence, drug safety and therapeutic effectiveness. During follow-up visits, in-depth interviews were conducted and the blister packs directly observed for the number of tablets remaining. The in-depth interviews documented day-by-day account of doses taken, number of tablets taken during each dose, time of each dose, reasons for any leftover or missed dose, and whether or not there was vomiting. Treatment adherence was classified as definitely nonadherent, incomplete adherence, and completely adherent. A total of 405 patients were screened; 299 were positive by rapid diagnostic testing and 216 by microscopy. The average age was 12 years and females represented 54.0%. All participants completed day 3 follow-up but 12.7% had leftover pills. Treatment adherence was 50.9% (95% CI 44.1, 57.8), 36.1% (95% CI 29.7, 42.9), and 13.0% (95% CI 8.8, 18.2) for completely adherent, incomplete adherence, and definitely nonadherent, respectively. All completely adherent patients were free of parasitemia on day 28 of follow-up. A total of 49 adverse events related to malaria symptoms were documented. Effort to improve adherence should be individualized as it is dependent on a number of factors such as the patients' temperament, the disease, support at home, and complexity of treatment.

Seasonal Variation in the Epidemiology of Asymptomatic Plasmodium falciparum Infections across Two Catchment Areas in Bongo District, Ghana.

Understanding the epidemiology of asymptomatic Plasmodium falciparum infections is critical for countries to move toward malaria elimination. Using different methods for parasite detection, we evaluated how seasonality, spatial location, and other factors affect the age-specific epidemiology of asymptomatic malaria in Bongo District, Ghana. Asymptomatic prevalence by microscopy decreased significantly from 42.5% at the end of the wet to 27.5% at the end of the dry season (P < 0.001). Using the 18S rRNA polymerase chain reactions (PCRs), all microscopy-negative samples were screened and prevalence of submicroscopic infections also decreased significantly from the wet (55.4%) to the dry (20.7%) season (P < 0.001). Combining detection methods, 74.4% and 42.5% of the population in the wet and dry seasons, respectively, had evidence of a P. falciparum infection. Interestingly in those > 20 years of age, we found evidence of infection in 64.3% of the population in the wet and 27.0% in the dry season. Using both microscopy and PCR, the asymptomatic P. falciparum reservoir peaks at the end of the wet season and infections in all age groups constitute the reservoir of malaria infection. At the end of the wet season, spatial heterogeneity in the prevalence and density of P. falciparum infections was observed between the two catchment areas surveyed in Bongo District. These results indicate that if elimination is to succeed, interventions will need to target not just P. falciparum infections in children but also in adults, and be implemented toward the end of the dry season in this area of West Africa.

Factors influencing adverse events reporting within the health care system: the case of artemisinin-based combination treatments in northern Ghana.

BACKGROUND: The use of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria was a policy recommended by World Health Organization. In 2004, Ghana changed her first-line anti-malarial drug policy to use ACT. This study examined factors affecting adverse events reporting in northern Ghana after the introduction of ACT. METHODS: This was a qualitative study based on sixty in-depth interviews with health workers, chemical shop owners and patients with malaria who were given ACT at the health facilities. Purposive sampling method was used to select study participants. The interviews were transcribed, coded into themes using Nvivo 9 software. The thematic analysis framework was used to analyse the data. RESULTS: Study respondents reported body weakness and dizziness as the most frequent side effects they had experienced from the used of ACT. Other side effects they reported were swollen testes, abdominal pain and shivering. These side effects were mostly associated with the use of artesunate-amodiaquine compared to other artemisinin-based combinations. Patients were not provided information about the side effects of the drugs and so did not report when they experienced them. Also long queues at health facilities and unfriendly health worker attitude were the main factors affecting adverse events reporting. Other factors such as wrong use of ACT at home, farming and commercial activities also affected effective adverse events reporting in the study area. CONCLUSION: Patients' lack of knowledge and health sector drawbacks affected side effect reporting on ACT. Intensive health education on likely side effects of ACT should be provided to patients by health workers. Also, improving health worker attitude toward clients will encourage patients to visit the health facilities when they react negatively to ACT and, subsequently, will improve on adverse events reporting.

Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana - A Cohort Study.

BACKGROUND: Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. METHODS AND FINDINGS: Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. CONCLUSIONS: There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger study is required to confirm consistency of findings.

Comparison of genomic signatures of selection on Plasmodium falciparum between different regions of a country with high malaria endemicity.

BACKGROUND: Genome wide sequence analyses of malaria parasites from widely separated areas of the world have identified contrasting population structures and signatures of selection. To compare relatively closely situated but ecologically contrasting regions within an endemic African country, population samples of Plasmodium falciparum clinical isolates were collected in Ghana from Kintampo in the central forest-savannah area, and Navrongo in a drier savannah area ~350 km to the north with more seasonally-restricted transmission. Parasite DNA was sequenced and paired-end reads mapped to the P. falciparum reference genome. RESULTS: High coverage genome wide sequence data for 85 different clinical isolates enabled analysis of 121,712 single nucleotide polymorphisms (SNPs). The local populations had similar proportions of mixed genotype infections, similar SNP allele frequency distributions, and eleven chromosomal regions had elevated integrated haplotype scores (|iHS|) in both. A between-population Rsb metric comparing extended haplotype homozygosity indicated a stronger signal within Kintampo for one of these regions (on chromosome 14) and in Navrongo for two of these regions (on chromosomes 10 and 13). At least one gene in each of these identified regions is a potential target of locally varying selection. The candidates include genes involved in parasite development in mosquitoes, members of variant-expressed multigene families, and a leading vaccine-candidate target of immunity. CONCLUSIONS: Against a background of very similar population structure and selection signatures in the P. falciparum populations of Ghana, three narrow genomic regions showed evidence indicating local differences in historical timing or intensity of selection. Sampling of closely situated populations across heterogeneous environments has potential to refine the mapping of important loci under temporally or spatially varying selection.

Adherence and uptake of artemisinin-based combination treatments for uncomplicated malaria: a qualitative study in northern Ghana.

BACKGROUND: Based on the recommendations of the World Health Organization in 2004, Ghana changed her antimalarial drug policy from mono-therapy to Artemisinin-based Combination Therapy (ACTs). The country is currently using three first line drugs artesunate-amodiaquine, artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated malaria. Despite this policy, little or no qualitative studies have been conducted to establish the factors influencing adherence to the new treatment for malaria. This study explored factors influencing adherence to the use of ACTs in northern Ghana. METHODS: This was a qualitative study comprising forty (40) in-depth interviews with patients with malaria who visited selected public and private health facilities and received ACTs. Systematic sampling technique was used to select participants who were given ACTs for the interviews. Nvivo 9 software was used to code the data into themes for further analysis. RESULTS: The study revealed very important differences in knowledge about ACTs. As expected, the less or illiterates could not mention the type of ACT they would prefer to use for treating their malaria. The educated ones had a good knowledge on ACTs and preferred artemether-lumefantrinee in treating their malaria. The reason was that the drug was good and it had minimal or no side effects. Individual attitudes toward the use of medications and the side effects associated with the use of these ACTs were found to be the main factors affecting adherence to the use of ACTs. Perceived cure of illness after the initial dose greatly affected adherence. Other factors such as forgetfulness and lack of information also influenced patient adherence to ACTs use. CONCLUSION: Individual knowledge, attitudes and behaviors greatly influence patients' adherence to ACTs use. Since ACTs take a number of days to complete, continuous education by health professionals could improve on adherence to ACTs use by patients with malaria.

Integrated community case management of fever in children under five using rapid diagnostic tests and respiratory rate counting: a multi-country cluster randomized trial.

Evidence on the impact of using diagnostic tests in community case management of febrile children is limited. This effectiveness trial conducted in Burkina Faso, Ghana, and Uganda, compared a diagnostic and treatment package for malaria and pneumonia with presumptive treatment with anti-malarial drugs; artemisinin combination therapy (ACT). We enrolled 4,216 febrile children between 4 and 59 months of age in 2009-2010. Compliance with the malaria rapid diagnostic test (RDT) results was high in the intervention arm across the three countries, with only 4.9% (17 of 344) of RDT-negative children prescribed an ACT. Antibiotic overuse was more common: 0.9% (4 of 446) in Uganda, 38.5% (114 of 296) in Burkina Faso, and 44.6% (197 of 442) in Ghana. Fever clearance was high in both intervention and control arms at both Day 3 (97.8% versus 96.9%, P = 0.17) and Day 7 (99.2% versus 98.8%, P = 0.17). The use of diagnostic tests limits overuse of ACTs. Its impact on antibiotic overuse and on fever clearance is uncertain.

Good clinical laboratory practices improved proficiency testing performance at clinical trials centers in Ghana and Burkina Faso.

BACKGROUND: The recent drive towards accreditation of clinical laboratories in Africa by the World Health Organization-Regional Office for Africa (WHO-AFRO) and the U.S Government is a historic step to strengthen health systems, provide better results for patients and an improved quality of results for clinical trials. Enrollment in approved proficiency testing (PT) programs and maintenance of satisfactory performance is vital in the process of accreditation. Passing proficiency testing surveys has posed a great challenge to many laboratories across sub-Saharan Africa. Our study was aimed at identifying the causes of unsatisfactory PT results in clinical research laboratories conducting or planning to conduct malaria vaccine trials sponsored by the National Institutes of Health (NIH). METHODOLOGY: PT reports for 2009 and 2010 from the College of American Pathologists (CAP) for the laboratories were reviewed as part of the process. Errors accounting for unsatisfactory results were classified into clerical, methodological, technical, problem with PT materials, and random errors. A training program on good clinical laboratory practices (GCLP) was developed for each center to address areas for improvement. RESULTS: The major cause of PT failure in the four centers was methodological. The application of GCLP improved the success rate in the PT surveys from 58% in 2009 to 88% in 2010. It also decreased the error rate on PT by 35%. CONCLUSION: A previous report from the CAP- PT participating laboratories indicated that the major causes of error were clerical. These types of errors were predominantly made in laboratories in the US, with much more experience in quality control, and varied significantly from what we found. In our centers in sub-Saharan Africa, methodological errors, and not clerical errors, accounted for the vast majority of errors. A process was started for continuous improvement which has decreased methodological errors by 35%, but more improvement is needed.

Haplotype analyses of haemoglobin C and haemoglobin S and the dynamics of the evolutionary response to malaria in Kassena-Nankana District of Ghana.

BACKGROUND: Haemoglobin S (HbS) and C (HbC) are variants of the HBB gene which both protect against malaria. It is not clear, however, how these two alleles have evolved in the West African countries where they co-exist at high frequencies. Here we use haplotypic signatures of selection to investigate the evolutionary history of the malaria-protective alleles HbS and HbC in the Kassena-Nankana District (KND) of Ghana. METHODOLOGY/PRINCIPAL FINDINGS: The haplotypic structure of HbS and HbC alleles was investigated, by genotyping 56 SNPs around the HBB locus. We found that, in the KND population, both alleles reside on extended haplotypes (approximately 1.5 Mb for HbS and 650 Kb for HbC) that are significantly less diverse than those of the ancestral HbA allele. The extended haplotypes span a recombination hotspot that is known to exist in this region of the genome SIGNIFICANCE: Our findings show strong support for recent positive selection of both the HbS and HbC alleles and provide insights into how these two alleles have both evolved in the population of northern Ghana.

Simultaneous administration of praziquantel, ivermectin and albendazole, in a community in rural northern Ghana endemic for schistosomiasis, onchocerciasis and lymphatic filariasis.

OBJECTIVES: To compare (i) side effects associated with the simultaneous adminstration of praziquantel, albendazole and ivermectin with side affects associated with albendazole and ivermectin only and (ii) coverage by volunteers distributing three or two drugs. METHODS: Two-arm comparative study in northern Ghana integrated praziquantel distribution into an existing lymphatic filariasis and onchocerciasis control programme using Community Directed Distributors. The control arm continued to distribute only ivermectin and albendazole. Dosages of ivermectin and praziquantel were based on height. Treatment was directly observed, and all two/three drugs were co-administered. Adverse effects were recorded based on passive surveillance. Parasitological, anthropometric and haematological data were collected at baseline. RESULTS: Prevalence of Schistosoma haematobium infection among 1001 (boys: 47.9% girls: 52.1%) school-age children (6-15 years) [intervention: 30.0% (CI: 23.1-34.2); control: 23.0% (CI: 18.9-27.0)], mean haemoglobin, weight and age were similar among the intervention and control groups. While 1676 (99.1%) compounds in the control area were visited and 15,020 (96.58%) people were treated, only 1375 (88.5%) compounds in the intervention area were visited and 8454 (80.97%) people treated (P < 0.001). The numbers of adverse effects were similar (intervention: 50/6896; control: 130/15,020). The most reported adverse effects was headache (intervention: 14/50; control: 13/130), followed by body weakness, which was reported more from the intervention group (intervention: 13/50, 95% CI: 14.6-40.3; control: 6/130, 95% CI: 1.7-9.8]. Sixty-six per cent (6896/10,441) of the eligible population received praziquantel. CONCLUSIONS: Reported adverse events were mild and managed at the subdistrict level with no cases of hospitalization; intensive health education will, however, be required to improve coverage.

Sulfadoxine-pyrimethamine-based intermittent preventive treatment, bed net use, and antenatal care during pregnancy: demographic trends and impact on the health of newborns in the Kassena Nankana District, northeastern Ghana.

Demographics and health practices of 2,232 pregnant women in rural northeastern Ghana and characteristics of their 2,279 newborns were analyzed to determine benefits associated with intermittent preventive treatment (IPTp), antenatal care, and/or bed net use during pregnancy. More than half reported bed net use, 90% reported at least two antenatal care visits, and > 82% took at least one IPTp dose of sulfadoxine-pyrimethamine. Most used a bed net and IPTp (45%) or IPTp alone (38%). Low birth weight (< 2,500 grams) characterized 18.3% of the newborns and was significantly associated with female sex, Nankam ethnicity, first-born status, and multiple births. Among newborns of primigravidae, IPTp was associated with a significantly greater birth weight, significantly fewer low birth weight newborns, improved hemoglobin levels, and less anemia. Babies of multigravidae derived no benefit to birth weight or hemoglobin level from single or multiple doses of sulfadoxine-pyrimethamine during pregnancy. No differences or benefits were seen when a bed net was the only protective factor.

Insecticide resistance profiles for malaria vectors in the Kassena-Nankana district of Ghana.

BACKGROUND: Malaria is a major public health problem in Ghana. The current strategy of the National Malaria Control Programme is based on effective case management and the use of insecticide treated bed nets among vulnerable groups such as children under-five years of age and pregnant women. Resistance to pyrethroids by Anopheles gambiae s.l. and Anopheles funestus has been reported in several African countries including neighbouring Burkina Faso. METHODS: Indoor resting Anopheles mosquitoes were collected. Blood-fed and gravid females were allowed to oviposit, eggs hatched and larvae reared to 1-3 days old adults and tested against permethrin 0.75%, deltamethrin 0.05%, cyfluthrin 0.15%, lambdacyhalothrin 0.1% and DDT 4%, based on WHO methodology. PCR analyses were carried out on a sub-sample of 192 of the An. gambiae for sibling species complex determination. Resistance to pyrethroids and DDT was determined by genotyping the knock-down resistance kdr gene mutations in the study area. RESULTS: A total of 9,749 1-3 days-old F1 female Anopheles mosquitoes were exposed to the insecticides. Among the pyrethroids, permethrin, 0.75% had the least knockdown effect, whilst cyfluthrin 0.15%, had the highest knock-down effect. Overall, no difference in susceptibility between An. gambiae 93.3% (95% CI: 92.5-94.1) and An. funestus 94.5% (95% CI: 93.7-95.3) was observed when exposed to the pyrethroids. Similarly, there was no difference in susceptibility between the two vector species (An. gambiae = 79.1% (95% CI: 76.6-81.8) and An. funestus = 83.5% (95% CI: 80.2-86.4) when exposed to DDT. Overall susceptibility to the insecticides was between 80% and 98%, suggesting that there is some level of resistance, except for cyfluthrin 0.15%. The kdr PCR assay however, did not reveal any kdr mutations. The analysis also revealed only the molecular M (Mopti) form. CONCLUSION: The findings in this study show that An. gambiae and An. funestus, the main malaria vector mosquitoes in the Kassena-Nankana district are susceptible to the insecticides being used in the treatment of bed nets in the malaria control programme. There is however, the need for continuous monitoring of the pyrethroids as the efficacy is not very high.

Understanding and retention of the informed consent process among parents in rural northern Ghana.

BACKGROUND: The individual informed consent model remains critical to the ethical conduct and regulation of research involving human beings. Parental informed consent process in a rural setting of northern Ghana was studied to describe comprehension and retention among parents as part of the evaluation of the existing informed consent process. METHODS: The study involved 270 female parents who gave consent for their children to participate in a prospective cohort study that evaluated immune correlates of protection against childhood malaria in northern Ghana. A semi-structured interview with questions based on the informed consent themes was administered. Parents were interviewed on their comprehension and retention of the process and also on ways to improve upon the existing process. RESULTS: The average parental age was 33.3 years (range 18-62), married women constituted a majority (91.9%), Christians (71.9%), farmers (62.2%) and those with no formal education (53.7%). Only 3% had ever taken part in a research and 54% had at least one relation ever participate in a research. About 90% of parents knew their children were involved in a research study that was not related to medical care, and 66% said the study procedures were thoroughly explained to them. Approximately, 70% recalled the study involved direct benefits compared with 20% for direct risks. The majority (95%) understood study participation was completely voluntary but only 21% recalled they could withdraw from the study without giving reasons. Younger parents had more consistent comprehension than older ones. Maternal reasons for allowing their children to take part in the research were free medical care (36.5%), better medical care (18.8%), general benefits (29.4%), contribution to research in the area (8.8%) and benefit to the community (1.8%). Parental suggestions for improving the consent process included devoting more time for explanations (46.9%), use of the local languages (15.9%) and obtaining consent at home (10.3%). CONCLUSION: Significant but varied comprehension of the informed consent process exists among parents who participate in research activities in northern Ghana and it appears the existing practices are fairly effective in informing research participants in the study area.

Amodiaquine in future combination treatment of malaria in Ghana.

A total of 198 patients were treated with amodiaquine for uncomplicated malaria. Parasite clearance at day 14 was 85.4 and 48% at day 28.

Severe falciparum malaria in young children of the Kassena-Nankana district of northern Ghana.

STUDY DESIGN: Severe falciparum malaria in children was studied as part of the characterization of the Kassena-Nankana District Ghana for future malaria vaccine trials. Children aged 6-59 months with diagnosis suggestive of acute disease were characterized using the standard WHO definition for severe malaria. RESULTS: Of the total children screened, 45.2% (868/1921) satisfied the criteria for severe malaria. Estimated incidence of severe malaria was 3.4% (range: 0.4-8.3%) cases per year. The disease incidence was seasonal: 560 cases per year, of which 70.4% occurred during the wet season (June-October). The main manifestations were severe anaemia (36.5%); prolonged or multiple convulsions (21.6%); respiratory distress (24.4%) and cerebral malaria (5.4%). Others were hyperpyrexia (11.1%); hyperparasitaemia (18.5%); hyperlactaemia (33.4%); and hypoglycaemia (3.2%). The frequency of severe anaemia was 39.8% in children of six to 24 months of age and 25.9% in children of 25-60 months of age. More children (8.7%) in the 25-60 months age group had cerebral malaria compared with 4.4% in the 6-24 months age group. The overall case fatality ratio was 3.5%. Cerebral malaria and hyperlactataemia were the significant risk factors associated with death. Severe anaemia, though a major presentation, was not significantly associated with risk of death. CONCLUSION: Severe malaria is a frequent and seasonal childhood disease in northern Ghana and maybe an adequate endpoint for future malaria vaccine trials.

A randomized comparative study of chloroquine, amodiaquine and sulphadoxine-pyrimethamine for the treatment of uncomplicated malaria in Ghana.

The study examined the efficacy of chloroquine (CQ), amodiaquine (AQ) and sulphadoxine-pyrimethamine (SP) for the treatment of uncomplicated Plasmodium falciparum malaria in Ghana. A total of 351 children were randomized to receive either of the three study drugs. Patients were evaluated using the WHO 14-day in vivo antimalarial testing guidelines. The 14-day adequate clinical and parasitological response analysis revealed that CQ, 46.7% (95% CI 37.5, 56.0) has the least efficacy compared with AQ, 86.1% (95% CI 78.3, 91.8) and SP, 77.6% (95% CI 68.9, 84.8). Late parasite failures were also lower and similar in the AQ and SP (9.6% and 10.3%) than in the CQ (32.5%) group. However, CQ and AQ groups showed better fever clearance compared with SP throughout except for day 7 and after when possibly due to its significant late clinical failures, clearance by CQ was lower. Our findings suggest that CQ is no longer useful in Ghana and should be replaced as a first-line treatment of malaria. Replacement of CQ preferably with AQ combination treatment will be an effective and an affordable alternative for the treatment of uncomplicated malaria.