Line Treatment For Uncomplicated Malaria Research Articles

Malaria Frontline Project: strategic approaches to improve malaria control program leveraging experiences from Kano and Zamfara States, Nigeria, 2016–2019

BackgroundThe Malaria Frontline Project (MFP) supported the National Malaria Elimination Program for effective program implementation in the high malaria-burden states of Kano and Zamfara adapting the National Stop Transmission of Polio (NSTOP) program elimination strategies.Project implementationThe MFP was implemented in 34 LGAs in the two states (20 out of 44 in Kano and all 14 in Zamfara). MFP developed training materials and job aids tailored to expected service delivery for primary and district health facilities and strengthened supportive supervision. Pre- and post-implementation assessments of intervention impacts were conducted in both states.ResultsA total of 158 (Kano:83; Zamfara:75) and 180 (Kano:100; Zamfara:80) healthcare workers (HCWs), were interviewed for pre-and post-implementation assessments, respectively. The proportions of HCWs with correct knowledge on diagnostic criteria were Kano: 97.5% to 92.0% and Zamfara: 94.7% to 98.8%; and knowledge of recommended first line treatment of uncomplicated malaria were Kano: 68.7% to 76.0% and Zamfara: 69.3% to 65.0%. The proportion of HCWs who adhered to national guidelines for malaria diagnosis and treatment increased in both states (Kano: 36.1% to 73.0%; Zamfara: 39.2% to 67.5%) and HCW knowledge to confirm malaria diagnosis slightly decreased in Kano State but increased in Zamfara State (Kano: 97.5% to 92.0%; Zamfara: 94.8% to 98.8%). HCWs knowledge of correct IPTp drug increased in both states (Kano: 81.9% to 94.0%; Zamfara: 85.3% to 97.5%).ConclusionMFP was successfully implemented using tailored training materials, job aids, supportive supervision, and data use. The project strategy can likely be adapted to improve the effectiveness of malaria program implementation in other Nigerian states, and other malaria endemic countries.

An assessment of the knowledge, practices and resources during the delivery of malaria health care services among private health care practitioners: a cross section study in the Mid-Western Region of Uganda

BackgroundApproximately 50 % of the population in Uganda seeks health care from private facilities but there is limited data on the quality of care for malaria in these facilities. This study aimed to document the knowledge, practices and resources during the delivery of malaria care services, among private health practitioners in the Mid-Western region of Uganda, an area of moderate malaria transmission.MethodsThis was a cross sectional study in which purposive sampling was used to select fifteen private-for-profit facilities from each district. An interviewer-administered questionnaire that contained both quantitative and open-ended questions was used. Information was collected on availability of treatment aides, knowledge on malaria, malaria case management, laboratory practices, malaria drugs stock and data management. We determined the proportion of health workers that adequately provided malaria case management according to national standards.ResultsOf the 135 health facilities staff interviewed, 61.48 % (52.91–69.40) had access to malaria treatment protocols while 48.89 % (40.19–57.63) received malaria training. The majority of facilities, 98.52 % (94.75–99.82) had malaria diagnostic services and the most commonly available anti-malarial drug was artemether-lumefantrine, 85.19 % (78–91), followed by Quinine, 74.81 % (67–82) and intravenous artesunate, 72.59 % (64–80). Only 14.07 % (8.69–21.10) responded adequately to the acceptable cascade of malaria case management practice. Specifically, 33.33 % (25.46–41.96) responded correctly to management of a patient with a fever, 40.00 % (31.67–48.79) responded correctly to the first line treatment for uncomplicated malaria, whereas 85.19 % (78.05–90.71) responded correctly to severe malaria treatment. Only 28.83 % submitted monthly reports, where malaria data was recorded, to the national database.ConclusionsThis study revealed sub-optimal malaria case management knowledge and practices at private health facilities with approximately 14 % of health care workers demonstrating correct malaria case management cascade practices. To strengthen the quality of malaria case management, it is recommended that the NMCD distributes current guidelines and tools, coupled with training; continuous mentorship and supportive supervision; provision of adequate stock of essential anti-malarials and RDTs; reinforcing communication and behavior change; and increasing support for data management at private health facilities.

Safety of Artemisinin Derivatives in the First Trimester of Pregnancy: A Controversial Story.

Artemisinin combination therapy (ACT) is recommended by the World Health Organization (WHO) as first line treatment for uncomplicated malaria both in adults and children. During pregnancy, ACT is considered safe only in the second and third trimester, since animal studies have demonstrated that artemisinin derivatives can cause foetal death and congenital malformation within a narrow time window in early embryogenesis. During this period, artemisinin derivatives induce defective embryonic erythropoiesis and vasculogenesis/angiogenesis in experimental models. However, clinical data on the safety profile of ACT in pregnant women have not shown an increased risk of miscarriage, stillbirth, or congenital malformation, nor low birth weight, associated with exposure to artemisinins in the first trimester. Although further studies are needed, the evidence collected up to now is prompting the WHO towards a change in the guidelines for the treatment of uncomplicated malaria, allowing the use of ACT also in the first trimester of pregnancy.

Dihydroartemisinin-piperaquine for the routine treatment of uncomplicated malaria in Northern Ghana

<p class="abstract"><strong>Background:</strong> Dihydroartemisinin-piperaquine is a first line treatment for uncomplicated malaria in Ghana. A facility-based study was undertaken to examine the effectiveness of the treatment in the routine health care system.</p><p class="abstract"><strong>Methods:</strong> The study was undertaken at the Navrongo demographic surveillance area. Patients presenting with acute febrile illness were enrolled after informed consented and confirmation by microscopy. Patients were randomized into supervised group who received treatment under direct observation and unsupervised group which had only the first treatment given under supervision. Treatment was according to bodyweight and 42 days follow-up was undertaken.</p><p class="abstract"><strong>Results:</strong> A total of 194 patients were enrolled; 54.1% were females and 51% had supervised treatment. The median age and weight were 6.7 years and 20.0 kg respectively. Mean baseline temperature, haemoglobin concentration and parasite density were, 37.6 <sup>o</sup>C, 11.1 g/dl and 11,098 parasites per microliter of blood respectively. Study completion rate was 93.3%, day 42 polymerase chain reaction-unadjusted adequate clinical and parasitological responses rate (ACPR) was 93.4% by evaluable and 87.1 % by intention-to-treat (ITT). The day 42 ACPR by evaluable was 92.3% in the supervised arm compared to 94.4% in the unsupervised arm. The day 42 ACPR by ITT was 85.7% in the supervised and 88.5% in the unsupervised arms. The fever resolution and haemoglobin concentration changes for the two arms were similar.</p><p class="abstract"><strong>Conclusions: </strong>The results show that dihydroartemisinin-piperaquine is effective and good first-line antimalarial in the routine health delivery system.</p>

Adherence to treatment guidelines for uncomplicated malaria at two public health facilities in Nigeria; Implications for the 'test and treat' policy of malaria case management.

ObjectivesAdherence to treatment guidelines for uncomplicated malaria is critical to the success of malaria case management. Poor adherence has implications for increased malaria burden, in view of the risk of widespread parasite resistance and treatment failures. This study analyzed the diagnostic and prescription pattern for uncomplicated malaria at two public health facilities, south east Nigeria, to assess the current state of compliance to policy guidelines on the use of artemisinin-based combination therapy (ACT).MethodsRetrospective audit of patients’ records, treated for uncomplicated malaria, between the months of January and March 2013, was undertaken at two public health facilities. Demographics, diagnostic information, medication and cost data were extracted. Questionnaires were distributed to providers to assess their malaria treatment intent. Data from the facilities were analyzed and compared for similarities and systematic differences, and conformity to malaria treatment policy, in terms of laboratory diagnosis, use of ACT, co-medication and cost of medication.ResultsA total of 2,171 records of patients who had been treated for uncomplicated malaria were analyzed. Of these, 1066 (49%) were sent for laboratory confirmation of malaria using mostly microscopy, out of which 480 (45%) tested positive. 51% (1105) of the prescriptions was on the basis of presumptive treatment. 58% of slide negative results received antimalarial drugs. 93% of patients received ACT, with artemether-lumefantrin, AL (50.5%) as the most prescribed antimalarial drug. Monotherapy accounted for 7% of prescriptions, comprising mostly sulphadoxine + pyrimethamine, SP (46.5%) and monotherapy artemisinin, AS (29.2%). 97% of the prescriptions received at least one co-medication. Antibiotics were prescribed to 50% of patients. Overall, median cost of medication was N1160.00 (US$7.48 (US$0.19 - 267.87) per case, higher in tertiary than the secondary facility. There were significant variations in treatment practices between the two facilities.ConclusionEvidence suggests good compliance to policy on the use of ACT as first line treatment for uncomplicated malaria. However, there exists significant scope for improved diagnosis and rational drug use, to enhance accuracy of treatment, reduced wastages and risks of adverse drug reactions, in line with the goals of ‘test and treat’ policy of malaria case management.

Efficacy and safety of Camosunate for the treatment of uncomplicated malaria in the University of Benin Teaching Hospital, Benin City, Nigeria

In Nigeria, nearly 110 million clinical cases of malaria are diagnosed per year, thus being a major public health problem. The problems of resistance resulted in the introduction of the artemisinin based combinations (ACT) by the WHO. Artesunate and amodiaquine (AS+AQ) is at present the world’s second most widely used ACT. This study is an assessment of the efficacy and safety of Camosunate (a brand of AS+AQ; Geneith Pharmaceutical Ltd., Oshodi, Lagos) in the treatment of uncomplicated malaria conducted at the University of Benin Teaching Hospital (UBTH). A cross-sectional assessment of the efficacy and safety of Camosunate was conducted over a period of one year using 120 patients selected after stratification, by random sampling technique. All recruited patients had slide-proven uncom- plicated malaria and were followed up for 28 days on commencement of Camosunate. Data was collected using a structured interviewer- administered questionnaire and was analysed using SPSS version 15. The overall efficacy of Camosunate was found to be 95.8%. Treatment was well tolerated as testified by the fact that there was no case withdrawal due to adverse drug reaction (ADR) or treatment emergent signs and symptoms (TESS). Also no evidence of toxicity was recorded. Camosunate is highly efficacious and well tolerated in this area of Nigeria and justifies its use as a first line treatment for uncomplicated malaria.

Availability and prescription practice of anti-malaria drugs in the private health sector in Yemen

Although the government of Yemen changed the national policy for treating malaria in November 2005 from chloroquine to combination drugs in the form of artesunate + sulphadoxine-pyrimethamine (SP) as first line and lumefantrine + artemether as second line treatment for uncomplicated malaria, clinicians in public and private health facilities continued to prescribe chloroquine because their knowledge about the new treatment policy was poor. A non-randomized trial of pre- and post-evaluation of the training and reporting interventions about prescription behaviors and availability of anti-malaria drugs among clinicians and pharmacists in the private sector in three governorates in Yemen was conducted. Adherence of clinicians in the private sector to the new national guidelines for anti-malaria drugs improved from 21% in pre-intervention period to 38% after the intervention for artesunate + SP being prescribed as the first-line treatment. Prescription of lumefantrine + artemether as the second-line anti-malaria treatment was also improved from 18% before the intervention to 22% post-intervention. Unfortunately the combination of halofantrine + SP continued to be frequently prescribed by clinicians in Sana'a city (18%). Artesunate + SP and quinine are increasing their marketing significantly from 8% in the pre-intervention period to 22% post-intervention (P-value 0.001). The study provides evidence of usefulness of the training intervention on the national guidelines for malaria treatment. Additionally, the involvement of private health-care providers in reporting procedures will promote the rational prescription and availability of anti-malaria drugs.

The effect of an anti-malarial subsidy programme on the quality of service provision of artemisinin-based combination therapy in Kenya: a cluster-randomized, controlled trial

BackgroundMany patients with suspected malaria in sub-Saharan Africa seek treatment from private providers, but this sector suffers from sub-standard medicine dispensing practices. To improve the quality of care received for presumptive malaria from the highly accessed private retail sector in western Kenya, subsidized pre-packaged artemether-lumefantrine (AL) was provided to private retailers, together with a one day training for retail staff on malaria diagnosis and treatment, job aids and community engagement activities.MethodsThe intervention was assessed using a cluster-randomized, controlled design. Provider and mystery-shopper cross-sectional surveys were conducted at baseline and eight months post-intervention to assess provider practices. Data were analysed based on cluster-level summaries, comparing control and intervention arms.ResultsOn average, 564 retail outlets were interviewed per year. At follow-up, 43% of respondents reported that at least one staff member had attended the training in the intervention arm. The intervention significantly increased the percentage of providers knowing the first line treatment for uncomplicated malaria by 24.2% points (confidence interval (CI): 14.8%, 33.6%; adjusted p=0.0001); the percentage of outlets stocking AL by 31.7% points (CI: 22.0%, 41.3%; adjusted p=0.0001); and the percentage of providers prescribing AL for presumptive malaria by 23.6% points (CI: 18.7%, 28.6%; adjusted p=0.0001). Generally outlets that received training and job aids performed better than those receiving one or none of these intervention components.ConclusionOverall, subsidizing ACT and retailer training can significantly increase the percentage of outlets stocking and selling AL for the presumptive treatment of malaria, but further research is needed on strategies to improve the provision of counselling advice to retail customers.

Exploring health providers’ and community perceptions and experiences with malaria tests in South-East Nigeria: a critical step towards appropriate treatment

BackgroundThe adoption of ACT as the first line treatment for uncomplicated malaria in Nigeria has concentrated attention on the role of testing in appropriate malaria treatment. There are calls at both national and global level for malaria treatment to be based on test result, but it is still unclear how testing can be incorporated into treatment-seeking and practices of health providers. This study explored community members and health providers’ perceptions and experiences with malaria tests in south east Nigeria.MethodsThe study was conducted in urban and rural areas of Enugu state in south-eastern Nigeria. A total of 18 focus group discussions with 179 community members including sub-groups of primary caregivers, adult men and adult women aged 15 years and above. Twenty- six (26) In-depth interviews were held with public and private health providers involved in prescribing medicines at public and private health facilities in the study area.ResultsBoth providers and community members were familiar with malaria tests and identified malaria tests as an important step to distinguish malaria from other illnesses with similar symptoms and as a means of delivering appropriate treatment. However, the logic of test-directed treatment was undermined by cost of test and a lack of testing facilities but above all concerns over the reliability of negative test results, with community members and providers observing inconsistencies between results and symptoms, and providers attributing inaccurate results to incompetencies of technicians. Recognition of malaria symptoms was deemed most important in determining the use of antimalarial drugs rather than the result of a malaria test.ConclusionThe results highlight important areas of intervention to promote appropriate malaria treatment. If tests are to play a role in patient management, demand and supply side interventions are needed to change people’s attitude towards malaria test results.

Utilization of the current national antimalarial treatment guidelines among doctors in army hospitals in Lagos, Nigeria

Introduction: Human malaria infection remains a problem of public health importance in many regions of the world. The infection continues to spread particularly in sub-Saharan Africa. In Nigeria, malaria and its treatment have been affected by factors like wrong diagnosis, wrong attitude of the people, unavailability of drugs, fake and substandard drugs, attitude and practices of medical and paramedical personnel. Nigeria’s national standard for malaria treatment was recently changed to artemisinin combination therapy. Methods: A descriptive study using a structured questionnaire was administered to all doctors (123) practicing in the three Army hospitals in Lagos. The study was done between March, 2009 and April, 2009. The findings were precoded; data entry and analysis was done using EPI INFO version 3.5.1 statistical software. Results: Presumptive/clinical diagnosis was still a common practice for diagnosing malaria among doctors, as well as the use of microscopy. None of the doctors had the facility for diagnosing malaria with rapid diagnostic test in their hospitals. Fifty one percent of the doctors stated that they utilized the current National antimalarial treatment guidelines. Significant proportion of the doctors used Artemisinin-based Combination Therapy (ACTs) as first line treatment of uncomplicated malaria in adults and children. Chloroquine was the commonest drug for first line treatment of uncomplicated malaria in pregnancy. Only 45.5% of the doctors had correct knowledge of Intermittent Preventive Treatment in pregnancy (IPTp), while 33.3% knew the stage of pregnancy in which a pregnant woman should receive IPTp with sulphadoxine-pyrimethamine. Awareness and the content of knowledge of the current National antimalarial treatment guideline were not affected by the category or current position of the doctors. Thirteen percent of the respondents had attended training/update workshop organized by the Federal Ministry of Health (FMOH) Roll Back Malaria programme on the current National antimalarial treatment guideline. Conclusion: The study showed that there is need to improve use of recommended antimalarial medicines for all categories of patients by doctors in Army Hospitals in Lagos. More effort should be made by the Federal Ministry of Health and other stakeholders to organize training and refresher courses on the current National antimalarial treatment guidelines for all categories of health care providers.

ORIGINAL ARTICLE: Probability of emergence of antimalarial resistance in different stages of the parasite life cycle

Understanding the evolution of drug resistance in malaria is a central area of study at the intersection of evolution and medicine. Antimalarial drug resistance is a major threat to malaria control and directly related to trends in malaria attributable mortality. Artemisinin combination therapies (ACT) are now recommended worldwide as first line treatment for uncomplicated malaria, and losing them to resistance would be a disaster for malaria control. Understanding the emergence and spread of antimalarial drug resistance in the context of different scenarios of antimalarial drug use is essential for the development of strategies protecting ACTs. In this study, we review the basic mechanisms of resistance emergence and describe several simple equations that can be used to estimate the probabilities of de novo resistance mutations at three stages of the parasite life cycle: sporozoite, hepatic merozoite and asexual blood stages; we discuss the factors that affect parasite survival in a single host in the context of different levels of antimalarial drug use, immunity and parasitaemia. We show that in the absence of drug effects, and despite very different parasite numbers, the probability of resistance emerging at each stage is very low and similar in all stages (for example per-infection probability of 10−10–10−9 if the per-parasite chance of mutation is 10−10 per asexual division). However, under the selective pressure provided by antimalarial treatment and particularly in the presence of hyperparasitaemia, the probability of resistance emerging in the blood stage of the parasite can be approximately five orders of magnitude higher than in the absence of drugs. Detailed models built upon these basic methods should allow us to assess the relative probabilities of resistance emergence in the different phases of the parasite life cycle.

Cost-effectiveness analysis of the available strategies for diagnosing malaria in outpatient clinics in Zambia.

BackgroundMalaria in Zambia accounts for about 4 million clinical cases and 8 000 deaths annually. Artemether-lumefantrine (ACT), a relatively expensive drug, is being used as first line treatment of uncomplicated malaria. However, diagnostic capacity in Zambia is low, leading to potentially avoidable wastage of drugs due to unnecessary anti malarial treatment.MethodsA cost-effectiveness evaluation of the three current alternatives to malaria diagnosis (clinical, microscopy and Rapid Diagnostic Tests- RDT) was conducted in 12 facilities from 4 districts in Zambia. The analysis was conducted along an observational study, thus reflecting practice in health facilities under routine conditions. Average and incremental cost effectiveness ratios were estimated from the providers' perspective. Effectiveness was measured in relation to malaria cases correctly diagnosed by each strategy.ResultsAverage cost-effectiveness ratios show that RDTs were more efficient (US$ 6.5) than either microscopy (US$ 11.9) or clinical diagnosis (US$ 17.1) for malaria case correctly diagnosed. In relation to clinical diagnoses the incremental cost per case correctly diagnosed and treated was US$ 2.6 and US$ 9.6 for RDT and microscopy respectively. RDTs would be much cheaper to scale up than microscopy. The findings were robust to changes in assumptions and various parameters.ConclusionRDTs were the most cost effective method at correctly diagnosing malaria in primary health facilities in Zambia when compared to clinical and microscopy strategies. However, the treatment prescription practices of the health workers can impact on the potential that a diagnostic test has to lead to savings on antimalarials. The results of this study will serve to inform policy makers on which alternatives will be most efficient in reducing malaria misdiagnosis by taking into account both the costs and effects of each strategy.

Efficacy of monotherapies and artesunate-based combination therapies in children with uncomplicated malaria in Somalia

In order to guide the antimalarial treatment policy of Somalia, we conducted therapeutic efficacy studies of routinely used antimalarial monotherapies as well as artemisinin-based combination therapies (ACTs) for uncomplicated malaria in three sentinel sites during 2003–2006. Therapeutic efficacy of chloroquine (CQ), amodiaquine (AQ) and sulfadoxine/pyrimetahmine (SP) monotherapies, and artesunate plus SP (AS + SP) or AQ (AS + AQ) were evaluated in children 6 months to 10 years old with uncomplicated malaria. For the assessment of the monotherapies, 2003 WHO protocol with 14-day follow-up was used while the 2005 WHO protocol with 28-day follow-up was used for testing the ACTs. Of the monotherapies, CQ performed very poorly with treatment failures varying from 76.5% to 88% between the sites. AQ treatment failure was low except for Janale site with treatment failure of 23.4% compared to 2.8% and 8% in Jamame and Jowhar, respectively. For SP, treatment failures from 7.8% to 12.2% were observed. A 28-day test of artemisinin-based combinations, AS + SP and AS + AQ, proved to be highly efficacious with cure rates of 98–100% supporting the choice of AS + SP combination as first line treatment for uncomplicated malaria for Somalia.

Malaria case-management under artemether-lumefantrine treatment policy in Uganda

BackgroundCase-management with artemether-lumefantrine (AL) is one of the key strategies to control malaria in many African countries. Yet, the reports on translation of AL implementation activities into clinical practice are scarce. Here the quality of AL case-management is reported from Uganda; approximately one year after AL replaced combination of chloroquine and sulphadoxine-pyrimethamine (CQ+SP) as recommended first line treatment for uncomplicated malaria.MethodsA cross-sectional survey, using a range of quality of care assessment tools, was undertaken at all government and private-not-for-profit facilities in four Ugandan districts. Main outcome measures were AL prescribing, dispensing and counseling practices in comparison with national guidelines, and factors influencing health workers decision to 1) treat for malaria, and 2) prescribe AL.Results195 facilities, 232 health workers and 1,763 outpatient consultations were evaluated. Of 1,200 patients who needed treatment with AL according to guidelines, AL was prescribed for 60%, CQ+SP for 14%, quinine for 4%, CQ for 3%, other antimalarials for 3%, and 16% of patients had no antimalarial drug prescribed. AL was prescribed in the correct dose for 95% of patients. Only three out of seven AL counseling and dispensing tasks were performed for more than 50% of patients. Patients were more likely to be treated for malaria if they presented with main complaint of fever (OR = 5.22; 95% CI: 3.61–7.54) and if they were seen by supervised health workers (OR = 1.63; 95% CI: 1.06–2.50); however less likely if they were treated by more qualified health workers (OR = 0.61; 95% CI: 0.40–0.93) and presented with skin problem (OR = 0.29; 95% CI: 0.15–0.55). AL was more likely prescribed if the appropriate weight-specific AL pack was in stock (OR = 6.15; 95% CI: 3.43–11.05) and when CQ was absent (OR = 2.16; 95% CI: 1.09–4.28). Routine AL implementation activities were not associated with better performance.ConclusionAlthough the use of AL was predominant over non-recommended therapies, the quality of AL case-management at the point of care is not yet optimal. There is an urgent need for innovative quality improvement interventions, which should be rigorously tested. Adequate availability of ACTs at the point of care will, however, ultimately determine the success of any performance interventions and ACT policy transitions.

An Open Label, Randomised Trial of Artesunate+Amodiaquine, Artesunate+Chlorproguanil-Dapsone and Artemether-Lumefantrine for the Treatment of Uncomplicated Malaria

BackgroundArtesunate+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.MethodsFive 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 FindingsIn 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.ConclusionsAS+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 RegistrationClinicalTrials.gov NCT00119145

Sulfadoxine-Pyrimethamine–Based Combinations for Malaria: A Randomised Blinded Trial to Compare Efficacy, Safety and Selection of Resistance in Malawi

BackgroundIn Malawi, there has been a return of Plasmodium falciparum sensitivity to chloroquine (CQ) since sulfadoxine-pyrimethamine (SP) replaced CQ as first line treatment for uncomplicated malaria. When used for prophylaxis, Amodiaquine (AQ) was associated with agranulocytosis but is considered safe for treatment and is increasingly being used in Africa. Here we compare the efficacy, safety and selection of resistance using SP or CQ+SP or artesunate (ART)+SP or AQ+SP for the treatment of uncomplicated falciparum malaria.Methodology and Findings455 children aged 1–5 years were recruited into a double-blinded randomised trial comparing SP to the three combination therapies. Using intention to treat analysis with missing outcomes treated as successes, and without adjustment to distinguish recrudescence from new infections, the day 28 adequate clinical and parasitological response (ACPR) rate for SP was 25%, inferior to each of the three combination therapies (p<0.001). AQ+SP had an ACPR rate of 97%, higher than CQ+SP (81%) and ART+SP (70%), p<0.001. Nineteen children developed a neutropenia of ≤0.5×103 cells/µl by day 14, more commonly after AQ+SP (p = 0.03). The mutation pfcrt 76T, associated with CQ resistance, was detected in none of the pre-treatment or post-treatment parasites. The prevalence of the pfmdr1 86Y mutation was higher after treatment with AQ+SP than after SP, p = 0.002.ConclusionsThe combination AQ+SP was highly efficacious, despite the low efficacy of SP alone; however, we found evidence that AQ may exert selective pressure for resistance associated mutations many weeks after treatment. This study confirms the return of CQ sensitivity in Malawi and importantly, shows no evidence of the re-emergence of pfcrt 76T after treatment with CQ or AQ. Given the safety record of AQ when used as a prophylaxis, our observations of marked falls in neutrophil counts in the AQ+SP group requires further scrutiny.Trial RegistrationControlled-Trials.com ISRCTN22075368

Challenges Associated with Scaling up Artemisinin Combination Therapy in Sub-Saharan Africa ; A Review Article

Malaria is the leading cause of morbidity and mortality in Sub-Saharan Africa. One key strategic intervention is provision of early diagnosis and prompt effective treatment. A major setback has been the development of drug resistance to commonly used antimalarials. To overcome this, most countries in Sub-Saharan Africa have adopted Artemisinin Combination Therapy (ACT) as a first line treatment for uncomplicated malaria. Artemether Lumefantrine (AL) and Artesunate Amodiaquine (ASAQ) are the main drugs of choice. There are key implementation issues, which may have a bearing on the scaling up of this new treatment. This article reviewed the published papers on ACT with focus on sustainability, compliance, and diagnosis. ACTs are costly, but highly effective. Their scaling up is the most cost effective malaria intervention currently available. Most countries rely heavily on the Global Fund for their scaling up. AL has a short shelf life, a complicated six-dose regimen that requires intake with fat to ensure sufficient bioavailability. High rates of adherence have been reported. Use of parasitic diagnosis is advocated to ensure rational use. Parasitic diagnostics like rapid test and microscopy are currently inadequate. The majority of malaria cases may continue to be diagnosed clinically leading to over prescription of drugs. ACTs are currently not available at the community level for home based management of malaria. Issues related to safety and rational use need to be addressed before their use in the informal health sector like community drug sellers and community health workers. The majority of malaria cases at the community level could go untreated or continue to be treated using less effective drugs. We conclude that ACTs are highly effective. A major challenge is ensuring rational use and access at the household level. It is hoped that addressing these issues will increase the likelihood that ACT achieves its intended goals of reducing morbidity and mortality due to malaria, and delaying the onset of drug resistance.

Continued efficacy of sulfadoxine–pyrimethamine as second line treatment for malaria in children in Guinea-Bissau

BackgroundSulfadoxine–pyrimethamine (S/P) is widely used for treatment of failures following the first line treatment for malaria in Africa. In Guinea-Bissau, it has been recommended as second line therapy by the National Malaria Programme since 1996. In order to monitor any change of the in vivo sensitivity, the efficacy of S/P was studied immediately before the introduction of the drug and 6–9 years later. MethodsChildren participating in clinical in vivo studies were given S/P if having late clinical treatment failure following the treatment with quinine, chloroquine, or amodiaquine. Parasitological and clinical failures were evaluated during a 35-day follow-up. During the first study period whole blood sulfadoxine concentrations were measured on day 7. ResultsAltogether, 56 children failed the initial treatment and were included in 1995/1996 as well as 55 children in 2002/2004. The PCR-uncorrected adequate clinical and parasitological response rates on day 28 were 94% and 91%, and on day 35 they were 89% and 91%, respectively, in the two periods. No difference between median blood drug concentration in children with and without treatment failure was observed. InterpretationThe efficacy of S/P as second line treatment for uncomplicated malaria has remained unchanged in spite of a relatively high level of genetic markers associated with Plasmodium falciparum resistance to S/P previously found in the area.

Traitement de première intention de l' accès palustre non compliquéà Plasmodium falciparum chez l'enfant: comparaison de l'halofantrine avec la méfloquine

Aims. - Halofantrine is the first regimen used for the treatment of uncomplicated Plasmodium falciparum malaria in children in France according to the recommendations of the French Consensus Conference held in 1999 and pending additional data in this population. In 1999, a high rate of clinical relapse after a single cure of halofantrine l $ ́ us to switch to mefloquine for first line treatment of uncomplicated malaria. The aims of this study were to evaluate this change of attitude and to compare the efficacy of halofantrine and mefloquine in the treatment of uncomplicated P. falciparum malaria in children. Patients and methods. - We retrospectively analysed 118 pediatric cases of malaria treated at Armand-Trousseau Children hospital in Paris between January 1 st, 1999 and December 31 st, 2000. Results. - 93 patients were treated for an uncomplicated case of P. falciparum malaria: 48 received a unique cure of halofantrine and 21 were treated with mefloquine. Nine patients relapsed, all having previously received halofantrine. No patient treated with mefloquine relapsed. Conclusion. - These results and other recent published data suggest to recommend mefloquine instead of halofantrine as first line treatment of uncomplicated P. falciparum malaria in children with respect to specific contra-indications. A larger evaluation of mefloquine is however necessary. The association atovaquone-proguanil (Malarone ®) is promising but needs to be evaluated in large pediatric studies in comparison with other treatments. Its indication as a curative treatment of uncomplicated malaria is, to date, restricted to adults and children over 12 years in France.