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Background: The development of resistance by Plasmodium falciparum to anti-malarial drugs impedes any benefits of the drug. In addition, absence or delayed availability of current anti-malarial drugs in remote areas has the potential to results to parasite escape and continuous transmission., Case Presentation: The case of a 29-year old pregnant woman from Biase Local Government Area in Cross River State Nigeria presenting with febrile illness and high body temperature of 38.7 °C was reported. She looked pale and vomited twice on arrival at the health facility. Her blood smear on the first day of hospitalization was positive for P. falciparum by RDT, microscopy (21,960 parasite/µl) and real-time PCR, with a PCV of 18%. She was treated with 600 mg intravenous quinine in 500 ml of 5% Dextrose/0.9% Saline 8-hourly for 24 h. On the second day of hospitalization, she complained of weakness, persistent high-grade fever and vaginal bleeding. A bulging amnion from an extended cervix was observed. Following venous blood collection for laboratory investigations, 600 µg of misoprostol was inserted into the posterior fornix of her vagina as part of her obstetric care. Parenteral quinine was discontinued, and she was given full therapeutic regimen of artemether-lumefantrine 80/480 mg tablets to be taken for 3 days beginning from the second day. Her blood samples on the second and third day of hospitalization remained positive for P. falciparum by all three diagnostic methods. Single nucleotide polymorphism (SNP) assay on all three P. falciparum isolates revealed the presence of variants associated with multiple drug resistant markers., Discussion: Infecting P. falciparum isolates may have been resistant to initial quinine treatment resulting from parasite cross-resistance with other quinoline associated resistant markers such as 86Y and 184 F., Conclusions: Therefore, the likely transmission of similarly resistant parasites in the study area calls for reinforcement of interventions and adherence to current World Health Organization guidelines in administering only approved drugs to individuals in order to mitigate parasite escape and eventual transmission to other susceptible individuals., (© 2022. The Author(s).)

Background: Intermittent preventive treatment could help prevent malaria in infants (IPTi) living in areas of moderate to high malaria transmission in sub-Saharan Africa. The World Health Organization (WHO) policy recommended IPTi in 2010, but its adoption in countries has been limited., Objectives: To evaluate the effects of intermittent preventive treatment (IPT) with antimalarial drugs to prevent malaria in infants living in malaria-endemic areas., Search Methods: We searched the following sources up to 3 December 2018: the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE (PubMed), Embase (OVID), LILACS (Bireme), and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) and the WHO International Clinical Trials Registry Platform (ICTRP) portal for ongoing trials up to 3 December 2018., Selection Criteria: We included randomized controlled trials (RCTs) that compared IPT to placebo or no intervention in infants (defined as young children aged between 1 to 12 months) in malaria-endemic areas., Data Collection and Analysis: The primary outcome was clinical malaria (fever plus asexual parasitaemia). Two review authors independently assessed trials for inclusion, evaluated the risk of bias, and extracted data. We summarized dichotomous outcomes and count data using risk ratios (RR) and rate ratios respectively, and presented all measures with 95% confidence intervals (CIs). We extracted protective efficacy values and their 95% CIs; when an included trial did not report this data, we calculated these values from the RR or rate ratio with its 95% CI. Where appropriate, we combined data in meta-analyses and assessed the certainty of the evidence using the GRADE approach., Main Results: We included 12 trials that enrolled 19,098 infants; all were conducted in sub-Saharan Africa. Three trials were cluster-RCTs. IPTi with sulfadoxine-pyrimethamine (SP) was evaluated in 10 trials from 1999 to 2013 (n = 15,256). Trials evaluating ACTs included dihydroartemisinin-piperaquine (1 trial, 147 participants; year 2013), amodiaquine-artesunate (1 study, 684 participants; year 2008), and SP-artesunate (1 trial, 676 participants; year 2008). The earlier studies evaluated IPTi with SP, and were conducted in Tanzania (in 1999 and 2006), Mozambique (2004), Ghana (2004 to 2005), Gabon (2005), Kenya (2008), and Mali (2009). One trial evaluated IPTi with amodiaquine in Tanzania (2000). Later studies included three conducted in Kenya (2008), Tanzania (2008), and Uganda (2013), evaluating IPTi in multiple trial arms that included artemisinin-based combination therapy (ACT). Although the effect size varied over time and between drugs, overall IPTi impacts on the incidence of clinical malaria overall, with a 30% reduction (rate ratio 0.70, 0.62 to 0.80; 10 studies, 10,602 participants). The effect of SP appeared to attenuate over time, with trials conducted after 2009 showing little or no effect of the intervention. IPTi with SP probably resulted in fewer episodes of clinical malaria (rate ratio 0.78, 0.69 to 0.88; 8 trials, 8774 participants, moderate-certainty evidence), anaemia (rate ratio 0.82, 0.68 to 0.98; 6 trials, 7438 participants, moderate-certainty evidence), parasitaemia (rate ratio 0.66, 0.56 to 0.79; 1 trial, 1200 participants, moderate-certainty evidence), and fewer hospital admissions (rate ratio 0.85, 0.78 to 0.93; 7 trials, 7486 participants, moderate-certainty evidence). IPTi with SP probably made little or no difference to all-cause mortality (risk ratio 0.93, 0.74 to 1.15; 9 trials, 14,588 participants, moderate-certainty evidence). Since 2009, IPTi trials have evaluated ACTs and indicate impact on clinical malaria and parasitaemia. A small trial of DHAP in 2013 shows substantive effects on clinical malaria (RR 0.42, 0.33 to 0.54; 1 trial, 147 participants, moderate-certainty evidence) and parasitaemia (moderate-certainty evidence)., Authors' Conclusions: In areas of sub-Saharan Africa, giving antimalarial drugs known to be effective against the malaria parasite at the time to infants as IPT probably reduces the risk of clinical malaria, anaemia, and hospital admission. Evidence from SP studies over a 19-year period shows declining efficacy, which may be due to increasing drug resistance. Combinations with ACTs appear promising as suitable alternatives for IPTi., (Copyright © 2021 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Background: Intermittent preventive treatment could help prevent malaria in infants (IPTi) living in areas of moderate to high malaria transmission in sub-Saharan Africa. The World Health Organization (WHO) policy recommended IPTi in 2010, but its adoption in countries has been limited., Objectives: To evaluate the effects of intermittent preventive treatment (IPT) with antimalarial drugs to prevent malaria in infants living in malaria-endemic areas., Search Methods: We searched the following sources up to 3 December 2018: the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE (PubMed), Embase (OVID), LILACS (Bireme), and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) and the WHO International Clinical Trials Registry Platform (ICTRP) portal for ongoing trials up to 3 December 2018., Selection Criteria: We included randomized controlled trials (RCTs) that compared IPT to placebo or no intervention in infants (defined as young children aged between 1 to 12 months) in malaria-endemic areas., Data Collection and Analysis: The primary outcome was clinical malaria (fever plus asexual parasitaemia). Two review authors independently assessed trials for inclusion, evaluated the risk of bias, and extracted data. We summarized dichotomous outcomes and count data using risk ratios (RR) and rate ratios respectively, and presented all measures with 95% confidence intervals (CIs). We extracted protective efficacy values and their 95% CIs; when an included trial did not report this data, we calculated these values from the RR or rate ratio with its 95% CI. Where appropriate, we combined data in meta-analyses and assessed the certainty of the evidence using the GRADE approach., Main Results: We included 12 trials that enrolled 19,098 infants; all were conducted in sub-Saharan Africa. Three trials were cluster-RCTs. IPTi with sulfadoxine-pyrimethamine (SP) was evaluated in 10 trials from 1999 to 2013 (n = 15,256). Trials evaluating ACTs included dihydroartemisinin-piperaquine (1 trial, 147 participants; year 2013), amodiaquine-artesunate (1 study, 684 participants; year 2008), and SP-artesunate (1 trial, 676 participants; year 2008). The earlier studies evaluated IPTi with SP, and were conducted in Tanzania (in 1999 and 2006), Mozambique (2004), Ghana (2004 to 2005), Gabon (2005), Kenya (2008), and Mali (2009). One trial evaluated IPTi with amodiaquine in Tanzania (2000). Later studies included three conducted in Kenya (2008), Tanzania (2008), and Uganda (2013), evaluating IPTi in multiple trial arms that included artemisinin-based combination therapy (ACT). Although the effect size varied over time and between drugs, overall IPTi impacts on the incidence of clinical malaria overall, with a 27% reduction (rate ratio 0.73, 0.65 to 0.82; 10 studies, 10,602 participants). The effect of SP appeared to attenuate over time, with trials conducted after 2009 showing little or no effect of the intervention. IPTi with SP probably resulted in fewer episodes of clinical malaria (rate ratio 0.79, 0.74 to 0.85; 8 trials, 8774 participants, moderate-certainty evidence), anaemia (rate ratio 0.82, 0.68 to 0.98; 6 trials, 7438 participants, moderate-certainty evidence), parasitaemia (rate ratio 0.66, 0.56 to 0.79; 1 trial, 1200 participants, moderate-certainty evidence), and fewer hospital admissions (rate ratio 0.85, 0.78 to 0.93; 7 trials, 7486 participants, moderate-certainty evidence). IPTi with SP probably made little or no difference to all-cause mortality (risk ratio 0.93, 0.74 to 1.15; 9 trials, 14,588 participants, moderate-certainty evidence). Since 2009, IPTi trials have evaluated ACTs and indicate impact on clinical malaria and parasitaemia. A small trial of DHAP in 2013 shows substantive effects on clinical malaria (RR 0.42, 0.33 to 0.54; 1 trial, 147 participants, moderate-certainty evidence) and parasitaemia (moderate-certainty evidence)., Authors' Conclusions: In areas of sub-Saharan Africa, giving antimalarial drugs known to be effective against the malaria parasite at the time to infants as IPT probably reduces the risk of clinical malaria, anaemia, and hospital admission. Evidence from SP studies over a 19-year period shows declining efficacy, which may be due to increasing drug resistance. Combinations with ACTs appear promising as suitable alternatives for IPTi. 2 December 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (3 Dec, 2018) were included., (Copyright © 2019 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Background: In 2011 the World Health Organization (WHO) recommended parenteral artesunate in preference to quinine as first-line treatment for people with severe malaria. Prior to this recommendation many countries, particularly in Africa, had begun to use artemether, an alternative artemisinin derivative. This Cochrane Review evaluates intramuscular artemether compared with both quinine and artesunate., Objectives: To assess the efficacy and safety of intramuscular artemether versus any other parenteral medication in the treatment of severe malaria in adults and children., Search Methods: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE, Embase, and LILACS, ISI Web of Science, conference proceedings, and reference lists of articles. We also searched the WHO International Clinical Trial Registry Platform, ClinicalTrials.gov, and the metaRegister of Controlled Trials (mRCT) for ongoing trials up to 7 September 2018. We checked the reference lists of all studies identified by the search. We examined references listed in review articles and previously compiled bibliographies to look for eligible studies., Selection Criteria: Randomized controlled trials (RCTs) comparing intramuscular artemether with intravenous/intramuscular quinine or artesunate for treating severe malaria., Data Collection and Analysis: The primary outcome was all-cause death. Two review authors independently screened each article by title and abstract, and examined potentially relevant studies for inclusion using an eligibility form. Two review authors independently extracted data and assessed risk of bias of included studies. We summarized dichotomous outcomes using risk ratios (RRs) and continuous outcomes using mean differences (MDs), and have presented both measures with 95% confidence intervals (CIs). Where appropriate, we combined data in meta-analyses and used the GRADE approach to summarize the certainty of the evidence., Main Results: We included 19 RCTs, enrolling 2874 adults and children with severe malaria, carried out in Africa (12 trials) and in Asia (7 trials).Artemether versus quinineFor children, there is probably little or no difference in the risk of death between intramuscular artemether and quinine (RR 0.97, 95% CI 0.77 to 1.21; 13 trials, 1659 participants, moderate-certainty evidence). Coma resolution time may be about five hours shorter with artemether (MD -5.45, 95% CI -7.90 to -3.00; six trials, 358 participants, low-certainty evidence). Artemether may make little difference to neurological sequelae (RR 0.84, 95% CI 0.66 to 1.07; seven trials, 968 participants, low-certainty evidence). Compared to quinine, artemether probably shortens the parasite clearance time by about nine hours (MD -9.03, 95% CI -11.43 to -6.63; seven trials, 420 participants, moderate-certainty evidence), and may shorten the fever clearance time by about three hours (MD -3.73, 95% CI -6.55 to -0.92; eight trials, 457 participants, low-certainty evidence).For adults, treatment with intramuscular artemether probably results in fewer deaths than treatment with quinine (RR 0.59, 95% CI 0.42 to 0.83; four trials, 716 participants, moderate-certainty evidence).Artemether versus artesunateArtemether and artesunate have not been directly compared in randomized trials in children.For adults, mortality is probably higher with intramuscular artemether (RR 1.80, 95% CI 1.09 to 2.97; two trials, 494 participants, moderate-certainty evidence)., Authors' Conclusions: Artemether appears to be more effective than quinine in children and adults. Artemether compared to artesunate has not been extensively studied, but in adults it appears inferior. These findings are consistent with the WHO recommendations that artesunate is the drug of choice, but artemether is acceptable when artesunate is not available.

Background: In 2011 the World Health Organization (WHO) recommended parenteral artesunate in preference to quinine as first-line treatment for people with severe malaria. Prior to this recommendation, many countries, particularly in Africa, had begun to use artemether, an alternative artemisinin derivative. This review evaluates intramuscular artemether compared with both quinine and artesunate., Objectives: To assess the efficacy and safety of intramuscular artemether versus any other parenteral medication in treating severe malaria in adults and children., Search Methods: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE and LILACS, ISI Web of Science, conference proceedings and reference lists of articles. We also searched the WHO clinical trial registry platform, ClinicalTrials.gov and the metaRegister of Controlled Trials (mRCT) for ongoing trials up to 9 April 2014., Selection Criteria: Randomized controlled trials (RCTs) comparing intramuscular artemether with intravenous or intramuscular antimalarial for treating severe malaria., Data Collection and Analysis: The primary outcome was all-cause death.Two authors independently assessed trial eligibility, risk of bias and extracted data. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD), and presented both measures with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses and assessed the quality of the evidence using the GRADE approach., Main Results: We included 18 RCTs, enrolling 2662 adults and children with severe malaria, carried out in Africa (11) and in Asia (7). Artemether versus quinine For children in Africa, there is probably little or no difference in the risk of death between intramuscular artemether and quinine (RR 0.96, 95% CI 0.76 to 1.20; 12 trials, 1447 participants, moderate quality evidence). Coma recovery may be about five hours shorter with artemether (MD -5.45, 95% CI -7.90 to -3.00; six trials, 358 participants, low quality evidence), and artemether may result in fewer neurological sequelae, but larger trials would be needed to confirm this (RR 0.84, 95% CI 0.66 to 1.07; seven trials, 968 participants, low quality evidence). Artemether probably shortens the parasite clearance time by about nine hours (MD -9.03, 95% CI -11.43 to -6.63; seven trials, 420 participants, moderate quality evidence), and may shorten the fever clearance time by about three hours (MD -3.73, 95% CI -6.55 to -0.92; eight trials, 457 participants, low quality evidence).For adults in Asia, treatment with intramuscular artemether probably results in fewer deaths than treatment with quinine (RR 0.59, 95% CI 0.42 to 0.83; four trials, 716 participants, moderate quality evidence). Artemether versus artesunate Artemether and artesunate have not been directly compared in randomized trials in African children.For adults in Asia, mortality is probably higher with intramuscular artemether (RR 1.80, 95% CI 1.09 to 2.97, two trials,494 participants, moderate quality evidence)., Authors' Conclusions: Although there is a lack of direct evidence comparing artemether with artesunate, artemether is probably less effective than artesunate at preventing deaths from severe malaria. In circumstances where artesunate is not available, artemether is an alternative to quinine.

Background: The use of anti-malarial drug combinations with artemisinin, or with one of its derivatives, is now widely recommended to overcome drug resistance in falciparum malaria. Fixed-dose combination of artemisinin and naphthoquine is a new generation artemisinin combination therapy (ACT) offered as a single dose therapy. The aim of the study was to assess the therapeutic efficacy, safety and tolerability of three dosage schedules of fixed-dose combination of artemisinin (125 mg) and naphthoquine (50 mg) for treating uncomplicated Plasmodium falciparum malaria among adolescents and adults in Calabar, South-east Nigeria., Method: A total of 121 patients aged ≥15 years with uncomplicated P. falciparum malaria were enrolled and randomly assigned to three dosage schedules: (A) 700 mg (four tablets) single dose; (B) 700 mg 12-hourly x two doses; and (C) 1,400 mg (eight tablets) single dose. Patients were observed for 28 days, with clinical, parasitological, and haematological assessments., Results: A total of 108 patients completed the study. The overall 28-day cure rate was 88.9%. Day 28-cure rates of the three dosage schedules were 85.3%, 93.1% and 88.9% for Group A, B and C respectively. Adverse events were few and mild, the commonest being weakness and headache; there was no serious adverse event., Conclusion: Concerns for emergence of parasite resistance due to the use of artemisinin-naphthoquine as single dose regimen is likely to compromise the usefulness of this potentially important combination treatment. A robust multi-centre trial is recommended to evaluate a three-day regimen with potentials to achieve high cure rates while minimizing the risk of emergence of resistant parasite strains.

Background: In malaria endemic areas, pre-school children are at high risk of severe and repeated malaria illness. One possible public health strategy, known as Intermittent Preventive Treatment in children (IPTc), is to treat all children for malaria at regular intervals during the transmission season, regardless of whether they are infected or not., Objectives: To evaluate the effects of IPTc to prevent malaria in preschool children living in endemic areas with seasonal malaria transmission., Search Methods: We searched the Cochrane Infectious Diseases Group Specialized Register (July 2011), CENTRAL (The Cochrane Library 2011, Issue 6), MEDLINE (1966 to July 2011), EMBASE (1974 to July 2011), LILACS (1982 to July 2011), mRCT (July 2011), and reference lists of identified trials. We also contacted researchers working in the field for unpublished and ongoing trials., Selection Criteria: Individually randomized and cluster-randomized controlled trials of full therapeutic dose of antimalarial or antimalarial drug combinations given at regular intervals compared with placebo or no preventive treatment in children aged six years or less living in an area with seasonal malaria transmission., Data Collection and Analysis: Two authors independently assessed eligibility, extracted data and assessed the risk of bias in the trials. Data were meta-analysed and measures of effects (ie rate ratio, risk ratio and mean difference) are presented with 95% confidence intervals (CIs). The quality of evidence was assessed using the GRADE methods., Main Results: Seven trials (12,589 participants), including one cluster-randomized trial, met the inclusion criteria. All were conducted in West Africa, and six of seven trials were restricted to children aged less than 5 years.IPTc prevents approximately three quarters of all clinical malaria episodes (rate ratio 0.26; 95% CI 0.17 to 0.38; 9321 participants, six trials, high quality evidence), and a similar proportion of severe malaria episodes (rate ratio 0.27, 95% CI 0.10 to 0.76; 5964 participants, two trials, high quality evidence). These effects remain present even where insecticide treated net (ITN) usage is high (two trials, 5964 participants, high quality evidence).IPTc probably produces a small reduction in all-cause mortality consistent with the effect on severe malaria, but the trials were underpowered to reach statistical significance (risk ratio 0.66, 95% CI 0.31 to 1.39, moderate quality evidence).The effect on anaemia varied between studies, but the risk of moderately severe anaemia is probably lower with IPTc (risk ratio 0.71, 95% CI 0.52 to 0.98; 8805 participants, five trials, moderate quality evidence).Serious drug-related adverse events, if they occur, are probably rare, with none reported in the six trials (9533 participants, six trials, moderate quality evidence). Amodiaquine plus sulphadoxine-pyrimethamine is the most studied drug combination for seasonal chemoprevention. Although effective, it causes increased vomiting in this age-group (risk ratio 2.78, 95% CI 2.31 to 3.35; two trials, 3544 participants, high quality evidence).When antimalarial IPTc was stopped, no rebound increase in malaria was observed in the three trials which continued follow-up for one season after IPTc., Authors' Conclusions: In areas with seasonal malaria transmission, giving antimalarial drugs to preschool children (age < 6 years) as IPTc during the malaria transmission season markedly reduces episodes of clinical malaria, including severe malaria. This benefit occurs even in areas where insecticide treated net usage is high.

Background: The combination of artesunate and mefloquine has been reported to be effective against multi-drug resistant Plasmodium falciparum malaria, which has been reported in Nigeria. The objective of this multi-centre study was to evaluate the efficacy, safety and tolerability of the co-packaged formulation of artesunate and mefloquine in the treatment of uncomplicated malaria in two weight groups: those between 15 - 29 kg and > or = 30 kg respectively., Methods: The trial was conducted in rural communities in the north-east, north-central, south-west and south-eastern parts of Nigeria. The WHO protocol for testing antimalarial drugs was followed. Outpatients having amongst other criteria, parasite density of > or =1,000 microl were enrolled. The co-packaged drugs were administered for 3 days at a dosage of artesunate, 4 mg/kg body wt/day and mefloquine, 25 mg/kg/body wt total) on days 0, 1 and 2. Patients were followed up for 28 days with the assessment of the parasitological parameters on days 1, 2, 3, 7, and 28., Results: Four hundred and forty-six (446) patients were enrolled and 431 completed the study. Cure rates in both treatment groups was >90% at day 28. The mean parasite clearance times in treatment groups I and II were 40.1 and 42.4 hours respectively. The combination of artesunate and mefloquine showed good gametocidal activity, (gametocyte clearance time of 42.0 & 45.6 hours in treatment groups I and II respectively). There were no serious adverse events. Other adverse events observed were headache, dizziness, vomiting and abdominal discomfort. There was no significant derangement in the haematological and biochemical parameters., Conclusion: This co-packaged formulation of artesunate + mefloquine (Artequin) is highly efficacious, safe and well-tolerated. It is recommended for the treatment of uncomplicated P. falciparum malaria in Nigeria.

Background: Malaria causes repeated illness in children living in endemic areas. Policies of giving antimalarial drugs at regular intervals (prophylaxis or intermittent treatment) are being considered for preschool children., Objectives: To evaluate prophylaxis and intermittent treatment with antimalarial drugs to prevent malaria in young children living in malaria-endemic areas., Search Strategy: We searched the Cochrane Infectious Diseases Group Specialized Register (August 2007), CENTRAL (The Cochrane Library 2007, Issue 3), MEDLINE (1966 to August 2007), EMBASE (1974 to August 2007), LILACS (1982 to August 2007), mRCT (February 2007), and reference lists of identified trials. We also contacted researchers., Selection Criteria: Individually randomized and cluster-randomized controlled trials comparing antimalarial drugs given at regular intervals (prophylaxis or intermittent treatment) with placebo or no drug in children aged one month to six years or less living in a malaria-endemic area., Data Collection and Analysis: Two authors independently extracted data and assessed methodological quality. We used relative risk (RR) or weighted mean difference with 95% confidence intervals (CI) for meta-analyses. Where we detected heterogeneity and considered it appropriate to combine the trials, we used the random-effects model (REM)., Main Results: Twenty-one trials (19,394 participants), including six cluster-randomized trials, met the inclusion criteria. Prophylaxis or intermittent treatment with antimalarial drugs resulted in fewer clinical malaria episodes (RR 0.53, 95% CI 0.38 to 0.74, REM; 7037 participants, 10 trials), less severe anaemia (RR 0.70, 95% CI 0.52 to 0.94, REM; 5445 participants, 9 trials), and fewer hospital admissions for any cause (RR 0.64, 95% CI 0.49 to 0.82; 3722 participants, 5 trials). We did not detect a difference in the number of deaths from any cause (RR 0.90, 95% CI 0.65 to 1.23; 7369 participants, 10 trials), but the CI do not exclude a potentially important difference. One trial reported three serious adverse events with no statistically significant difference between study groups (1070 participants). Eight trials measured morbidity and mortality six months to two years after stopping regular antimalarial drugs; overall, there was no statistically significant difference, but participant numbers were small., Authors' Conclusions: Prophylaxis and intermittent treatment with antimalarial drugs reduce clinical malaria and severe anaemia in preschool children.

Background: Malaria causes repeated illness in children living in endemic areas. Policies of giving antimalarial drugs at regular intervals (prophylaxis or intermittent treatment) are being considered for preschool children., Objectives: To evaluate chemoprophylaxis and intermittent treatment with antimalarial drugs to prevent malaria in young children living in malaria endemic areas., Search Strategy: We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), and reference lists of identified trials. We also contacted researchers., Selection Criteria: Randomized and quasi-randomized controlled trials comparing antimalarial drugs given at regular intervals (prophylaxis or intermittent treatment) with placebo or no drug in children aged one month to six years or less living in an area where malaria is endemic., Data Collection and Analysis: We independently extracted data and assessed methodological quality. We used relative risk (RR) or weighted mean difference with 95% confidence intervals (CI) for meta-analyses. Where we detected heterogeneity and considered it appropriate to combine the trials, we used the random-effects model (REM)., Main Results: Nineteen trials (14,393 participants) met the inclusion criteria. Children receiving antimalarial drugs as prophylaxis or intermittent treatment had fewer clinical malaria episodes (RR 0.52, 95% CI 0.35 to 0.77, REM; 4051 participants, 8 trials), and severe anaemia was less common (RR 0.54, 95% CI 0.42 to 0.68; 2727 participants, 8 trials). We did not detect a difference in the number of deaths from any cause (RR 0.82, 95% CI 0.65 to 1.04; 7929 participants, 9 trials), but the confidence intervals do not exclude a potentially important difference. None of the trials reported serious adverse events. Three trials measured morbidity and mortality six months to two years after stopping regular antimalarial drugs; overall, there was no statistically significant difference, but participant numbers were small., Authors' Conclusions: Prophylaxis and intermittent treatment with antimalarial drugs reduce clinical malaria and severe anaemia in preschool children. There is insufficient evidence to detect an effect on mortality.

In a population-based study involving 4019 patients in 20 peripheral health facilities in Nigeria, the outcome of presumptive malaria treatment with MSP was compared to that of CQ. The study was conducted between January 1995 and January 1996. Patients aged 6 months or more with a clinical diagnosis of malaria based on history of fever and axillary temperature > 37.5 degrees C were either treated with MSP (250 mg mefloquine, 500 mg sulphadoxine, and 25 mg pyrimethamine per tablet) or CQ (150 mg chloroquine base per tablet). The clinical cure rate was assessed by the disappearance of clinical signs and symptoms over a 7-day period. Tolerability was assessed by the incidence of adverse events (adverse drug reaction and intercurrent illness). The result shows that the clinical care rate of suspected malaria was 97.6% with MSP and 85.6% with CQ. The incidence of adverse event was 9.5% with MSP and 9.2% with CQ. The withdrawal rate was 2.0% with MSP and 5.0% with CQ; 3.5% of the patients in the CQ group withdrew due to adverse events compared to 0.47% with MSP. In conclusion it was observed that in addition to superior efficacy of MSP over CQ, fever clearance rate with MSP was comparable to that of CQ. The study also demonstrated that two tablets maximum dose of MSP is safe and effective in a large population of Nigeria malaria patients.

The efficacy and tolerability of single, low-dose mefloquine, sulfadoxine-pyrimethamine (MSP) combination was compared with chloroquine (CQ) for malaria treatment in a malaria-endemic area of Nigeria with multiple drug-resistant Plasmodium falciparum. The two drug regimens (MSP and CQ) were tested in a 12-month prospective population study. The patients were divided into two groups. Group 1 patients were treated presumptively, based on malaria symptoms. Group 2 patients were treated based on a parasitologic diagnosis using the World Health Organization seven-day in vivo test and extended to a 28-day follow-up period. Tolerability was assessed by the incidence and intensity of adverse events. One thousand nine hundred thirty-five patients visiting 10 health facilities, including the University of Calabar Teaching Hospital, were enrolled. The study showed that the low-dose MSP was efficacious, with day 7 response rates of 95% and 91% for (presumptive) Group 1 and (in vivo) Group 2, respectively, while CQ had day 7 response rates of 82% and 66% in Groups 1 and 2, respectively. The low-dose MSP was significantly (P < 0.0001) more efficacious, with faster fever and parasite clearance times than CQ in this area of CQ-resistant P. falciparum malaria. Eight patients treated with CQ, including seven severe cases (RII-RIII) were successfully re-treated with MSP. Adverse events were generally more common among those treated with MSP (29%) than those treated with CQ (17%). However, the adverse events caused by both drugs were mild to moderate and self-limited. The MSP combination appears to be a good substitute for CQ, in view of multiple drug resistance, especially in areas with severe (RII-RIII) malaria.