WITHDRAWN: Artemether-lumefantrine for treating uncomplicated falciparum malaria.

BACKGROUND: Artemether-lumefantrine is being recommended by the World Health Organization for treating uncomplicated malaria. It is expensive. We sought evidence of its superiority over existing treatment regimens. OBJECTIVES: To compare artemether-lumefantrine with other antimalarial drugs for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (May 2005), CENTRAL (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to May 2005), EMBASE (1988 to May 2005), conference proceedings, and reference lists of articles. We contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA: Randomized and quasi-randomized trials comparing artemether-lumefantrine administered orally with standard treatment regimens (single drug or combination). DATA COLLECTION AND ANALYSIS: Two reviewers independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data. Parasitaemia on day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. Adverse event information was collected from the studies. MAIN RESULTS: Six trials (1698 participants) tested a four dose regimen. Failure rates for artemether-lumefantrine tended to be higher (comparisons included sulfadoxine-pyrimethamine, halofantrine, and mefloquine; difference statistically significant for mefloquine). When compared with chloroquine, artemether-lumefantrine was better in two studies, but the failure rate for chloroquine at these sites was over 50%. Two trials (419 participants) tested a six dose regimen against mefloquine plus artesunate. Artemether-lumefantrine was associated with higher failure rates but the studies were small. AUTHORS' CONCLUSIONS: The four dose regimen of artemether-lumefantrine seems to be less effective than most other current antimalarial regimens. The six dose regimen is largely untested. The authors are aware that some recently published trials may change the results of this review, and are preparing an update. These trials are referenced in 'Studies awaiting assessment'.

Primaquine for preventing relapses in people with Plasmodium vivax malaria.

BACKGROUND: Plasmodium vivax infections contribute to a significant proportion of the malaria infections in many countries. Primaquine is the most widely used drug for treating the dormant liver stage. Different primaquine dosing regimens are in use. OBJECTIVES: To compare primaquine regimens for preventing relapses in people with P. vivax malaria. SEARCH STRATEGY: In 2006, we searched the Cochrane Infectious Diseases Group's Specialized Register (January), CENTRAL (The Cochrane Library 2006, Issue 3), MEDLINE (October), EMBASE (January), LILACS (January). We also checked conference proceedings and reference lists, and contacted researchers, the World Health Organization (WHO), malaria mailing lists, and pharmaceutical companies. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing primaquine plus chloroquine with chloroquine alone, and the standard primaquine regimen (15 mg/day for 14 days) with other primaquine-containing regimens in people with vivax malaria. DATA COLLECTION AND ANALYSIS: All authors independently assessed trial eligibility and quality, and extracted data. We calculated odds ratios (OR) with 95% confidence intervals (CI) for dichotomous data, and used the random-effects model if there was significant heterogeneity. MAIN RESULTS: Nine trials (3423 participants) met the inclusion criteria. Compared with chloroquine alone, five-day primaquine plus chloroquine was no better at preventing relapses (OR 1.04, 95% CI 0.64 to 1.69, random-effects model; 2104 participants; 3 trials), while 14-day primaquine plus chloroquine was significantly better (OR 0.24, 95% CI 0.12 to 0.45, random-effects model; 1071 participants, 6 trials). Limited data suggest the advantage for the 14-day primaquine regimen persisted for over six months (OR 0.41, 95% CI 0.29 to 0.60; 585 participants, 2 trials). Direct comparisons of the 14-day and five-day primaquine plus chloroquine regimens also confirm the superiority of the longer course (OR 13.33, 95% CI 3.45 to 51.44; 186 participants, 2 trials). Adverse effects were poorly reported, with three trials reporting skin rash, vertigo, headache, abdominal pain and/or nausea, and two trials reporting that primaquine was well tolerated. AUTHORS' CONCLUSIONS: Primaquine (15 mg/kg/day for 14 days) plus chloroquine is more effective than chloroquine alone or primaquine (15 mg/kg for 5 days) plus chloroquine in preventing relapses of vivax malaria. Primaquine (five days) plus chloroquine appears no better than chloroquine. Countries should follow the WHO's recommendation for 14-day primaquine plus chloroquine regimen. Alternative regimens need to be evaluated in randomized controlled trials, which should also consider variations in regional P. vivax strains and the possibility of primaquine resistance, reinfection, and adherence in those who relapse.

Malaria chemoprophylaxis in sickle cell disease.

BACKGROUND: Malaria is the most common precipitating cause of crises in sickle cell disease in malaria-endemic countries. Health professionals often recommend life-long malaria chemoprophylaxis for people with sickle cell disease living in these areas. It is therefore important we have good evidence of benefit. OBJECTIVES: To assess the effects of routine malaria chemoprophylaxis in people with sickle cell disease. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (January 2006), Cochrane Cystic Fibrosis and Genetic Disorders Group Specialized Register (July 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to January 2006), EMBASE (1974 to January 2006), LILACS (1982 to January 2006), and reference lists. We also contacted organizations and pharmaceutical companies. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing chemoprophylaxis with any antimalarial drug given for a minimum of three months compared with a placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria, assessed methodological quality, and extracted data. Dichotomous data were analysed using relative risks (RR) and presented with 95% confidence intervals (CI). MAIN RESULTS: Two trials with a total of 223 children with homozygous sickle cell disease met the inclusion criteria. A randomized controlled trial in Nigeria compared two different antimalarial drugs with a placebo, and reported that chemoprophylaxis reduced sickle cell crises (RR 0.17, 95% CI 0.04 to 0.83; 97 children), hospital admissions (RR 0.27, 95% CI 0.12 to 0.63; 97 participants), and blood transfusions (RR 0.16, 95% CI 0.05 to 0.56; 97 participants). A quasi-randomized controlled trial of 126 children in Uganda compared an antimalarial drug plus antibiotics with no antimalarial plus placebo. Chemoprophylaxis reduced the number of episodes of malaria and dactylitis, and increased mean haemoglobin values in this trial. AUTHORS' CONCLUSIONS: It is beneficial to give routine malaria chemoprophylaxis in sickle cell disease in areas where malaria is endemic.

Artemether-lumefantrine (four-dose regimen) for treating uncomplicated falciparum malaria.

BACKGROUND: The World Health Organization recommends artemether-lumefantrine, an expensive drug, as a treatment for uncomplicated malaria. We sought evidence of the superiority of the four-dose regimen over existing treatments. OBJECTIVES: To evaluate the four-dose regimen of artemether-lumefantrine for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (October 2005), CENTRAL (The Cochrane Library 2005, Issue 3), MEDLINE (1966 to October 2005), EMBASE (1988 to October 2005), LILACS (1982 to October 2005), conference proceedings, and reference lists of articles. We also contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA: Randomized controlled trials comparing four doses of artemether-lumefantrine with standard treatment regimens (single drug or combination), or six doses of artemether-lumefantrine, for treating uncomplicated falciparum malaria. DATA COLLECTION AND ANALYSIS: Two authors independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data, including adverse events. Total failure by day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. MAIN RESULTS: Seven trials (2057 participants) tested a four-dose regimen. More people tended to fail treatment with artemether-lumefantrine than with other drugs, including sulfadoxine-pyrimethamine (247 participants, 1 trial), halofantrine (86 participants, 1 trial), and mefloquine (233 participants, 1 trial; difference statistically significant for mefloquine). When compared with chloroquine, artemether-lumefantrine was better in two trials (378 participants), but over 50% of the participants treated with chloroquine had total failure by day 28. Fewer people failed treatment with the six-dose regimen compared to the four-dose regimen (RR 7.71, 95% CI 2.99 to 19.88; 306 participants, 1 trial). AUTHORS' CONCLUSIONS: The four-dose regimen of artemether-lumefantrine seems to be less effective than regimens against which it has been tested. The six-dose regimen is superior to four-dose regimen.

Chemoprophylaxis and intermittent treatment for preventing malaria in 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.

Artemether-lumefantrine (six-dose regimen) for treating uncomplicated falciparum malaria.

BACKGROUND: The World Health Organization recommends artemether-lumefantrine for treating uncomplicated malaria. We sought evidence of superiority of the six-dose regimen over existing treatment regimens as well as its effectiveness in clinical situations. OBJECTIVES: To evaluate the six-dose regimen of artemether-lumefantrine for treating uncomplicated falciparum malaria. 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), conference proceedings, and reference lists of articles. We also contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA: Randomized controlled trials comparing six doses of artemether-lumefantrine administered orally with standard treatment regimens (single drug or combination), or supervised with unsupervised treatment, for uncomplicated falciparum malaria. DATA COLLECTION AND ANALYSIS: Two authors independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data, including adverse events. Total failure by day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. MAIN RESULTS: Nine trials (4547 participants) tested the six-dose regimen. Total failure at day 28 for artemether-lumefantrine was lower when compared with amodiaquine (270 participants, 1 trial), amodiaquine plus sulfadoxine-pyrimethamine (507 participants, 1 trial), but not with chloroquine plus sulfadoxine-pyrimethamine (201 participants, 2 trials). In comparisons with artemisinin derivative combinations, artemether-lumefantrine performed better than amodiaquine plus artesunate (668 participants, 2 trials), worse than mefloquine plus artesunate (270 participants, 4 trials), and no differently to dihydroartemisinin-napthoquine-trimethoprim (89 participants, 1 trial). AUTHORS' CONCLUSIONS: The six-dose regimen of artemether-lumefantrine appears more effective than antimalarial regimens not containing artemisinin derivatives.

Intrarectal quinine for treating Plasmodium falciparum malaria.

BACKGROUND: In children with falciparum malaria, quinine administered rectally may be easier to use and less painful than intramuscular or intravenous administration. However, it may be less effective. OBJECTIVES: To compare intrarectal quinine with intravenous or intramuscular quinine for treating malaria caused by Plasmodium falciparum. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (July 2004), CENTRAL (The Cochrane Library Issue 3, 2004), MEDLINE (1966 to July 2004), EMBASE (1974 to July 2004), LILACS (1982 to July 2004), and CINAHL (1982 to July 2004). We also searched conference proceedings, contacted individual researchers and a pharmaceutical company, and checked reference lists. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing intrarectal quinine with intramuscular and intravenous quinine for treating people with uncomplicated and severe falciparum malaria. DATA COLLECTION AND ANALYSIS: We independently assessed trial quality and extracted data, including adverse event data. We analysed dichotomous data using odds ratios and weighted mean difference for continuous data. MAIN RESULTS: Eight randomized controlled trials (involving 1247 children) fulfilled the inclusion criteria. The same principal investigator led seven of the trials. Five trials compared intrarectal with intravenous quinine, and six trials compared it with intramuscular treatment. We detected no statistically significant difference between intrarectal and intravenous or intramuscular routes for death, parasite clearance by 48 hours and 7 days, parasite clearance time, fever clearance time, coma recovery time, duration of hospitalization, and time to drinking. The trials reporting on these outcomes were small, which resulted in large confidence intervals for all outcomes apart from duration of hospitalization. One large trial (898 children) reported that intrarectal was less painful than intramuscular administration. AUTHORS' CONCLUSIONS: We detected no difference in the effect on parasites and clinical illness for intrarectal quinine, but most trials were small. Pain may be less with intrarectal quinine. Further larger trials, in patients with severe malaria and in adults, are required before the intrarectal route can be recommended.

Topical umbilical cord care at birth.

BACKGROUND: Umbilical cord infection caused many neonatal deaths before aseptic techniques were used. OBJECTIVES: To assess the effects of topical cord care in preventing cord infection, illness and death. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (September 2003) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003). We also contacted experts in the field. SELECTION CRITERIA: Randomized and quasi-randomized trials of topical cord care compared with no topical care, and comparisons between different forms of care. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and extracted data. MAIN RESULTS: Twenty-one studies (8959 participants) were included, the majority of which were from high-income countries. No systemic infections or deaths were observed in any of the studies reviewed. No difference was demonstrated between cords treated with antiseptics compared with dry cord care or placebo. There was a trend to reduced colonization with antibiotics compared to topical antiseptics and no treatment. Antiseptics prolonged the time to cord separation. Use of antiseptics was associated with a reduction in maternal concern about the cord. REVIEWERS' CONCLUSIONS: Good trials in low-income settings are warranted. In high-income settings, there is limited research which has not shown an advantage of antibiotics or antiseptics over simply keeping the cord clean. Quality of evidence is low.

Malaria chemoprophylaxis in sickle cell disease.

BACKGROUND: Malaria illness is associated with sickle cell crises. Health professionals often recommend life-long malaria chemoprophylaxis for people with sickle cell disease living in malaria endemic areas. It is therefore important we have good evidence of benefit. OBJECTIVES: To assess the effects of routine malaria chemoprophylaxis in people with sickle cell disease. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register (March 2003), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2003), MEDLINE (1966 to March 2003), EMBASE (1988 to March 2003), and LILACS (2001, 39a Edition CD-ROM), and reference lists of articles. We contacted individual researchers working in sickle cell disease research to identify any unpublished trials. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing chemoprophylaxis with any antimalarial drug given for a minimum of 3 months compared to placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria. MAIN RESULTS: One quasi-randomized controlled trial from Uganda gave antimalarial drugs and antibiotic prophylaxis together to 126 children with homozygous sickle cell disease. The authors reported the intervention group had fewer episodes of malaria, dactylitis, and higher mean haemoglobin values. REVIEWER'S CONCLUSIONS: There is very little direct evidence to support or refute giving routine chemoprophylaxis in sickle cell disease in areas where malaria is endemic.

Food prepared in iron cooking pots as an intervention for reducing iron deficiency anaemia in developing countries: a systematic review.

OBJECTIVE: To complete a systematic review of the effect of preparing food cooked in iron pots on haemoglobin concentrations and to assess compliance with pot use. DESIGN AND SEARCH STRATEGY: We searched The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, The Cochrane Controlled trials Register, The Cochrane Methodology Register, Health Technology Assessment Database and NHS Economic Evaluation Database (Cochrane Library, Issue 3, 2002). Medline (1966 to May 2002) and EMBASE (1988 to May 2002). Reference lists of published trials were examined for other potentially relevant trials and authors of selected trials were contacted to obtain information about ongoing or unpublished trials. Selection criteria included randomized trials which compared the effect of food cooked in cast iron pots with food cooked in noncast iron pots on participants of a minimum age of 4 months. One reviewer applied inclusion criteria to potentially relevant trials. Two reviewers assessed trial quality and extracted data. RESULTS: Three trials were eligible for inclusion in the review. There is some evidence from these studies that eating food prepared in iron pots increases the haemoglobin concentration of anaemic/iron deficient individuals. This effect seems to be modified by compliance, users age, and the presence of malaria and hookworm. Compliance with pot use varies considerably between countries depending on several factors, including: size of the cooking pot, targeted user group, whether the pot is used as an extra or replacement pot, and familiarity with cast iron pots. CONCLUSION: The introduction of iron pots or improving their use in communities in developing countries for the preparation of food maybe a promising innovative intervention for reducing iron deficiency and iron deficiency anaemia. Further research is required to monitor the use and effectiveness of this intervention.