-
Revista Chilena de Infectologia :... Oct 2009Loxoscelism represents a major public health problem for which there are no standard therapeutic interventions. (Review)
Review
INTRODUCTION
Loxoscelism represents a major public health problem for which there are no standard therapeutic interventions.
OBJECTIVE
To review available scientific evidence on management of Loxoscelism
METHOD
Systematic review of clinical studies. The search included multiple databases (Medline, Lilacs, Embase, Web of Sciences, Cinahl, Pre-Cinahl, Paperfirst, Proceedingsfirst, Dissertations and Theses, Toxline, Cochrane Library), handsearch of references, and contact with experts.
RESULTS
Three clinical trials of poor methodological quality were identified from 5,207 references found. One trial (n = 31), concluded that the use of dapsone was associated with fewer local complications than surgical treatment. A second study (n = 46), concluded that the use of dapsone was superior to clorfenamine for skin lesions. A third study (n = 95) concluded that there was no differences between the use of oral dapsone, antivenom against anti-Loxosceles reclusa or a combination of both.
CONCLUSIONS
There is insufficient evidence based on good quality studies to recommend treatment guidelines for individuals with skin or visceral loxoscelism.
Topics: Clinical Trials as Topic; Evidence-Based Medicine; Humans; Skin Diseases; Spider Bites
PubMed: 19915750
DOI: No ID Found -
The Cochrane Database of Systematic... Oct 2009Idiopathic thrombocytopenic purpura (ITP) is a common hematologic disorder caused by immune-mediated thrombocytopenia. The magnitude of the maternal-fetal risk of ITP... (Review)
Review
BACKGROUND
Idiopathic thrombocytopenic purpura (ITP) is a common hematologic disorder caused by immune-mediated thrombocytopenia. The magnitude of the maternal-fetal risk of ITP during pregnancy is controversial. Labour management of pregnant women with ITP remains controversial. Management of ITP during pregnancy is complex because of the disparity between maternal and fetal platelet counts.
OBJECTIVES
To assess the effectiveness and safety of corticosteroids, intravenous immunoglobulin, vinca alkaloids, danazol, dapsone, and any other types of pharmacological treatments for the treatment of idiopathic thrombocytopenic purpura during pregnancy.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (February 2009), LILACS (1982 to 8 February 2009), ClinicalTrials.gov (8 February 2009), Current Controlled Trials (16 February 2009), Google Scholar (16 February 2009) and ongoing and unpublished trials cited in the reference lists of relevant articles.
SELECTION CRITERIA
Randomised controlled trials (RCTs) on any medical treatments for idiopathic thrombocytopenia purpura during pregnancy.
DATA COLLECTION AND ANALYSIS
Two review authors independently evaluated methodological quality and extracted trial data. Any disagreement was resolved by discussion or by consulting a third review author.
MAIN RESULTS
This review included one RCT in which 38 women (41 pregnancies) were randomised, with only 26 women (28 pregnancies) being analysed.This RCT comparing the effect of betamethasone (1.5 mg/day) with no medication found no statistically significant difference in neonatal thrombocytopenia (risk ratio (RR) 1.12, 95% confidence interval (CI) 0.62 to 2.05) and neonatal bleeding (RR 1.00, 95% CI 0.24 to 4.13). Review authors conducted an intention-to-treat analysis which showed similar findings: RR 1.18, 95% CI 0.57 to 2.45 and RR 1.05, 95% CI 0.24 to 4.61, respectively. Maternal death, perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage were not studied by this RCT.
AUTHORS' CONCLUSIONS
Current evidence indicates that compared to no medication, betamethasone did not reduce the risk of neonatal thrombocytopenia and neonatal bleeding in ITP during pregnancy. There is insufficient evidence to support the use of betamethasone for treating ITP. This Cohrane review does not provide evidence about other medical treatments for ITP during pregnancy. This systematic review also identifies the need for well-designed, adequately powered randomised clinical trials for this medical condition during pregnancy. Unless randomised clinical trials provide evidence of a treatment effect and the trade off between potential benefits and harms are established, policy-makers, clinicians, and academics should not use betamethasone for ITP in pregnant women. Any future trials on medical treatments for treating ITP during pregnancy should test a variety of important maternal, neonatal or both outcome measures, including maternal death, perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage.
Topics: Betamethasone; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Hematologic; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia, Neonatal Alloimmune
PubMed: 19821437
DOI: 10.1002/14651858.CD007722.pub2 -
The Cochrane Database of Systematic... Oct 2009Discoid lupus erythematosus is a chronic form of cutaneous (skin) lupus which can cause permanent scarring if treatment is inadequate. Many drugs have been used to treat... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Discoid lupus erythematosus is a chronic form of cutaneous (skin) lupus which can cause permanent scarring if treatment is inadequate. Many drugs have been used to treat this disease and some of these are potentially very toxic.
OBJECTIVES
To assess the effects of drugs for discoid lupus erythematosus.
SEARCH STRATEGY
In June 2009 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 2, 2009), MEDLINE, EMBASE, LILACS, and online ongoing trials registers. The reference lists of relevant reviews were searched. Index Medicus (1956 to 1966) was handsearched and we approached authors for information about unpublished trials.
SELECTION CRITERIA
We included all randomised trials of drugs to treat people with discoid lupus erythematosus. Drugs included in the search were azathioprine, chloroquine, clofazimine, corticosteroids, (oral and topical), dapsone, gold, interferon alpha-2a, methotrexate, phenytoin, retinoids, sulphasalazine, thalidomide, topical calcineurin blockers (pimecrolimus and tacrolimus), and biological agents (etanercept, efalizimab, infliximab, and rituximab).
DATA COLLECTION AND ANALYSIS
Two reviewers independently examined each retrieved study for eligibility.
MAIN RESULTS
Two trials involving 136 participants were included. No new trials were included in this update.In a cross-over study of 12 weeks duration, fluocinonide 0.05% cream (a potent topical corticosteroid), appeared to be better than hydrocortisone 1% cream (a mild corticosteroid) when the first arm of the trial involving 78 participants was analysed at 6 weeks. Clearing or excellent improvement was seen in 27% of people using fluocinonide and in 10% of those using hydrocortisone, giving a 17% absolute benefit in favour of fluocinonide (95% CI 0.0 to 0.34, NNT (Number needed to treat) 6).In the second trial, acitretin (50mg/day) was compared with hydroxychloroquine (400mg/day) in 58 people in a parallel trial of 8 weeks duration. There was marked improvement or clearing in 46% of people using acitretin and in 50% of those on hydroxychloroquine but there was no significant difference between the 2 interventions. The adverse effects were more frequent and more severe in the acitretin group. In this trial clearing of erythema was measured and found to be better in the hydroxychloroquine group (RR 0.61, 95% CI 0.36 to 1.06).
AUTHORS' CONCLUSIONS
Fluocinonide cream may be more effective than hydrocortisone in treating people with discoid lupus erythematosus. Hydroxychloroquine and acitretin appear to be of equal efficacy, although adverse effects are more frequent and more severe with acitretin. There is not enough reliable evidence about other drugs used to treat discoid lupus erythematosus.
Topics: Acitretin; Dermatologic Agents; Fluocinonide; Humans; Hydrocortisone; Hydroxychloroquine; Lupus Erythematosus, Discoid; Randomized Controlled Trials as Topic
PubMed: 19821298
DOI: 10.1002/14651858.CD002954.pub2 -
The Cochrane Database of Systematic... Jan 2009A range of interventions have been described for treatment of pemphigus, however the optimal therapeutic strategy has not been established. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A range of interventions have been described for treatment of pemphigus, however the optimal therapeutic strategy has not been established.
OBJECTIVES
To assess the efficacy and safety of all interventions used in the management of pemphigus vulgaris and pemphigus foliaceus.
SEARCH STRATEGY
We searched the Cochrane Skin Group Specialised Register (October 2008), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2008), MEDLINE (2003 to October 2008), EMBASE (2005 to October 2008), LILACS (1981 to October 2008), Ongoing Trials Registers, reference lists of articles, conference proceedings from international pemphigus meetings and contacted experts in the field.
SELECTION CRITERIA
Randomised controlled trials of any intervention in pemphigus vulgaris or pemphigus foliaceus.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed quality and extracted data from studies. All investigators were contacted for further information. Adverse events were identified from included studies.
MAIN RESULTS
Eleven studies with a total of 404 participants (337 pemphigus vulgaris, 27 pemphigus foliaceus and 40 not specified ) were identified. The quality of included studies was not high, the majority of studies did not report allocation concealment, and power was limited by very small sample sizes. Interventions assessed included prednisolone dose regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor and traditional Chinese medicine. Ten studies included participants with newly diagnosed or newly active recurrent disease, and one trial included participants in maintenance phase.There was sufficient data for 4 meta-analyses, each pooling results of two studies only. For the majority of interventions, results were inconclusive. We found some interventions to be superior for certain outcomes, although we were unable to conclude which treatments are superior overall. Mycophenolate was more effective in achieving disease control than azathioprine (1 study; n=40; RR 0.72; 95% CI 0.52 to 0.99, NNT 3.7). There was evidence of a steroid-sparing benefit of azathioprine (1 study; n=57; MWD -3919 mg prednisolone; 95% CI -6712 to -1126) and cyclophosphamide (1 study; n=54; MWD -3355 mg prednisolone; 95% CI -6144 to -566) compared to glucocorticoids alone. Topical epidermal growth factor decreased time to control (1 study; n=20; HR 2.35; 95% CI 1.62 to 3.41).
AUTHORS' CONCLUSIONS
There is inadequate information available at present to ascertain the optimal therapy for pemphigus vulgaris or pemphigus foliaceus. Further research is required, especially to assess the optimal glucocorticoid dose, the role of adjuvant immunosuppressive medications, and long-term adverse events to improve harm:benefit analyses.
Topics: Glucocorticoids; Humans; Immunosuppressive Agents; Pemphigus; Randomized Controlled Trials as Topic
PubMed: 19160272
DOI: 10.1002/14651858.CD006263.pub2 -
BMJ Clinical Evidence Jul 2008Pneumocystis pneumonia (PCP) is a common AIDS-defining opportunistic illness in people with HIV infection, but its incidence has fallen with use of prophylactic... (Review)
Review
INTRODUCTION
Pneumocystis pneumonia (PCP) is a common AIDS-defining opportunistic illness in people with HIV infection, but its incidence has fallen with use of prophylactic treatment. Without treatment, PCP is likely to be fatal in people with AIDS, so placebo-controlled studies would be considered unethical.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of first-line antipneumocystis treatments for Pneumocystis pneumonia in people infected with HIV? What are the effects of adjuvant corticosteroids in people receiving first-line antipneumocystis treatments for Pneumocystis pneumonia in people infected with HIV? What are the effects of treatments for Pneumocystis pneumonia in people infected with HIV who have not responded to first-line antipneumocystis treatment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 22 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adjuvant corticosteroids, aerosolised or intravenous pentamidine, atovaquone, clindamycin-primaquone, treatment after failure of first-line treatment, trimethoprim-dapsone, and trimethoprim-sulfamethoxazole (TMP-SMX, co-trimoxazole).
Topics: AIDS-Related Opportunistic Infections; Administration, Oral; Adrenal Cortex Hormones; Atovaquone; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 19445734
DOI: No ID Found -
Annals of Internal Medicine May 2007Nonchemotherapy drug-induced agranulocytosis is a rare adverse reaction that is characterized by a decrease in peripheral neutrophil count to less than 0.5 x 10(9)... (Review)
Review
BACKGROUND
Nonchemotherapy drug-induced agranulocytosis is a rare adverse reaction that is characterized by a decrease in peripheral neutrophil count to less than 0.5 x 10(9) cells/L due to immunologic or cytotoxic mechanisms.
PURPOSE
To systematically review case reports of drugs that are definitely or probably related to agranulocytosis.
DATA SOURCES
English-language and German-language reports in MEDLINE (1966 to 2006) or EMBASE (1989 to 2006) and in bibliographies of retrieved articles.
STUDY SELECTION
Published case reports of patients with nonchemotherapy drug-induced agranulocytosis.
DATA EXTRACTION
One reviewer abstracted details about cases and assessed causality between drug intake and agranulocytosis by using World Health Organization assessment criteria.
DATA SYNTHESIS
Causality assessments of 980 reported cases of agranulocytosis were definite in 56 (6%), probable in 436 (44%), possible in 481 (49%), and unlikely in 7 (1%). A total of 125 drugs were definitely or probably related to agranulocytosis. Drugs for which more than 10 reports were available (carbimazole, clozapine, dapsone, dipyrone, methimazole, penicillin G, procainamide, propylthiouracil, rituximab, sulfasalazine, and ticlopidine) accounted for more than 50% of definite or probable reports. Proportions of fatal cases decreased between 1966 and 2006. More patients with a neutrophil count nadir less than 0.1 x 10(9) cells/L had fatal complications than did those with a neutrophil count nadir of 0.1 x 10(9) cells/L or greater (10% vs. 3%; P < 0.001). Patients treated with hematopoietic growth factors had a shorter median duration of neutropenia (8 days vs. 9 days; P = 0.015) and, among asymptomatic patients at diagnosis, had a lower proportion of infectious or fatal complications (14% vs. 29%; P = 0.030) than patients without such treatment.
LIMITATIONS
Case reports cannot provide rates of drug-induced complications, sometimes incompletely assess or describe important details, and sometimes emphasize atypical features and outcomes.
CONCLUSIONS
Many drugs can cause nonchemotherapy drug-induced agranulocytosis. Case fatality may be decreasing over time with the availability of better treatment.
Topics: Agranulocytosis; Drug-Related Side Effects and Adverse Reactions; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Risk Factors
PubMed: 17470834
DOI: 10.7326/0003-4819-146-9-200705010-00009 -
BMJ Clinical Evidence Nov 2007Malaria transmission occurs most frequently in environments with humidity over 60% and ambient temperature of 25-30 degrees C. Risks increase with longer visits and... (Review)
Review
INTRODUCTION
Malaria transmission occurs most frequently in environments with humidity over 60% and ambient temperature of 25-30 degrees C. Risks increase with longer visits and depend on activity. Infection can follow a single mosquito bite. Incubation is usually 10-14 days but can be up to 18 months depending on the strain of parasite.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug preventive interventions in adult travellers? What are the effects of drug prophylaxis in adult travellers? What are the effects of antimalaria vaccines in travellers? What are the effects of antimalaria interventions in child travellers, pregnant travellers, and in airline pilots? We searched: Medline, Embase, The Cochrane Library and other important databases up to February 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 69 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acoustic buzzers, aerosol insecticides, amodiaquine, air conditioning and electric fans, atovaquone-proguanil, biological control measures, chloroquine (alone or with proguanil), diethyltoluamide (DEET), doxycycline, full-length and light-coloured clothing, insecticide-treated clothing/nets, mefloquine, mosquito coils and vaporising mats, primaquine, pyrimethamine-dapsone, pyrimethamine-sulfadoxine, smoke, topical (skin-applied) insect repellents, and vaccines.
Topics: Administration, Oral; Animals; Antimalarials; Bedding and Linens; Chloroquine; Humans; Insect Repellents; Insecticides; Malaria; Travel
PubMed: 19450348
DOI: No ID Found -
The Cochrane Database of Systematic... Jul 2006Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10 to 20% during the initial infection and increases substantially with the need for mechanical ventilation. It was suggested that in these patients corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality.
OBJECTIVES
To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxemia (arterial oxygen partial pressure <70 mmHg or alveolar-arterial gradient >35 mmHg on room air).
SEARCH STRATEGY
We searched Medline (January 1980-December 2004), EMBASE (January 1985-December 2004) and The Cochrane Library (Issue 4, 2004) without language restrictions to identify randomised controlled trials that compared adjunctive corticosteroids to control in HIV-infected patients with PCP. We further reviewed the reference lists from previously published overviews, we searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts of the field, and searched reference lists of identified publications for citations of additional relevant articles.
SELECTION CRITERIA
Trials were considered eligible for this review if they compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, used random allocation, and reported mortality data. We excluded trials in patients with no or mild hypoxemia (arterial oxygen partial pressure >70 mmHg or an alveolar-arterial gradient <35 mmHg on room air) and trials with a follow-up of less than 30 days.
DATA COLLECTION AND ANALYSIS
Two teams of reviewers independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups by using a random effects model.
MAIN RESULTS
Six studies were included in the review and meta-analysis. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval [CI], 0.32-0.98) at 1 month and 0.68 (95% CI, 0.50-0.94) at 3-4 months of follow-up. To prevent 1 death, numbers needed to treat are 9 patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. Only the 3 largest trials provided data on the need for mechanical ventilation with a risk ratio of 0.38 (95% CI, 0.20-0.73) in favour of adjunctive corticosteroids.
AUTHORS' CONCLUSIONS
The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but evidence from this review suggests a beneficial effect for patients with substantial hypoxemia.
Topics: AIDS-Related Opportunistic Infections; Adrenal Cortex Hormones; Chemotherapy, Adjuvant; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 16856118
DOI: 10.1002/14651858.CD006150 -
The Cochrane Database of Systematic... Oct 2005Malaria causes repeated illness in children living in endemic areas. Policies of giving antimalarial drugs at regular intervals (prophylaxis or intermittent treatment)... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Antimalarials; Child, Preschool; Chloroquine; Dapsone; Humans; Infant; Malaria; Pyrimethamine; Randomized Controlled Trials as Topic
PubMed: 16235340
DOI: 10.1002/14651858.CD003756.pub2 -
The Cochrane Database of Systematic... Oct 2004In Africa, malaria is often resistant to chloroquine and sulfadoxine-pyrimethamine. Chlorproguanil-dapsone is a potential alternative. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In Africa, malaria is often resistant to chloroquine and sulfadoxine-pyrimethamine. Chlorproguanil-dapsone is a potential alternative.
OBJECTIVES
To compare chlorproguanil-dapsone with other antimalarial drugs for treating uncomplicated falciparum malaria.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group Specialized Register (May 2004), CENTRAL (The Cochrane Library Issue 2, 2004), MEDLINE (1966 to May 2004), EMBASE (1988 to May 2004), LILACS (May 2004), Biosis Previews (1985 to May 2004), conference proceedings, and reference lists, and contacted researchers working in this field.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials comparing chlorproguanil-dapsone to other antimalarial drugs.
DATA COLLECTION AND ANALYSIS
Two reviewers independently applied the inclusion criteria, extracted data, and assessed methodological quality. We calculated the relative risk (RR) for dichotomous data and weighted mean difference for continuous data, and presented them with 95% confidence intervals (CI).
MAIN RESULTS
Six trials (n = 3352) met the inclusion criteria. Chlorproguanil-dapsone (with 1.2 mg chlorproguanil) as a single dose had fewer treatment failures than chloroquine (1 trial), but more treatment failures and people with parasitaemia at day 28 than sulfadoxine-pyrimethamine (3 trials). Two trials compared the three-dose chlorproguanil-dapsone (with 2 mg chlorproguanil) regimen with sulfadoxine-pyrimethamine in new attendees. There were fewer treatment failures with chlorproguanil-dapsone by day 7 (RR 0.30, CI 0.19 to 0.49; n = 827, 1 trial) and day 14 (RR 0.36, CI 0.24 to 0.53; n = 1709, 1 trial). Neither trial reported total failures by day 28. A further trial was carried out in participants selected because they had previously failed sulfadoxine-pyrimethamine. Adverse event reporting was inconsistent between trials, but chlorproguanil-dapsone was associated with more adverse events leading to discontinuation of treatment compared with sulfadoxine-pyrimethamine (RR 4.54, CI 1.74 to 11.82; n = 829, 1 trial). It was also associated with more red blood cell disorders (RR 2.86, CI 1.33 to 6.13; n = 1850, 1 trial).
REVIEWERS' CONCLUSIONS
There are insufficient data about the effects of the current standard chlorproguanil-dapsone regimen (three-dose, 2 mg chlorproguanil). Randomized controlled trials that follow up to day 28, record adverse events, and use an intention-to-treat analysis are required to inform any policy decisions.
Topics: Adult; Antimalarials; Child; Dapsone; Drug Combinations; Humans; Malaria; Proguanil; Randomized Controlled Trials as Topic
PubMed: 15495106
DOI: 10.1002/14651858.CD004387.pub2