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Travel Medicine and Infectious Disease 2018We evaluated existing data on the prophylactic efficacy of atovaquone-proguanil (AP) in order to determine whether prophylaxis in travellers can be discontinued on the... (Review)
Review
BACKGROUND
We evaluated existing data on the prophylactic efficacy of atovaquone-proguanil (AP) in order to determine whether prophylaxis in travellers can be discontinued on the day of return from a malaria-endemic area instead of seven days after return as per currently recommended post-travel schedule.
METHODS
PubMed and Embase databases were searched to identify relevant studies. This PROSPERO-registered systematic review followed PRISMA guidelines. The search strategy included terms or synonyms relevant to AP combined with terms to identify articles relating to prophylactic use of AP and inhibitory and half-life properties of AP. Studies considered for inclusion were: randomized controlled trials, cohort studies, quasi-experimental studies, open-label trials, patient-control studies, cross-sectional studies; as well as case-series and non-clinical studies. Data on study design, characteristics of participants, interventions, and outcomes were extracted. Primary outcomes considered relevant were prophylactic efficacy and prolonged inhibitory activity and half-life properties of AP.
RESULTS
The initial search identified 1,482 publications, of which 40 were selected based on screening. Following full text review, 32 studies were included and categorized into two groups, namely studies in support of the current post-travel regimen (with a total of 2,866 subjects) and studies in support of an alternative regimen (with a total of 533 subjects).
CONCLUSION
There is limited direct and indirect evidence to suggest that an abbreviated post-travel regimen for AP may be effective. Proguanil, however, has a short half-life and is essential for the synergistic effect of the combination. Stopping AP early may result in mono-prophylaxis with atovaquone and possibly select for atovaquone-resistant parasites. Furthermore, the quality of the studies in support of the current post-travel regimen outweighs the quality of the studies in support of an alternative short, post-travel regimen, and the total sample size of the studies to support stopping AP early comprises a small percentage of the total sample size of the studies performed to establish the efficacy of the current AP regimen. Additional research is required - especially from studies evaluating impact on malaria parasitaemia and clinical illness and conducted among travellers in high malaria risk settings - before an abbreviated regimen can be recommended in current practice.
PROSPERO REGISTRATION NUMBER
CRD42017055244.
Topics: Antimalarials; Atovaquone; Drug Administration Schedule; Drug Combinations; Drug Synergism; Endemic Diseases; Humans; Malaria; Post-Exposure Prophylaxis; Proguanil; Travel; Travel-Related Illness
PubMed: 29242073
DOI: 10.1016/j.tmaid.2017.12.005 -
The Journal of Antimicrobial... Mar 2018Atovaquone/proguanil, registered as Malarone®, is a fixed-dose combination recommended for first-line treatment of uncomplicated Plasmodium falciparum malaria in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atovaquone/proguanil, registered as Malarone®, is a fixed-dose combination recommended for first-line treatment of uncomplicated Plasmodium falciparum malaria in non-endemic countries and its prevention in travellers. Mutations in the cytochrome bc1 complex are causally associated with atovaquone resistance.
METHODS
This systematic review assesses the clinical efficacy of atovaquone/proguanil treatment of uncomplicated malaria and examines the extent to which codon 268 mutation in cytochrome b influences treatment failure and recrudescence based on published information.
RESULTS
Data suggest that atovaquone/proguanil treatment efficacy is 89%-98% for P. falciparum malaria (from 27 studies including between 18 and 253 patients in each case) and 20%-26% for Plasmodium vivax malaria (from 1 study including 25 patients). The in vitro P. falciparum phenotype of atovaquone resistance is an IC50 value >28 nM. Case report analyses predict that recrudescence in a patient presenting with parasites carrying cytochrome b codon 268 mutation will occur on average at day 29 (95% CI: 22, 35), 19 (95% CI: 7, 30) days longer than if the mutation is absent.
CONCLUSIONS
Evidence suggests atovaquone/proguanil treatment for P. falciparum malaria is effective. Late treatment failure is likely to be associated with a codon 268 mutation in cytochrome b, though recent evidence from animal models suggests these mutations may not spread within the population. However, early treatment failure is likely to arise through alternative mechanisms, requiring further investigation.
Topics: Atovaquone; Drug Combinations; Drug Resistance, Multiple; Drug Therapy, Combination; Electron Transport Complex III; Humans; Malaria, Falciparum; Malaria, Vivax; Mutation; Plasmodium falciparum; Proguanil; Travel; Treatment Failure
PubMed: 29237012
DOI: 10.1093/jac/dkx431 -
The Cochrane Database of Systematic... Oct 2017Mefloquine is one of four antimalarial agents commonly recommended for preventing malaria in travellers to malaria-endemic areas. Despite its high efficacy, there is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mefloquine is one of four antimalarial agents commonly recommended for preventing malaria in travellers to malaria-endemic areas. Despite its high efficacy, there is controversy about its psychological side effects.
OBJECTIVES
To summarize the efficacy and safety of mefloquine used as prophylaxis for malaria in travellers.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published on the Cochrane Library; MEDLINE; Embase (OVID); TOXLINE (https://toxnet.nlm.nih.gov/newtoxnet/toxline.htm); and LILACS. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; http://www.who.int/ictrp/en/) and ClinicalTrials.gov (https://clinicaltrials.gov/ct2/home) for trials in progress, using 'mefloquine', 'Lariam', and 'malaria' as search terms. The search date was 22 June 2017.
SELECTION CRITERIA
We included randomized controlled trials (for efficacy and safety) and non-randomized cohort studies (for safety). We compared prophylactic mefloquine with placebo, no treatment, or an alternative recommended antimalarial agent. Our study populations included all adults and children, including pregnant women.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the eligibility and risk of bias of trials, extracted and analysed data. We compared dichotomous outcomes using risk ratios (RR) with 95% confidence intervals (CI). Prespecified adverse outcomes are included in 'Summary of findings' tables, with the best available estimate of the absolute frequency of each outcome in short-term international travellers. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 20 RCTs (11,470 participants); 35 cohort studies (198,493 participants); and four large retrospective analyses of health records (800,652 participants). Nine RCTs explicitly excluded participants with a psychiatric history, and 25 cohort studies stated that the choice of antimalarial agent was based on medical history and personal preference. Most RCTs and cohort studies collected data on self-reported or clinician-assessed symptoms, rather than formal medical diagnoses. Mefloquine efficacyOf 12 trials comparing mefloquine and placebo, none were performed in short-term international travellers, and most populations had a degree of immunity to malaria. The percentage of people developing a malaria episode in the control arm varied from 1% to 82% (median 22%) and 0% to 13% in the mefloquine group (median 1%).In four RCTs that directly compared mefloquine, atovaquone-proguanil and doxycycline in non-immune, short-term international travellers, only one clinical case of malaria occurred (4 trials, 1822 participants). Mefloquine safety versus atovaquone-proguanil Participants receiving mefloquine were more likely to discontinue their medication due to adverse effects than atovaquone-proguanil users (RR 2.86, 95% CI 1.53 to 5.31; 3 RCTs, 1438 participants; high-certainty evidence). There were few serious adverse effects reported with mefloquine (15/2651 travellers) and none with atovaquone-proguanil (940 travellers).One RCT and six cohort studies reported on our prespecified adverse effects. In the RCT with short-term travellers, mefloquine users were more likely to report abnormal dreams (RR 2.04, 95% CI 1.37 to 3.04, moderate-certainty evidence), insomnia (RR 4.42, 95% CI 2.56 to 7.64, moderate-certainty evidence), anxiety (RR 6.12, 95% CI 1.82 to 20.66, moderate-certainty evidence), and depressed mood during travel (RR 5.78, 95% CI 1.71 to 19.61, moderate-certainty evidence). The cohort studies in longer-term travellers were consistent with this finding but most had larger effect sizes. Mefloquine users were also more likely to report nausea (high-certainty evidence) and dizziness (high-certainty evidence).Based on the available evidence, our best estimates of absolute effect sizes for mefloquine versus atovaquone-proguanil are 6% versus 2% for discontinuation of the drug, 13% versus 3% for insomnia, 14% versus 7% for abnormal dreams, 6% versus 1% for anxiety, and 6% versus 1% for depressed mood. Mefloquine safety versus doxycyclineNo difference was found in numbers of serious adverse effects with mefloquine and doxycycline (low-certainty evidence) or numbers of discontinuations due to adverse effects (RR 1.08, 95% CI 0.41 to 2.87; 4 RCTs, 763 participants; low-certainty evidence).Six cohort studies in longer-term occupational travellers reported our prespecified adverse effects; one RCT in military personnel and one cohort study in short-term travellers reported adverse events. Mefloquine users were more likely to report abnormal dreams (RR 10.49, 95% CI 3.79 to 29.10; 4 cohort studies, 2588 participants, very low-certainty evidence), insomnia (RR 4.14, 95% CI 1.19 to 14.44; 4 cohort studies, 3212 participants, very low-certainty evidence), anxiety (RR 18.04, 95% CI 9.32 to 34.93; 3 cohort studies, 2559 participants, very low-certainty evidence), and depressed mood (RR 11.43, 95% CI 5.21 to 25.07; 2 cohort studies, 2445 participants, very low-certainty evidence). The findings of the single cohort study reporting adverse events in short-term international travellers were consistent with this finding but the single RCT in military personnel did not demonstrate a difference between groups in frequencies of abnormal dreams or insomnia.Mefloquine users were less likely to report dyspepsia (RR 0.26, 95% CI 0.09 to 0.74; 5 cohort studies, 5104 participants, low certainty-evidence), photosensitivity (RR 0.08, 95% CI 0.05 to 0.11; 2 cohort studies, 1875 participants, very low-certainty evidence), vomiting (RR 0.18, 95% CI 0.12 to 0.27; 4 cohort studies, 5071 participants, very low-certainty evidence), and vaginal thrush (RR 0.10, 95% CI 0.06 to 0.16; 1 cohort study, 1761 participants, very low-certainty evidence).Based on the available evidence, our best estimates of absolute effect for mefloquine versus doxycyline were: 2% versus 2% for discontinuation, 12% versus 3% for insomnia, 31% versus 3% for abnormal dreams, 18% versus 1% for anxiety, 11% versus 1% for depressed mood, 4% versus 14% for dyspepsia, 2% versus 19% for photosensitivity, 1% versus 5% for vomiting, and 2% versus 16% for vaginal thrush.Additional analyses, including comparisons of mefloquine with chloroquine, added no new information. Subgroup analysis by study design, duration of travel, and military versus non-military participants, provided no conclusive findings.
AUTHORS' CONCLUSIONS
The absolute risk of malaria during short-term travel appears low with all three established antimalarial agents (mefloquine, doxycycline, and atovaquone-proguanil).The choice of antimalarial agent depends on how individual travellers assess the importance of specific adverse effects, pill burden, and cost. Some travellers will prefer mefloquine for its once-weekly regimen, but this should be balanced against the increased frequency of abnormal dreams, anxiety, insomnia, and depressed mood.
Topics: Adult; Antimalarials; Atovaquone; Child; Chloroquine; Doxycycline; Drug Combinations; Drug Resistance; Drug Therapy, Combination; Humans; Malaria, Falciparum; Mefloquine; Primaquine; Proguanil; Randomized Controlled Trials as Topic; Travel-Related Illness
PubMed: 29083100
DOI: 10.1002/14651858.CD006491.pub4 -
Travel Medicine and Infectious Disease 2017With increased international travel over the world the need for safe and effective chemoprophylaxis for malaria is as great as ever. The choice of regimen is difficult,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With increased international travel over the world the need for safe and effective chemoprophylaxis for malaria is as great as ever. The choice of regimen is difficult, as effectiveness should be weighted against potential adverse effects. Although, some studies have reported high prophylactic efficacy of primaquine, there is no comprehensive evidence comparing its prophylactic effectiveness as well as toxicity. To fill the gap, this systematic review and meta-analysis study was carried out.
METHODS
Using MeSH terms, 756 records were detected through searching "Pubmed", "Embase","Web of Science"and "Cochrane" databases. From these,7 relevant full-text articles with 14 comparisons for final quantitative meta-analysis were included in our review. In order to make a comparison between the studies, Risk Ratios(RRs) and their 95% confidence intervals(CIs) were estimated.
RESULTS
Overall,74% reduction in the incidence of parasitaemia by primaquine versus other prophylactic regimens was estimated(RRoverall = 0.26, CI 95%:0.16-0.41--RRvivax = 0.16, CI 95%:0.07-0.36--RRfalciparum = 0.31, CI 95%:0.18-0.55). The incidence rate ratios for adverse effects showed no statistically significant difference between primaquine and control groups (p > 0.05).
CONCLUSIONS
For persons without G6PD deficiency, who are not pregnant, primaquine is the most effective presently available prophylactic for P. vivax malaria and comparable to such regimens as doxycycline, mefloquine and atovaquone-proguanil for the prevention of P. falciparum malaria.
Topics: Antibiotic Prophylaxis; Antimalarials; Humans; Malaria, Falciparum; Malaria, Vivax; Parasitemia; Plasmodium falciparum; Plasmodium vivax; Primaquine; Travel
PubMed: 28450185
DOI: 10.1016/j.tmaid.2017.04.005 -
Malaria Journal Feb 2016Pregnancy has been reported to alter the pharmacokinetic properties of anti-malarial drugs, including the different components of artemisinin-based combination therapy... (Review)
Review
BACKGROUND
Pregnancy has been reported to alter the pharmacokinetic properties of anti-malarial drugs, including the different components of artemisinin-based combination therapy (ACT). However, small sample sizes make it difficult to draw strong conclusions based on individual pharmacokinetic studies. The aim of this review is to summarize the evidence of the influence of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations.
METHODS
A PROSPERO-registered systematic review to identify clinical trials that investigated the influence of pregnancy on the pharmacokinetic properties of different forms of ACT was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2015. The following components of ACT that are currently recommend by the World Health Organization as first-line treatment of malaria in pregnancy were reviewed: artemisinin, artesunate, dihydroartemisinin, lumefantrine, amodiaquine, mefloquine, sulfadoxine, pyrimethamine, piperaquine, atovaquone and proguanil.
RESULTS
The literature search identified 121 reports, 27 original studies were included. 829 pregnant women were included in the analysis. Comparison of the available studies showed lower maximum concentrations (Cmax) and exposure (AUC) of dihydroartemisinin, the active metabolite of all artemisinin derivatives, after oral administration of artemether, artesunate and dihydroartemisinin in pregnant women. Low day 7 concentrations were commonly seen in lumefantrine studies, indicating a low exposure and possibly reduced efficacy. The influence of pregnancy on amodiaquine and piperaquine seemed not to be clinically relevant. Sulfadoxine plasma concentration was significantly reduced and clearance rates were higher in pregnancy, while pyrimethamine and mefloquine need more research as no general conclusion can be drawn based on the available evidence. For atovaquone, the available data showed a lower maximum concentration and exposure. Finally, the maximum concentration of cycloguanil, the active metabolite of proguanil, was significantly lower, possibly compromising the efficacy.
CONCLUSION
These findings suggest that reassessment of the dose of the artemisinin derivate and some components of ACT are necessary to ensure the highest possible efficacy of malaria treatment in pregnant women. However, for most components of ACT, data were insufficient and extensive research with larger sample sizes will be necessary to identify the exact influences of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations. In addition, different clinical studies used diverse study designs with various reported relevant outcomes. Future pharmacokinetic studies could benefit from more uniform designs, in order to increase quality, robustness and effectiveness.
STUDY REGISTRATION
CRD42015023756 (PROSPERO).
Topics: Antimalarials; Artemisinins; Drug Combinations; Female; Humans; Malaria; Plasmodium falciparum; Plasmodium ovale; Plasmodium vivax; Pregnancy
PubMed: 26891915
DOI: 10.1186/s12936-016-1160-6 -
The Cochrane Database of Systematic... Oct 2015
Meta-Analysis Review
Topics: Adult; Antimalarials; Atovaquone; Child; Chloroquine; Doxycycline; Drug Combinations; Drug Resistance; Drug Therapy, Combination; Humans; Malaria, Falciparum; Mefloquine; Primaquine; Proguanil; Randomized Controlled Trials as Topic; Travel
PubMed: 26436859
DOI: 10.1002/14651858.CD006491.pub3 -
Clinical Pharmacokinetics Nov 2011Malaria is a serious parasitic infection, which affects millions of people worldwide. As pregnancy has been shown to alter the pharmacokinetics of many medications, the... (Review)
Review
Malaria is a serious parasitic infection, which affects millions of people worldwide. As pregnancy has been shown to alter the pharmacokinetics of many medications, the efficacy and safety of antimalarial drug regimens may be compromised in pregnant women. The objective of this review is to systematically review published literature on the pharmacokinetics of antimalarial agents in pregnant women. A search of MEDLINE (1948-May 2011), EMBASE (1980-May 2011), International Pharmaceutical Abstracts (1970-May 2011), Google and Google Scholar was conducted for articles describing the pharmacokinetics of antimalarials in pregnancy (and supplemented by a bibliographic review of all relevant articles); all identified studies were summarized and evaluated according to the level of evidence, based on the classification system developed by the US Preventive Services Task Force. Identified articles were included in the review if the study had at least one group that reported at least one pharmacokinetic parameter of interest in pregnant women. Articles were excluded from the review if no pharmacokinetic information was reported or if both pregnant and non-pregnant women were analysed within the same group. For quinine and its metabolites, there were three articles (one level II-1 and two level III); for artemisinin compounds, two articles (both level III); for lumefantrine, two articles (both level III); for atovaquone, two articles (both level III); for proguanil, three articles (one level II-1 and two level III); for sulfadoxine, three articles (all level II-1); for pyrimethamine, three articles (all level II-1); for chloroquine and its metabolite, four articles (three level II-1 and one level II-3); for mefloquine, two articles (one level II-1 and one level III); and for azithromycin, two articles (one level II-1 and one level III). Although comparative trials were identified, most of these studies were descriptive and classified as level III evidence. The main findings showed that pharmacokinetic parameters are commonly altered in pregnancy for the majority of recommended agents. Importantly, first-line regimens of artemisinin-based compounds, lumefantrine, chloroquine and pyrimethamine/sulfadoxine may undergo significant changes that could decrease therapeutic efficacy. These changes are usually due to increases in the apparent oral clearance and volume of distribution that commonly occur in pregnant women, and may result in decreased exposure and increased therapeutic failure. In order to assess the clinical implications of these changes and to provide safe and effective dosage regimens, there is an immediate need for dose-optimization studies of all recommended first- and second-line agents used in pregnant women with malaria.
Topics: Anti-Bacterial Agents; Antimalarials; Artemisinins; Atovaquone; Chloroquine; Drug Therapy, Combination; Ethanolamines; Female; Fluorenes; Humans; Lumefantrine; Malaria; Mefloquine; Pregnancy; Pregnancy Complications, Parasitic; Proguanil; Pyrimethamine; Quinine; Sulfadoxine
PubMed: 21973268
DOI: 10.2165/11594550-000000000-00000 -
The Cochrane Database of Systematic... Feb 2011To prevent the development of drug resistance, the World Health Organization (WHO) recommends treating malaria with combination therapy. Azithromycin, an antibiotic with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To prevent the development of drug resistance, the World Health Organization (WHO) recommends treating malaria with combination therapy. Azithromycin, an antibiotic with antimalarial properties, may be a useful additional option for antimalarial therapy.
OBJECTIVES
To compare the use of azithromycin alone or in combination with other antimalarial drugs with the use of alternative antimalarial drugs for treating uncomplicated malaria caused by Plasmodium falciparum or Plasmodium vivax.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group Specialized Register (August 2010); CENTRAL (The Cochrane Library Issue 3, 2010); MEDLINE (1966 to August 2010); EMBASE (1974 to August 2010); LILACS (August 2010); the metaRegister of Controlled Trials (mRCT, August 2010); conference proceedings; and reference lists. We also contacted researchers and a pharmaceutical company.
SELECTION CRITERIA
Randomized controlled trials comparing azithromycin, either alone or combined with another antimalarial drug, with another antimalarial drug used alone or combined with another antimalarial drug, or with azithromycin combined with another antimalarial drug if different combinations or doses of azithromycin were used. The primary outcome was treatment failure by day 28, defined as parasitological or clinical evidence of treatment failure between the start of treatment and day 28. Secondary outcomes included treatment failure by day 28 corrected for new infections confirmed by polymerase chain reaction (PCR), fever and parasite clearance time, and adverse events.
DATA COLLECTION AND ANALYSIS
Two people independently applied the inclusion criteria, extracted data and assessed methodological quality. We used risk ratio (RR) and 95% confidence intervals (CI).
MAIN RESULTS
Fifteen trials met the inclusion criteria (2284 participants, 69% males, 16% children). They were conducted in disparate malaria endemic areas, with the earlier studies conducted in Thailand (five) and India (two), and the more recent studies (eight) spread across three continents (South America, Africa, Asia). The 15 studies involved 41 treatment arms, 12 different drugs, and 28 different treatment regimens. Two studies examined P. vivax.Three-day azithromycin (AZ) monotherapy did not perform well for P. vivax or P. falciparum (Thailand: P. vivax failure rate 0.5 g daily, 56%, 95% CI 31 to 78. India: P. vivax failure rate 1 g daily,12%, 95% CI 7 to 21; P. falciparum failure rate 1 g daily, 64%, 95% CI 36 to 86.) A 1 g azithromycin and 0.6 g chloroquine combination daily for three days for uncomplicated P. falciparum infections was associated with increased treatment failure in India and Indonesia compared with the combination of sulphadoxine-pyrimethamine and chloroquine (pooled RR 2.66, 95% CI 1.25 to 5.67), and compared with the combination atovaquone-proguanil in a multicentre trial in Columbia and Surinam (RR 24.72, 95% CI 6.16 to 99.20). No increased risk of treatment failure was seen in two studies in Africa with mefloquine as the comparator drug (pooled RR 2.02, 95% CI 0.51 to 7.96, P = 0.3); the pooled RR for PCR-corrected data for the combination versus mefloquine was 1.01, 95% CI 0.18 to 5.84 (P = 1.0). An increased treatment failure risk was seen when comparing azithromycin in a dose of 1.2 to 1.5 mg in combination with artesunate (200 mg per day for three days) with artemether-lumefantrine (pooled RR 3.08, 95% CI 2.09 to 4.55; PCR-corrected pooled RR 3.63, 95% CI 2.02 to 6.52).Serious adverse events and treatment discontinuation were similar across treatment arms. More adverse events were reported when comparing the 1 g azithromycin/ 0.6 g chloroquine combination with mefloquine (pooled RR 1.20, 95% CI 1.06 to 1.36) or atovaquone-proguanil (RR 1.41, 95% CI 1.09 to1.83).
AUTHORS' CONCLUSIONS
Currently, there is no evidence for the superiority or equivalence of azithromycin monotherapy or combination therapy for the treatment of P. falciparum or P. vivax compared with other antimalarials or with the current first-line antimalarial combinations. The available evidence suggests that azithromycin is a weak antimalarial with some appealing safety characteristics. Unless the ongoing dose, formulation and product optimisation process results in a universally efficacious product, or a specific niche application is identified that is complementary to the current scala of more efficacious antimalarial combinations, azithromycin's future for the treatment of malaria does not look promising.
Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Artesunate; Atovaquone; Azithromycin; Chloroquine; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluorenes; Humans; Malaria, Falciparum; Malaria, Vivax; Male; Mefloquine; Proguanil; Pyrimethamine; Randomized Controlled Trials as Topic; Sulfadoxine; Treatment Failure
PubMed: 21328286
DOI: 10.1002/14651858.CD006688.pub2 -
BMJ Clinical Evidence Jun 2010Opportunistic infections can occur in up to 40% of people with HIV infection and a CD4 count less than 250/mm(3), although the risks are much lower with use of highly... (Review)
Review
INTRODUCTION
Opportunistic infections can occur in up to 40% of people with HIV infection and a CD4 count less than 250/mm(3), although the risks are much lower with use of highly active antiretroviral treatment.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of prophylaxis for Pneumocystis jirovecii pneumonia (PCP) and toxoplasmosis? What are the effects of antituberculosis prophylaxis in people with HIV infection? What are the effects of prophylaxis for disseminated Mycobacterium avium complex (MAC) disease for people with, and without, previous MAC disease? What are the effects of prophylaxis for cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella zoster virus (VZV)? What are the effects of prophylaxis for invasive fungal disease in people with, and without, previous fungal disease? What are the effects of discontinuing prophylaxis against opportunistic pathogens in people on highly active antiretroviral treatment (HAART)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2008 (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 43 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: aciclovir; antituberculosis prophylaxis; atovaquone; azithromycin (alone or plus rifabutin); clarithromycin (alone, or plus rifabutin and ethambutol); discontinuing prophylaxis for CMV, MAC, and PCP; ethambutol added to clarithromycin; famciclovir; fluconazole; isoniazid; itraconazole; oral ganciclovir; rifabutin (alone or plus macrolides); trimethoprim-sulfamethoxazole; and valaciclovir.
Topics: AIDS-Related Opportunistic Infections; Fluconazole; HIV Infections; Humans; Isoniazid; Opportunistic Infections; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 21418688
DOI: No ID Found -
BMJ Clinical Evidence Jul 2010Malaria transmission occurs most frequently in environments with humidity greater than 60% and ambient temperature of 25 °C to 30 °C. Risks increase with longer... (Review)
Review
INTRODUCTION
Malaria transmission occurs most frequently in environments with humidity greater than 60% and ambient temperature of 25 °C to 30 °C. Risks increase with longer visits and depend on activity. Infection can follow a single mosquito bite. Incubation is usually 10 to 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 non-pregnant adult travellers? What are the effects of drug prophylaxis in non-pregnant adult travellers? What are the effects of antimalaria vaccines in adult and child 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 November 2009 (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 79 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: aerosol insecticides, amodiaquine, air conditioning and electric fans, atovaquone-proguanil, biological control measures, chloroquine (alone or with proguanil), diethyltoluamide (DEET), dietary supplementation, doxycycline, electronic mosquito repellents, full-length and light-coloured clothing, insecticide-treated clothing/nets, mefloquine, mosquito coils and vapourising mats, primaquine, pyrimethamine-dapsone, pyrimethamine-sulfadoxine, smoke, topical (skin-applied) insect repellents, and vaccines.
Topics: Antimalarials; Bedding and Linens; Chloroquine; Humans; Malaria; Mefloquine; Primaquine; Travel
PubMed: 21418669
DOI: No ID Found