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Clinical Microbiology and Infection :... Apr 2021While the landscape of vaccine and treatment candidates against the novel coronavirus disease 2019 (COVID-19) has been reviewed systematically, prophylactic candidates...
BACKGROUND
While the landscape of vaccine and treatment candidates against the novel coronavirus disease 2019 (COVID-19) has been reviewed systematically, prophylactic candidates remain unexplored.
OBJECTIVES
To map pre- and postexposure prophylactic (PrEP and PEP) candidate for COVID-19.
DATA SOURCES
PubMed/Medline, Embase, International Committee of Medical Journal Editors and International Clinical Trials Registry Platform clinical trial registries and medRxiv.
STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS
All studies in humans or animals and randomized controlled trials (RCTs) in humans reporting primary data on prophylactic candidates against COVID-19, excluding studies focused on key populations.
INTERVENTIONS
PrEP and PEP candidate for COVID-19.
METHODS
Systematic review and qualitative synthesis of COVID-19 PrEP and PEP studies and RCTs complemented by search of medRxiv and PubMed and Embase for studies reporting RCT outcomes since systematic review search completion.
RESULTS
We identified 13 studies (from 2119 database records) and 117 RCTs (from 5565 RCTs listed in the registries) that met the inclusion criteria. Non-RCT studies reported on cross-sectional studies using hydroxychloroquine (HCQ) in humans (n = 2) or reported on animal studies (n = 7), most of which used antibodies. All five completed RCTs focused on the use of HCQ as either PrEP or PEP, and these and the cross-sectional studies reported no prophylactic effect. The majority of ongoing RCTs evaluated HCQ or other existing candidates including non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, anti(retro)virals or use of vitamins and supplements.
CONCLUSIONS
The key message from completed studies and RCTs seems to be that HCQ does not work. There is little evidence regarding other compounds, with all RCTs using candidates other than HCQ still ongoing. It remains to be seen if the portfolio of existing molecules being evaluated in RCTs will identify successful prophylaxis against COVID-19 or if there is a need for the development of new candidates.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Antimalarials; Antiviral Agents; COVID-19; Humans; Hydroxychloroquine; Post-Exposure Prophylaxis; Pre-Exposure Prophylaxis; Randomized Controlled Trials as Topic; SARS-CoV-2; Vaccines
PubMed: 33476807
DOI: 10.1016/j.cmi.2021.01.013 -
BMJ Clinical Evidence Mar 2008Infection with Toxoplasma gondii is asymptomatic or mild in immunocompetent people and leads to lifelong immunity, but it can have serious consequences in pregnancy.... (Review)
Review
INTRODUCTION
Infection with Toxoplasma gondii is asymptomatic or mild in immunocompetent people and leads to lifelong immunity, but it can have serious consequences in pregnancy. About five per thousand non-immune pregnant women may acquire toxoplasma infection, with a 10-100% risk of transmission to the baby. Risks of transmission to the baby are higher later in pregnancy, but risks of infection causing harm to the baby are greater earlier in pregnancy.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects on mother and baby of treating toxoplasmosis during pregnancy? What are the effects of treating toxoplasmosis in neonates exposed to toxoplasmosis prenatally? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2007 (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 four 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: antiparasitic drugs in pregnancy, antiparasitic drugs in neonates.
Topics: Acute Disease; Antiparasitic Agents; Humans; Incidence; Pregnancy Complications, Parasitic; Toxoplasma; Toxoplasmosis; Toxoplasmosis, Congenital
PubMed: 19450322
DOI: No ID Found -
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 Lancet. Global Health Jul 2023Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of submicroscopic malaria infections in pregnant women in Asia, the Americas, and Africa using aggregated and individual participant data (IPD).
METHODS
For this systematic review and meta-analysis, studies (published Jan 1, 1997 to Nov 10, 2021) with information on both microscopic and submicroscopic infections during pregnancy from Asia, the Americas, or Africa, identified in the Malaria-in-Pregnancy Library, were eligible. Studies (or subgroups or study groups) that selected participants on the basis of the presence of fever or a positive blood smear were excluded to avoid selection bias. We obtained IPD (when available) and aggregated data. Estimates of malaria transmission intensity and sulfadoxine-pyrimethamine resistance, matched by study location and year, were obtained using publicly available data. One-stage multivariable logit and multinomial models with random intercepts for study site were used in meta-analysis to assess prevalence of and risk factors for submicroscopic infections during pregnancy and at delivery. This study is registered with PROSPERO, number CRD42015027342.
FINDINGS
The search identified 87 eligible studies, 68 (78%) of which contributed to the analyses. Of these 68 studies, 45 (66%) studies contributed IPD (48 869 participants) and 23 (34%) studies contributed aggregated data (11 863 participants). During pregnancy, median prevalence estimates were 13·5% (range 0·0-55·9, 66 substudies) for submicroscopic and 8·0% (0·0-50·6, 66 substudies) for microscopic malaria. Among women with positive Plasmodium nucleic acid amplification tests (NAATs), the median proportion of submicroscopic infections was 58·7% (range 0·0-100); this proportion was highest in the Americas (73·3%, 0·0-100), followed by Asia (67·2%, 36·4-100) and Africa (56·5%, 20·5-97·7). In individual patient data analysis, compared with women with no malaria infections, those with submicroscopic infections were more likely to present with fever in Africa (adjusted odds ratio 1·32, 95% CI 1·02-1·72; p=0·038) but not in other regions. Among women with NAAT-positive infections in Asia and the Americas, Plasmodium vivax infections were more likely to be submicroscopic than Plasmodium falciparum infections (3·69, 2·45-5·54; p<0·0001). Risk factors for submicroscopic infections among women with NAAT-positive infections in Africa included older age (age ≥30 years), multigravidity, and no HIV infection.
INTERPRETATION
During pregnancy, submicroscopic infections are more common than microscopic infections and are associated with fever in Africa. Malaria control in pregnancy should target both microscopic and submicroscopic infections.
FUNDING
Bill & Melinda Gates Foundation through the Worldwide Antimalarial Resistance Network.
Topics: Female; Humans; Pregnancy; Adult; Prevalence; Malaria; Antimalarials; Malaria, Falciparum; Risk Factors
PubMed: 37276878
DOI: 10.1016/S2214-109X(23)00194-8 -
Expert Opinion on Drug Safety Mar 2021: A century-long history in 8-aminoquinolines, the only anti-malaria drug class preventing malaria relapse, has resulted in the approval of tafenoquine by the U.S. Food... (Meta-Analysis)
Meta-Analysis
: A century-long history in 8-aminoquinolines, the only anti-malaria drug class preventing malaria relapse, has resulted in the approval of tafenoquine by the U.S. Food and Drug Administration (FDA) and the Australian Therapeutic Goods Administration (TGA) and to date registration in Brazil and Thailand. Tafenoquine is an alternative anti-relapse treatment for vivax malaria and malaria prophylaxis. It should not be given in pregnancy, during lactation of infants with glucose-6-phosphate dehydrogenase (G6PD) unknown or deficient status, and in those with G6PD deficiency or psychiatric illness.: This systematic review assesses tafenoquine associated adverse events in English-language, human clinical trials. Meta-analysis of commonly reported adverse events was conducted and grouped by comparison arms.: Tafenoquine, either for radical cure or prophylaxis, is generally well tolerated in adults. There is no convincing evidence for neurologic, ophthalmic, and cardiac toxicities. Psychotic disorder which has been attributed to higher doses is a contraindication for the chemoprophylaxis indication and psychiatric illness is a warning for the radical cure indication. Pregnancy assessment and quantitative G6PD testing are required. The optimal radical curative regimen including the tafenoquine dose along with its safety for parts of Southeast Asia, South America, and Oceania needs further assessment.
Topics: Adult; Aminoquinolines; Animals; Antimalarials; Dose-Response Relationship, Drug; Glucosephosphate Dehydrogenase Deficiency; Humans; Malaria, Vivax; Mental Disorders
PubMed: 33306921
DOI: 10.1080/14740338.2021.1859476 -
Pharmaceutics Jul 2022Ectoparasites are pathogens that can infect the skin and cause immense pain, discomfort, and disease. They are typically managed with insecticides. However, the... (Review)
Review
Ectoparasites are pathogens that can infect the skin and cause immense pain, discomfort, and disease. They are typically managed with insecticides. However, the fast-emerging antimicrobial resistance and the slow rate of development of new bio-actives combined with environmental and health concerns over the continued use of neurotoxic insecticides warrant newer and alternative methods of control. Tea tree oil (TTO), as an alternative agent, has shown remarkable promise against ectoparasites in recent studies. To our knowledge, this is the first systematic review to assess preclinical and clinical studies exploring the antiparasitic activity of TTO and its components against clinically significant ectoparasites, such as mites, scabies mites, house dust mites, lice, fleas, chiggers, and bed bugs. We systematically searched databases, including PubMed, MEDLINE (EBSCOhost), Embase (Scopus), CENTRAL, Cochrane Library, CINAHL, ScienceDirect, Web of Science, SciELO, and LILACS in any language from inception to 4 April 2022. Studies exploring the therapeutic activity of TTO and its components against the ectoparasites were eligible. We used the ToxRTool (Toxicological data reliability assessment) tool, the Joanna Briggs Institute (JBI) critical appraisal tools, and the Jadad scale to assess the methodological qualities of preclinical (in vitro and in vivo) studies, non-randomised controlled trials (including cohort, case series, and case studies), and randomised controlled trials, respectively. Of 497 identified records, 71 studies were included in this systematic review, and most (66%) had high methodological quality. The findings of this review revealed the promising efficacy of TTO and its components against ectoparasites of medical importance. Most importantly, the compelling in vitro activity of TTO against ectoparasites noted in this review seems to have translated well into the clinical environment. The promising outcomes observed in clinical studies provide enough evidence to justify the use of TTO in the pharmacotherapy of ectoparasitic infections.
PubMed: 36015213
DOI: 10.3390/pharmaceutics14081587 -
The Cochrane Database of Systematic... Sep 2014In 2011 the World Health Organization (WHO) recommended parenteral artesunate in preference to quinine as first-line treatment for people with severe malaria. Prior to... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Adolescent; Adult; Africa; Antimalarials; Artemether; Artemisinins; Artesunate; Asia; Child; Child, Preschool; Humans; Infant; Injections, Intramuscular; Malaria, Cerebral; Malaria, Falciparum; Oceania; Quinine; Randomized Controlled Trials as Topic
PubMed: 25209020
DOI: 10.1002/14651858.CD010678.pub2 -
Journal of General Internal Medicine Nov 2020There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain.
OBJECTIVE
We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19.
METHODS
Two reviewers searched for published and pre-published relevant articles between December 2019 and 8 June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa Scale. The quality of evidence was graded as per the GRADE approach.
RESULTS
We reviewed 12 observational and 3 randomized trials which included 10,659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46], time to fever resolution (mean difference - 0.54 days (- 1.19-011)) or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes.
AUTHORS' CONCLUSION
The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.
Topics: Bias; Chloroquine; Humans; Hydroxychloroquine; Research Design; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 32885373
DOI: 10.1007/s11606-020-06146-w -
The Cochrane Database of Systematic... Apr 2013Ocular infestation with Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea and consequently lead to complications such as... (Review)
Review
BACKGROUND
Ocular infestation with Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea and consequently lead to complications such as glaucoma, cataract, and posterior synechiae.
OBJECTIVES
The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids for ocular toxoplasmosis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to October 2012), EMBASE (January 1980 to October 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We searched the reference lists of included studies for any additional studies not identified by the electronic searches. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 October 2012.
SELECTION CRITERIA
We planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with active ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, or different doses or times of initiation of corticosteroids.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles and abstracts retrieved from the electronic searches. We retrieved full-text articles of studies categorized as 'unsure' or 'include' after review of the abstracts. Two authors independently reviewed each full-text article. Discrepancies were resolved through discussion.
MAIN RESULTS
The electronic searches retrieved 368 titles and abstracts. We reviewed 20 full-text articles. We identified no trials eligible for inclusion in this systematic review.
AUTHORS' CONCLUSIONS
Although research has identified wide variation in practices regarding use of corticosteroids, our systematic review did not identify evidence from randomized controlled trials for the role of corticosteroids in the management of ocular toxoplasmosis. Several questions remain unanswered by well-conducted randomized trials in this context, including whether use of corticosteroids is more effective than use of anti-parasitic therapy alone, when corticosteroids should be initiated in the treatment regimen (early versus late course of treatment), and which dosage and duration of steroid use is best. These questions are easily amenable to research using a randomized controlled design and they are ethical due to the absence of evidence to support or discourage use of corticosteroids for this condition. The question of foremost importance, however, is whether they should be used as adjunct therapy (that is, additional) to anti-parasitic agents.
Topics: Adrenal Cortex Hormones; Chemotherapy, Adjuvant; Humans; Toxoplasmosis, Ocular
PubMed: 23633342
DOI: 10.1002/14651858.CD007417.pub2 -
BMJ Clinical Evidence Jul 2008Cystitis is a bacterial infection of the lower urinary tract which causes pain when passing urine, and causes urgency, haematuria, and suprapubic pain not associated... (Review)
Review
INTRODUCTION
Cystitis is a bacterial infection of the lower urinary tract which causes pain when passing urine, and causes urgency, haematuria, and suprapubic pain not associated with passing urine. Recurrent cystitis is usually defined as three episodes of urinary tract infection in the previous 12 months, or two episodes in the previous 6 months.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: Which interventions prevent further recurrence of cystitis in women experiencing at least two infections per year? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2007 (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 14 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: continuous antibiotic prophylaxis (trimethoprim, co-trimoxazole, nitrofurantoin, cefaclor, or a quinolone or cephalexin); continuous prophylaxis with methenamine hippurate; cranberry juice and cranberry products; oestrogen (topical) in postmenopausal women; passing urine after intercourse; postcoital antibiotic prophylaxis; single-dose self-administered antibiotic.
Topics: Acute Disease; Bacterial Infections; Cystitis; Female; Humans; Incidence; Nitrofurantoin; Prospective Studies; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections
PubMed: 19445741
DOI: No ID Found