-
Malaria Journal May 2017Assessing the quality of medicines in low-middle income countries (LMICs) relies primarily on human inspection and screening technologies, where available. Field studies... (Review)
Review
BACKGROUND
Assessing the quality of medicines in low-middle income countries (LMICs) relies primarily on human inspection and screening technologies, where available. Field studies and surveys have frequently utilized screening tests to analyse medicines sampled at the point of care, such as health care facilities and medicine outlets, to provide a snap shot of medicine quality in a specific geographical area. This review presents an overview of the screening tests typically employed in surveys to assess anti-malarial medicine quality, summarizes the analytical methods used, how findings have been reported and proposes a reporting template for future studies.
METHODS
A systematic search of the peer-reviewed and grey literature available in the public domain (including national and multi-national medicine quality surveys) covering the period 1990-2016 was undertaken. Studies were included if they had used screening techniques to assess the quality of anti-malarial medicines. As no standardized set of guidelines for the methodology and reporting of medicine quality surveys exist, the included studies were assessed for their standard against a newly proposed list of criteria.
RESULTS
The titles and abstracts of 4621 records were screened and only 39 were found to meet the eligibility criteria. These 39 studies utilized visual inspection, disintegration, colorimetry and Thin Layer Chromatography (TLC) either as components of the Global Pharma Health Fund (GPHF) MiniLab or as individual tests. Overall, 30/39 studies reported employing confirmatory testing described in international pharmacopeia to verify the quality of anti-malarials post assessment by a screening test. The authors assigned scores for the 23 criteria for the standard of reporting of each study.
CONCLUSIONS
There is considerable heterogeneity in study design and inconsistency in reporting of field surveys of medicine quality. A lack of standardization in the design and reporting of studies of medicine quality increases the risk of bias and error, impacting on the generalizability and reliability of study results. The criteria proposed for reporting on the standard of studies in this review can be used in conjunction with existing medicine quality survey guidelines as a checklist for designing and reporting findings of studies. The review protocol has been registered with PROSPERO (CRD42015026782).
Topics: Antimalarials; Drug Evaluation, Preclinical; Humans; Quality Control
PubMed: 28506234
DOI: 10.1186/s12936-017-1852-6 -
PloS One 2013Cotrimoxazole (CTX) has been used for half a century. It is inexpensive hence the reason for its almost universal availability and wide clinical spectrum of use. In the... (Review)
Review
INTRODUCTION
Cotrimoxazole (CTX) has been used for half a century. It is inexpensive hence the reason for its almost universal availability and wide clinical spectrum of use. In the last decade, CTX was used for prophylaxis of opportunistic infections in HIV infected people. It also had an impact on the malaria risk in this specific group.
OBJECTIVE
We performed a systematic review to explore the efficacy and safety of CTX used for P.falciparum malaria treatment and prophylaxis.
RESULT
CTX is safe and efficacious against malaria. Up to 75% of the safety concerns relate to skin reactions and this increases in HIV/AIDs patients. In different study areas, in HIV negative individuals, CTX used as malaria treatment cleared 56%-97% of the malaria infections, reduced fever and improved anaemia. CTX prophylaxis reduces the incidence of clinical malaria in HIV-1 infected individuals from 46%-97%. In HIV negative non pregnant participants, CTX prophylaxis had 39.5%-99.5% protective efficacy against clinical malaria. The lowest figures were observed in zones of high sulfadoxine-pyrimethamine resistance. There were no data reported on CTX prophylaxis in HIV negative pregnant women.
CONCLUSION
CTX is safe and still efficacious for the treatment of P.falciparum malaria in non-pregnant adults and children irrespective of HIV status and antifolate resistance profiles. There is need to explore its effect in pregnant women, irrespective of HIV status. CTX prophylaxis in HIV infected individuals protects against malaria and CTX may have a role for malaria prophylaxis in specific HIV negative target groups.
Topics: Antimalarials; Humans; Malaria, Falciparum; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 23451110
DOI: 10.1371/journal.pone.0056916 -
Parasitology Jul 2013Parasitic protozoa comprise diverse aetiological agents responsible for important diseases in humans and animals including sleeping sickness, Chagas disease,... (Review)
Review
Parasitic protozoa comprise diverse aetiological agents responsible for important diseases in humans and animals including sleeping sickness, Chagas disease, leishmaniasis, malaria, toxoplasmosis and others. They are major causes of mortality and morbidity in tropical and subtropical countries, and are also responsible for important economic losses. However, up to now, for most of these parasitic diseases, effective vaccines are lacking and the approved chemotherapeutic compounds present high toxicity, increasing resistance, limited efficacy and require long periods of treatment. Many of these parasitic illnesses predominantly affect low-income populations of developing countries for which new pharmaceutical alternatives are urgently needed. Thus, very low research funding is available. Amidine-containing compounds such as pentamidine are DNA minor groove binders with a broad spectrum of activities against human and veterinary pathogens. Due to their promising microbicidal activity but their rather poor bioavailability and high toxicity, many analogues and derivatives, including pro-drugs, have been synthesized and screened in vitro and in vivo in order to improve their selectivity and pharmacological properties. This review summarizes the knowledge on amidines and analogues with respect to their synthesis, pharmacological profile, mechanistic and biological effects upon a range of intracellular protozoan parasites. The bulk of these data may contribute to the future design and structure optimization of new aromatic dicationic compounds as novel antiparasitic drug candidates.
Topics: Amidines; Animals; Antiprotozoal Agents; Humans; Intracellular Space; Microscopy, Electron, Transmission; Parasites; Pentamidine; Protozoan Infections; Ultrasonography
PubMed: 23561006
DOI: 10.1017/S0031182013000292 -
PLoS Neglected Tropical Diseases Apr 2018The soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms, infect 1.5 billion people worldwide and cause an estimated burden of 3.3... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review, meta-analysis and individual patient data analysis.
BACKGROUND
The soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms, infect 1.5 billion people worldwide and cause an estimated burden of 3.3 million disability-adjusted life years (DALYs). Current control strategies focus on morbidity reduction through preventive chemotherapy (PC) but the most commonly used recommended drugs (albendazole and mebendazole) are particularly inefficacious against T. trichiura. This, together with the threat of emerging drug resistance, calls for new control strategies, including co-administration with other anthelminthics. Ivermectin plus albendazole is widely used against lymphatic filariasis, but its efficacy and safety against STH infections has not yet been fully understood.
METHODS AND FINDINGS
We conducted a systematic literature review and meta-analysis on the efficacy and safety of ivermectin-albendazole co-administration in five different databases (i.e. PubMed, ISI Web of Science, ScienceDirect, CENTRAL and clinicaltrials.gov) from 1960 to January 2018. Four studies reporting efficacy of ivermectin-albendazole against STH infections and five studies on its safety met the selection criteria and were included for quantitative analysis. Ivermectin-albendazole was significantly associated with lower risk (risk ratio (RR) = 0.44, 95% confidence interval (CI) = 0.31-0.62) for T. trichiura infection after treatment compared to albendazole alone. The co-administration revealed no or only a marginal benefit on cure and egg reduction rates over albendazole alone for A. lumbricoides and hookworm infections. Adverse events (AEs) occurring after ivermectin-albendazole co-administration were mostly mild and transient. Overall, the number of individuals reporting any AE was not different (RR = 1.09, 95% CI = 0.87-1.36) in co-treated and albendazole-treated patients. However, although not statistically significant, sub-group analysis showed a tendency for slightly more AEs in patients with filariasis treated with ivermectin-albendazole compared to those treated with albendazole alone (RR = 1.29, 95% CI = 0.81-2.05).
CONCLUSIONS
Our findings suggest a good tolerability and higher efficacy of ivermectin-albendazole against T. trichiura compared to the current standard single-dose albendazole treatment, which supports the use of this co-administration in PC programs. Large-scale definitive randomized controlled trials are required to confirm our results.
Topics: Albendazole; Animals; Anthelmintics; Helminthiasis; Helminths; Humans; Ivermectin; Treatment Outcome
PubMed: 29702653
DOI: 10.1371/journal.pntd.0006458 -
Acta Tropica Dec 2018Mebendazole (MBZ), a benzimidazole compound, has received attention in treating patients with giardiasis because it has shown beneficial effects both in vitro and in... (Meta-Analysis)
Meta-Analysis Review
Mebendazole (MBZ), a benzimidazole compound, has received attention in treating patients with giardiasis because it has shown beneficial effects both in vitro and in vivo. The aim of this study was to assess with a systematic review and meta-analysis of randomized controlled trials (RCTs) the efficacy of MBZ compared to other antigiardial agents in children. We searched RCTs of MBZ for the treatment of Giardia infections published in PubMed and EBSCOhost. Application of inclusion and exclusion criteria, data extraction, and assessment of methodological quality were independently performed in duplicate. The primary outcome was the parasitological cure. We included 7 RCTs in the systematic review (639 patients). There was no clinical difference in the parasitological cure between MBZ and metronidazole (MTZ). The relative risk (RR) was 0.81 [95% Confidence Interval 0.61-1.09], with high heterogeneity (4 trials, I = 81%). The prediction interval expected to cover the results of a new trial was wide enough (0.22-2.96) to support both a clinically relevant difference favouring either MBZ or MTZ. The decision to support any treatment should be based not only on efficacy but also safety and cost. Although our results suggest that MBZ may be an effective treatment option for children with Giardia infection, they should also be interpreted and translated into clinical practice with caution, as the evidence is based on a limited number of RCTs presenting high heterogeneity.
Topics: Antinematodal Agents; Child; Giardiasis; Humans; Mebendazole
PubMed: 30092225
DOI: 10.1016/j.actatropica.2018.08.001 -
The Cochrane Database of Systematic... Oct 2009Malaria infects 10,000 to 30,000 international travellers each year. It can be prevented through anti-mosquito measures and drug prophylaxis. However, antimalaria drugs... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Malaria infects 10,000 to 30,000 international travellers each year. It can be prevented through anti-mosquito measures and drug prophylaxis. However, antimalaria drugs have adverse effects which are sometimes serious.
OBJECTIVES
To compare the effects of currently used antimalaria drugs when given as prophylaxis to non-immune adult and child travellers who are travelling to regions with Plasmodium falciparum resistance to chloroquine. Specifically, to assess the efficacy, safety, and tolerability of atovaquone-proguanil, doxycycline, and mefloquine compared to each other, and also when compared to chloroquine-proguanil and to primaquine.
SEARCH STRATEGY
In August 2009 we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 4), MEDLINE, EMBASE, LILACS, BIOSIS, mRCT, and reference lists. We handsearched conference proceedings and one specialist journal, and contacted researchers and drug companies. We searched PubMed for drug-related deaths.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials of any antimalaria drug regimen currently used by non-immune international travellers.
DATA COLLECTION AND ANALYSIS
We independently extracted data and assessed eligibility and risk of bias using a standardized data collection form. We resolved any disagreement through discussion. We combined dichotomous outcomes using risk ratio (RR) and continuous data using mean difference (MD), presenting both with 95% confidence intervals (CI).
MAIN RESULTS
Eight trials (4240 participants) met the inclusion criteria. Evidence on comparative efficacy from head-to-head comparisons was limited. Atovaquone-proguanil compared to doxycycline had similar adverse events reported. Compared to mefloquine, atovaquone-proguanil users had fewer reports of any adverse effect (RR 0.72, 95% CI 0.6 to 0.85), gastrointestinal adverse effects (RR 0.54, 95% CI 0.42 to 0.7), neuropsychiatric adverse events (RR 0.86, 95% CI 0.75 to 0.99), and neuropsychiatric adverse effects (RR 0.49, 95% CI 0.38 to 0.63), besides a better total mood disturbance score (MD -7.20, 95% CI -10.79 to -3.61). Similarly, doxycycline users had fewer reported neuropsychiatric events than mefloquine users (RR 0.84, 95% CI 0.73 to 0.96). We also examined these three regimens against chloroquine-proguanil; this latter regimen had more reports of any adverse effect (RR 0.84, 95% CI 0.73 to 0.96) and of gastrointestinal adverse effects (RR 0.71, 95% CI 0.6 to 0.85).
AUTHORS' CONCLUSIONS
Atovaquone-proguanil and doxycycline are the best tolerated regimens, and mefloquine is associated with adverse neuropsychiatric outcomes.
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: 19821371
DOI: 10.1002/14651858.CD006491.pub2 -
The Cochrane Database of Systematic... Apr 2009Entamoeba histolytica infection is common in developing countries, and up to 100,000 individuals with severe disease die every year. Adequate therapy for amoebic colitis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Entamoeba histolytica infection is common in developing countries, and up to 100,000 individuals with severe disease die every year. Adequate therapy for amoebic colitis is necessary to reduce the severity of illness, prevent development of complicated disease and extraintestinal spread, and decrease transmission.
OBJECTIVES
To evaluate antiamoebic drugs for treating amoebic colitis.
SEARCH STRATEGY
In September 2008, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (2008, Issue 3), MEDLINE, EMBASE, LILACS, mRCT, and conference proceedings. We contacted individual researchers, organizations, and pharmaceutical companies, and checked reference lists.
SELECTION CRITERIA
Randomized controlled trials of antiamoebic drugs given alone or in combination, compared with placebo or another antiamoebic drug for treating adults and children diagnosed with amoebic colitis.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the eligibility and methodological quality of trials, and extracted and analysed the data. We calculated clinical and parasitological failure rates, relapse, and adverse events as risk ratios (RR) with 95% confidence intervals (CIs), using a random-effects model. We determined statistical heterogeneity and explored possible sources of heterogeneity using subgroup analyses. We carried out sensitivity analysis using trial quality to assess the robustness of the results.
MAIN RESULTS
Thirty-seven trials, enrolling 4487 participants, met the inclusion criteria. Only one trial used adequate methods for randomization and allocation concealment, was blinded, and analysed all randomized participants. Only one trial used a E. histolytica stool antigen test. Tinidazole reduced clinical failure compared with metronidazole (RR 0.28, 95% CI 0.15 to 0.51; 477 participants, eight trials) and was associated with fewer adverse events. Compared with metronidazole, combination therapy resulted in fewer parasitological failures (RR 0.36, 95% CI 0.15 to 0.86; 720 participants, 3 trials).
AUTHORS' CONCLUSIONS
Tinidazole is more effective in reducing clinical failure compared with metronidazole and has fewer associated adverse events. Combination drug therapy is more effective in reducing parasitological failure compared with metronidazole alone. However, these results are based on trials with poor methodological quality so there is uncertainty in these conclusions. Further trials of the efficacy of antiamoebic drugs, with better methodological quality, are recommended. More accurate tests to detect E. histolytica are needed, particularly in countries where concomitant infection with other bacteria and parasites is common.
Topics: Amebicides; Animals; Drug Therapy, Combination; Dysentery, Amebic; Entamoeba histolytica; Humans; Metronidazole; Randomized Controlled Trials as Topic; Tinidazole
PubMed: 19370624
DOI: 10.1002/14651858.CD006085.pub2 -
The Cochrane Database of Systematic... Jan 2019Infection with the protozoan Entamoeba histolytica is common in low- and middle-income countries, and up to 100,000 people with severe disease die every year. Adequate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Infection with the protozoan Entamoeba histolytica is common in low- and middle-income countries, and up to 100,000 people with severe disease die every year. Adequate therapy for amoebic colitis is necessary to reduce illness, prevent development of complicated disease and extraintestinal spread, and decrease transmission.
OBJECTIVES
To evaluate antiamoebic drugs for treating amoebic colitis.
SEARCH METHODS
We searched the available literature up to 22 March 2018. We searched the Cochrane Infectious Diseases Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, mRCT, and conference proceedings. We contacted individual researchers, organizations, and pharmaceutical companies, and we checked reference lists.
SELECTION CRITERIA
Randomized controlled trials of antiamoebic drugs given alone or in combination, compared with placebo or another antiamoebic drug, for treating adults and children with a diagnosis of amoebic colitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the eligibility and methodological quality of trials and extracted and analysed the data. We calculated clinical and parasitological failure rates and rates of relapse and adverse events as risk ratios (RRs) with 95% confidence intervals (CIs), using a random-effects model. We determined statistical heterogeneity and explored possible sources of heterogeneity using subgroup analyses. We carried out sensitivity analysis by using trial quality to assess the robustness of reported results.
MAIN RESULTS
In total, 41 trials (4999 participants) met the inclusion criteria of this review. In this update, we added four trials to the 37 trials included in the first published review version. Thirty trials were published over 20 years ago. Only one trial used adequate methods of randomization and allocation concealment, was blinded, and analysed all randomized participants. Only one trial used an E histolytica stool antigen test, and two trials used amoebic culture.Tinidazole may be more effective than metronidazole for reducing clinical failure (RR 0.28, 95% CI 0.15 to 0.51; 477 participants, eight trials; low-certainty evidence) and is probably associated with fewer adverse events (RR 0.65, 95% CI 0.46 to 0.92; 477 participants, 8 trials; moderate-certainty evidence). Compared with metronidazole, combination therapy may result in fewer parasitological failures (RR 0.36, 95% CI 0.15 to 0.86; 720 participants, 3 trials; low-certainty evidence), but we are uncertain which combination is more effective than another. Evidence is insufficient to allow conclusions regarding the efficacy of other antiamoebic drugs.
AUTHORS' CONCLUSIONS
Compared with metronidazole, tinidazole may be more effective in reducing clinical failure and may be associated with fewer adverse events. Combination drug therapy may be more effective for reducing parasitological failure compared with metronidazole alone. However, these results are based mostly on small trials conducted over 20 years ago with a variety of poorly defined outcomes. Tests that detect E histolytica more accurately are needed, particularly in countries where concomitant infection with other bacteria and parasites is common.
Topics: Amebicides; Animals; Drug Therapy, Combination; Dysentery, Amebic; Entamoeba histolytica; Humans; Metronidazole; Randomized Controlled Trials as Topic; Tinidazole
PubMed: 30624763
DOI: 10.1002/14651858.CD006085.pub3 -
Tropical Medicine & International... Mar 2022Lymphatic filariasis is a serious public health issue. Recent studies showed that a single dosage of triple therapy (Ivermectin, Diethylcarbamazepine, and Albendazole)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Lymphatic filariasis is a serious public health issue. Recent studies showed that a single dosage of triple therapy (Ivermectin, Diethylcarbamazepine, and Albendazole) is more effective than dual therapy (Ivermectin plus Albendazole or Diethylcarbamazepine plus Albendazole) for clearing microfilaria from the blood. We aimed to evaluate the efficacy and safety of triple therapy versus dual therapy in patients infected with microfilaria and communities endemic to lymphatic filariasis.
METHODS
For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science until 24th June 2021. We included randomized control trials that compared triple with dual therapy given to patients with lymphatic filariasis or endemic communities. This study was registered with PROSPERO (CRD42021266724).
RESULTS
We included eight articles after the screening process. Triple therapy caused more clearance of microfilaria in the blood (RR: 1.52; 95% CI: 1.15, 2.02; p = 0.003), while dual therapy caused more clearance of the circulating filariae antigen in the blood (RR: 0.76; 95% CI: 0.65, 0.88; p = 0.0003), both 12 months after drug administration. The triple therapy had a similar adverse effect compared with the dual therapy group.
CONCLUSION
Based on the greater efficacy in the clearance of microfilaria and the safety of triple therapy, it constitutes a better strategy for the eradication programs of lymphatic filariasis in endemic regions. However, further studies are needed to confirm our results.
Topics: Albendazole; Animals; Diethylcarbamazine; Drug Therapy, Combination; Elephantiasis, Filarial; Filaricides; Humans; Ivermectin; Microfilariae
PubMed: 35080325
DOI: 10.1111/tmi.13727 -
Tropical Medicine & International... Jan 1997To assess the efficacy of treatment of parasitological excretion of cysts and trophozoites and symptoms of patients with giardiasis, a systematic review of published... (Review)
Review
To assess the efficacy of treatment of parasitological excretion of cysts and trophozoites and symptoms of patients with giardiasis, a systematic review of published randomized clinical trials was conducted through extensive searches in Medline, Embase and Current Contents from 1966 till 1996 as well as manual reviews of 28 journals. The methodological quality of all trials was assessed by guidelines of the Cochrane Collaboration. Thirty-one trials were included, only one of which had no serious methodological flaws. The mean score of parasitological examination was 4.8 out of a possible 15. There was a considerable effect in cure rate of treatment versus placebo (odds 9.3, 95% CI 4.69-18.4), but all 3 trials in this comparison had serious flaws. Metronidazole treatment over more than 3 days seems to achieve a better parasitological cure rate than other long treatment courses (pooled odds 2.6, 95% 1.7-3.8), but trials are clinically and statistically heterogeneous. Single-dose therapy is as effective as longer treatment courses (pooled odds 0.67, 95% 0.31-1.44). Within the single-dose regimens tinidazole (2 g) reaches a higher parasitological cure rate than other short therapies (pooled odds 55, 95% CI 3.7-8.3) with relatively few side-effects. Placebo-controlled trials with parasitological and clinical outcomes are needed.
Topics: Antiprotozoal Agents; Giardiasis; Humans; Metronidazole; Randomized Controlled Trials as Topic; Tinidazole
PubMed: 9018304
DOI: 10.1046/j.1365-3156.1997.d01-132.x