Treatment of soil-transmitted helminth infections in pregnancy: a systematic review and meta-analysis of maternal outcomes.

BACKGROUND: Gestational helminth infections are correlated to adverse outcomes including maternal anaemia; as such, treatment is recommended. However, little published high-quality data exist around the efficacy, safety and tolerability of anti-helminthics in pregnancy. We therefore conducted a systematic review and synthesized the available data on maternal outcomes following gestational treatment of intestinal nematodes to help guide clinical decision-making. METHODS: Five electronic databases were searched for studies reporting the efficacy, safety or tolerability of anti-helminthic drugs for gestational treatment of intestinal nematodes. Studies were systematically screened followed by data extraction. Trial quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. We conducted a narrative synthesis followed by meta-analyses using random effects models as appropriate. Data were summarized using qualitative and quantitative measures for specific parasitic infections as well as efficacy and safety of anti-parasitic agents. Outcomes of interest included maternal anaemia, minor adverse outcomes, pregnancy loss, pre-mature delivery, prevalence of infection and cure rate. RESULTS: Twenty-three studies were included. Gestational treatment with albendazole had cure rates up to 90% for hookworm and Ascaris, but only 50% for Trichuris. Mebendazole had an overall cure rate of ≤ 70% for Ascaris, hookworm and Trichuris. Pooled relative risk reduction of hookworm prevalence at delivery with albendazole compared to placebo was 90% (95% confidence interval, 0.09-0.15; n = 2; I2 = 0%). Rate of pregnancy loss and haemoglobin concentration did not differ between albendazole or mebendazole vs placebo, and rates of pre-term delivery were similar in albendazole-treated pregnant women vs controls. Ivermectin demonstrated a cure rate of 29% for hookworm and 56% for Trichuris in pregnant women. No serious adverse events were attributable to any drug studied. CONCLUSIONS: With increased international travel and migration of vulnerable populations, practitioners will encounter nematode infections in pregnant patients. Our analysis supports that albendazole in pregnancy has high cure rates for soil-transmitted helminths and is safe for the mother.

Quality of anthelminthic medicines available in Jimma Ethiopia.

Soil-transmitted helminthiasis and schistosomiasis are major public health problems in Ethiopia. Mass deworming of at-risk population using a single dose administration of 400mg albendazole (ABZ) or 500mg mebendazole (MBZ) for treatment of common intestinal worms and 40mg of praziquantel (PZQ) per kg body weight for treatment of schistosomiasis is one of the strategies recommended by World Health Organization (WHO) in order to control the morbidity of soil-transmitted helminthiasis and schistosomiasis. Since storage condition, climate, way of transportation and distribution route could all affect the quality of medicines, regular assessment by surveys is very critical to ensure the therapeutic outcome, to minimize risk of toxicity to the patient and resistance of parasites. Therefore, this study was conducted to assess the pharmaceutical quality of ABZ, MBZ and PZQ tablet brands commonly available in Jimma town (south west Ethiopia). Retail pharmacies (n=10) operating in Jimma town were selected using simple random sampling method. Samples of anthelminthic medicines available in the selected pharmacies were collected. Sample information was recorded and encompassed trade name, active ingredient name, manufacturer's name and full address, labeled medicine strength, dosage form, number of units per container, dosage statement, batch/lot number, manufacturing and expiry dates, storage information and presence of leaflets/package insert. Moreover, a first visual inspection was performed encompassing uniformity of color, uniformity of size, breaks, cracks, splits, embedded surface spots or visual contaminations. Finally, physico-chemical quality attributes investigated encompassed mass uniformity, quantity of active pharmaceutical ingredient (API), disintegration and dissolution, all following Pharmacopoeial test methods The physical characteristics of dosage form, packaging and labeling information of all samples complied with criteria given in the WHO checklists. The mass uniformity of tablets of each brand of ABZ, MBZ and PZQ complied with the pharmacopoeial specification limits, i.e no more than 2 individual masses >5% of average tablet weight, and none deviate by more than 10%. The quantity of APIs in all investigated tablet brands were within the 90-110% label claim (l.c.) limits, ranging between 95.05 and 110.09% l.c. Disintegration times were in line with the pharmacopoeial specification limit for immediate release (IR) tablets, ranging between 0.5 and 13min. However, the dissolution results (mean±SD, n=6) of one ABZ brand (i.e. Wormin®, Q=59.21±0.99% at 30min) and two PZQ brands (i.e. Bermoxel®, Q=63.43%±0.7 and Distocide®, Q=62.43%±1.67, at 75min) showed poor dissolution, failing the United States Pharmacopoeia (USP) dissolution specification limit.

Quality of medicines commonly used in the treatment of soil transmitted helminths and giardia in ethiopia: a nationwide survey.

BACKGROUND: The presence of poor quality medicines in the market is a global threat on public health, especially in developing countries. Therefore, we assessed the quality of two commonly used anthelminthic drugs [mebendazole (MEB) and albendazole (ALB)] and one antiprotozoal drug [tinidazole (TNZ)] in Ethiopia. METHODS/PRINCIPAL FINDINGS: A multilevel stratified random sampling, with as strata the different levels of supply chain system in Ethiopia, geographic areas and government/privately owned medicines outlets, was used to collect the drug samples using mystery shoppers. The three drugs (106 samples) were collected from 38 drug outlets (government/privately owned) in 7 major cities in Ethiopia between January and March 2012. All samples underwent visual and physical inspection for labeling and packaging before physico-chemical quality testing and evaluated based on individual monographs in Pharmacopoeias for identification, assay/content, dosage uniformity, dissolution, disintegration and friability. In addition, quality risk was analyzed using failure mode effect analysis (FMEA) and a risk priority number (RPN) was assigned to each quality attribute. A clinically rationalized desirability function was applied in quantification of the overall quality of each medicine. Overall, 45.3% (48/106) of the tested samples were substandard, i.e. not meeting the pharmacopoeial quality specifications claimed by their manufacturers. Assay was the quality attribute most often out-of-specification, with 29.2% (31/106) failure of the total samples. The highest failure was observed for MEB (19/42, 45.2%), followed by TNZ (10/39, 25.6%) and ALB (2/25, 8.0%). The risk analysis showed that assay (RPN = 512) is the most critical quality attribute, followed by dissolution (RPN = 336). Based on Derringer's desirability function, samples were classified into excellent (14/106,13%), good (24/106, 23%), acceptable (38/106, 36%%), low (29/106, 27%) and bad (1/106,1%) quality. CONCLUSIONS/SIGNIFICANCE: This study evidenced that there is a relatively high prevalence of poor quality MEB, ALB and TNZ in Ethiopia: up to 45% if pharmacopoeial acceptance criteria are used in the traditional, dichotomous approach, and 28% if the new risk-based desirability approach was applied. The study identified assay as the most critical quality attributes. The country of origin was the most significant factor determining poor quality status of the investigated medicines in Ethiopia.

Comparative study of the quality and efficacy of originator and generic albendazole for mass treatment of soil-transmitted nematode infections in Nepal.

The quality and efficacy of two locally manufactured generic albendazole (ABZ) products (Curex and Royal Drug) used for deworming children in Nepal since 1999 were tested against the originator product (GlaxoSmithKline (GSK)). The study included disintegration and dissolution testing according to the Indian Pharmacopoeia (IP) and the United States Pharmacopeia (USP), respectively, as well as a randomised controlled clinical trial comparing cure rates (CR) and egg reduction rates (ERR) for Ascaris lumbricoides, Trichuris trichiura and hookworm infections. Stool samples from 1277 children were examined before and 21 days after treatment. For A. lumbricoides, GSK (97.0%) and Royal Drug (95.0%) ABZ achieved significantly higher CRs than Curex ABZ (82.6%); however, all products achieved ERRs >90%. For T. trichiura, Curex ABZ showed significantly lower ERRs (63.2%). For hookworms, GSK ABZ performed significantly better (CR 74.3%, ERR 87.1%) than Royal Drug ABZ (CR 53.3%, ERR 80.8%) and Curex ABZ (CR 50.7%, ERR 73.1%). Only the GSK product passed both disintegration and dissolution tests according to the IP and USP. Both generic products failed the dissolution tests. Curex ABZ showed poor disintegration. Despite its lower efficacy, the cheaper Curex product achieved good results in controlling morbidity due to soil-transmitted helminth infections. This study shows that the cost effectiveness of drugs used in mass deworming campaigns should not be inferred on the basis of a single quality testing parameter.

Tratamiento de la neurocisticercosis con albendazol. Experiencia en Medellín, Colombia

Se evaluó la eficacia del albendazol en el tratamiento de 20 pacientes con neurocisticercosis, sin complicaciones graves y con lesiones quísticas en parenquima cerebral, que no tomaran el medi de contraste, por medio de tomografía computadorizada. Todos los casos tuvieron prueba de ELISA positiva para anticuerpos contra cisticercos, en suero o en líquido cefalorraquídeo. Los pacientes fueron hospitalizados durante el tratamiento. Este consistió en albendazol por vía oral a la dosis de 15 mg/kg/día, subdividido en dos tomas por día, durante ocho días. No se usaron esteroides de rutina, pero fueron necesarios en tres pacientes. La mayoría de los casos recibieron concomitantemente tratamiento antiepiléptico. Los pacientes fueron seguidos entre seis meses y dos años. El principal criterio de eficacia fue la comparación de la tomografía computarizada pretratamiento y a los seis meses; se hizo además evaluación clínica e inmunológica. El número de quistes existentes en los 20 pacientes se redujo de 239 a 119 (50 por ciento de reducción). En siete casos (35 por ciento) hubo desaparición de todos los quistes. En siete pacientes (35 por ciento) el número de quistes se redujo. En los seis pacientes restantes (30 por ciento) no hubo cambio en el número de quistes. En los 13 casos que permanecieron con quistes, hubo moderada reducción del tamaño en 11 (promedio inicial 12.3 mm y promedio final 9.6 mm). En los dos pacientes restantes los quistes permanecieron iguales. En total se observó que la reducción promedio del tamaño de los quistes fue de 49 por ciento en los 20 pacientes. Se observaron efectos colaterales durante el tratamiento en el 60 por ciento de los casos