Use Of Mebendazole Research Articles

Mebendazole induces apoptosis and inhibits migration via the reactive oxygen species-mediated STAT3 signaling downregulation in non-small cell lung cancer.

The incidence and mortality of non-small cell lung cancer (NSCLC) are extremely high. Previous research has confirmed that the signal transducer and activator of the transcription 3 (STAT3) protein critically participate in the tumorigenesis of NSCLC. Mebendazole (MBZ) has exerts a larger number of pharmacological activities and has anticancer effects in lung cancer, but its mechanism of action remains unclear. This study thus aimed to clarify the impacts of MBZ on NSCLC cell. Cell proliferation, migration, and apoptosis were investigated via cell counting kit 8 (CCK-8) assay, Transwell assay, colony formation assay, wound-healing assay, and flow cytometry. Reactive oxygen species (ROS) were detected with a multifunctional microplate reader. Markers of cell migration and apoptosis were detected with Western blotting. The transcriptional activity of STAT3 was detected via luciferase assay. ROS scavenger N-acetylcysteine (NAC) was used to determine the effect of MBZ on NSCLC via ROS-regulated STAT3 inactivation and apoptosis. A xenograft model was constructed in vivo to investigate the role of MBZ in NSCLC tumor growth. The findings demonstrated that MBZ inhibited NSCLC cell proliferation and migration while promoting apoptosis through triggering ROS generation. In addition, the Janus kinase 2 (JAK2)-STAT3 signaling pathway was abrogated with the treatment of MBZ. NAC could distinctly weaken MBZ-induced apoptosis and STAT3 inactivation. Moreover, MBZ inhibited the tumor growth of NSCLC in vivo. In summary, MBZ inhibited NSCLC cell viability and migration by inducing cell apoptosis via the ROS-JAK2-STAT3 signaling pathway. These data provide a theoretical basis for the use of MBZ in treating NSCLC.

The Use of Mebendazole in COVID-19 Patients: An Observational Retrospective Single Center Study.

An in-silico screen identified mebendazole with potential antiviral activity that could be a repurposed drug against SARS-CoV-2. Mebendazole is a well-tolerated and cheap antihelminthic agent that is readily available worldwide and thus could be a therapeutic tool in the fight against COVID-19. This is an observational retrospective study of PCR-confirmed COVID-19 patients who received mebendazole with the intention-to-treat. The study included an inpatient cohort (157 inpatients) and an outpatient cohort (185 outpatients). Of the 157 inpatients and 185 outpatients, 68 (43.3%) and 94 (50.8%) received mebendazole, respectively. Patients who presented within the same timeframe but did not receive mebendazole were used as controls. Patients received standard-of-care treatment including remdesivir, dexamethasone, and anticoagulants as deemed necessary by the treating physician. The following clinical outcomes were evaluated: for the inpatient cohort, length of stay (LOS) at the hospital, need for ventilation (combined invasive and noninvasive), and mortality; for the outpatient cohort, time to symptom resolution, need for hospitalization, and mortality. For the inpatient cohort, the median age did not differ between the treatment and control groups; 62 (56, 67) vs. 62 (56, 68), P, and there was a comparable proportion of males in both groups; 43 (63%) vs. 55 (62%), P=0.85. The hospital LOS was 3.5 days shorter in the treatment group compared to the control group (P < 0.001). There were fewer patients who required invasive or noninvasive ventilation in the treatment group, 2 (2.9%) vs. 7 (7.9%), and the mortality rate is lower in the treatment group, 3 (4.4%) vs. 8 (9.0%), though the differences did not reach statistical significance. For the outpatient cohort, the median age was lower in the treatment group compared with the control group; 40 (34, 48) vs. 48 (41, 54), P < 0.001. There was a comparable proportion of males between both groups; 50 (53%) vs. 52 (57%), P=0.59. Patients in the treatment group were 3.3 days closer to symptom resolution (P < 0.001). There were numerically fewer patients requiring hospitalization in the treatment group compared with the control group, 3 (3.2%) vs. 6 (6.6%), though this did not reach statistical significance (P=0.33). In this retrospective observational study, the use of mebendazole in COVID-19 patients was associated with shorter hospitalizations in the inpatient cohort and shorter durations of symptom resolution in the outpatient cohort. The findings from this small observational study are hypothesis-generating and preclude drawing conclusions about clinical efficacy. Further studies are needed to examine the role of mebendazole in the treatment of COVID-19 patients.

Study of the Use of Antinematode Drugs, Mebendazole and Pyrantel, in Galicia (Spain) from 2016 to 2020.

To the best of our knowledge, there is no study on the use of drugs focused on the consumption of antinematode drugs in any region of the world. In the present study, we analyzed and evaluated the use of mebendazole and pyrantel in the provinces of Galicia (Spain), as well as described the variability of the consumption of both drugs between these provinces from 2016 to 2020. A descriptive, cross-sectional, and retrospective study of the consumption of these drugs, expressed in defined daily dose per 1000 inhabitants per day (DHD), was carried out. The DHD values for both drugs were small, although clearly higher, both on average and in variability, in the case of mebendazole. The difference in the mean DHD between both drugs and the geographical differences observed was statistically significant. The seasonal differences were statistically significant for both active principles, with lower values in summer. The active principle most consumed in all the provinces and years was mebendazole. The main consequence of the excessive use of this drug compared to pyrantel may be the increased risk of the development of resistance and of therapeutic failure, as well as the consequent limitation of pharmacological options in the future.

Abstract PO012: In silico drug repurposing identifies mebendazole as a treatment option for chemoresistant hepatoblastoma

Abstract Resistance to conventional chemotherapy remains a huge challenge in the clinical management and treatment of hepatoblastoma, the most common liver tumor of childhood. The in silico repurposing of drugs with known pharmacokinetics and safety profiles, which have been approved for other indications, represents a promising strategy to identify new drugs effective in chemoresistant hepatoblastoma. In this study, we integrated RNA sequencing-derived gene expression data into the pharmacologic perturbation prediction tool Connectivity Map (CMap) and identified the clinical widely used anthelmintic drug mebendazole as a putative drug to circumvent chemoresistance in hepatoblastoma. Consequently, we experimentally validated the efficacy of mebendazole in permanent and patient-derived xenograft cell lines that are resistant to cisplatin, the therapeutic backbone of hepatoblastoma treatment. Viability assays clearly indicated a potent reduction of tumor cell growth upon mebendazole treatment in a dose-dependent manner. In contrast, similar mebendazole concentrations had little inhibitory effect on the growth of normal neonatal and adult skin fibroblasts. The combination of mebendazole and cisplatin revealed a strong synergistic effect, which was comparable to the one seen with cisplatin and doxorubicin (cardiotoxic), the current standard treatment for high-risk hepatoblastoma patients. Moreover, mebendazole treatment resulted in reduced colony formation capability, induction of apoptosis, and cell cycle arrest of hepatoblastoma cells. Immunofluorescent staining of alpha-tubulin showed that mebendazole causes blockage of microtubule formation and subsequent RNA sequencing analyses confirmed the transcriptional downregulation of tubulins as the major mode of action of mebendazole treatment. Most importantly, mebendazole significantly reduced tumor growth in a subcutaneous xenograft transplantation mouse model. In conclusion, our results strongly support the clinical use of mebendazole as a replacement for doxorubicin in the treatment of chemoresistant hepatoblastoma. This could potentially not only improve outcome but also reduce severe long-term side effects. Citation Format: Qian Li, Salih Demir, Xuanwen Bao, Alexandra Wagner, Yanxin Fan, Stefano Cairo, Roland Kappler. In silico drug repurposing identifies mebendazole as a treatment option for chemoresistant hepatoblastoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr PO012.

Targeting the Unwindosome by Mebendazole Is a Vulnerability of Chemoresistant Hepatoblastoma.

Simple SummaryHepatoblastoma patients with tumors that do not respond to preoperative chemotherapy often experience incomplete surgical resection and thus poor outcomes. By analyzing the gene expression data of chemoresistant and responsive tumors using sophisticated drug prediction software we identified mebendazole, a medication usually used to treat parasitic worm infestations, as a putative drug to circumvent chemoresistance. We evaluated the efficacy of this drug in cell culture models of hepatoblastoma and found that both short- and long-term tumor cell growth were significantly inhibited upon treatment. Moreover, we identified the cellular and molecular consequences of mebendazole treatment to be the arrest of cell division and the induction of programmed cell death by the deregulation of genes involved in the unwindosome. Most importantly, mebendazole also proved effective when tested in a mouse model carrying a patient-derived tumor. Our results demonstrate the successful repurposing of mebendazole as a new treatment option for chemoresistant hepatoblastoma.Resistance to conventional chemotherapy remains a huge challenge in the clinical management of hepatoblastoma, the most common liver tumor in childhood. By integrating the gene expression data of hepatoblastoma patients into the perturbation prediction tool Connectivity Map, we identified the clinical widely used anthelmintic mebendazole as a drug to circumvent chemoresistance in permanent and patient-derived xenograft cell lines that are resistant to cisplatin, the therapeutic backbone of hepatoblastoma treatment. Viability assays clearly indicated a potent reduction of tumor cell growth upon mebendazole treatment in a dose-dependent manner. The combination of mebendazole and cisplatin revealed a strong synergistic effect, which was comparable to the one seen with cisplatin and doxorubicin, the current treatment for high-risk hepatoblastoma patients. Moreover, mebendazole treatment resulted in reduced colony and tumor spheroid formation capabilities, cell cycle arrest, and induction of apoptosis of hepatoblastoma cells. Mechanistically, mebendazole causes blockage of microtubule formation and transcriptional downregulation of genes encoding the unwindosome, which are highly expressed in chemoresistant tumors. Most importantly, mebendazole significantly reduced tumor growth in a subcutaneous xenograft transplantation mouse model without side effects. In conclusion, our results strongly support the clinical use of mebendazole in the treatment of chemoresistant hepatoblastoma and highlight the potential theranostic value of unwindosome-associated genes.

Treatment efficacy and re-infection rates of soil-transmitted helminths following mebendazole treatment in schoolchildren, Northwest Ethiopia

BackgroundTransmission of soil-transmitted helminth (STH) infection remains high in Ethiopia. This study aimed at assessing the therapeutic efficacy of mebendazole against soil-transmitted helminths and determining the re-infection rates of the parasites among schoolchildren in Northwest Ethiopia.MethodsA school-based cross-sectional study was conducted. Data was collected using a structured questionnaire. Stool specimens were examined using direct wet mount microscopy and Kato-Katz methods. Schoolchildren who tested positive for soil-transmitted helminths were treated with 500 mg single-dose of mebendazole. Cure and egg reduction rates were evaluated 2 to 3 weeks post treatment. Moreover, the re-infection rate of these parasites among those who were cured was determined 1 year after treatment. Data were analyzed using SPSS version 20. P value < 0.05 was considered as statistically significant.ResultA drug efficacy study was conducted on 62, 52, and 14 children infected by Ascaris lumbricoides (A. lumbricoides), hookworm, and Trichuris trichiura (T. trichiura), respectively. The cure rates (CR) of mebendazole against A. lumbricoides, hookworm, and T. trichiura were found to be 96.9%, 23.1%, and, 28.6%, respectively. The egg reduction rate (ERR) of A. lumbricoides was found to be 99.6% whereas 49.6% and 56.3% were reported for hookworm and T. trichiura, respectively. Eighty schoolchildren who were treated and cured from any STH infections were included for the determination of re-infection rate. Out of 80 children, 36.3% (29/80) were found to be re-infected after 1 year: 22 (75.9%), 6 (20.7%), and 1 (1.3%) of study participants were re-infected with A. lumbricoides, hookworm, and both infections, respectively. All re-infections were grouped under the “light infection” category.ConclusionMebendazole was found to be highly effective against A. lumbricoides, but had relatively low efficacy against hookworms and T. trichiura. These results bring into question the use of mebendazole in STH mass drug administration (MDA) programs in this region if albendazole, a drug with higher efficacy against hookworms, is available. Moreover, a significant number of treated children were re-infected with either or both of A. lumbricoides or hookworms 1 year after treatment emphasizing the need for better integrated intestinal helminthiasis control measures.

N-Substituted Prodrugs of Mebendazole Provide Improved Aqueous Solubility and Oral Bioavailability in Mice and Dogs.

Mebendazole (MBZ) was developed as a broad-spectrum anthelmintic but has recently shown efficacy as an anticancer agent. The use of MBZ for cancer, however, is challenging due to its poor solubility leading to poor bioavailability. Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics. Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility. When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph. In dogs, 12 showed a 3.8-fold higher plasma AUC0- t with oral bioavailability of 41% compared to 11% for MBZ-C. In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.

Targeting acute myeloid leukemia by drug-induced c-MYB degradation.

Despite advances in our understanding of the molecular basis for particular subtypes of acute myeloid leukemia (AML), effective therapy remains a challenge for many individuals suffering from this disease. A significant proportion of both pediatric and adult AML patients cannot be cured and since the upper limits of chemotherapy intensification have been reached, there is an urgent need for novel therapeutic approaches. The transcription factor c-MYB has been shown to play a central role in the development and progression of AML driven by several different oncogenes, including mixed lineage leukemia (MLL)-fusion genes. Here, we have used a c-MYB gene expression signature from MLL-rearranged AML to probe the Connectivity Map database and identified mebendazole as a c-MYB targeting drug. Mebendazole induces c-MYB degradation via the proteasome by interfering with the heat shock protein 70 (HSP70) chaperone system. Transient exposure to mebendazole is sufficient to inhibit colony formation by AML cells, but not normal cord blood-derived cells. Furthermore, mebendazole is effective at impairing AML progression in vivo in mouse xenotransplantation experiments. In the context of widespread human use of mebendazole, our data indicate that mebendazole-induced c-MYB degradation represents a safe and novel therapeutic approach for AML.

Plasma pharmacokinetics and muscle residue dynamics of mebendazole in Carassius auratus.

Mebendazole is approved for use in aquatic animals and is widely used in Chinese aquaculture. We developed a pharmacokinetic and residue analysis for mebendazole levels in the goldfish (Carassius auratus). Plasma and muscle samples of C.auratus were taken after oral administration of 10mg/kg mebendazole. The maximal drug plasma concentration of 0.55mg/L was achieved at 48hr and then declined with the elimination half-life (T1/2β ) of 7.99hr. Administration of 10mg/kg by oral gavage for 5 successive days resulted in a peak mebendazole concentration of 0.70mg/kg in muscle at 96hr after the last dose. The drug was then eliminated at a relatively slow rate from muscle with T1/2β of 68.41hr. There was no detectable mebendazole in any muscle samples at 24days postadministration. The AUClast in plasma and muscle was 19.42 and 105.33mghr/L, respectively. These data provide information for dosage recommendations and withdrawal time determinations for mebendazole use in aquariums.

Hydatid Cyst of the Heart.

Cystic hydatid disease is responsible for the loss of 1 to 3 million disability-adjusted life years every year. Infestation of the heart, though rare, can result in serious complications if left untreated. We retrospectively collected information on 19 patients with cardiac hydatid cyst admitted at the Center for Cardiac Surgery of Ibn Al-Bitar Hospital in Baghdad from July 2007 to July 2011 who were either in need of a cardiac surgery for treating hydatid cysts or presented with emergency conditions. Nine (47%) patients presented with left-sided heart failure and mitral valve dysfunction, 5 (26%) patients had hydatid cysts in the pericardium, 3 (16%) patients had hydatid cyst in the right ventricle and presented with right-sided heart failure, and 2 (11%) patients who presented with cardiac arrhythmias had infestation in the interventricular septum. Removal of cysts following open-heart surgery was successful and was followed by the use of mebendazole or albendazole for 5 years. We conclude that cardiac hydatid cyst that leads to various cardiac symptoms can be successfully managed and should be considered as a diagnostic possibility in patients with cardiac symptoms in endemic areas.

Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors

The microtubule inhibitor vincristine is currently used to treat a variety of brain tumors, including low-grade glioma and anaplastic oligodendroglioma. Vincristine, however, does not penetrate well into brain tumor tissue, and moreover, it displays dose-limiting toxicities, including peripheral neuropathy. Mebendazole, a Food and Drug Administration-approved anthelmintic drug with a favorable safety profile, has recently been shown to display strong therapeutic efficacy in animal models of both glioma and medulloblastoma. Importantly, appropriate formulations of mebendazole yield therapeutically effective concentrations in the brain. Mebendazole has been shown to inhibit microtubule formation, but it is not known whether its potency against tumor cells is mediated by this inhibitory effect. To investigate this, we examined the effects of mebendazole on GL261 glioblastoma cell viability, microtubule polymerization and metaphase arrest, and found that the effective concentrations to inhibit these functions are very similar. In addition, using mebendazole as a seed for the National Cancer Institute (NCI) COMPARE program revealed that the top-scoring drugs were highly enriched in microtubule-targeting drugs. Taken together, these results indicate that the cell toxicity of mebendazole is indeed caused by inhibiting microtubule formation. We also compared the therapeutic efficacy of mebendazole and vincristine against GL261 orthotopic tumors. We found that mebendazole showed a significant increase in animal survival time, whereas vincristine, even at a dose close to its maximum tolerated dose, failed to show any efficacy. In conclusion, our results strongly support the clinical use of mebendazole as a replacement for vincristine for the treatment of brain tumors.

Safety of Mebendazole Use During Lactation: A Case Series Report.

IntroductionMebendazole is an effective drug widely used in the treatment of parasitic infections. Although theoretically considered as safe during lactation, no studies have evaluated its potential adverse effects in infants of breastfeeding mothers.ObjectivesWe aimed to evaluate the safety of mebendazole in infants of lactating women treated with the drug.MethodsWomen referred for consultation regarding mebendazole use were invited to participate in the study. Overall 45 lactating women treated with various protocols of mebendazole were recruited in this case series study.ResultsRegardless of the treatment protocol used (single or repeated doses) mebendazole was well tolerated and was not associated with any adverse effects in infants of lactating mothers. There was mild GI irritability in two treated women.ConclusionThis study provides first evidence in humans as to the safety of mebendazole in breastfeeding.Electronic supplementary materialThe online version of this article (doi:10.1007/s40268-016-0142-z) contains supplementary material, which is available to authorized users.

ATPS-83REPURPOSING MEBENDAZOLE AS A REPLACEMENT FOR VINCRISTINE FOR THE TREATMENT OF BRAIN TUMORS

The microtubule inhibitor vincristine is currently used to treat a number of brain tumors, including newly diagnosed diffuse low-grade and anaplastic glioma. Vincristine however does not penetrate well into brain tumor tissue and moreover, it displays dose-limiting toxicities, including peripheral neuropathy. Mebendazole, an anti-helminthic with an excellent safety profile, has recently been shown to display strong therapeutic efficacy in animal models of both glioma and medulloblastoma (Bai R-Y et al, 2011 and Bai R-Y et al, 2014). In addition, appropriate formulations of mebendazole yield therapeutically effective concentrations in the brain (Bai R-Y et al, 2015). Mebendazole has been shown to inhibit microtubule formation, but it is not known whether its potency against tumor cells is mediated by this microtubule inhibitory effect. To investigate this, we examined the effects of mebendazole on GL261 glioblastoma cell viability, metaphase arrest and microtubule polymerization and found that the effective concentrations to inhibit these functions are very similar. In addition, using mebendazole as a seed for the NCI COMPARE program revealed that the top-scoring drugs were highly enriched in microtubule-targeting drugs. Taken together, these results indicate that the cell toxicity of mebendazole indeed is caused by inhibiting microtubule formation. We also have compared the therapeutic efficacies of mebendazole and vincristine against GL261 orthotopic tumors at their respective maximum tolerated doses (respectively 100 mg/kg/day and 1 mg/kg/week). We found that mebendazole showed a 61% increase in animal survival time, whereas vincristine failed to show any efficacy. However, we did observe significant neuropathy (as measured by sensory allodynia) induced by mebendazole treatment, similar to that caused by vincristine. In conclusion, our results strongly support the clinical use of mebendazole as a replacement for vincristine for the treatment of brain tumors.

Highlights of This Issue

Tumor-targeting monoclonal antibodies represent a major advance in oncology therapy; however, due to their limited brain permeability, mAbs are not generally effective against brain tumors. Conjugation of an anti-HER2 mAb with Angiopep-2, a peptide recognized by LRP1 (low-density lipoprotein receptor-related protein 1), results in ANG4043, which enters brain physiologically, targets HER2+ tumors, and increases survival in mice bearing intracranial tumors. The Angiopep conjugation to mAbs, as well as to previously reported small molecules, is applicable in general to create brain-penetrant therapeutics for brain malignancies and other CNS disorders.Activation of the Hedgehog pathway is a feature of many different types of cancer, including highly lethal brain tumors. Accordingly, small molecules that can antagonize Hedgehog signaling are being developed as new anticancer drugs. Larsen and colleagues demonstrate that mebendazole, a widely used antiparasitic, can inhibit Hedgehog pathway activation by preventing the formation of the primary cilium, a tubulin-based cellular organelle that functions as a signaling hub. The off-label use of mebendazole as a Hedgehog inhibitor provides a promising new option for the management of brain tumors and other tumor types in which Hedgehog activation is prevalent.HSP90 inhibitors simultaneously affect multiple cancer-related proteins; therefore, they have potential use in advanced cancer treatment. However, because HSP90 also functions in normal cells, it is essential to balance efficacy and toxicity to maximize the antitumor potential of HSP90 inhibitors. Ohkubo and colleagues report on the biological activity of TAS-116, a novel, orally active HSP90α and β selective inhibitor. TAS-116 showed antitumor activity without detectable ocular toxicities in a rat model, due to greater TAS-116 distribution in target tumor tissues than in non-target eye tissues. The favorable therapeutic index of TAS-116 thus highlights its therapeutic potential.Treatment options for breast cancer brain metastases are limited and new therapies are needed. Here, Meisen and colleagues discovered the relationship of multifunctional brain angiogenesis inhibitor 1 (BAI1) and nestin expression with breast cancer brain metastases. Higher BAI1 expression is associated with better patient survival and higher nestin expression is significantly correlated with breast cancer lung and brain metastases. The application of 34.5ENVE, a Nestin-targeted oncolytic virus expressing a therapeutic extracellular fragment of BAI1 destroyed breast cancer brain metastases in two different immune-competent murine models of the disease. The results of these studies warrant the clinical investigation of 34.5ENVE for breast cancer brain metastases.

Have Worms Lost Their Luster?

Childhood infections with some helminths have been reported to reduce the risk of acquiring some immune-mediated diseases like sensitization to allergens, asthma and inflammatory bowel disease. Denmark keeps a medical registry that collects data on disease prevalence and medication use throughout the country. Mebendazole frequently is used to treat pinworm (Enterobius vermicularis) infection. In this population-based analysis of a cohort of 924,749 children, prescriptions for Mebendazole were used as a surrogate marker for pinworm infection. Children who received this medication were compared to children who did not, for the frequency of asthma, type I diabetes, juvenile arthritis, ulcerative colitis and Crohn’s disease. It was found that Mebendazole use, and by inference pinworm infection, did not appear to reduce the risk for acquiring any of these immune-mediated diseases.

Effects of three benzimidazoles on growth, general morphology and ultrastructure ofTritrichomonas foetus

Tritrichomonas foetus is a venereal pathogen of cattle, which causes infertility, early embryonic death or abortion. In order to evaluate the potential trichomonicidal activity of benzimidazoles, the effects of thiabendazole, mebendazole and albendazole were analyzed on the multiplication, general morphology and ultrastructure of T. foetus. It was found that mebendazole presented the highest IC(50%) (2.3 microM), when compared with albendazole (IC(50%)=9.4 microM) and thiabendazole (IC(50%)=142.6 microM), and that such effects were irreversible. Concerning microscopic analysis, thiabendazole- and mebendazole-treated cells presented increased volume, internalization of the flagella, disruption or multiplication of the nucleus, multiple organelles and cytoplasmic vacuolization. Albendazole-treated cells exhibited slight alterations, because the parasite became slightly rounded, its flagella were not internalized but the cytoplasm was vacuolated. Mebendazole was indeed highly effective as an in vitro trichomonicidal agent, and this might open up new possibilities for the use of mebendazole in the therapy of bovine trichomoniasis.

Population‐based case–control study of mebendazole in pregnant women for birth outcomes

The objectives of the study was to check the embryotoxic-teratogenic and fetotoxic effect of mebendazole (Vermox; Richter, Budapest, Hungary) treatment during pregnancy. Mebendazole use during pregnancy was evaluated in mothers of babies born with congenital abnormalities and in matched control mothers of babies born without congenital abnormalities in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. Of 22,843 women who had newborns or fetuses with congenital abnormalities, 14 were found to have been treated with mebendazole for intestinal nematoda infections/diseases during pregnancy (crude POR: 1.8 with 95% CI: 0.7-4.2). Of 38,151 women who had newborns without any defects (controls), the same number (14) were found to have been treated with mebendazole during pregnancy. Six different congenital abnormality groups were evaluated and a higher prevalence of mebendazole use in these mothers throughout pregnancy was not found. Gestational age and birth weight were analyzed in control infants born to mothers with or without mebendazole treatment. The mean gestational age was somewhat longer and mean birth weight was larger in newborn infants born to mothers with mebendazole treatment. Thus, treatment with mebendazole during pregnancy did not indicate a teratogenic and fetotoxic risk to the embryo or fetus, though the numbers of treated cases and controls in this study were limited.

Mebendazole use during pregnancy

Mebendazole use during pregnancy

Use of anthelminthic drugs during pregnancy

Use of anthelminthic drugs during pregnancy

The benefits of screening must outweigh the risks and costs.

By instituting a simple screening program, Lohiya et al were almost able to eliminate enterobiasis from their population of institutional residents. Despite the initial cost of mass treatment, they realized a decrease in their overall costs within two years of starting the program. The authors' success provides an opportunity to review screening programs and consider when and why some can be effective, while others, although equally important, can be ineffective or even harmful to patients. Population screening can be done with three purposes in mind. First, screening can be carried out for the direct benefit of patients. Many of our interventions based in the community, such as offering blood pressure checks at health fairs, are geared toward helping individuals. Second, screening can be used for the protection of others. Several such tests are routinely conducted on donated blood products to prevent the transmission of infectious agents. Finally, screening can be performed simply to gather baseline information on individuals or populations. When assessing the potential value of any screening program, it is important to clarify the purpose of the program. The screening program presented here benefited both the screened persons, who were guaranteed treatment after a single positive test result, and other residents of the facility, particularly the roommates of infected people. Of course, screening for all possible conditions, even in a selected group, is impossible and undesirable. Unless screening is being conducted to provide data for academic or public health use, various factors should be considered. The condition that is being screened for should be either sufficiently common or devastating to warrant the time and expense. Neonatal screening programs for metabolic disorders identify only a few abnormalities in the population, but among them are preventable cases of severe neurologic disability. Early diagnosis must be associated with better outcomes. Major concerns regarding the outcomes of patients who are screened and treated for early prostate cancer have made screening with the prostate-specific antigen test a controversial issue. The treatment that produces better outcomes must also be available to the screened population. The screening technique must be sensitive enough to identify most cases. The screening technique must be specific enough to avoid an excess of unnecessary treatments. Attempts to use pelvic sonography as a screening tool for ovarian cancer resulted in an unacceptably high rate of unneeded laparotomies. The possible consequences of false-positive results need to be considered when planning any screening program. The cost and risks of screening should not outweigh the benefits. Cost includes the financial burden of the screening program and follow-up and the potential personal cost to the people being screened in money, time, and effort. Is there excessive anxiety or inconvenience associated with the screening test or the follow-up needed for positive test results? How does this balance against the possible benefit for each patient? When Indiana instituted mandatory screening for the human immunodeficiency virus (HIV) as a requirement for a marriage license, false-positive results greatly outnumbered true-positive results. Within one year of beginning the program, a substantial proportion of Indiana residents were driving across state lines for their marriage licenses to avoid the expense of the HIV test. People were inconvenienced, and the state lost substantial revenues—all with little benefit. The enterobiasis screening policy adopted at Fairview Developmental Center succeeded for several reasons. Enterobiasis, although not devastating, was common at the center, with an annual incidence of 15% to 31% in the years preceding the program. Early diagnosis and treatment of those infected and their close contacts led to better care for both the people tested and their roommates. Mebendazole is readily available and affordable, and this treatment exposed residents to few adverse effects. Due to the low cost and low toxicity associated with mebendazole use, specificity in screening and treatment were successfully compromised to increase sensitivity. Contact screening imposed in the earlier policy entailed an invasive and a resource-consuming process that probably had poor sensitivity for identifying newly infected persons. The improved screening technique and more aggressive/expansive treatment policy described by Lohiya et al decreased infection rates and overall cost.