Albendazole

Albendazole is an anthelmintic.

Effect of 3 years of biannual mass drug administration with albendazole on lymphatic filariasis and soil-transmitted helminth infections: a community-based study in Republic of the Congo.[Pubmed:28372977]

Lancet Infect Dis. 2017 Jul;17(7):763-769.

BACKGROUND: The standard treatment strategy of mass drug administration with ivermectin plus Albendazole for lymphatic filariasis cannot be applied in central Africa, because of the risk of serious adverse events in people with high Loa loa microfilaraemia. Thus, alternative strategies are needed. We investigated one such alternative strategy for mass drug administration for elimination of lymphatic filariasis and soil-transmitted helminth infections in Republic of the Congo. METHODS: In 2012, we started a 3 year community trial of biannual mass administration of Albendazole in a village in Republic of the Congo. All volunteering inhabitants aged 2 years or older were offered Albendazole (400 mg) every 6 months. Infection with Wuchereria bancrofti was diagnosed with a rapid card immunochromatographic test for antigenaemia. People with antigenaemia were tested for microfilaraemia by night blood smears. Individuals were also tested for soil-transmitted helminth infections (ie, hookworm, Ascaris lumbricoides, Trichuris trichiura) with the Kato-Katz method. Assessment surveys were done at 12, 24, and 36 months. The main outcome measure was change in infection rates from baseline to year 3. FINDINGS: Therapeutic coverage was more than 80% in all six rounds of mass administration of Albendazole. Between 2012 and 2015, W bancrofti antigenaemia and microfilaraemia rates in the community fell significantly, from 17.3% (95% CI 14.7-20.0) to 4.7% (3.3-6.6; p<0.0001) and from 5.3% (3.9-7.1) to 0.3% (0.1-1.2; p<0.0001), respectively. The geometric mean microfilaria count in microfilaraemic people fell from 199.4 (120.4-330.5) per mL in 2012 to 39.1 (95% CIs not computed) per mL in 2015 (p=0.0095). Hookworm infection was undetectable after 1 year. Between 2012 and 2015, the number of A lumbricoides eggs expelled per g of faeces fell from 9844.6 (8209.0-11 480.0) to 724.4 (340.7-1114.2; p<0.0001), and of T trichiura eggs from 1107.4 (878.5-1336.3) to 366.0 (255.7-476.2; p<0.0001). INTERPRETATION: Our findings strongly support WHO's provisional strategy of biannual mass administration of Albendazole to eliminate lymphatic filariasis in areas where loiasis is co-endemic and ivermectin cannot be safely mass administered. FUNDING: Bill & Melinda Gates Foundation.

Exposure of Heligmosomoides polygyrus and Trichuris muris to albendazole, albendazole sulfoxide, mebendazole and oxantel pamoate in vitro and in vivo to elucidate the pathway of drug entry into these gastrointestinal nematodes.[Pubmed:28371660]

Int J Parasitol Drugs Drug Resist. 2017 Aug;7(2):159-173.

Millions of people are treated with anthelmintics to control soil-transmitted helminth infections; yet, drug distribution in the plasma and gastrointestinal tract compartments and the pathway of drug uptake into gastrointestinal nematodes responsible for the pharmacological effect are unknown. We assessed the distribution and uptake of Albendazole, Albendazole sulfoxide, Albendazole sulfone in the hookworm Heligmosomoides polygyrus in vitro and in vivo as well as the distribution and uptake of Albendazole, mebendazole, and oxantel pamoate in the whipworm Trichuris muris in vitro and in vivo. Oral and intraperitoneal treatments (100 mg/kg) were studied. Drug quantities in helminths and host compartments (stomach, the contents and mucosa of the small and large intestine, and the plasma) were determined using HPLC-UV/vis and anthelmintic activities were recorded using phenotypic readout. The influence of 1-aminobenzotriazole (ABT), an irreversible and unspecific cytochrome P450 inhibitor, on Albendazole disposition in mice harboring H. polygyrus was evaluated. In vivo, Albendazole was found in quantities up to 10 nmol per ten H. polygyrus and up to 31 nmol per ten T. muris. ABT did not change the levels of Albendazole or its metabolites in the plasma of mice harboring H. polygyrus or in H. polygyrus, whereas drug levels in the gastrointestinal tract of host mice doubled. Mebendazole and oxantel pamoate quantities per ten T. muris were as high as 21 nmol and 34 nmol, respectively. Albendazole revealed a very dynamic distribution and high rate of metabolism, hence, H. polygyrus and T. muris are exposed to Albendazole and both metabolites via multiple pathways. Diffusion through the cuticle seems to be the crucial pathway of oxantel pamoate uptake into T. muris, and likely also for mebendazole. No relationship between concentrations measured in helminths and concentrations in plasma, intestinal content and mucosa of mice, or drug efficacy was noted for any of the drugs studied.

Anthelmintic drug albendazole arrests human gastric cancer cells at the mitotic phase and induces apoptosis.[Pubmed:28352336]

Exp Ther Med. 2017 Feb;13(2):595-603.

As microtubules have a vital function in the cell cycle, oncologists have developed microtubule inhibitors capable of preventing uncontrolled cell division, as in the case of cancer. The anthelmintic drug Albendazole (ABZ) has been demonstrated to inhibit hepatocellular, ovarian and prostate cancer cells via microtubule targeting. However, its activity against human gastric cancer (GC) cells has remained to be determined. In the present study, ABZ was used to treat GC cells (MKN-45, SGC-7901 and MKN-28). A a CCK-8 cell proliferation assay was performed to assess the effects of ABZ on cell viability and cell cycle changes were assessed using flow cytometry. SGC-7901 cells were selected for further study, and flow cytometry was employed to determine the apoptotic rate, immunofluorescence analysis was employed to show changes of the microtubule structure as well as the subcellular localization and expression levels of cyclin B1, and western blot analysis was used to identify the dynamics of microtubule assembly. The expression levels of relevant proteins, including cyclin B1 and Cdc2, the two subunits of mitosis-promoting factor as well as apoptosis-asociated proteins were also assessed by western blot analysis. The results showed that ABZ exerted its anti-cancer activity in GC cell lines by disrupting microtubule formation and function to cause mitotic arrest, which is also associated with the accumulation of cyclin B1, and consequently induces apoptosis.

The effect of three-monthly albendazole treatment on Th2 responses: Differential effects on IgE and IL-5.[Pubmed:28370210]

Parasite Immunol. 2017 Jun;39(6).

Helminth parasites induce a strong Th2 response, characterized by high levels of IgE and elevated signature cytokines such as IL-5. As many global deworming programmes are underway, there is concern that this might lead to emergence of Th1-mediated pathologies when the counterbalancing helminth-induced Th2 response is absent. Therefore, we assessed the effect of deworming on Th2-mediated responses in a household-clustered randomized controlled trial in Indonesia. Total plasma IgE and whole-blood IL-5 responses to mitogen phytohaemagglutinin (PHA) were measured in 1494 and 682 subjects, respectively, at baseline, 9 and 21 months after three-monthly single-dose treatment with Albendazole or placebo. Anthelmintic treatment did not result in complete removal of helminth infections in the community. However, treatment significantly decreased IgE levels in Albendazole- compared to placebo-treated subjects. IL-5 responses to PHA were not significantly affected by anthelmintic treatment and tended to increase in Albendazole-treated subjects, indicating that intensive treatment of helminth parasites has different outcomes on B-cell (IgE levels) and T-cell (IL-5) responses. The data shows that 2 years of deworming can have differential effects on responses typified as Th2-mediated, which needs to be taken into account when examining the impact of helminths on noncommunicable diseases.

Albendazole is a member of the benzimidazole compounds used as a drug indicated for the treatment of a variety of worm infestations.

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