**1. Introduction**

396 Current Topics in Tropical Medicine

Zumla, A.I. & James, D.G. (2002). Immunologic aspects of tropical lung disease. *Clinics in* 

Lymphatic filarial nematode parasites, mainly *Wuchereria bancrofti* and *Brugia malayi,* are causing agents of lymphatic filariasis in humans, which can be effectively treated with antifilarial drugs including diethylcarbamazine (DEC) and ivermectin. Albendazole, an effective benzimidazole compound, acts as a board-spectrum anthelminthic drug, and when combined with either one of antifilarial drugs, it exerts synergistic effects on reduction of peripheral microfilaremia in lymphatic filariasis cases. However, the varying parasite infection levels in those treated with DEC or ivermectin alone or in combination with albendazole are due to differences in drug responses. The additional clearance of infection with albendazole relative to what is observed with DEC or ivermectin alone suggests that albendazole has different parasite target(s). The homologous *-tubulin* gene of human and veterinary filariids that β-tubulin homologs have conserved domains structurally related to other orthologs among the nematodes, cestodes, trematodes and vertebrate hosts, is responsible for benzimidazole susceptibility. The genetic inheritance of resistance in nematode parasites can undergo under selection of benzimidazole compounds in a way that albendazole resistance mechanism involves one of two single amino acid substitutions from phenylalanine to tyrosine in parasite β-tubulin at position 167 or 200. This genetically-stable marker has shown promise for molecular diagnosis and monitoring of *W. bancrofti* infections that carry responsible genotypes associated with benzimidazole susceptibility or resistance. In particular, this approach can augment the surveillance and monitoring of mass treatment impacts on the parasite populations in target areas where long-running elimination programs for lymphatic filariasis are implemented at a large-scale by using a regionally-adopted combination therapy with antifilarial drugs, recommended by the World Health Organization.

Molecular Diagnosis and Monitoring of Benzimidazole Susceptibility of Human Filariids 399

human lymphatic system, i.e., lymphatic vessels, with 5-15 years of life expectancy (Table 1). Only when its fecundic lifespan is capable of mating does the lymphatic-dwelling female worm produce advanced stage of sheathed larvae called "microfilariae". These short-living offsprings then penetrate the blood circulation. For a complete life cycle, the microfilariae are ingested by susceptible female mosquito during a blood meal in which they can develop further into larval stages L1-L2 to infective L3 stage. Transmission occurs when the infected mosquito transmits this L3 stage to susceptible persons during other blood meals. The naturally acquired transmission is associated with both intrinsic and extrinsic factors that

Fig. 2. An explanatory model of human-parasite-vector interactions and favorable factors that influence its adaptation in hosts. The lymphatic filarial infections in humans depend on extrinsic factors of incoming L3 inocula and host recognition and location, and a proportion of adult worms with fecundicity and mating probability. Transmission is influenced by host-vector combination (host location and recognition of mosquito feeding habits), microfilarial loads in blood with timing of microfilariae release, and vectoral capacity (longevity and low refractoriness). Long lifespan of the mosquito and timing of L3 release

As such, understanding of how these filarial nematode parasites can be removed from the human hemisphere is to understand basically the biology of their life cycle. How do the parasite taxa succeed their complete life cycle in the certain conditions under which they evoke host exploitation strategies? The biology of the parasitic symbionts can disclosure the parasite diversity and fitness shaped by hosts and environmental constraints that the

are favorable factors of transmission.

can regulate the parasitic worm burdens in an endemic population (Fig. 2).
