Imported bancroftian filariasis: diethylcarbamazine response and benzimidazole susceptibility of Wuchereria bancrofti in dynamic cross-border migrant population targeted by the National Program to Eliminate Lymphatic Filariasis in South Thailand.
The implementation on the Thailand-Myanmar border of annual mass drug administration (MDA) of a single 6 mg/kg dose of diethylcarbamazine (DEC) plus 400mg albendazole, part of the National Program to Eliminate Lymphatic Filariasis (PELF), has been challenging. In particular, chain migration of cross-border Myanmar workers at risk for nocturnally periodic Wuchereria bancrofti infection can lead to imported bancroftian filariasis (IBF) in Thailand. IBF is targeted for multiple-dose MDA with 300 mg DEC, in addition to what is recommended by the World Health Organization (WHO). The dynamic Myanmar migrants in Phang-nga, southern Thailand were sampled to test whether the responsible W. bancrofti has a genetic predisposition of benzimidazole exposure, and IBF exhibits DEC susceptibility. The long-term migrants had more access to DEC. IBF in W. bancrofti antigenemic (microfilaremic vs. amicrofilaremic) short-term migrants exhibited susceptibility to a 300-mg single-dose DEC treatment. During the course of a 3-month follow-up, antigenemia was significantly reduced, but microfilaremia was fluctuated. Surprisingly, a newly recognized Mansonella infection co-existing among W. bancrofti-affected Myanmar migrants elicited microfilaremia clearance within a month after treatment. As a result of the presence of genetically stable W. bancrofti beta-tubulin (Wbtubb) gene responsible for benzimidazole susceptibility, IBF did not possess a genetic predisposition for benzimidazole exposure. Point mutations at positions Phe167Tyr and Phe200Tyr were not detected by Wbtubb locus-specific nested PCR and sequencing. This study has the potential to help guide not only the Thai/Myanmar PELF surveillance and monitoring of mass treatment impacts on W. bancrofti, but also the other endemic countries allied with the Global Program to Eliminate Lymphatic Filariasis (GPELF).
Bhumiratana
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A
Department of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok 10400, Thailand. phabr@mahidol.ac.th
Pechgit
P
P
Koyadun
S
S
Siriaut
C
C
Yongyuth
P
P
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004049:Diethylcarbamazine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004605:Elephantiasis, Filarial / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology / Q000517:prevention & control; D005369:Filaricides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D002052:Myanmar; D009313:National Health Programs; D021261:Parasitic Sensitivity Tests; D016415:Sequence Alignment; D013785:Thailand / Q000453:epidemiology; D014171:Transients and Migrants; D016896:Treatment Outcome; D014404:Tubulin / Q000737:chemistry / Q000235:genetics; D014958:Wuchereria bancrofti / Q000187:drug effects*; D055815:Young Adult
D001562:Benzimidazoles; D005369:Filaricides; D014404:Tubulin; C031000:benzimidazole; D004049:Diethylcarbamazine