RESUMEN
BACKGROUND: Albendazole (ABZ), a benzimidazole (BZ) anthelmintic (AH), is commonly used for treatment of soil-transmitted helminths (STHs). Its regular use increases the possibility that BZ resistance may develop, which, in veterinary nematodes is caused by single nucleotide polymorphisms (SNPs) in the ß-tubulin gene at positions 200, 167 or 198. The relative importance of these SNPs varies among the different parasitic nematodes of animals studied to date, and it is currently unknown whether any of these are influencing BZ efficacy against STHs in humans. We assessed ABZ efficacy and SNP frequencies before and after treatment of Ascaris lumbricoides, Trichuris trichiura and hookworm infections. METHODS: Studies were performed in Haiti, Kenya, and Panama. Stool samples were examined prior to ABZ treatment and two weeks (Haiti), one week (Kenya) and three weeks (Panama) after treatment to determine egg reduction rate (ERR). Eggs were genotyped and frequencies of each SNP assessed. FINDINGS: In T. trichiura, polymorphism was detected at codon 200. Following treatment, there was a significant increase, from 3.1% to 55.3%, of homozygous resistance-type in Haiti, and from 51.3% to 67.8% in Kenya (ERRs were 49.7% and 10.1%, respectively). In A. lumbricoides, a SNP at position 167 was identified at high frequency, both before and after treatment, but ABZ efficacy remained high. In hookworms from Kenya we identified the resistance-associated SNP at position 200 at low frequency before and after treatment while ERR values indicated good drug efficacy. CONCLUSION: Albendazole was effective for A. lumbricoides and hookworms. However, ABZ exerts a selection pressure on the ß-tubulin gene at position 200 in T. trichiura, possibly explaining only moderate ABZ efficacy against this parasite. In A. lumbricoides, the codon 167 polymorphism seemed not to affect drug efficacy whilst the polymorphism at codon 200 in hookworms was at such low frequency that conclusions cannot be drawn.
Asunto(s)
Albendazol/uso terapéutico , Ancylostomatoidea/genética , Antihelmínticos/uso terapéutico , Ascaris lumbricoides/genética , Infecciones por Nematodos/tratamiento farmacológico , Trichuris/genética , Tubulina (Proteína)/genética , Adolescente , Ancylostomatoidea/aislamiento & purificación , Animales , Ascaris lumbricoides/aislamiento & purificación , Niño , Preescolar , Estudios Transversales , Resistencia a Medicamentos , Genotipo , Haití , Humanos , Lactante , Kenia , Masculino , Infecciones por Nematodos/parasitología , Panamá , Polimorfismo de Nucleótido Simple , Resultado del Tratamiento , Trichuris/aislamiento & purificaciónRESUMEN
BACKGROUND: Few studies have investigated the relative influence of individual susceptibility versus household exposure factors versus regional clustering of infection on soil transmitted helminth (STH) transmission. The present study examined reinfection dynamics and spatial clustering of Ascaris lumbricoides, Trichuris trichiura and hookworm in an extremely impoverished indigenous setting in rural Panamá over a 16 month period that included two treatment and reinfection cycles in preschool children. METHODOLOGY/PRINCIPLE FINDINGS: Spatial cluster analyses were used to identify high prevalence clusters for each nematode. Multivariate models were then used (1) to identify factors that differentiated households within and outside the cluster, and (2) to examine the relative contribution of regional (presence in a high prevalence cluster), household (household density, asset-based household wealth, household crowding, maternal education) and individual (age, sex, pre-treatment eggs per gram (epg) feces, height-for-age, latrine use) factors on preschool child reinfection epgs for each STH. High prevalence spatial clusters were detected for Trichuris and hookworm but not for Ascaris. These clusters were characterized by low household density and low household wealth indices (HWI). Reinfection epg of both hookworm and Ascaris was positively associated with pre-treatment epg and was higher in stunted children. Additional individual (latrine use) as well as household variables (HWI, maternal education) entered the reinfection models for Ascaris but not for hookworm. CONCLUSIONS/SIGNIFICANCE: Even within the context of extreme poverty in this remote rural setting, the distinct transmission patterns for hookworm, Trichuris and Ascaris highlight the need for multi-pronged intervention strategies. In addition to poverty reduction, improved sanitation and attention to chronic malnutrition will be key to reducing Ascaris and hookworm transmission.
Asunto(s)
Ascariasis/epidemiología , Infecciones por Uncinaria/epidemiología , Tricuriasis/epidemiología , Ancylostomatoidea/aislamiento & purificación , Animales , Ascaris lumbricoides/aislamiento & purificación , Preescolar , Análisis por Conglomerados , Salud de la Familia , Femenino , Geografía , Humanos , Lactante , Masculino , Panamá/epidemiología , Recurrencia , Población Rural , Factores Socioeconómicos , Trichuris/aislamiento & purificaciónRESUMEN
Chronic infection over a 16-month period and stunting of preschool children were compared between more spatially dense versus dispersed households in rural Panamá. Chronic protozoan infection was associated with higher household density, lower household wealth index, poor household water quality, yard defecation, and the practice of not washing hands with soap before eating. Models for chronic diarrhea confirmed the importance of household wealth, water quality, sanitation, and hygiene practices. Furthermore, chronic protozoan infection was an important predictor for low height-for-age, along with low household wealth index scores, but not household density. Thus, despite better access to health related infrastructure in the more densely populated households, chronic protozoan infection was more common, and was associated with higher rates of child stunting, compared with more dispersed households.