Hookworm Infection among School Age Children in Kintampo North Municipality, Ghana: Nutritional Risk Factors and Response to Albendazole Treatment

Humphries, Debbie; Simms, B. T.; Davey, Dylan; Otchere, Joseph; Quagraine, Josephine; Terryah, Shawn; Newton, Samuel S.; Berg, Elyssa; Harrison, Lisa M.; Boakye, Daniel; Wilson, Michael D.; Cappello, Michael

doi:10.4269/ajtmh.12-0605

Cited by 49 publications

(61 citation statements)

References 61 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8,[19][20][21][22] We report here the use of a molecular approach to detect resistance-associated SNPs in hookworms (N. americanus) infecting SAC in the Kintampo North Municipality in central Ghana, complementing prior studies characterizing the prevalence and intensity of infection and response to albendazole. [23][24][25] Our findings show that hookworm egg samples in Kintampo contain SNPs that could be associated with benzimidazole resistance. We also show that albendazole treatment is associated with an increase in the proportion of two SNPs (F167Y and F200Y) in parasites collected from subjects not cured by albendazole.…”

Section: Introductionmentioning

confidence: 70%

“…After obtaining informed adult guardian/ parental consent, SAC were assented and invited to respond to a demographic and behavior questionnaire. 23 Sample collection. Hookworm egg samples were collected as part of a 2010 field study in the Kintampo North Municipality, which assessed the impact of host nutrition on hookworm infection status and response to deworming with albendazole.…”

Section: Methodsmentioning

confidence: 99%

“…Hookworm egg samples were collected as part of a 2010 field study in the Kintampo North Municipality, which assessed the impact of host nutrition on hookworm infection status and response to deworming with albendazole. 23 School-aged children (ages 6-11 years; n = 279) provided fresh fecal samples, which were analyzed for the presence of STH eggs using Kato-Katz microscopy, according to WHO guidelines. 26 Hookworm infection was identified in 109/279 subjects (39%), each of whom was referred to Ghana Health Service staff for directly observed treatment with a single dose (400 mg) of albendazole (GlaxoSmithKline, Middlesex, United Kingdom).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Genetic Markers of Benzimidazole Resistance among Human Hookworms (Necator americanus) in Kintampo North Municipality, Ghana

Orr

Quagraine

Suwondo

et al. 2019

The American Journal of Tropical Medicine and Hygiene

Self Cite

View full text Add to dashboard Cite

Hookworm infection causes anemia, malnutrition, and growth delay, especially in children living in sub-Saharan Africa. The World Health Organization recommends periodic mass drug administration (MDA) of anthelminthics to school-age children (SAC) as a means of reducing morbidity. Recently, questions have been raised about the effectiveness of MDA as a global control strategy for hookworms and other soil-transmitted helminths (STHs). Genomic DNA was extracted from Necator americanus hookworm eggs isolated from SAC enrolled in a cross-sectional study of STH epidemiology and deworming response in Kintampo North Municipality, Ghana. A polymerase chain reaction (PCR) assay was then used to identify single-nucleotide polymorphisms (SNPs) associated with benzimidazole resistance within the N. americanus β-tubulin gene. Both F167Y and F200Y resistance-associated SNPs were detected in hookworm samples from infected study subjects. Furthermore, the ratios of resistant to wild-type SNP at these two loci were increased in posttreatment samples from subjects who were not cured by albendazole, suggesting that deworming drug exposure may enrich resistance-associated mutations. A previously unreported association between F200Y and a third resistanceassociated SNP, E198A, was identified by sequencing of F200Y amplicons. These data confirm that markers of benzimidazole resistance are circulating among hookworms in central Ghana, with unknown potential to impact the effectiveness and sustainability of chemotherapeutic approaches to disease transmission and control.

show abstract

Section: Introductionmentioning

confidence: 70%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Genetic Markers of Benzimidazole Resistance among Human Hookworms (Necator americanus) in Kintampo North Municipality, Ghana

Orr

Quagraine

Suwondo

et al. 2019

The American Journal of Tropical Medicine and Hygiene

Self Cite

View full text Add to dashboard Cite

show abstract

“…1,2 Current treatment revolves around mass drug administration (MDA) with benzimidazole anthelmintics (primarily albendazole), but widespread anthelmintic resistance in veterinary husbandry and reports of low efficacy of albendazole in human therapy suggest that new anthelmintics are urgently needed. 3,4 One of the more promising new anthelmintics in development for STHs is the crystal (Cry) protein Cry5B, derived from Bacillus thuringiensis , 5 which has been shown to be highly effective against in vivo infections of STHs such as Ascaris 6 and hookworm. 7 Cry5B is a member of the three-domain B. thuringiensis Cry proteins, which are pore-forming proteins that target the invertebrate (insect/nematode) intestine, in the case of Cry5B by binding to invertebrate-specific glycolipids present on the apical surface of the nematode intestine.…”

mentioning

confidence: 99%

Protection and Delivery of Anthelmintic Protein Cry5B to Nematodes Using Mesoporous Silicon Particles

Miller

et al. 2015

ACS Nano

View full text Add to dashboard Cite

The ability of nano- and microparticles of partially oxidized mesoporous silicon (pSi) to sequester, protect, and deliver the anthelmintic pore-forming protein Cry5B to nematodes is assessed in vitro and in vivo. Thermally oxidized pSi particles are stable under gastric conditions and show relatively low toxicity to nematodes. Fluorescence images of rhodamine-labeled pSi particles within the nematodes Caenorhabditis elegans and Ancylostoma ceylanicum show that ingestion is dependent on particle size: particles of a 0.4 ± 0.2 μm size are noticeably ingested by both species within 2 h of introduction in vitro, whereas 5 ±2 μm particles are excluded from C. elegans but enter the pharynx region of A. ceylanicum after 24 h. The anthelmintic protein Cry5B, a pore-forming crystal (Cry) protein derived from Bacillus thuringiensis, is incorporated into the pSi particles by aqueous infiltration. Feeding of Cry5B-loaded pSi particles to C. elegans leads to significant intoxication of the nematode. Protein-loaded particles of size 0.4 μm display the highest level of in vitro toxicity toward C. elegans on a drug-mass basis. The porous nanostructure protects Cry5B from hydrolytic and enzymatic (pepsin) degradation in simulated gastric fluid (pH 1.2) for time periods up to 2 h. In vivo experiments with hookworm-infected hamsters show no significant reduction in worm burden with the Cry5B-loaded particles, which is attributed to slow release of the protein from the particles and/or short residence time of the particles in the duodenum of the animal.

show abstract

“…The ongoing expansion of anthelmintic coverage in humans threatens a similar outcome 3,4 . Reduced cure rates suggestive of benzimidazole resistance have been reported for human soil-transmitted helminths, including the etiological agents of hookworm infection, trichuriasis, and ascariasis [5][6][7][8][9] . The sustainability of chemotherapy-based parasite control is jeopardized by our deficient knowledge of potential mechanisms of anthelmintic resistance and a paucity of molecular markers to detect and slow the spread of resistance alleles in parasite populations.…”

Section: Introductionmentioning

confidence: 99%

Discovery of unique loci that underlie nematode responses to benzimidazoles

Zamanian

Cook²,

Zdraljevic³

et al. 2017

Preprint

View full text Add to dashboard Cite

Parasitic nematodes impose a debilitating health and economic burden across much of the world. Nematode resistance to anthelmintic drugs threatens parasite control efforts in both human and veterinary medicine. Despite this threat, the genetic landscape of potential resistance mechanisms to these critical drugs remains largely unexplored. Here, we exploit natural variation in the model nematodes Caenorhabditis elegans and Caenorhabditis briggsae to discover quantitative trait loci (QTL) that control sensitivity to benzimidazoles widely used in human and animal medicine. High-throughput phenotyping of albendazole, fenbendazole, mebendazole, and thiabendazole responses in panels of recombinant lines led to the discovery of over 15 QTL in C. elegans and four QTL in C. briggsae associated with divergent responses to these anthelmintics. Many of these QTL are conserved across benzimidazole derivatives, but others show drug and dose specificity. We used near-isogenic lines to recapitulate and narrow the C. elegans albendazole QTL of largest effect and identified candidate variants correlated with the resistance phenotype. These QTL do not overlap with known benzimidazole resistance genes from parasitic nematodes and present specific new leads for the discovery of novel mechanisms of nematode benzimidazole resistance. Analyses of orthologous genes reveal significant conservation of candidate benzimidazole resistance genes in medically important parasitic nematodes. These data provide a basis for extending these approaches to other anthelmintic drug classes and a pathway towards validating new markers for anthelmintic resistance that can be deployed to improve parasite disease control.Author Summary: The treatment of roundworm (nematode) infections in both humans and animals relies on a small number of anti-parasitic drugs. Resistance to these drugs has appeared in veterinary parasite populations and is a growing concern in human medicine. A better understanding of the genetic basis for parasite drug resistance can be used to help maintain the effectiveness of anti-parasitic drugs and to slow or to prevent the spread of drug resistance in parasite populations. This goal is hampered by the experimental intractability of nematode parasites. Here, we use non-parasitic model nematodes to systematically explore responses to the critical benzimidazole class of anti-parasitic compounds. Using a quantitative genetics approach, we discovered unique genomic intervals that control drug effects, and we identified differences in the genetic architectures of drug responses across compounds and doses. We were able to narrow a major-effect genomic region associated with albendazole resistance and to establish that candidate genes discovered in our genetic mappings are largely conserved in important human and animal parasites. This work provides new leads for understanding parasite drug resistance and contributes a powerful template that can be extended to other anti-parasitic drug classes. IntroductionParasitic nematodes impose a debil...

show abstract

Hookworm Infection among School Age Children in Kintampo North Municipality, Ghana: Nutritional Risk Factors and Response to Albendazole Treatment

Cited by 49 publications

References 61 publications

Genetic Markers of Benzimidazole Resistance among Human Hookworms (Necator americanus) in Kintampo North Municipality, Ghana

Genetic Markers of Benzimidazole Resistance among Human Hookworms (Necator americanus) in Kintampo North Municipality, Ghana

Protection and Delivery of Anthelmintic Protein Cry5B to Nematodes Using Mesoporous Silicon Particles

Discovery of unique loci that underlie nematode responses to benzimidazoles

Contact Info

Product

Resources

About