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NIINE Research Project

NIINE Research Project

Project Lead(s)
Project Background 

Hookworms infect nearly one billion people worldwide, and are a leading cause of anemia and malnutrition in resource-limited countries. Current global strategies to control hookworm and other Soil Transmitted Helminths rely on repeated mass drug administration (MDA) with albendazole. Recent evidence confirms that deworming drugs are losing effectiveness against hookworm in endemic areas, and the emergence of genetically mediated resistance would have potentially devastating public health implications. Our studies in adults and school-age children conducted in the Kintampo North Municipality (KNM), Ghana confirm the overall poor efficacy of albendazole, progressive reduction in efficacy and increase in numbers of non-respondents. We hypothesize that treatment responses and reinfections are associated with individual, community practices, and parasites’ genetics, implying that there is multifactorial mechanism of hookworm treatment failure. In order to test this hypothesis, we are conducting research in four specific domains; epidemiology, immunology, parasite population genetics and identification of molecular biomarkers of albendazole resistance for monitoring and surveillance of MDA. This TMRC project supports collaborative research and training to build capacity in parasitic diseases research, building on the longstanding record of the Ghana-Yale Partnership for Global Health 

Objectives/Research Areas 

Investigations into the epidemiology of soil-transmitted helminthiasis focusing on individual and community risk factors of infection and reinfection using a) GIS technology and mathematical modelling and b) the effect of human gut microbiome on hookworm and schistosomiasis infections and on responses to anthelminthic treatments. 

Nationwide mapping of the distribution and intensities of STH in Ghana to aid the efforts of GHS NTDs Program to achieve its elimination goals by 2030 

Key Findings 
  • Cure rates and egg reduction rates with single dose albendazole treatment was well below the WHO recommended criteria for the drug’s efficacy. 
  • Response to albendazole treatment varied widely by individuals and communities
  • Albendazole treatment was more effective in individuals 6 or more hours after meals
  • Viable N. americanus eggs occur in stool specimens of dogs and pigs in communities implicating zoonotic role in the disease transmission.
  • Biannual treatments with single dose albendazole resulted in the levelling off hookworm prevalence after 4 years implying that this strategy alone may not be sufficient for hookworm elimination
  • Albendazole treatment results in increased drug-tolerant Necator americanus parasites
Ongoing Activities  

Specific Aim 1: To identify host modifiable factors associated with improved response to single-dose albendazole, the Hookworm Exposure and Treatment (HEAT) project will measure albendazole absorption following treatment and monitor response to single-dose albendazole following treatment in the context of the longitudinal study.  

Specific Aim 2: To identify individual and community-level factors associated with hookworm reinfection, project 1 will conduct a three-year longitudinal community study of hookworm transmission and reinfection.  

Specific Aim 3: To develop a comprehensive anthelminthic response map (AR-Map) of sentinel sites in Ghana to aid in monitoring and surveillance of the effectiveness of national deworming programs in Ghana.

Specific Aim 4: Develop sensitive in vitro and molecular tests to monitor MDA effectiveness and detect emerging hookworm resistance.

Key Publications  
  1. Humphries D, Mosites, E, Otchere J, et al. (2011). Epidemiology of hookworm infection in Kintampo North Municipality, Ghana: Patterns of malaria coinfection, anaemia, and albendazole treatment failure. American Journal of Tropical Medicine and Hygiene, 84(5): 792–800
  2. Humphries D, Nguyen S, Boakye D, Wilson M & Cappello M. (2012). The promise and pitfalls of mass drug administration to control intestinal helminth infections (a Review). Current Opinion in Infectious Diseases, 25: DOI:10.1097/QCO.0b013e328357e4cf
  3. Dziedzom Komi de Souza, Priscilla Owusu, Michael Wilson (2012). Impact of Climate Change on the Geographic Scope of Diseases. In: Netra Chhetri (Editor): Human and Social Dimensions of Climate Change. First Edition. Chapter: 12: Publisher: InTechOpen. DOI: 10.5772/50646 
  4. Debbie Humphries, Benjamin T. Simms, Dylan Davey, Joseph Otchere, Josephine Quagraine, Shawn Terryah, Samuel Newton, Elyssa Berg, Lisa M. Harrison, Daniel Boakye, Michael Wilson & Michael Cappello (2013). Hookworm infection among school-age children in Kintampo North Municipality, Ghana: Nutritional risk factors and response to albendazole treatment. American Journal of Tropical Medicine and Hygiene, 89(3): 540–548.
  5. Wilson MD, De Souza DK & Ayi I. (2016). Soil-transmitted helminthiasis. In: Neglected Tropical Diseases. John Gyapong and Boakye Boatin (editors). Springer, Heidelberg, pp 289-317.
  6. RYAN H. BOYKO, LISA MARIE HARRISON, DEBBIE HUMPHRIES, ALISON P. GALVANI, JEFFREY P. TOWNSEND, JOSEPH OTCHERE, MICHAEL D. WILSON & MICHAEL CAPPELLO. Dogs and pigs are transport hosts of Necator americanus: Molecular evidence for a zoonotic mechanism of human hookworm transmission in Ghana. Zoonoses Public Health 2020,1–10. DOI: 10.1111/zph.12708.
Community Engagement Activities  
Community-entry durbars in nine rural communities in the Kintampo North Municipality, Ghana
External Collaborator(s) 
Michael Cappello MD, Yale School of Medicine Yale University, New Haven, CT, USA
Dr Debbie Humphries, Yale School of Public Health, New Haven, CT, USA
Dr Mike Osei-Atweneboana, Director, Water Research Institute, CSIR, Accra, Ghana
Dr K. Asante Poku, Director, Kintampo Health Research Centre, Kintampo, Ghana
Dr Eyram Schwinger, Department of Mathematics, University of Ghana, Legon, Accra, Ghana
National Institute of Allergy and Infectious Diseases, Grant/Award Numbers: AI099623 and U19AI129916 U19