Dr. Jubin Osei-Mensah, Vera Serwaa Opoku, Francis Adjei Osei, Dr. Mrs. Linda Batsa Debrah, Prof. Alexander Yaw Debrah, Ruth Boateng, Eglah Agyeiwaa Appiah, Aliu Mohammed, Seth Wiredu, Paul Antwi, Nancy Ackam, Abu Abudu Rahamani, Eunice Kuutiero, Derrick Adu Mensah, Fatima Amponsah Fordjour, Ernest Amanor, Peter Akosah Gyamfi and Wellington Owusu.

Dr. Jubin Osei-Mensah, Vera Serwaa Opoku, Francis Adjei Osei, Dr. Mrs. Linda Batsa Debrah, Prof. Alexander Yaw Debrah, Ruth Boateng, Eglah Agyeiwaa Appiah, Aliu Mohammed, Seth Wiredu, Paul Antwi, Nancy Ackam, Abu  Abudu Rahamani, Eunice Kuutiero, Derrick Adu Mensah, Fatima Amponsah Fordjour, Ernest Amanor, Peter Akosah Gyamfi and Wellington Owusu.

Prof. Alexander Yaw Debrah
Group Leader
Prof. Alexander Yaw Debrah
Phone: +233 209341317
Fax: +233 3220 62017
E-Mail: yadebrah@yahoo.com; yadebrah.chs@knust.edu.gh
Dr. Mrs. Linda Batsa Debrah
Project Coordinator
Dr. Mrs. Linda Batsa Debrah
Phone: +233208174244
Fax: 00233322062017
E-Mail: lindrousy@yahoo.com

Students & Staff

Post-Doctoral Research Fellow: Dr. Jubin Osei-Mensah

Project Manager: Francis Adjei Osei

Doctoral Students:
Vera Serwaa Opoku,
Derrick Adu Mensah,
Abu Abudu Rahamani

Master Students:
Nancy Ackam, Peter Akosah Gyamfi, Eglah Agyeiwaa Appiah
Others: Francis Dorman (Financial Administrator /Accountant), Ruth Boateng (Cook), Ernest Amanor (National Service Personnel)

Scientific Staff (laboratory and field):
Yusif Mubarik, Rasheed Adjei-Mensah, Wellington Owusu, Eunice Kuutiero, Fatima Amponsah Fordjour

Drivers: Seth Wiredu, Paul Antwi

Field Security personnel: Moses Tampugre, Stephen A. Adabor

Overview

The group focuses on diseases caused by filarial nematodes namely lymphatic filariasis (LF), onchocerciasis and mansonellosis. Research into these neglected tropical diseases is of importance in reducing morbidities and deaths associated with these infections. The groups’ research areas include clinical trials in LF and onchocerciasis aimed at finding best therapeutic regimen for the treatment of these diseases; molecular and genetic studies in LF and onchocerciasis ; and identification of biomarkers in development of lymphedema.

Meeting the study participants in the community
(A) Meeting the study participants in the community
(B) Washing of lymphedema legs

Research Projects

Tackling the obstacles of Filariasis and Podoconiosis disease control (TAKeOFF)

Previous studies with doxycycline (200mg/d) treatment for lymphedema (LE) resulted in amelioration of the lymphedema legs.  Although this intervention was successful, it requires some medical supervision because of the 200mg dose used. However, in many African rural health settings where this disease is endemic, there are not enough medical personnel to carry out this supervision. Therefore, we are investigating whether a dose reduction to 100 mg/d which could be self-medicated, will show equivalent beneficial effects on LE pathology. Furthermore, this study seeks to establish a filarial clinical trial and research platform (F-CuRE) to address patient needs and deliver a novel health tool at the national levels.

The efficacy of rifapentine plus moxifloxacin against onchocerciasis (MORION)

Current strategies in the control and prevention of this disease relies on the annual mass drug administration (MDA) of ivermectin which is mainly microfilaricidal, hence female worms resume microfilariae repopulation to levels high enough for transmission. Contrary to ivermectin, doxycycline has been shown to have macrofilaricidal effect on the adult worms, however, it is not recommended for MDA due to its long treatment duration.

This study seeks to find a drug or drug combination with macrofilaricidal activity given for shorter treatment duration. Previous studies conducted by our research group in mice models revealed that the combination of rifapentine and moxifloxacin given for 4 to 7 days had macrofilaricidal effect on the adult worm.

The transfer from this treatment data in mice to treatment in humans is realistic hence the carrying out of this study. If successful, treatment durations for onchocerciasis will be shortened and transmission ceased.

 

Risk for HIV Infections through Nematodes (RHINO)

 

Helminths affect the world’s poor and provoke a chronic disease state in one-fourth of the world's population. The disproportionately high prevalence of human immunodeficiency virus (HIV) in communities of sub-Saharan Africa has led to the hypothesis that concomitant helminth infections might increase the risk of HIV transmission.

In previous studies our group revealed for the first time an increased risk for HIV acquisition in individuals infected with the filarial nematode Wuchereria bancrofti. In this study, we seek to determine if infections with Onchocerca volvulus and Wuchereria bancrofti increase an individual’s risk of acquiring HIV and to decipher whether HIV susceptibility is driven or influenced by distinct immunological changes/ pathways in the host due to these filarial infections.

Long term translation of these findings to other helminth-HIV scenarios would constitute another major benefit in the global eradication efforts against these parasites.

First-Stage Genome Wide Association Study (GWAS) of Lymphatic Filariasis Pathology

Current control regimes by the World Health Organization (WHO) aim at decreasing transmission by reducing the levels of microfilariae (larvae, MF) in infected individuals. This can be achieved if the molecular basis of developing a particular pathology is known.

Our earlier cross-sectional, candidate gene studies have been successful; however, the associations discovered explain only a fraction of the genetic causes of lymphatic filariasis. Therefore, we propose a GWAS to comprehensively discover genetic factors involved in the pathophysiology of this complex infectious disease.

This study will lead to a long term multistage GWAS-design, which finally will lead to a deep understanding of the underlying disease pathophysiology

Rapid diagnosis of onchocerciasis using urinary biomarkers

Current diagnostic methods in filariasis are still far from being satisfactory. Most of them are based on the detection of microfilariae (MF) rather than infection with adult worms, which are long-lived (10-14 years) and would resume MF production once mass drug administration (MDA) with the primarily microfilaricidal drugs is stopped too early. For onchocerciasis, no reliable antigen test exists and the  currently used invasive skin snip method is painful, labour intensive and insensitive, especially once the prevalence falls to very low levels. A rapid, field applicable tool to identify and differentiate patients with high L. loa MF loads from onchocerciasis patients is also needed.

Given the imperfections of currently available diagnostic tools for filariasis, particularly with regard to the invasive and insensitive nature of parasitological diagnosis, an urgent need exists for sensitive and specific biomarkers that can be detected in a non-invasive manner and are specific for onchocerciasis.

Comparison of Ivermectin alone with Albendazole (ALB) plus Ivermectin (IVM) in their Efficacy against Onchocerciasis (DOLF)

A clinical trial was performed in an endemic area of Central Ghana to address the question whether ivermectin (IVM) combined with albendazole (ALB) at higher doses and given more than once per year might generate sustained reduction in microfilariae (Mf) by reducing female fertility or by killing adult worms in onchocerciasis.

In total 272 Mf-positive participants, with at least one palpable onchocercoma were treated with either 1) IVM 200µg/kg annually (0, 12, 24 months; N = 68), 2) IVM 200µg/kg biannually (0, 6, 12, 18, 24 months; N = 68), 3) IVM 200µg/kg plus ALB 800mg annually (N = 70) or 4) IVM 200µg/kg plus ALB 800mg biannually (N = 66).

In conclusion, addition of ALB to IVM did not improve the efficacy against female worm fertility or the macrofilaricidal effect. However, the increase from annual to biannual drug administration resulted in a sustained increase of Mf negative individuals.

Publications

1. Lagatie O, Verheyen A, Nijs E, Van Dorst B, Batsa Debrah L, Debrah A, Supali T, Sartono E, Stuyver LJ. Evaluation of the Diagnostic Performance of Onchocerca volvulus Linear Epitopes in a Peptide Enzyme-Linked Immunosorbent Assay. Am J Trop Med Hyg (2018). doi: 10.4269/ajtmh.17-0756.
2. Globisch D, Eubanks LM, Shirey RJ, Pfarr KM, Wanji S, Debrah AY, et al. Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG). Bioorg Med Chem Lett. 2017 Aug 1;27(15):3436–40.
3. Debrah LB, Albers A, Debrah AY, Brockschmidt FF, Becker T, Herold C, et al. Single nucleotide polymorphisms in the angiogenic and lymphangiogenic pathways are associated with lymphedema caused by Wuchereria bancrofti. Hum Genomics. 2017 Nov 9;11(1):26.
4. Debrah LB, Nausch N, Opoku VS, Owusu W, Mubarik Y, Berko DA, et al. Epidemiology of Mansonella perstans in the middle belt of Ghana. Parasit Vectors. 2017 Jan 7;10(1):15.
5. Klarmann-Schulz U, Specht S, Debrah AY, Batsa L, Ayisi-Boateng NK, Osei-Mensah J, et al. Comparison of Doxycycline, Minocycline, Doxycycline plus Albendazole and Albendazole Alone in Their Efficacy against Onchocerciasis in a Randomized, Open-Label, Pilot Trial. Basáñez M-G, editor. PLoS Negl Trop Dis. 2017 Jan 5;11(1):e0005156.
6. Prodjinotho UF, von Horn C, Debrah AY, Batsa Debrah L, Albers A, Layland LE, et al. Pathological manifestations in lymphatic filariasis correlate with lack of inhibitory properties of IgG4 antibodies on IgE-activated granulocytes. Mitre E, editor. PLoS Negl Trop Dis. 2017 Jul 24;11(7):e0005777.
7. Nausch N, Antwi-Berko D, Mubarik Y, Abass KM, Owusu W, Owusu-Dabo E, et al. Analysis of Mycobacterium ulcerans-specific T-cell cytokines for diagnosis of Buruli ulcer disease and as potential indicator for disease progression. Small PLC, editor. PLoS Negl Trop Dis. 2017 Feb 27;11(2):e0005415.
8. Stanton MC, Mkwanda SZ, Debrah AY, Batsa L, Biritwum N-K, Hoerauf A, et al. Developing a community-led SMS reporting tool for the rapid assessment of lymphatic filariasis morbidity burden: case studies from Malawi and Ghana. BMC Infect Dis. 2015 May 16;15(1):214.
9. Arndts K, Klarmann-Schulz U, Batsa L, Debrah AY, Epp C, Fimmers R, et al. Reductions in microfilaridermia by repeated ivermectin treatment are associated with lower Plasmodium-specific Th17 immune responses in Onchocerca volvulus-infected individuals. Parasit Vectors. 2015 Mar 28;8(1):184.
10. Garms R, Badu K, Owusu-Dabo E, Baffour-Awuah S, Adjei O, Debrah AY, et al. Assessments of the transmission of Onchocerca volvulus by Simulium sanctipauli in the Upper Denkyira District, Ghana, and the intermittent disappearance of the vector. Parasitol Res. 2015 Mar 17;114(3):1129–37.
11. Katawa G, Layland LE, Debrah AY, von Horn C, Batsa L, Kwarteng A, et al. Hyperreactive onchocerciasis is characterized by a combination of Th17-Th2 immune responses and reduced regulatory T cells. Makepeace BL, editor. PLoS Negl Trop Dis. 2015 Jan 8;9(1):e3414.
12. Arndts K, Specht S, Debrah AY, Tamarozzi F, Klarmann Schulz U, Mand S, et al. Immunoepidemiological profiling of onchocerciasis patients reveals associations with microfilaria loads and ivermectin intake on both individual and community levels. Fischer PU, editor. PLoS Negl Trop Dis. 2014 Feb 20;8(2):e2679.
13. Debrah AY, Batsa L, Albers A, Mand S, Toliat MR, Nürnberg P, et al. Transforming growth factor-β1 variant Leu10Pro is associated with both lack of microfilariae and differential microfilarial loads in the blood of persons infected with lymphatic filariasis. Hum Immunol. 2011 Nov;72(11):1143–8.
14. Arndts K, Deininger S, Specht S, Klarmann U, Mand S, Adjobimey T, et al. Elevated adaptive immune responses are associated with latent infections of Wuchereria bancrofti. Doenhoff M, editor. PLoS Negl Trop Dis. 2012 Apr 3;6(4):e1611.
15. Hoerauf A, Pfarr K, Mand S, Debrah AY, Specht S. Filariasis in Africa–treatment challenges and prospects. Clin Microbiol Infect. 2011 Jul;17(7):977–85.
16. Debrah AY, Mand S, Marfo-Debrekyei Y, Batsa L, Albers A, Specht S, et al. Macrofilaricidal Activity in Wuchereria bancrofti after 2 Weeks Treatment with a Combination of Rifampicin plus Doxycycline. J Parasitol Res. 2011;2011:201617.
17. Mand S, Debrah AY, Klarmann U, Mante S, Kwarteng A, Batsa L, et al. The role of ultrasonography in the differentiation of the various types of filaricele due to bancroftian filariasis. Acta Trop. 2011 Sep;120 Suppl 1:S23-32.
18. Attout T, Hoerauf A, Dénécé G, Debrah AY, Marfo-Debrekyei Y, Boussinesq M, et al. Lymphatic vascularisation and involvement of Lyve-1+ macrophages in the human onchocerca nodule. Unutmaz D, editor. PLoS One. 2009 Dec 9;4(12):e8234.
19. Debrah AY, Specht S, Klarmann-Schulz U, Batsa L, Mand S, Marfo-Debrekyei Y, et al. Doxycycline Leads to Sterility and Enhanced Killing of Female Onchocerca volvulus Worms in an Area With Persistent Microfilaridermia After Repeated Ivermectin Treatment: A Randomized, Placebo Controlled, Double-Blind Trial. Clin Infect Dis. 2015 Aug 15;61(4):517–26.
20. Mand S, Debrah AY, Klarmann U, Batsa L, Marfo-Debrekyei Y, Kwarteng A, et al. Doxycycline improves filarial lymphedema independent of active filarial infection: a randomized controlled trial. Clin Infect Dis. 2012 Sep 1;55(5):621–30.
21. Lagatie O, Merino M, Batsa Debrah L, Debrah AY, Stuyver LJ. An isothermal DNA amplification method for detection of Onchocerca volvulus infection in skin biopsies. Parasit Vectors. 2016 Dec 1;9(1):624.
22. Hoerauf A, Specht S, Büttner M, Pfarr K, Mand S, Fimmers R, et al. Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis: a randomized placebo-controlled study. Med Microbiol Immunol. 2008 Sep 26;197(3):335.
23. Pfarr KM, Debrah AY, Specht S, Hoerauf A. Filariasis and lymphoedema. Parasite Immunol. 2009 Nov 7;31(11):664–72.
24. Hoerauf A, Specht S, Marfo-Debrekyei Y, Büttner M, Debrah AY, Mand S, et al. Efficacy of 5-week doxycycline treatment on adult Onchocerca volvulus. Parasitol Res. 2009 Jan 11;104(2):437–47.
25. Specht S, Mand S, Marfo-Debrekyei Y, Debrah AY, Konadu P, Adjei O, et al. Efficacy of 2- and 4-week rifampicin treatment on the Wolbachia of Onchocerca volvulus. Parasitol Res. 2008 Nov 5;103(6):1303–9.
26. Hoerauf A, Marfo-Debrekyei Y, Büttner M, Debrah AY, Konadu P, Mand S, et al. Effects of 6-week azithromycin treatment on the Wolbachia endobacteria of Onchocerca volvulus. Parasitol Res. 2008 Jul 18;103(2):279–86.
27. Mand S, Pfarr K, Sahoo PK, Satapathy AK, Specht S, Klarmann U, et al. Macrofilaricidal activity and amelioration of lymphatic pathology in bancroftian filariasis after 3 weeks of doxycycline followed by single-dose diethylcarbamazine. Am J Trop Med Hyg. 2009 Oct 1;81(4):702–11.
28. Debrah AY, Mand S, Marfo-Debrekyei Y, Batsa L, Pfarr K, Lawson B, et al. Reduction in levels of plasma vascular endothelial growth factor-A and improvement in hydrocele patients by targeting endosymbiotic Wolbachia sp. in Wuchereria bancrofti with doxycycline. Am J Trop Med Hyg. 2009 Jun;80(6):956–63.
29. Hoerauf A, Specht S, Büttner M, Pfarr K, Mand S, Fimmers R, et al. Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis: a randomized placebo-controlled study. Med Microbiol Immunol. 2008 Sep;197(3):295–311.
30. Debrah AY, Mand S, Marfo-Debrekyei Y, Batsa L, Pfarr K, Buttner M, et al. Macrofilaricidal effect of 4 weeks of treatment with doxycycline on Wuchereria bancrofti. Trop Med Int Health. 2007 Dec;12(12):1433–41.
31. Debrah AY, Mand S, Toliat MR, Marfo-Debrekyei Y, Batsa L, Nürnberg P, et al. Plasma vascular endothelial growth Factor-A (VEGF-A) and VEGF-A gene polymorphism are associated with hydrocele development in lymphatic filariasis. Am J Trop Med Hyg. 2007 Oct;77(4):601–8.
32. Debrah AY, Mand S, Specht S, Marfo-Debrekyei Y, Batsa L, Pfarr K, et al. Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis. PLoS Pathog. 2006 Sep;2(9):e92.
33. Turner JD, Mand S, Debrah AY, Muehlfeld J, Pfarr K, McGarry HF, et al. A randomized, double-blind clinical trial of a 3-week course of doxycycline plus albendazole and ivermectin for the treatment of Wuchereria bancrofti infection. Clin Infect Dis. 2006 Apr 15;42(8):1081–9.
34. Debrah AY, Mand S, Marfo-Debrekyei Y, Larbi J, Adjei O, Hoerauf A. Assessment of microfilarial loads in the skin of onchocerciasis patients after treatment with different regimens of doxycycline plus ivermectin. Filaria J. 2006 Feb 5;5:1.
35. Hoerauf A, Mand S, Fischer K, Kruppa T, Marfo-Debrekyei Y, Debrah AY, et al. Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production. Med Microbiol Immunol. 2003 Nov;192(4):211–6.

Funding

  • DFG (Deutsche Forschungsgesellschaft)
  • German Federal Ministry of Education and Research (BMBF)
  • University of Bonn, Germany
  • Medical Research Council (MRC), UK
  • Bill and Melinda Gates Foundation 

Alumni

PhD

  1. John Larbi

Title: Anti filarial T-cell responses in Onchocerciasis; Protective responses to recombinant Onchocerca volvulus antigens and regulatory mechanisms

Year: 2005

  1. Alexander Yaw Debrah

Title:  Lymphatic Filariasis- Targeting Wolbachia Endosymbiotic Bacteria in the Treatment and Diagnosis, and Analysis of Cytokine and Cytokine Receptor Polymorphisms in Disease Manifestation

Year: 2007

  1. Yeboah Marfo-Debrekyei

Title: Assessment of the efficacy of different regimens of Azithromycin and doxycycline to deplete Wolbachia endosymbiont bacteria in Onchocerca volvulus adult worm

Year: 2008

  1. Mrs. Linda Batsa Debrah

Title: Anti-Wolbachia Treatment Of Lymphatic Filariasis And Genetic Analysis Of The Pathology Of Lymphedema As A Clinical Manifestation Of The Disease

Year: 2012

  1. Alexander Kwarteng

Title: Transcriptomics and Immune Profiles of Asymptomatic Filarial-Infected Individuals

Year: 2015

  1. Jubin Osei-Mensah

Title: Analyses Of Genetic Polymorphisms Of Cytokines And Angiogenic Molecules In Patent And Latent Manifestations Of Lymphatic Filariasis

Year: 2016

  1. Daniel Antwi-Berko

Title: Immune Modulatory Effects of Mansonella perstans and Plasmodium species co-infection with Mycobacterium ulcerans disease in Ghana

Year: 2016

Master of Philosophy

  1. Professor Alexander Yaw Debrah (2003):“Analysis of microfilarial loads in the skin of onchocerciasis patients after treatment with doxycycline and ivermectin ”
  2. Mrs. Linda Batsa Debrah(2005):

Title: Doxycycline Targeting of Wolbachia Endosymbiontic bacteria in the Treatment of Wolbachia Bacteria Infections in the Western Region of Ghana

Year: 2005

  1. Alexander Kwarteng

Title: Evaluation of Antiwolbachial treatment in the pathogenesis of lymphedema development

Year: 2010

  1. Jubin Osei-Mensah

Title: Effect of doxycycline treatment on Onchocerca volvulus worms that respond poorly to Ivermectin

Year: 2011

  1. Nana Kwame Ayisi Boateng

Title: Impact Of Mass Drug Administration Of Ivermectin And Albendazole On The Prevalence Of Lymphatic Filariasis In The Nzema East And Ahanta West Districts

Year: 2014

  1. Kenneth Bentum Otabil

Title: Role of doxycycline in the amelioration of filarial hydrocele

Year:2011

  1. Daniel Antwi Berko

Title: The Impact Of Ivermectin Mass Drug Administration On The Level Of Endemicity And Intensity Of Onchocerca Volvulus Infection In The Adansi South District Of Ghana

Year: 2014

  1. Yusif Mubarik

Title: Microfilaridermia assessment of the efficacy of Ivermectin alone and Ivermectin plus Albendazole against Onchocerciasis

Year: 2015

  1. Wellington Owusu

Title: Assessment Of Microfilarial Load In The Blood Of Patients With Mansonella perstans Infection After Anti-Wolbachial Treatment With Doxycycline

Year: 2016

  1. Vera Serwaa Opoku

Title: Epidemiological Studies On The Disease And Vector Of Mansonella perstans In The Asante Akim North District Of Ghana

Year: 2016

  1. Fatima Amponsah Fordjour

Title: Assessing the Involvement of Nuclear Factor Kappa Light Chain Enhancer of Activated B-cells inhibitor alpha in filarial lymphedema development

Year: 2017

  1. Monica Ahiadorme

Title: The impact of ten years of ivermectin mass drug administration on the level of endemicity and intensity of Onchocerca Volvulus infection in the Aowin District of Ghana

Year: 2016

  1. Daniel Tagoe

Title:

Year