Mansonella perstans effects on BCG vaccine-induced protection against childhood tuberculosis as well as tuberculosis disease severity and recovery in Ghana and Cameroon
Final Report Abstract
The MAP-TB project was based on the results from the MAP2-Co project, which focused on Mansonella perstans epidemiology, the role of Wolbachia endosymbionts and how M. perstans influence host immunity, especially the polarization of immune responses against mycobacterial infections (i.e. Buruli disease and tuberculosis). During the initial project, collaborations between the partner institutes from Germany (Bonn and Düsseldorf) and Africa (Cameroon and Ghana) have been established providing the basis for the MAP-TB project. The main objectives of the MAP-TB project were: i) to identify ecological and environmental characterisations for M. perstans vector abundance and transmission; ii) to decipher if M. perstans infections influence tuberculosis (TB) disease severity and time to recovery as well as Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccination efficacy in children. Regarding the epidemiology objective, we revealed that dense equatorial rainforest is crucial for the transmission of M. perstans. Moreover, we identified Culicoides milnei as the major vector of M. perstans in Cameroon and Culicoides grahamii as the potential M. perstans vector in the middle belt region of Ghana. Based on these findings, we established an in vitro culture of M. perstans providing a platform for drug testing and assessment of the biology of this neglected filarial nematode. Furthermore, we obtained enough parasite material for complete mitochondrial genome sequencing of M. perstans and the establishment of an M. perstans-specific-loop mediated isothermal amplification (LAMP) assay which facilitated the detection of M. perstans infections in humans and vectors in the field. 144 patients with tuberculosis and 247 healthy adults and children/adolescents with contact to respective index cases were recruited in the Ashanti region of Ghana. Regarding parasite infections, the most prevalent was Plasmodium falciparum in 43 % of co-infected patients with tuberculosis, but unexpectedly only low numbers of participants (tuberculosis patients, n=2; contacts, n=1) had M. perstans infections. This observation prompted us to adapt the objectives of the MAP-TB project and we decided to investigate the impact of immunopathology in the peripheral blood of tuberculosis patients, the impact of parasite co-infection on tuberculosis and treatment efficacy, and the impact of BCG vaccination on M. tuberculosis infection-induced tuberculin skin test conversion in children/adolescents who are contacts of tuberculosis patients. We revealed a distinct immunopathology in a subset of patients with acute tuberculosis that was mediated by an inflammatory plasma cytokine milieu, the ameliorating effects of parasite co-infections on immunopathology and accelerated sputum conversion in co-infected patients during therapy; an impaired monocyte and T-cell cytokine expression in patients with tuberculosis, IL-6 as a biomarker candidate for detection of M. tuberculosis infection and a delayed tuberculin skin test (TST) conversion in BCG vaccinated child contacts of tuberculosis patients.
Publications
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In vitro maintenance of Mansonella perstans microfilariae and its relevance for drug screening. Experimental Parasitology, 206, 107769.
Njouendou, Abdel Jelil; Kien, Chi Anizette; Esum, Mathias E.; Ritter, Manuel; Chounna, Ndongmo Winston Patrick; Fombad, Fanny Fri; Gandjui, Narcisse Victor T.; Njiokou, Flobert; Enyong, Peter; Pfarr, Kenneth; Turner, Joseph; Layland, Laura E.; Hoerauf, Achim & Wanji, Samuel
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Two-Hit in vitro T-Cell Stimulation Detects Mycobacterium tuberculosis Infection in QuantiFERON Negative Tuberculosis Patients and Healthy Contacts From Ghana. Frontiers in Immunology, 10.
Adankwah, Ernest; Lundtoft, Christian; Güler, Alptekin; Franken, Kees L. M. C.; Ottenhoff, Tom H. M.; Mayatepek, Ertan; Owusu-Dabo, Ellis; Phillips, Richard Odame; Nausch, Norman & Jacobsen, Marc
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CD27 expression of T-cells discriminates IGRA-negative TB patients from healthy contacts in Ghana. Microbes and Infection, 22(1), 65-68.
Adankwah, Ernest; Güler, Alptekin; Mayatepek, Ertan; Phillips, Richard Odame; Nausch, Norman & Jacobsen, Marc
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Complete Mitochondrial Genome Sequence of Mansonella perstans. Microbiology Resource Announcements, 9(30).
Chung, Matthew; Aluvathingal, Jain; Bromley, Robin E.; Nadendla, Suvarna; Fombad, Fanny F.; Kien, Chi A.; Gandjui, Narcisse V. T.; Njouendou, Abdel J.; Ritter, Manuel; Sadzewicz, Lisa; Tallon, Luke J.; Wanji, Samuel; Hoerauf, Achim; Pfarr, Kenneth & Dunning, Hotopp Julie C.
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Dataset on in vitro maintenance of Mansonella perstans microfilariae and drug testing. Data in Brief, 28, 104930.
Njouendou, Abdel Jelil; Ritter, Manuel; Kien, Chi Anizette; Esum, Mathias E.; Ndongmo, Winston Patrick Chounna; Fombad, Fanny Fri; Gandjui, Narcisse Victor T.; Njiokou, Flobert; Enyong, Peter; Pfarr, Kenneth; Turner, Joseph; Layland, Laura E.; Hoerauf, Achim & Wanji, Samuel
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Differential susceptibility of Onchocerca volvulus microfilaria to ivermectin in two areas of contrasting history of mass drug administration in Cameroon: relevance of microscopy and molecular techniques for the monitoring of skin microfilarial repopulation within six months of direct observed treatment. BMC Infectious Diseases, 20(1).
Abong, Raphael Awah; Amambo, Glory N.; Chounna, Ndongmo Patrick W.; Njouendou, Abdel Jelil; Ritter, Manuel; Beng, Amuam Andrew; Esum, Mathias Eyong; Deribe, Kebede; Fru-Cho, Jerome; Fombad, Fanny F.; Nji, Theobald Mue; Enyong, Peter Ivo; Poole, Catherine B.; Pfarr, Kenneth; Hoerauf, Achim; Carlow, Clotilde K. S. & Wanji, Samuel
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Establishment of an in vitro culture system to study the developmental biology of Onchocerca volvulus with implications for anti-Onchocerca drug discovery and screening. PLOS Neglected Tropical Diseases, 15(2), e0008513.
Gandjui, Narcisse V. T.; Njouendou, Abdel J.; Gemeg, Eric N.; Fombad, Fanny F.; Ritter, Manuel; Kien, Chi A.; Chunda, Valerine C.; Fru, Jerome; Esum, Mathias E.; Hübner, Marc P.; Enyong, Peter A.; Hoerauf, Achim & Wanji, Samuel
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Interleukin-6 and Mycobacterium tuberculosis dormancy antigens improve diagnosis of tuberculosis. Journal of Infection, 82(2), 245-252.
Adankwah, Ernest; Nausch, Norman; Minadzi, Difery; Abass, Mohammed K.; Franken, Kees L.M.C.; Ottenhoff, Tom H.M.; Mayatepek, Ertan; Phillips, Richard O. & Jacobsen, Marc
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Lower IL-7 Receptor Expression of Monocytes Impairs Antimycobacterial Effector Functions in Patients with Tuberculosis. The Journal of Immunology, 206(10), 2430-2440.
Adankwah, Ernest; Harelimana, Jean De Dieu; Minadzi, Difery; Aniagyei, Wilfred; Abass, Mohammed K.; Batsa, Debrah Linda; Owusu, Dorcas O.; Mayatepek, Ertan; Phillips, Richard O. & Jacobsen, Marc
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The Mbam drainage system and onchocerciasis transmission post ivermectin mass drug administration (MDA) campaign, Cameroon. PLOS Neglected Tropical Diseases, 15(1), e0008926.
Abong, Raphael Awah; Amambo, Glory Ngongeh; Hamid, Ali Ahamat; Enow, Belinda Agbor; Beng, Amuam Andrew; Nietcho, Franck Noel; Nji, Theobald Mue; Njouendou, Abdel Jelil; Ritter, Manuel; Esum, Mathias Eyong; Deribe, Kebede; Cho, Jerome Fru; Fombad, Fanny Fri; Enyong, Peter Ivo; Poole, Catherine; Pfarr, Kenneth; Hoerauf, Achim; Carlow, Clotilde & Wanji, Samuel
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Cytokine‐induced transient monocyte IL‐7Ra expression and the serum milieu in tuberculosis. European Journal of Immunology, 52(6), 958-969.
Harelimana, Jean De Dieu; Ahor, Hubert Senanu; Benner, Bastian; Hellmuth, Sabine; Adankwah, Ernest; Minadzi, Difery; Aniagyei, Wilfred; Lamptey, Millicent Naa Koshie; Arthur, Joseph; Yeboah, Augustine; Abass, Mohammed K.; Debrah, Linda Batsa; Owusu, Dorcas O.; Mayatepek, Ertan; Seyfarth, Julia; Phillips, Richard O. & Jacobsen, Marc
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Plasma cytokine levels characterize disease pathogenesis and treatment response in tuberculosis patients. Infection, 51(1), 169-179.
Vivekanandan, Monika M.; Adankwah, Ernest; Aniagyei, Wilfred; Acheampong, Isaac; Yeboah, Augustine; Arthur, Joseph F.; Lamptey, Millicent N. K.; Abass, Mohammed K.; Gawusu, Amidu; Kumbel, Francis; Osei-Yeboah, Francis; Debrah, Linda Batsa; Owusu, Dorcas O.; Debrah, Alexander; Mayatepek, Ertan; Seyfarth, Julia; Phillips, Richard O. & Jacobsen, Marc
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Application of loop mediated isothermal amplification (LAMP) assays for the detection of Onchocerca volvulus, Loa loa and Mansonella perstans in humans and vectors. Frontiers in Tropical Diseases, 3.
Amambo, Glory Ngongeh; Innocentia, Ngong; Abong, Raphael Awah; Fombad, Fanny Fri; Njouendou, Abdel Jelil; Nietcho, Franck; Ekanya, Relindis; Kien, Chi Anizette; Ebai, Rene; Lenz, Benjamin; Ritter, Manuel; Esum, Mathias Eyong; Deribe, Kebede; Cho, Jerome Fru; Beng, Amuam Andrew; Enyong, Peter Ivo; Li, Zhiru; Hübner, Marc P.; Pfarr, Kenneth ... & Wanji, Samuel
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BCG-Vaccinated Children with Contact to Tuberculosis Patients Show Delayed Conversion of Mycobacterium tuberculosis-Specific IFN-γ Release. Vaccines, 11(4), 855.
Owusu, Dorcas O.; Adankwah, Ernest; Aniagyei, Wilfred; Acheampong, Isaac; Minadzi, Difery; Yeboah, Augustine; Arthur, Joseph F.; Lamptey, Millicent; Vivekanandan, Monika M.; Abass, Mohammed K.; Kumbel, Francis; Osei-Yeboah, Francis; Gawusu, Amidu; Batsa, Debrah Linda; Debrah, Alexander; Mayatepek, Ertan; Seyfarth, Julia; Phillips, Richard O. & Jacobsen, Marc
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Diminished Interleukin-7 receptor expression on T-cell subsets in tuberculosis patients. Human Immunology, 84(10), 543-550.
Acheampong, Isaac; Minadzi, Difery; Adankwah, Ernest; Aniagyei, Wilfred; Vivekanandan, Monika M.; Yeboah, Augustine; Arthur, Joseph F.; Lamptey, Millicent; Abass, Mohammed K.; Kumbel, Francis; Osei-Yeboah, Francis; Gawusu, Amidu; Laing, Edwin F.; Batsa, Debrah Linda; Owusu, Dorcas O.; Debrah, Alexander; Mayatepek, Ertan; Seyfarth, Julia; Phillips, Richard O. & Jacobsen, Marc
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Impaired T-cell response to phytohemagglutinin (PHA) in tuberculosis patients is associated with high IL-6 plasma levels and normalizes early during anti-mycobacterial treatment. Infection, 51(4), 1013-1023.
Vivekanandan, Monika M.; Adankwah, Ernest; Aniagyei, Wilfred; Acheampong, Isaac; Minadzi, Difery; Yeboah, Augustine; Arthur, Joseph F.; Lamptey, Millicent; Abass, Mohammed K.; Kumbel, Francis; Osei-Yeboah, Francis; Gawusu, Amidu; Debrah, Linda Batsa; Owusu, Dorcas O.; Debrah, Alexander; Mayatepek, Ertan; Seyfarth, Julia; Phillips, Richard O. & Jacobsen, Marc
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Monocyte pathology in human tuberculosis is due to plasma milieu changes and aberrant STAT signalling. Immunology, 170(1), 154-166.
Ahor, Hubert Senanu; Schulte, Rebecca; Adankwah, Ernest; Harelimana, Jean De Dieu; Minadzi, Difery; Acheampong, Isaac; Vivekanandan, Monika M.; Aniagyei, Wilfred; Yeboah, Augustine; Arthur, Joseph F.; Lamptey, Millicent; Abass, Mohammed K.; Kumbel, Francis; Osei‐Yeboah, Francis; Gawusu, Amidu; Debrah, Linda Batsa; Owusu, Dorcas O.; Debrah, Alexander; Mayatepek, Ertan ... & Jacobsen, Marc
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Immunopathology in human pulmonary tuberculosis: Inflammatory changes in the plasma milieu and impaired host immune cell functions. Immunology, 172(2), 198-209.
Ahor, Hubert Senanu; Vivekanandan, Monika; Harelimana, Jean De Dieu; Owusu, Dorcas O.; Adankwah, Ernest; Seyfarth, Julia; Phillips, Richard & Jacobsen, Marc
