EDCTP Alumni Network

Fostering excellence and collaboration in the next generation of researchers

Call Career Development Fellowship (CDF)
Programme EDCTP2
Start Date 2017-06-01
End Date 2020-05-31
Project Code TMA2015CDF979
Status Active

Title

Rapid detection of Mycobaterium ulcerans infection by recombinase polymerase amplification

Objectives

This study is to explore the potential of using recombinase polymerase amplification (RPA) as a tool for Buruli ulcer diagnosis. RPA has emerged as a novel isothermal technology for use in molecular diagnosis of infectious diseases. This means that it can be carried out at room temperature in unsophisticated laboratories in West Africa close to patients. The key goal is to develop a diagnostic test for the early detection of Buruli ulcer in symptomatic patients with sufficient positive predictive value to put patients on appropriate treatment.

Host Organisation

Institution Country
Kwame Nkrumah University of Science and Technology Ghana

Study Design

Cross-sectional study

Sites

Ashanti Akim North
Ahafo Ano North
Upper Denkyira Districts

Phd Study

Title University Start Date End Date
Cellular immune response to mycobacterium ulcerans infection Kwame Nkrumah University of Science and Technology 2011-08-01 2015-06-01

Students Supervised

Type Name Title University Start Date End Date
Mphil Hubert S. Ahor Mr Kwame Nkrumah University of Science and Technology 2017 2019
Mphil Louis Kyei-Tuffour Mr Kwame Nkrumah University of Science and Technology 2018 2020

Results & Outcomes

Ongoing

Publications

Simpson H et al. Mapping the global distribution of Buruli ulcer: a systematic review with evidence consensus. Lancet Glob Health. 2019 Jul;7(7):e912-e922. doi: 10.1016/S2214-109X(19)30171-8
Frimpong M et al. Rapid detection of Mycobacterium ulcerans with isothermal recombinase polymerase amplification assay. PLoS Negl Trop Dis. 2019 Feb 1;13(2):e0007155. doi: 10.1371/journal.pntd.0007155
Frimpong, Michael, et al. "Paradoxical reactions in Buruli ulcer after initiation of antibiotic therapy: Relationship to bacterial load." PLoS neglected tropical diseases 13.8 (2019): e0007689
Frimpong, M.; Ahor, H.S.; Sakyi, S.A.; Agbavor, B.; Akowuah, E.; Phillips, R.O. Rapid Extraction Method of Mycobacterium ulcerans DNA from Clinical Samples of Suspected Buruli Ulcer Patients. Diagnostics 2019, 9, 204
Amoako, Y.A., Frimpong, M., Awuah, D.O. et al. Providing insight into the incubation period of Mycobacterium ulcerans disease: two case reports. J Med Case Reports 13, 218 (2019). https://doi.org/10.1186/s13256-019-2144-2

Current Organisation

Kumasi Centre for Collaborative Research in Tropical Medicine

Current Job Title

Research Fellow

Students Supervised

Type Name Title University Start Date End Date
Mphil Hubert S. Ahor Mr. Kwame Nkrumah University of Science and Technology 2017 2019
MSc. Abigail Agbanyo Ms. Kwame Nkrumah University of Science and Technology 2017 2019
MPhil Louis Kyei-Tuffour Mr Kwame Nkrumah University of Science and Technology 2018 2020
MPhil Venus Boakyewaa Frempong Ms Kwame Nkrumah University of Science and Technology 2019 2021

Memberships

Role Committee/board Start Date End Date
Reviewer PLOS NTD 2017

Education

Institution Degree Year
Kwame Nkrumah University of Science and Technology, Ghana PhD 2015-06-01
Ludwig Maximilian University, Munich, Germany PGDip 2013-03-01

Areas Of Specialisation

Neglected Infectious Diseases (NID) Point-of-care tests Molecular diagnostics

Grants

Grant Code:
SGPII/0114/033
Source of funding:
African Research Network for Neglected Tropical Diseases
Amount:
15000
Role:
Principal Investigator
Start Date:
2019-01-01
End Date:
2020-01-01
Grant Code:
Source of funding:
TWAS
Amount:
8550
Role:
Researcher
Start Date:
2019-01-01
End Date:
2019-01-01

Publications

Authors:
Phillips RO, Robert J, Abass KM, Thompson W, Sarfo FS, Wilson T, Sarpong G, Gateau T, Chauty A, Omollo R, Ochieng Otieno M, Egondi TW, Ampadu EO, Agossadou D, Marion E, Ganlonon L, Wansbrough-Jones M, Grosset J, Macdonald JM, Treadwell T, Saunderson P, Paintsil A, Lehman L, Frimpong M, Sarpong NF, Saizonou R, Tiendrebeogo A, Ohene SA, Stienstra Y, Asiedu KB, van der Werf TS , Phillips, R.O., Robert, J., Abass, K.M., Thompson, W., Sarfo, F.S., Wilson, T., Sarpong, G., Gateau, T., Chauty, A., Omollo, R. and Otieno, M.O., 2020. Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial. The Lancet.
Date:
2020-04-01
Journal:
Lancet
Content:

Background

Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions.

Methods

We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437.

Findings

Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10–29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, −0·5% (–5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1–2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts.

Interpretation

Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer.

Identifiers:
Authors:
Date:
2014-06-01
Journal:
Emerging Infectious Diseases
Content:
Authors:
Frimpong M, Ahor HS, Sakyi SA, Agbavor B, Akowuah E, Phillips RO , Frimpong M, Ahor HS, Sakyi SA, Agbavor B, Akowuah E, Phillips RO. Rapid Extraction Method of Mycobacterium ulcerans DNA from Clinical Samples of Suspected Buruli Ulcer Patients. Diagnostics (Basel). 2019;9(4):204. Published 2019 Nov 26. doi:10.3390/diagnostics9040204
Date:
2019-11-26
Journal:
Diagnostics (Basel)
Content:

Isothermal amplification techniques such as recombinase polymerase amplification (RPA) and loop-mediated isothermal amplification (LAMP) for diagnosing Buruli ulcer, a necrotic skin disease caused by Mycobacterium ulcerans, have renewed hope for the molecular diagnosis of clinically suspected Buruli ulcer cases in endemic districts. If these techniques are applied at district-level hospitals or clinics, they will help facilitate early case detection with prompt treatment, thereby reducing disability and associated costs of disease management. The accuracy as well as the application of these molecular techniques at point of need is dependent on simple and fast DNA extraction. We have modified and tested a rapid extraction protocol for use with an already developed recombinase polymerase amplification assay. The entire procedure from "sample in, extraction and DNA amplification" was conducted in a mobile suitcase laboratory within 40 min. The DNA extraction procedure was performed within 15 min, with only two manipulation/pipetting steps needed. The diagnostic sensitivity and specificity of this extraction protocol together with M. ulcerans RPA in comparison with standard DNA extraction with real-time PCR was 87% (n = 26) and 100% (n = 13), respectively. We have established a simple, fast and efficient protocol for the extraction and detection of M. ulcerans DNA in clinical samples that is adaptable to field conditions.

Identifiers:
Authors:
Asare, R.
Opoku-Okrah, C.
Danquah, K.O.
Opare-Sem, O.
Addai-Mensah, O.
Gyamfi, D.
Amponsah, F.A.
Afriyie, E.Y.
Duneeh, R.V.
Ofosu, D.N.
Frimpong, M.
Date:
2019-01-01
Journal:
Leukemia Research
Content:
Authors:
Michael Frimpong , author
Hubert Senanu Ahor , author
Samuel Asamoah Sakyi , author
Bernadette Agbavor , author
Emmanuel Akowuah , author
Richard Odame Phillips , author
Date:
2019-11-26
Journal:
Diagnostics
Content:
Identifiers:
Authors:
Date:
2016-01-01
Journal:
CHRONIC WOUND CARE MANAGEMENT AND RESEARCH
Content:
Identifiers:
Authors:
Date:
2015-05-18
Journal:
Journal of Tropical Diseases and Public Health
Content:
Identifiers:
Authors:
Date:
2018-01-19
Journal:
BMC infectious diseases
Content:
Non-typhoidal Salmonella (NTS) cause the majority of bloodstream infections in Ghana, however the mode of transmission and source of invasive NTS in Africa are poorly understood. This study compares NTS from water sources and invasive bloodstream infections in rural Ghana. Blood from hospitalised, febrile children and samples from drinking water sources were analysed for Salmonella spp. Strains were serotyped to trace possible epidemiological links between human and water-derived isolates.. Antibiotic susceptibility testing was performed, In 2720 blood culture samples, 165 (6%) NTS were isolated. S. Typhimurium (70%) was the most common serovar followed by S. Enteritidis (8%) and S. Dublin (8%). Multidrug resistance (MDR) was found in 95 (58%) NTS isolates, including five S. Enteritidis.
Identifiers:
Authors:
Michael Frimpong , author
Shirley Victoria Simpson , author
Hubert Senanu Ahor , author
Abigail Agbanyo , author
Solomon Gyabaah , author
Bernadette Agbavor , author
Ivy Brago Amanor , author
Kennedy Kwasi Addo , author
Susanne Böhlken-Fascher , author
Jonas Kissenkötter , author
Ahmed Abd El Wahed , author
Richard Odame Phillips , author
Date:
2020-08-26
Journal:
Content:
Authors:
Michael Frimpong , author
Katharina Roeltgen , editor
Hubert Senanu Ahor , author
Ahmed Abd El Wahed , author
Bernadette Agbavor , author
Francisca Naana Sarpong , author
Kenneth Laing , author
Mark Wansbrough-Jones , author
Richard Odame Phillips , author
Date:
2019-02-01
Journal:
PLOS Neglected Tropical Diseases
Content:
Identifiers:
Authors:
Michael Frimpong , author
Katharina Roeltgen , editor
Bernadette Agbavor , author
Mabel Sarpong Duah , author
Aloysius Loglo , author
Francisca N. Sarpong , author
Justice Boakye-Appiah , author
Kabiru M. Abass , author
Mathias Dongyele , author
George Amofa , author
Wilson Tuah , author
Margaret Frempong , author
Yaw A. Amoako , author
Mark Wansbrough-Jones , author
Richard O. Phillips , author
Date:
2019-08-26
Journal:
PLOS Neglected Tropical Diseases
Content:
Identifiers:
Authors:
Collinson S, Frimpong VNB, Agbavor B, Montgomery B, Oppong M, Frimpong M, Amoako YA, Marks M, Phillips RO , Collinson, S., Frimpong, V.N., Agbavor, B., Montgomery, B., Oppong, M., Frimpong, M., Amoako, Y.A., Marks, M. and Phillips, R.O., 2020. Barriers to Buruli ulcer treatment completion in the Ashanti and Central Regions, Ghana. PLOS Neglected Tropical Diseases, 14(5), p.e0008369
Date:
2020-05-26
Journal:
PLOS Neglected Tropical Diseases
Content:

Author summary

Buruli ulcer (BU) is a chronic ulcerating tropical skin disease known to particularly affect vulnerable populations. Without early detection and effective treatment it can lead to disfigurement, disability and stigma. In order to improve outcomes, we need to understand what factors prevent patients from accessing and completing treatment, however these factors are often not well understood. Factors considered to potentially affect treatment completion include access to care and type of treatment. In this study we analysed data available from clinical records of patients treated in Ghana to identify whether type of treatment and common patient characteristics were associated with treatment completion. We found that treatment completion was higher in patients who took a newly introduced oral treatment compared to those who took the traditional injectable treatment. We did not find a difference in treatment completion between patients living close to the clinic and those living further away, however we found that those living further were more likely to present with more advanced disease. The results from this study suggest that management for patients living far from care needs to be improved. The newly recommended oral treatment makes it feasible to provide care away from health centres and the improved treatment completion seen in this study supports its use. However, further research should be conducted to determine how fully community based care can best be provided.

Identifiers:
Authors:
Sarpong-Duah, M.
Frimpong, M.
Beissner, M.
Saar, M.
Laing, K.
Sarpong, F.
Loglo, A.D.
Abass, K.M.
Frempong, M.
Sarfo, F.S.
Bretzel, G.
Wansbrough-Jones, M.
Phillips, R.O.
Date:
2017-01-01
Journal:
PLoS Neglected Tropical Diseases
Content:
Authors:
Yaw Ampem Amoako , author
Claire Fuller , editor
Nancy Ackam , author
John-Paul Omuojine , author
Michael Ntiamoah Oppong , author
Abena Gyawu Owusu-Ansah , author
Mohammed Kabiru Abass , author
George Amofa , author
Elizabeth Ofori , author
Michael Frimpong , author
Freddie Bailey , author
David Hurst Molyneux , author
Richard Odame Phillips , author
Date:
2021-06-01
Journal:
PLOS Neglected Tropical Diseases
Content:
Identifiers:
Authors:
Simpson H , Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK
Deribe K , Wellcome Trust Brighton and Sussex Centre for Global Health Research, Brighton and Sussex Medical School, Brighton, UK
Tabah EN , National Yaws, Leishmaniasis, Leprosy and Buruli Ulcer Control Programme, Yaoundé, Cameroon
Peters A , The National Tuberculosis, Leprosy and Buruli Ulcer Control Programme, Abuja, Nigeria
Maman I , National Reference Laboratory for Buruli ulcer disease in Togo
Frimpong M , School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Ampadu E , National Buruli Ulcer Control Program, Ghana Health Service, Accra, Ghana
Phillips R , School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Saunderson P , American Leprosy Missions, Greenville, SC, USA
Pullan RL , Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK
Cano J , Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK
Date:
2019-07-01
Journal:
Lancet Global Health
Content:

BACKGROUND: Buruli ulcer can cause disfigurement and long-term loss of function. It is underdiagnosed and under-reported, and its current distribution is unclear. We aimed to synthesise and evaluate data on Buruli ulcer prevalence and distribution.

METHODS: We did a systematic review of Buruli ulcer prevalence and used an evidence consensus framework to describe and evaluate evidence for Buruli ulcer distribution worldwide. We searched PubMed and Web of Science databases from inception to Aug 6, 2018, for records of Buruli ulcer and Mycobacterium ulcerans detection, with no limits on study type, publication date, participant population, or location. English, French, and Spanish language publications were included. We included population-based surveys presenting Buruli ulcer prevalence estimates, or data that allowed prevalence to be estimated, in the systematic review. We extracted geographical data on the occurrence of Buruli ulcer cases and M ulcerans detection from studies of any type for the evidence consensus framework; articles that did not report original data were excluded. For the main analysis, we extracted prevalence estimates from included surveys and calculated 95% CIs using Byar's method. We included occurrence records, reports to WHO and the Global Infectious Diseases and Epidemiology Network, and surveillance data from Buruli ulcer control programmes in the evidence consensus framework to grade the strength of evidence for Buruli ulcer endemicity. This study is registered with PROSPERO, number CRD42018116260.

FINDINGS: 2763 titles met the search criteria. We extracted prevalence estimates from ten studies and occurrence data from 208 studies and five unpublished surveillance datasets. Prevalence estimates within study areas ranged from 3·2 (95% CI 3·1-3·3) cases per 10 000 population in Côte d'Ivoire to 26·9 (23·5-30·7) cases per 10 000 population in Benin. There was evidence of Buruli ulcer in 32 countries and consensus on presence in 12.

INTERPRETATION: The global distribution of Buruli ulcer is uncertain and potentially wider than currently recognised. Our findings represent the strongest available evidence on Buruli ulcer distribution so far and have many potential applications, from directing surveillance activities to informing burden estimates

Identifiers:
Authors:
Frimpong M , Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Ahor HS , Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Wahed AAE , Division of Microbiology and Animal Hygiene, Georg-August University, Goettingen, Germany
Agbavor B , Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Sarpong FN , Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Laing K , Institute for Infection and Immunity, St. George's University of London, London, United Kingdom
Wansbrough-Jones M , Institute for Infection and Immunity, St. George's University of London, London, United Kingdom
Phillips RO , School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Date:
2019-02-01
Journal:
PLoS Neglected Tropical Diseases
Content:

BACKGROUND: Access to an accurate diagnostic test for Buruli ulcer (BU) is a research priority according to the World Health Organization. Nucleic acid amplification of insertion sequence IS2404 by polymerase chain reaction (PCR) is the most sensitive and specific method to detect Mycobacterium ulcerans (M. ulcerans), the causative agent of BU. However, PCR is not always available in endemic communities in Africa due to its cost and technological sophistication. Isothermal DNA amplification systems such as the recombinase polymerase amplification (RPA) have emerged as a molecular diagnostic tool with similar accuracy to PCR but having the advantage of amplifying a template DNA at a constant lower temperature in a shorter time. The aim of this study was to develop RPA for the detection of M. ulcerans and evaluate its use in Buruli ulcer disease.

METHODOLOGY AND PRINCIPAL FINDINGS: A specific fragment of IS2404 of M. ulcerans was amplified within 15 minutes at a constant 42°C using RPA method. The detection limit was 45 copies of IS2404 molecular DNA standard per reaction. The assay was highly specific as all 7 strains of M. ulcerans tested were detected, and no cross reactivity was observed to other mycobacteria or clinically relevant bacteria species. The clinical performance of the M. ulcerans (Mu-RPA) assay was evaluated using DNA extracted from fine needle aspirates or swabs taken from 67 patients in whom BU was suspected and 12 patients with clinically confirmed non-BU lesions. All results were compared to a highly sensitive real-time PCR. The clinical specificity of the Mu-RPA assay was 100% (95% CI, 84-100), whiles the sensitivity was 88% (95% CI, 77-95).

CONCLUSION: The Mu-RPA assay represents an alternative to PCR, especially in areas with limited infrastructure.

Identifiers:
Authors:
Date:
2019-07-01
Journal:
The Lancet Global Health
Content:
Identifiers:
Authors:
Kwarteng, A.
Dissou-Arthur, Y.
Sylverken, A.
Frimpong, M.
Terkper, S.A.
Owusu-Dabo, E.
Date:
2018-01-01
Journal:
Cogent Education
Content:
Authors:
Amoako YA, Frimpong M, Awuah DO, Plange-Rhule G, Boakye-Yiadom E, Agbavor B, Sarpong F, Ahor H, Adu E, Danso KG, Abass MK, Asiedu K, Wansbrough-Jones M, Phillips RO , Amoako YA, Frimpong M, Awuah DO, et al. Providing insight into the incubation period of Mycobacterium ulcerans disease: two case reports. J Med Case Rep. 2019;13(1):218. Published 2019 Jul 18. doi:10.1186/s13256-019-2144-2
Date:
2019-07-18
Journal:
Journal of Medical Case Reports
Content:

Background: Buruli ulcer caused by Mycobacterium ulcerans is endemic in parts of West Africa and is most prevalent among the 5-15 years age group; Buruli ulcer is uncommon among neonates. The mode of transmission and incubation period of Buruli ulcer are unknown. We report two cases of confirmed Buruli ulcer in human immunodeficiency virus-unexposed, vaginally delivered term neonates in Ghana.

Case presentation: Patient 1: Two weeks after hospital delivery, a baby born to natives of the Ashanti ethnic group of Ghana was noticed by her mother to have a papule with associated edema on the right anterior chest wall and neck that later ulcerated. There was no restriction of neck movements. The diagnosis of Buruli ulcer was confirmed on the basis of a swab sample that had a positive polymerase chain reaction result for the IS2404 repeat sequence of M. ulcerans. Patient 2: This patient, from the Ashanti ethnic group in Ghana, had the mother noticing a swelling in the baby's left gluteal region 4 days after birth. The lesion progressively increased in size to involve almost the entire left gluteal region. Around the same time, the mother noticed a second, smaller lesion on the forehead and left side of neck. The diagnosis of Buruli ulcer was confirmed by polymerase chain reaction when the child was aged 4 weeks. Both patients 1 and 2 were treated with oral rifampicin and clarithromycin at recommended doses for 8 weeks in addition to appropriate daily wound dressing, leading to complete healing. Our report details two cases of polymerase chain reaction-confirmed Buruli ulcer in children whose lesions appeared at ages 14 and 4 days, respectively. The mode of transmission of M. ulcerans infection is unknown, so the incubation period is difficult to estimate and is probably dependent on the infective dose and the age of exposure. In our study, lesions appeared 4 days after birth in patient 2. Unless the infection was acquired in utero, this would be the shortest incubation period ever recorded.

Conclusions: Buruli ulcer should be included in the differential diagnosis of neonates who present with characteristic lesions. The incubation period of Buruli ulcer in neonates is probably shorter than is reported for adults.

Identifiers:
Authors:
Dekker D1,2, Krumkamp R3,4, Eibach D3,4, Sarpong N5, Boahen KG5, Frimpong M5, Fechtner E3, Poppert S3, Hagen RM6, Schwarz NG3, Adu-Sarkodie Y7, Owusu-Dabo E5, Im J8, Marks F8,9, Frickmann H6,10, May J3,4 , 1 Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine (BNITM), Bernhard-Nocht-Str. 74, D-20359, Hamburg, Germany. dekker@bnitm.de. 2 German Center for Infection Research (DZIF), Hamburg-Borstel, Lübeck, Germany. dekker@bnitm.de. 3 Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine (BNITM), Bernhard-Nocht-Str. 74, D-20359, Hamburg, Germany. 4 German Center for Infection Research (DZIF), Hamburg-Borstel, Lübeck, Germany. 5 Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana. 6 Bundeswehr Hospital of Hamburg, Germany, Department of Tropical Medicine at the Bernhard Nocht Institute, Bernhard-Nocht-Str. 74, D-20359, Hamburg, Germany. 7 Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana. 8 Epidemiology Unit, International Vaccine Institute (IVI), Seoul, Republic of Korea. 9 The Department of Medicine, The University of Cambridge, Cambridge, UK. 10 Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, Schillingallee 70, 18055, Rostock, Germany.
Date:
2018-01-19
Journal:
BMC Infect Dis
Content:

BACKGROUND: Non-typhoidal Salmonella (NTS) cause the majority of bloodstream infections in Ghana, however the mode of transmission and source of invasive NTS in Africa are poorly understood. This study compares NTS from water sources and invasive bloodstream infections in rural Ghana.

METHODS: Blood from hospitalised, febrile children and samples from drinking water sources were analysed for Salmonella spp. Strains were serotyped to trace possible epidemiological links between human and water-derived isolates.. Antibiotic susceptibility testing was performed, RESULTS: In 2720 blood culture samples, 165 (6%) NTS were isolated. S. Typhimurium (70%) was the most common serovar followed by S. Enteritidis (8%) and S. Dublin (8%). Multidrug resistance (MDR) was found in 95 (58%) NTS isolates, including five S. Enteritidis. One S. Typhimurium showed reduced fluroquinolone susceptibility. In 511 water samples, 19 (4%) tested positive for S. enterica with two isolates being resistant to ampicillin and one isolate being resistant to cotrimoxazole. Serovars from water samples were not encountered in any of the clinical specimens.

CONCLUSION: Water analyses demonstrated that common drinking water sources were contaminated with S. enterica posing a potential risk for transmission. However, a link between S. enterica from water sources and patients could not be established, questioning the ability of water-derived serovars to cause invasive bloodstream infections

Identifiers:
Authors:
Kwarteng, A.
Frimpong, M.
Sylverken, A.A.
Arthur, Y.D.
Ahuno, S.T.
Owusu-Dabo, E.
Date:
2017-01-01
Journal:
Cogent Education
Content:
Authors:
Michael Frimpong , author
Shirley Victoria Simpson , author
Hubert Senanu Ahor , author
Abigail Agbanyo , author
Solomon Gyabaah , author
Bernadette Agbavor , author
Ivy Brago Amanor , author
Kennedy Kwasi Addo , author
Susanne Böhlken-Fascher , author
Jonas Kissenkötter , author
Ahmed Abd El Wahed , author
Richard Odame Phillips , author
Date:
2020-10-06
Journal:
Tropical Medicine and Infectious Disease
Content:
Identifiers:
Authors:
Date:
2014-10-01
Journal:
Antimicrobial Agents and Chemotherapy
Content:
Identifiers:
Authors:
Augustina Angelina Sylverken , author
Philip El-Duah , author
Michael Owusu , author
Julia Schneider , author
Richmond Yeboah , author
Ayisi-Boateng Ayisi-Boateng , author
Richmond Gorman , author
Eric Adu , author
Alexander Kwarteng , author
Michael Frimpong , author
Sherihane Aryeetey , author
Jesse Addo Asamoah , author
Yaw Ampem Amoako , author
John Humphrey Amuasi , author
Jörn Beheim-Schwarzbach , author
Ellis Owusu-Dabo , author
Yaw Adu-Sarkodie , author
Kwasi Obiri-Danso , author
Victor Max Corman , author
Christian Drosten , author
Richard Phillips , author
Date:
2020-09-15
Journal:
Content:
Authors:
Hope Simpson , author
Gerd Pluschke , editor
Earnest Njih Tabah , author
Richard O. Phillips , author
Michael Frimpong , author
Issaka Maman , author
Edwin Ampadu , author
Joseph Timothy , author
Paul Saunderson , author
Rachel L. Pullan , author
Jorge Cano , author
Date:
2021-03-03
Journal:
PLOS Neglected Tropical Diseases
Content:
Identifiers:
Authors:
Sarpong-Duah M, Frimpong M, Beissner M, Saar M, Laing K, Sarpong F, Loglo AD, Abass KM, Frempong M, Sarfo FS, Bretzel G, Wansbrough-Jones M, Phillips RO , Sarpong-Duah M, Frimpong M, Beissner M, et al. Clearance of viable Mycobacterium ulcerans from Buruli ulcer lesions during antibiotic treatment as determined by combined 16S rRNA reverse transcriptase /IS 2404 qPCR assay. PLoS Negl Trop Dis. 2017;11(7):e0005695. Published 2017 Jul 3. doi:10.1371/journal.pntd.0005695
Date:
2017-07-03
Journal:
PLoS Neglected Tropical Diseases
Content:

Introduction: Buruli ulcer (BU) caused by Mycobacterium ulcerans is effectively treated with rifampicin and streptomycin for 8 weeks but some lesions take several months to heal. We have shown previously that some slowly healing lesions contain mycolactone suggesting continuing infection after antibiotic therapy. Now we have determined how rapidly combined M. ulcerans 16S rRNA reverse transcriptase / IS2404 qPCR assay (16S rRNA) became negative during antibiotic treatment and investigated its influence on healing.

Methods: Fine needle aspirates and swab samples were obtained for culture, acid fast bacilli (AFB) and detection of M. ulcerans 16S rRNA and IS2404 by qPCR (16S rRNA) from patients with IS2404 PCR confirmed BU at baseline, during antibiotic and after treatment. Patients were followed up at 2 weekly intervals to determine the rate of healing. The Kaplan-Meier survival analysis was used to analyse the time to clearance of M. ulcerans 16S rRNA and the influence of persistent M ulcerans 16S rRNA on time to healing. The Mann Whitney test was used to compare the bacillary load at baseline in patients with or without viable organisms at week 4, and to analyse rate of healing at week 4 in relation to detection of viable organisms.

Results: Out of 129 patients, 16S rRNA was detected in 65% of lesions at baseline. The M. ulcerans 16S rRNA remained positive in 78% of patients with unhealed lesions at 4 weeks, 52% at 8 weeks, 23% at 12 weeks and 10% at week 16. The median time to clearance of M. ulcerans 16S rRNA was 12 weeks. BU lesions with positive 16S rRNA after antibiotic treatment had significantly higher bacterial load at baseline, longer healing time and lower healing rate at week 4 compared with those in which 16S rRNA was not detected at baseline or had become undetectable by week 4.

Conclusions: Current antibiotic therapy for BU is highly successful in most patients but it may be possible to abbreviate treatment to 4 weeks in patients with a low initial bacterial load. On the other hand persistent infection contributes to slow healing in patients with a high bacterial load at baseline, some of whom may need antibiotic treatment extended beyond 8 weeks. Bacterial load was estimated from a single sample taken at baseline. A better estimate could be made by taking multiple samples or biopsies but this was not ethically acceptable.

Identifiers:
Authors:
Date:
2014-06-19
Journal:
PLOS Neglected Tropical Diseases
Content:
Identifiers:
Authors:
Frimpong M, Agbavor B, Duah MS, Loglo A, Sarpong FN, Boakye-Appiah J, Abass KM, Dongyele M, Amofa G, Tuah W, Frempong M, Amoako YA, Wansbrough-Jones M, Phillips RO , Frimpong M, Agbavor B, Duah MS, et al. Paradoxical reactions in Buruli ulcer after initiation of antibiotic therapy: Relationship to bacterial load. PLoS Negl Trop Dis. 2019;13(8):e0007689. Published 2019 Aug 26. doi:10.1371/journal.pntd.0007689
Date:
2019-08-26
Journal:
PLoS Neglected Tropical Diseases
Content:

Background: We investigated the relationship between bacterial load in Buruli ulcer (BU) lesions and the development of paradoxical reaction following initiation of antibiotic treatment.

Methods: This was a longitudinal study involving BU patients from June 2013 to June 2017. Fine needle aspirates (FNA) and swab samples were obtained to establish the diagnosis of BU by PCR. Additional samples were obtained at baseline, during and after treatment (if the lesion had not healed) for microscopy, culture and combined 16S rRNA reverse transcriptase/ IS2404 qPCR assay. Patients were followed up at regular intervals until complete healing.

Results: Forty-seven of 354 patients (13%) with PCR confirmed BU had a PR, occurring between 2 and 42 (median 6) weeks after treatment initiation. The bacterial load, the proportion of patients with positive M. ulcerans culture (15/34 (44%) vs 29/119 (24%), p = 0.025) and the proportion with positive microscopy results (19/31 (61%) vs 28/90 (31%), p = 0.003) before initiation of treatment were significantly higher in the PR compared to the no PR group. Plaques (OR 5.12; 95% CI 2.26-11.61; p<0.001), oedematous (OR 4.23; 95% CI 1.43-12.5; p = 0.009) and category II lesions (OR 2.26; 95% CI 1.14-4.48; p = 0.02) were strongly associated with the occurrence of PR. The median time to complete healing (28 vs 13 weeks, p <0.001) was significantly longer in the PR group.

Conclusions: Buruli ulcer patients who develop PR are characterized by high bacterial load in lesion samples taken at baseline and a higher rate of positive M. ulcerans culture. Occurrence of a PR was associated with delayed healing.

Identifiers:
Authors:
Aloysius D. Loglo , author
Michael Frimpong , author
Mabel Sarpong Duah , author
Fred Sarfo , author
Francisca N. Sarpong , author
Bernadette Agbavor , author
Justice K. Boakye-Appiah , author
Kabiru M. Abass , author
Mathias Dongyele , author
Margaret Frempong , author
Sacha Pidot , author
Mark Wansbrough-Jones , author
Timothy P. Stinear , author
Virginie Roupie , author
Kris Huygen , author
Richard O. Phillips , author
Date:
2018-07-31
Journal:
PeerJ
Content:
Identifiers:
Authors:
Date:
2015-03-27
Journal:
International Journal of Environmental Research and Public Health
Content:
Identifiers:
Authors:
Niang, F.
Sarfo, F.S.
Frimpong, M.
Guenin-Macé, L.
Wansbrough-Jones, M.
Stinear, T.
Phillips, R.O.
Demangel, C.
Date:
2015-01-01
Journal:
Scientific Reports
Content:
Identifiers:
Authors:
Amoako, Y.A.
Frimpong, M.
Awuah, D.O.
Plange-Rhule, G.
Boakye-Yiadom, E.
Agbavor, B.
Sarpong, F.
Ahor, H.
Adu, E.
Danso, K.G.
Abass, M.K.
Asiedu, K.
Wansbrough-Jones, M.
Phillips, R.O.
Date:
2019-01-01
Journal:
Journal of Medical Case Reports
Content:
Authors:
Wadagni AC, Steinhorst J, Barogui YT, Catraye PM, Gnimavo R, Abass KM, Amofa G, Frimpong M, Sarpong FN, van der Werf TS, Phillips R, Sopoh GE, Johnson CR, Stienstra Y , Wadagni AC, Steinhorst J, Barogui YT, et al. Buruli ulcer treatment: Rate of surgical intervention differs highly between treatment centers in West Africa. PLoS Negl Trop Dis. 2019;13(10):e0007866. Published 2019 Oct 28. doi:10.1371/journal.pntd.0007866
Date:
2019-10-28
Journal:
PLoS Neglected Tropical Diseases
Content:

Background: Antibiotic treatment proved itself as the mainstay of treatment for Buruli ulcer disease. This neglected tropical disease is caused by Mycobacterium ulcerans. Surgery persists as an adjunct therapy intended to reduce the mycobacterial load. In an earlier clinical trial, patients benefited from delaying the decision to operate. Nevertheless, the rate of surgical interventions differs highly per clinic.Methods: A retrospective study was conducted in six different Buruli ulcer (BU) treatment centers in Benin and Ghana. BU patients clinically diagnosed between January 2012 and December 2016 were included and surgical interventions during the follow-up period, at least one year after diagnosis, were recorded. Logistic regression analysis was carried out to estimate the effect of the treatment center on the decision to perform surgery, while controlling for interaction and confounders.Results: A total of 1193 patients, 612 from Benin and 581 from Ghana, were included. In Benin, lesions were most frequently (42%) categorized as the most severe lesions (WHO criteria, category III), whereas in Ghana lesions were most frequently (44%) categorized as small lesions (WHO criteria, category I). In total 344 (29%) patients received surgical intervention. The percentage of patients receiving surgical intervention varied between hospitals from 1.5% to 72%. Patients treated in one of the centers in Benin were much more likely to have surgery compared to the clinic in Ghana with the lowest rate of surgical intervention (RR = 46.7 CI 95% [17.5-124.8]). Even after adjusting for confounders (severity of disease, age, sex, limitation of movement at joint at time of diagnosis, ulcer and critical sites), rates of surgical interventions varied highly. Conclusion: The decision to perform surgery to reduce the mycobacterial load in BU varies highly per clinic. Evidence based guidelines are needed to guide the role of surgery in the treatment of BU.

Identifiers:
Authors:
Loglo AD , Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Frimpong M , Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Sarpong Duah M , Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Sarfo F , School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Sarpong FN , Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Agbavor B , Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Boakye-Appiah JK , Institute of Infection and Immunity, St George's University of London, London, UK
Abass KM , Agogo Presbyterian Hospital, Agogo, Ghana
Dongyele M , Tepa Government Hospital, Tepa, Ghana
Frempong M , School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Pidot S , Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia
Wansbrough-Jones M , Institute of Infection and Immunity, St George's University of London, London, UK
Stinear TP , Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia
Roupie V , Service Immunology, Scientific Institute of Public Health, Brussels, Belgium
Huygen K , Service Immunology, Scientific Institute of Public Health, Brussels, Belgium
Phillips RO , Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Date:
2018-07-31
Journal:
PeerJ
Content:

Background: Buruli ulcer is a disease of the skin and soft tissues caused by infection with a slow growing pathogen, Mycobacterium ulcerans. A vaccine for this disease is not available but M. ulcerans possesses a giant plasmid pMUM001 that harbours the polyketide synthase (PKS) genes encoding a multi-enzyme complex needed for the production of its unique lipid toxin called mycolactone, which is central to the pathogenesis of Buruli ulcer. We have studied the immunogenicity of enzymatic domains in humans with M. ulcerans disease, their contacts, as well as non-endemic areas controls.

Methods: Between March 2013 and August 2015, heparinized whole blood was obtained from patients confirmed with Buruli ulcer. The blood samples were diluted 1 in 10 in Roswell Park Memorial Institute (RPMI) medium and incubated for 5 days with recombinant mycolactone PKS domains and mycolyltransferase antigen 85A (Ag85A). Blood samples were obtained before and at completion of antibiotic treatment for 8 weeks and again 8 weeks after completion of treatment. Supernatants were assayed for interferon-γ (IFN-γ) and interleukin-5 (IL-5) by enzyme-linked immunosorbent assay. Responses were compared with those of contacts and non-endemic controls.

Results: More than 80% of patients and contacts from endemic areas produced IFN-γ in response to all the antigens except acyl carrier protein type 3 (ACP3) to which only 47% of active Buruli ulcer cases and 71% of contacts responded. The highest proportion of responders in cases and contacts was to load module ketosynthase domain (Ksalt) (100%) and enoylreductase (100%). Lower IL-5 responses were induced in a smaller proportion of patients ranging from 54% after ketoreductase type B stimulation to only 21% with ketosynthase type C (KS C). Among endemic area contacts, the, highest proportion was 73% responding to KS C and the lowest was 40% responding to acyltransferase with acetate specificity type 2. Contacts of Buruli ulcer patients produced significantly higher IFN-γ and IL-5 responses compared with those of patients to PKS domain antigens and to mycolyltransferase Ag85A of M. ulcerans. There was low or no response to all the antigens in non-endemic areas controls. IFN-γ and IL-5 responses of patients improved after treatment when compared to baseline results.

Discussion: The major response to PKS antigen stimulation was IFN-γ and the strongest responses were observed in healthy contacts of patients living in areas endemic for Buruli ulcer. Patients elicited lower responses than healthy contacts, possibly due to the immunosuppressive effect of mycolactone, but the responses were enhanced after antibiotic treatment. A vaccine made up of the most immunogenic PKS domains combined with the mycolyltransferase Ag85A warrants further investigation.

Identifiers:

Projects

Fellow:
Michael Frimpong
Collaborators:
Name Country Institution
Prof. Richard Phillips Ghana Kumasi Centre for Collaborative Research
Dr. Michael Frimpong Ghana Kumasi Centre for Collaborative Research
Objectives:
Provide diagnostic support to the district to confirm cases of skin NTDs (Buruli ulcer, Yaws and Leprosy).
Sites:
Ashanti Akim North District
Sekyere Afram Plains
Nkoransa South District
Upper Denkyira East District
Upper Denkyira West District
Wassa Amenfi East
Wa Municipal
Study Design:
Cross sectional study
Subjects:
All suspected cases of skin NTDs
Start Date:
2018-06-01
End Date:
2020-05-31

Send a Message