EDCTP Alumni Network

Fostering excellence and collaboration in the next generation of researchers

Call Senior Fellowship (SF)
Programme EDCTP2
Start Date 2018-04-01
End Date 2023-03-31
Project Code TMA2016SF1509
Status Active

Title

Evaluation of a nitric oxide generating dressing (EDX) to improve management of Buruli ulcer disease

Objectives

PRIMARY OBJECTIVES • A comparison of rate of healing of ulcers between EDX110 with oral rifampicin and clarithromycin (“EDX-RC”) and Vaseline gauze dressings with oral rifampicin and clarithromycin (“VG-RC”). SECONDARY OBJECTIVES • To compare the tolerability of the two dressings • To evaluate the relationship between treatment, the immune profile and healing in each treatment arm • To compare the rate of bacterial killing of M. ulcerans in each treatment arm EXPLORATORY OBJECTIVES • To evaluate the quality and cosmetic appearance of healing • To document healing in lesions that have not ulcerated within 2 weeks of start of treatment. • To document recurrence rate and paradoxical reactions in the two treatment arms.

Host Organisation

Institution Country
Kwame Nkrumah University of Science and Technology (KNUST) Ghana

Participants

Name Institution Country
220 Kumasi Center for Collaborative Research into Tropical Medicine Ghana

Study Design

A prospective randomised open-blinded end-point (PROBE) study of EDX dressing, compared to current standard of care. The design will comply with site-specific protocols for routine best practice ulcer care using vaseline gauze dressings. The comparator will consist of EDX110 applied to the wound, combined with standard antibiotic treatment. In both groups, dressing treatment will continue until the wound has healed plus up to 7 days. The duration of antibiotic treatment will be 8 weeks.

Sites

Agogo Presbyterian Hospital (APH) in the Asante- Akim district
Tepa government hospital, in the Ahafo Ano North district
Dunkwa government hospital in the Upper Denkyira district in the central region.

Phd Study

Title University Start Date End Date
Immunopathogenesis of M. ulcerans University of London 2002-03-01 2005-06-01

Students Supervised

Type Name Title University Start Date End Date
PhD Jonathan Kofi Adjei Mphil Kwame Nkrumah University of Science and Technology 2019 2023
PhD Bernadette Agbavor Mphil Kwame Nkrumah University of Science and Technology 2019 2023
PhD Nancy Ackam Mphil Kwame Nkrumah University of Science and Technology 2019 2023
PhD Isaac Acheampong Mphil Kwame Nkrumah University of Science and Technology 2021 2025
Mphil Wilfred Aniagyei Bsc Kwame Nkrumah University of Science and Technology 2019 2021
Mphil Venus N. B. Frimpong Bsc Kwame Nkrumah University of Science and Technology 2019 2021
Mphil Difery Minadzi Bsc Kwame Nkrumah University of Science and Technology 2019 2021
Mphil Monika M. Vivekanandan Bsc Kwame Nkrumah University of Science and Technology 2019 2021
Mphil Rejoice A. Arthur Bsc Kwame Nkrumah University of Science and Technology 2019 2021

Results & Outcomes

In this thesis, I have studied the immune response in peripheral blood and at the site of disease of Ghanaian patients with Buruli ulcer caused by M. ulcerans infection. A modified polymerase chain reaction for M. ulcerans in punch biopsies was optimized and evaluated alongside Ziehl Neelsen staining for acid fast bacilli, culture and histology for selection of patients with Buruli ulcer. PCR was 98% sensitive whereas microscopy, culture and histology were 42%, 49% and 82% sensitive respectively. Studies of cytokine production in whole blood after stimulation with M. ulcerans and M. tuberculosis antigens showed that the IL-10 response started early and declined after healing whereas the IFN-g response developed later and was maintained after healing. There was cross reactivity between M. ulcerans and M. tuberculosis antigens but M. ulcerans sonicate was more specific. Studies of the local immune response using real time PCR to measure cytokine mRNA showed that Th1 and Th2 cytokines were expressed concurrently and there was no significant difference between ulcers and nodules but the median IFN-g mRNA expression for ulcers was higher than that in nodules reflecting what was found in the systemic response. Interleukin-8, associated with an acute neutrophilic response, was co-expressed with IL-1b, TNF-a, IL-12p35 and IL-12p40 whereas IFN-g, TNF-a, IL-12p35, IL-12p40, IL-1a, IL-8 and IL-15 expression was found in lesions containing granulomas.

Current Organisation

Kwame Nkrumah University of Science and Technology

Current Job Title

Scientific Director (KCCR), Associate Professor of Medicine

Awards

2019 National Institute of Health Research (NIHR) UK Award: Improving experiences of severe stigmatizing skin diseases in Ghana and Ethiopia

Students Supervised

Type Name Title University Start Date End Date
PhD Michael Frimpong Dr KNUST 2012 2015

Memberships

Role Committee/board Start Date End Date
Manuscript Reviewer PLOS Neglected Tropical Disease 2009

Education

Institution Degree Year
KNUST, Ghana BSc Human Biology 1990-05-01

Areas Of Specialisation

Neglected Infectious Diseases (NID)

Grants

Grant Code:
C0857
Source of funding:
AREF
Amount:
19999.39
Role:
Principal Investigator
Start Date:
2021-01-01
End Date:
2021-01-01
Grant Code:
2019_A150
Source of funding:
Else Kroner Fresenius Stiftung
Amount:
347235.00
Role:
Researcher
Start Date:
2020-01-01
End Date:
2023-01-01
Grant Code:
CSA2019ERC- 2671
Source of funding:
European and Developing Countries Clinical Trials Partnership (EDCTP)
Amount:
281038.75
Role:
Principal Investigator
Start Date:
2020-01-01
End Date:
2023-01-01
Grant Code:
RIA2016E-1609
Source of funding:
European and Developing Countries Clinical Trials Partnership (EDCTP)
Amount:
9997501
Role:
Principal Investigator
Start Date:
2018-01-01
End Date:
2022-01-01
Grant Code:
3486/17
Source of funding:
ANESVAD
Amount:
430092
Role:
Principal Investigator
Start Date:
2018-01-01
End Date:
2020-01-01
Grant Code:
Source of funding:
National Institute for Health Research
Amount:
4999182
Role:
Principal Investigator
Start Date:
2019-01-01
End Date:
2023-01-01
Grant Code:
GA:JA1479/9-1
Source of funding:
German Research Foundation
Amount:
769610
Role:
Principal Investigator
Start Date:
2019-01-01
End Date:
2022-01-01

Publications

Authors:
Frimpong, Michael; Simpson, Shirley Victoria; Ahor, Hubert Senanu; Agbanyo, Abigail; Gyabaah, Solomon; Agbavor, Bernadette; Amanor, Ivy Brago; Addo, Kennedy Kwasi; Böhlken-Fascher, Susanne; Kissenkötter, Jonas;
Date:
2020-10-06
Journal:
Tropical medicine and infectious disease
Content:

Yaws is a skin debilitating disease caused by Treponema pallidum subspecies pertenue with most cases reported in children. World Health Organization (WHO) aims at total eradication of this disease through mass treatment of suspected cases followed by an intensive follow-up program. However, effective diagnosis is pivotal in the successful implementation of this control program. Recombinase polymerase amplification (RPA), an isothermal nucleic acid amplification technique offers a wider range of differentiation of pathogens including those isolated from chronic skin ulcers with similar characteristics such as Haemophilus ducreyi (H. ducreyi). We have developed a RPA assay for the simultaneous detection of Treponema pallidum (T. pallidum) and H. ducreyi (TPHD-RPA). The assay demonstrated no cross-reaction with other pathogens and enable detection of T. pallidum and H. ducreyi within 15 min at 42 ◦C. The RPA assay was validated with 49 clinical samples from individuals confirmed to have yaws by serological tests. Comparing the developed assay with commercial multiplex real-time PCR, the assay demonstrated 94% and 95% sensitivity for T. pallidum and H. ducreyi, respectively and 100% specificity. This simple novel TPHD-RPA assay enables the rapid detection of both T. pallidum and H. ducreyi in yaws-like lesions. This test could support the yaws eradication efforts by ensuring reliable diagnosis, to enable monitoring of program success and planning of follow-up interventions at the community level.

Identifiers:
Authors:
Frimpong, Michael; Kyei-Tuffuor, Louis; Fondjo, Linda Ahenkorah; Ahor, Hubert Senanu; Adjei-Kusi, Priscilla; Maiga-Ascofare, Oumou; Phillips, Richard Odame;
Date:
2021-01-23
Journal:
Acta Tropica
Content:

Accurate diagnosis of urogenital schistosomiasis is vital for surveillance/control programs as well as achieving the WHO 2012–2020 road map for the total eradication of schistosomiasis. Recombinase polymerase amplification (RPA) has emerged as a rapid and simple molecular tool adaptable for fewer resources with diagnostic accuracy similar to polymerase chain reaction (PCR). This rapid molecular assay employs the use of enzymes for the amplification of nucleic acid taget at a constant temperature. The aim of this study was to validate a real-time RPA assay targeting the Dra 1 repittitive sequence of Schistosoma (S.) haematobium and evaluate its use in urogenital schistosomiasis diagnosis. S. haematobium Dra 1 molecular DNA standard was applied to determine the assay's analytical sensitivity. DNA extracts of S. haematobium, other Schistosoma species, protozoa and bacteria species were used to determine the specificity of the RPA assay. Clinical performance of the assay was validated with a panel of 135 urine samples from volunteers of schistosomiasis endemic communities. The developed assay was evaluated with urine samples extracted by just boiling and with SpeedXtract® DNA extraction kit. A specific fragment of S. haematobium Dra 1 repetitive sequence was amplified within 15 minutes at a constant 42˚C using the developed S. haematobium RPA assay. The detection limit was 15 copies of Dra1 molecular DNA standard per reaction. There was no cross-reaction with other protozoan and bacterial species except Schistosoma species, S. mansoni and S. japonicum. Using 135 urine samples, Schistosoma RPA assay had a clinical sensitivity and specificity of 98.4% (95% CI, 91.6-100) and 100% (95% CI, 94.9-99) respectively when compared to S. haematobium Dra 1 qPCR assay. The diagnostic performance of S. haematobium real-time RPA assay was not affected by the use of crude DNA extracted samples. The S. haematobium RPA assay can serve as an alternative to PCR, especially in low resource settings.

Identifiers:
Authors:
Alferink, Marike; de Zeeuw, Janine; Sopoh, Ghislain; Agossadou, Chantal; Abass, Karibu M; Phillips, Richard O; Loth, Susanne; Jutten, Emma; Barogui, Yves T; Stewart, Roy E;
Date:
2015-01-06
Journal:
PloS one
Content:
Identifiers:
Authors:
Di Cristanziano, Veronica; D´ Alfonso, Rossella; Berrilli, Federica; Sarfo, Fred Stephen; Santoro, Maristella; Fabeni, Lavinia; Knops, Elena; Heger, Eva; Kaiser, Rolf; Dompreh, Albert;
Date:
2019-09-14
Journal:
Plos one
Content:

Background: Sub-Saharan Africa is endemic for intestinal parasites and distinguished for the largest burden of HIV cases. Blastocystis sp. is one of the most common protists infecting humans but its role in human disease is still controversial. Aim of this study was to investigate the prevalence of Blastocystis sp. in HIV positive and negative adults in Ghana and its association with immune status and other risk factors.

Methods: 122 HIV positive outpatients and 70 HIV negative blood donors from the Komfo Anokye Teaching Hospital in Kumasi, Ghana, were included in the present study. Demographic, clinical and laboratory data were collected and HIV positive patients distinguished for CD4+ T cell count <200 cells/μl (n = 54) and >200 cells/μl (n = 68). A Blastocystis's phylogenetic analysis was performed to determine sample subtype (ST).

Results: The prevalence of Blastocystis sp. in adult HIV positive individuals was lower than in HIV negative persons (6.6% vs. 20.0%, p = 0.008) and Blastocystis sp. ST1 was the most prevalent strain. Within HIV positive participants, the prevalence of Blastocystis sp. was lower in those individuals with CD4+ T cell count <200 cells/μl than in patients with higher CD4+ T cell count (1.9% vs. 10.3%, p = 0.076). Multiple regression analysis revealed that Blastocystis sp. was inversely associated with an obese Body Mass Index (BMI) in HIV negative persons (p = 0.040). Presence of Blastocystis sp. was correlated with higher CD4+ T cell count in HIV positive participants (p = 0.049).

Conclusion: It is largely reported that people living with HIV (PLHIV) in Africa are affected from parasite infections and that co-infections may adversely impact on their immune status, accelerating progress to AIDS and worsening gastrointestinal manifestations. Differently, in this study Blastocystis sp. was associated with a better immune status jointly with a healthy body weight while it seems to be reduced with the progression of HIV infection. This data agree with recent suggestions that Blastocystis sp. can represent a component of the healthy gut microbiota.

Identifiers:
Authors:
Debrah, Linda Batsa; Nausch, Norman; Opoku, Vera Serwaa; Owusu, Wellington; Mubarik, Yusif; Berko, Daniel Antwi; Wanji, Samuel; Layland, Laura E; Hoerauf, Achim; Jacobsen, Marc;
Date:
2017-01-07
Journal:
Parasites & vectors
Content:
Identifiers:
Authors:
Eberhardt, Kirsten Alexandra; Sarfo, Fred Stephen; Dompreh, Albert; Kuffour, Edmund Osei; Geldmacher, Christof; Soltau, Mareike; Schachscheider, Marei; Drexler, Jan Felix; Eis-Hübinger, Anna Maria; Häussinger, Dieter;
Date:
2015-03-06
Journal:
Clinical Infectious Diseases
Content:
Identifiers:
Authors:
Amoako, Yaw Ampem; Phillips, Richard Odame; Arthur, Joshua; Abugri, Mark Ayaaba; Akowuah, Emmanuel; Amoako, Kwabena Oppong; Marfo, Benjamin Aboagye; Frimpong, Michael; van der Werf, Tjip; Ravensbergen, Sofanne Jacobine;
Date:
2020-10-22
Journal:
PLOS Neglected Tropical Diseases
Content:

Background

There is a dearth of data on scabies from Ghana. In September 2019, local health authorities in the East Mamprusi district of northern Ghana received reports of scabies from many parts of the district. Due to on-going reports of more cases, an assessment team visited the communities to assess the effect of the earlier individual treatment on the outbreak. The assessment team furthermore aimed to contribute to the data on scabies burden in Ghana and to demonstrate the use of the International Alliance for the Control of Scabies (IACS) diagnostic tool in a field survey in a resource limited setting.

Methodology/Principal findings

This was a cross sectional study. Demographic information and medical history was collected on all participants using a REDCap questionnaire. A standardised skin examination of exposed regions of the body was performed on all participants. Scabies was diagnosed based on the criteria of the International Alliance for the Control of Scabies (IACS). Participants were mostly female (61.5%) and had a median age of 18.8 years (IQR 13–25). Two hundred out of 283 (71%) of participants had scabies with most (47%) presenting with moderate disease. Impetigo was found in 22% of participants with scabies and 10.8% of those without scabies [RR 2.27 (95% CI 1.21–4.27)]. 119 participants who received scabies treatment in the past months still had clinical evidence of the disease. 97% of participants reported a recent scabies contact. Scabies was commoner in participants ≤16 years compared to those >16 years [RR 3.06 (95% CI 1.73–5.45)].

Conclusion/Significance

The prevalence of scabies was extremely high. The lack of a systematic approach to scabies treatment led to recurrence and ongoing community spread. The IACS criteria was useful in this outbreak assessment in Ghana. Alternative strategies such as Mass drug administration may be required to contain outbreaks early in such settings.

Identifiers:
Authors:
Powell, Richard C; Klinke, Ian; Jazeel, Tariq; Daley, Patricia; Kamata, Ng'wanza; Heffernan, H; Swain, Adam; McConnell, Fiona; Barry, Andrew; Phillips, Richard;
Date:
2016-05-07
Journal:
Political Geography
Content:
Identifiers:
Authors:
Velink, Anita; Woolley, Rebecca J; Phillips, Richard O; Abass, Kabiru M; van der Werf, Tjip S; Agumah, Emmanuel; de Zeeuw, Janine; Klis, Sandor; Stienstra, Ymkje;
Date:
2016-10-12
Journal:
PLoS neglected tropical diseases
Content:
Identifiers:
Authors:
Frimpong, Michael
Date:
2020-12-01
Journal:
Archives of virology
Content:

Following the detection of the first imported case of COVID-19 in the northern sector of Ghana, we molecularly charac-terized and phylogenetically analysed sequences, including three complete genome sequences, of severe acute respiratory syndrome coronavirus 2 obtained from nine patients in Ghana. We performed high-throughput sequencing on nine samples that were found to have a high concentration of viral RNA. We also assessed the potential impact that long-distance transport of samples to testing centres may have on sequencing results. Here, two samples that were similar in terms of viral RNA concentration but were transported from sites that are over 400 km apart were analyzed. All sequences were compared to previous sequences from Ghana and representative sequences from regions where our patients had previously travelled. Three complete genome sequences and another nearly complete genome sequence with 95.6% coverage were obtained. Sequences with coverage in excess of 80% were found to belong to three lineages, namely A, B.1 and B.2. Our sequences clustered in two different clades, with the majority falling within a clade composed of sequences from sub-Saharan Africa. Less RNA fragmentation was seen in sample KATH23, which was collected 9 km from the testing site, than in sample TTH6, which was collected and transported over a distance of 400 km to the testing site. The clustering of several sequences from sub-Saharan Africa suggests regional circulation of the viruses in the subregion. Importantly, there may be a need to decentralize testing sites and build more capacity across Africa to boost the sequencing output of the subregion.

Identifiers:
Authors:
Loglo, Aloysius D; Frimpong, Michael; Duah, Mabel Sarpong; Sarfo, Fred; Sarpong, Francisca N; Agbavor, Bernadette; Boakye-Appiah, Justice K; Abass, Kabiru M; Dongyele, Mathias; Frempong, Margaret;
Date:
2018-07-31
Journal:
PeerJ
Content:
Identifiers:
Authors:
Frimpong, Michael; Amoako, Yaw A; Anim, Kwadwo B; Ahor, Hubert S; Yeboah, Richmond; Arthur, Joshua; Dakorah, Justin S; Gborgblovor, Delphine; Akrofi, Samuel; Sekyi-Djan, Phyllis;
Date:
2020-12-31
Journal:
Ghana Medical Journal
Content:

Across the globe, the outbreak of the COVID-19 pandemic is causing distress with governments doing everything in their power to contain the spread of the novel coronavirus (SARS-CoV-2) to prevent morbidity and mortality. Actions are being implemented to keep health care systems from being overstretched and to curb the outbreak. Any policy responses aimed at slowing down the spread of the virus and mitigating its immediate effects on health care systems require a firm basis of information about the absolute number of currently infected people, growth rates, and locations/hotspots of infections. The only way to obtain this base of information is by conducting numerous tests in a targeted way. Currently, in Ghana, there is a centralized testing approach, that takes 4-5 days for samples to be shipped and tested at central reference laboratories with results communicated to the district, regional and national
stakeholders. This delay in diagnosis increases the risk of ongoing transmission in communities and vulnerable institutions. We have validated, evaluated and deployed an innovative diagnostic tool on a mobile laboratory platform to accelerate the COVID-19 testing. A preliminary result of 74 samples from COVID-19 suspected cases has a positivity rate of 12% with a turn-around time of fewer than 3 hours from sample taking to reporting of results, significantly reducing the waiting time from days to hours, enabling expedient response by the health system for contact tracing to reduce transmission and additionally improving case management.

Identifiers:
Authors:
Barogui, Yves Thierry; Klis, Sandor-Adrian; Johnson, Roch Christian; Phillips, Richard O; van der Veer, Eveline; van Diemen, Cleo; van der Werf, Tjip S; Stienstra, Ymkje;
Date:
2016-10-04
Journal:
PLoS neglected tropical diseases
Content:
Identifiers:
Authors:
Frimpong, Michael; Ahor, Hubert Senanu; Sakyi, Samuel Asamoah; Agbavor, Bernadette; Akowuah, Emmanuel; Phillips, Richard Odame;
Date:
2019-11-26
Journal:
Diagnostics
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:
Layden, Jennifer E; Phillips, Richard O; Owusu-Ofori, Shirley; Sarfo, Fred Stephen; Kliethermes, Stephanie; Mora, Nallely; Owusu, Dorcas; Nelson, Kenrad; Opare-Sem, Ohene; Dugas, Lara;
Date:
2016-01-06
Journal:
Clinical infectious diseases
Content:
Identifiers:
Authors:
Rolling, T; Heinemann, M; Phillips, RO; Vinnemeier, CD; Rolling, C; Tannich, E;
Date:
2020-10-12
Journal:
Malaria Journal
Content:

Background: Ghana is among the high-burden countries for malaria infections and recently reported a notable increase in malaria cases. While asymptomatic parasitaemia is increasingly recognized as a hurdle for malaria elimination, studies on asymptomatic malaria are scarce, and usually focus on children and on non-falciparum species. The present study aims to assess the prevalence of asymptomatic Plasmodium falciparum and non-falciparum infections in Ghanaian adults in the Ashanti region during the high transmission season. Methods: Asymptomatic adult residents from five villages in the Ashanti Region, Ghana, were screened for Plasmodium species by rapid diagnostic test (RDT) and polymerase chain reaction (PCR) during the rainy season. Samples tested positive were subtyped using species-specific real-time PCR. For all Plasmodium ovale infections additional sub-species identification was performed. Results: Molecular prevalence of asymptomatic Plasmodium infection was 284/391 (73%); only 126 (32%) infections were detected by RDT. While 266 (68%) participants were infected with Plasmodium falciparum, 33 (8%) were infected with Plasmodium malariae and 34 (9%) with P. ovale. The sub-species P. ovale curtisi and P. ovale wallikeri were identified to similar proportions. Non-falciparum infections usually presented as mixed infections with P. falciparum. Conclusions: Most adult residents in the Ghanaian forest zone are asymptomatic Plasmodium carriers. The high Plasmodium prevalence not detected by RDT in adults highlights that malaria eradication efforts must target all members of the population. Beneath Plasmodium falciparum, screening and treatment must also include infections with P. malariae, P. o. curtisi and P. o. wallikeri.

Identifiers:
Authors:
Ayisi-Boateng, Nana K; Owusu, Michael; Tawiah, Phyllis; Ampah, Brenda A; Sylverken, Augustina A; Wusu-Ansah, Osei K; Sarfo, Fred S; Phillips, Richard O;
Date:
2020-12-31
Journal:
Ghana Medical Journal
Content:

Background: In high-income countries, mortality related to hospitalized patients with the Coronavirus disease 2019 (COVID-19) is approximately 4-5%. However, data on COVID-19 admissions from sub-Saharan Africa are scanty.
Objective: To describe the clinical profile and determinants of outcomes of patients with confirmed COVID-19 admitted at a hospital in Ghana.
Methods: A prospective study involving 25 patients with real time polymerase chain reaction confirmed COVID-19 admitted to the treatment centre of the University Hospital, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana from 1st June to 27th July, 2020. They were managed and followed up for outcomes. Data were analysed descriptively, and predictors of mortality assessed using a multivariate logistic regression modelling.
Results: The mean age of the patients was 59.3 ± 20.6 years, and 14 (56%) were males. The main symptoms at presentation were breathlessness (68%) followed by fever (56%). The cases were categorized as mild (6), moderate (6), severe (10) and critical (3). Hypertension was the commonest comorbidity present in 72% of patients. Medications used in patient management included dexamethasone (68%), azithromycin (96%), and hydroxychloroquine (4%). Five of 25 cases died (Case fatality ratio 20%). Increasing age and high systolic blood pressure were associated with mortality.
Conclusion: Case fatality in this sample of hospitalized COVID-19 patients was high. Thorough clinical assessment, severity stratification, aggressive management of underlying co-morbidities and standardized protocols incountry might improve outcomes.

Identifiers:
Authors:
Amoako, YA; Frimpong, M; Awuah, DO; Plange-Rhule, G; Boakye-Yiadom, E; Agbavor, B; Sarpong, F; Ahor, H; Adu, E; Danso, KG;
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:
Phillips, Richard Odame; Steinmetz, Alexis; Nichols, Justin; Adomako, Emmanuel; Ofori, Emmanuel; Antonio, Emilia; Peprah-Addae, Collins; Adams, William;
Date:
2018-07-28
Journal:
BMC infectious diseases
Content:
Identifiers:
Authors:
Sarpong-Duah, Mabel; Frimpong, Michael; Beissner, Marcus; Saar, Malkin; Laing, Ken; Sarpong, Francisca; Loglo, Aloysius Dzigbordi; Abass, Kabiru Mohammed; Frempong, Margaret; Sarfo, Fred Stephen;
Date:
2017-03-27
Journal:
PLoS neglected tropical diseases
Content:
Identifiers:
Authors:
Adankwah, Ernest; Güler, Alptekin; Mayatepek, Ertan; Phillips, Richard Odame; Nausch, Norman; Jacobsen, Marc;
Date:
2019-07-18
Journal:
Microbes and infection
Content:

IFN-γ release assays (IGRAs) have suboptimal sensitivity for detection of Mycobacterium tuberculosis (Mtb) infection and cannot discriminate between tuberculosis (TB) patients and healthy -potentially Mtb infected- contacts (HCs). In a case-control study, we determined T-cell phenotypes of IGRAs in TB patients (n = 20) and HCs (n = 20) from Ghana. CD27 expression of T-cells was significantly lower in TB patients as compared to HCs independent from Mtb-specificity. CD27 expression discriminated both study groups - including TB patients with low or indeterminate IGRA results - effectively. We conclude that CD27 is a promising biomarker for diagnosis of TB patients with inconclusive IGRA results.

Identifiers:
Authors:
El-Duah, Philip; Dei, Dickson; Binger, Tabea; Sylverken, Augustina; Wollny, Robert; Tasiame, William; Oppong, Samuel; Adu-Sarkodie, Yaw; Emikpe, Benjamin; Folitse, Raphael;
Date:
2020-07-20
Journal:
One Health Outlook
Content:

Background

Hepatitis E virus (HEV) is a major cause of human hepatitis worldwide. Zoonotic genotypes of the virus have been found in diverse animal species with pigs playing a major role. Putative risk of zoonotic infection from livestock particularly swine in Sub-Saharan Africa including Ghana is poorly understood due to scarcity of available data, especially HEV sequence information.

Methods

Serum samples were collected from cattle, sheep, goats and pigs from Kumasi in the Ashanti region of Ghana. Samples were subjected to nested RT-PCR screening and quantification of HEV RNA-positive samples using real-time RT-PCR and the World Health Organization International Standard for HEV. Testing of all pig samples for antibodies was done by ELISA. Sanger sequencing and genotyping was performed and one representative complete genome was generated to facilitate genome-wide comparison to other available African HEV sequences by phylogenetic analysis.

Results

A total of 420 samples were available from cattle (n = 105), goats (n = 124), pigs (n = 89) and sheep (n = 102). HEV Viral RNA was detected only in pig samples (10.1%). The antibody detection rate in pigs was 77.5%, with positive samples from all sampling sites. Average viral load was 1 × 105 (range 1.02 × 103 to 3.17 × 105) International Units per mL of serum with no statistically significant differences between age groups (≤ 6 month, > 6 months) by a T-test comparison of means (t = 1.4272, df = 7, p = 0.1966). Sequences obtained in this study form a monophyletic group within HEV genotype 3. Sequences from Cameroon, Ghana, Burkina Faso and Madagascar were found to share a most recent common ancestor; however this was not the case for other African HEV sequences.

Conclusion

HEV genotype 3 is highly endemic in pigs in Ghana and likely poses a zoonotic risk to people exposed to pigs. HEV genotype 3 in Ghana shares a common origin with other virus strains from Sub-Saharan Africa.

Identifiers:
Authors:
Villa, Giovanni; Abdullahi, Adam; Owusu, Dorcas; Smith, Colette; Azumah, Marilyn; Sayeed, Laila; Austin, Harrison; Awuah, Dominic; Beloukas, Apostolos; Chadwick, David;
Date:
2020-01-05
Journal:
EClinicalMedicine
Content:

Background: This prospective pilot study explored same-day point-of-care viral load testing in a setting in Ghana that has yet to implement virological monitoring of antiretroviral therapy (ART). Methods: Consecutive patients accessing outpatient care while on ART underwent HIV-1 RNA quantification by Xpert. Those with viraemia at the first measurement (T0) received immediate adherence counselling and were reassessed 8 weeks later (T1). Predictors of virological status were determined by logistic regression analysis. Drug resistance-associated mutations (RAMs) were detected by Sanger sequencing. Findings: At T0, participants had received treatment for a median of 8·9 years; 297/333 (89·2%) were on NNRTI-based ART. The viral load was ≥40 copies/mL in 164/333 (49·2%) patients and ≥1000 copies/mL in 71/333 (21·3%). In the latter group, 50/65 (76·9%) and 55/65 (84·6%) harboured NRTI and NNRTI RAMs, respectively, and 27/65 (41·5%) had ≥1 tenofovir RAM. Among 150/164 (91·5%) viraemic patients that reattended at T1, 32/150 (21·3%) showed resuppression <40 copies/mL, comprising 1/65 (1·5%) subjects with T0 viral load ≥1000 copies/mL and 31/85 (36·5%) subjects with lower levels. A T0 viral load ≥1000 copies/mL and detection of RAMs predicted ongoing T1 viraemia independently of self-reported adherence levels. Among participants with T0 viral load ≥1000 copies/mL, 23/65 (35·4%) showed resuppression <1000 copies/mL; the response was more likely among those with higher adherence levels and no RAMs. Interpretation: Same-day point-of-care viral load testing was feasible and revealed poor virological control and suboptimal resuppression rates despite adherence counselling. Controlled studies should determine optimal triaging modalities for same-day versus deferred viral load testing. Funding: University of Liverpool, South Tees Infectious Diseases Research Fund

Identifiers:
Authors:
Phillips, Richard O; Seyfarth, Julia; Sarfo-Kantanka, Osei; Rosenbauer, Joachim; Jacobsen, Marc;
Date:
2019-12-11
Journal:
Journal of Diabetes
Content:

Highlights Type 1 diabetes onset age in Kumasi/Ghana has a peak at around 17 to 20 years, whereas the peak is at 11 to 12 years in North Rhine-Westphalia, Germany. Higher proportions of females were found in the type 1 diabetes cohort from Ghana, and males were more frequent in the German cohort.

Identifiers:
Authors:
Phillips, Richard Odame; Phanzu, Delphin Mavinga; Beissner, Marcus; Badziklou, Kossi; Luzolo, Elysée Kalundieko; Sarfo, Fred Stephen; Halatoko, Wemboo Afiwa; Amoako, Yaw; Frimpong, Michael; Kabiru, Abass Mohammed;
Date:
2015-09-01
Journal:
PLoS Negl Trop Dis
Content:
Identifiers:
Authors:
Owusu, Dorcas Ohui; Phillips, Richard; Owusu, Michael; Sarfo, Fred Stephen; Frempong, Margaret;
Date:
2020-10-07
Journal:
BMC Research Notes
Content:

Objective: Approximately 70% of all hepatitis C (HCV) infections develop chronic disease. Active or exacerbated chronic hepatitis C infection subsequently progress to liver disease. The role of T-cells secretions in achieving viral clearance is still not well understood. Thus, the current study was set to determine the relationship between the T cell cytokine profiles, biochemical parameters and persistent HCV infection or spontaneous recovery. Results: Twenty-five percent (41/163) of the anti-HCV positive participants had recovered from HCV and had significantly higher concentration of IL-10 compared to those with active HCV infection (P < 0.012). Other circulating cytokines measured; IL-2, IFN gamma, TNF alpha, IL-5 and IL-17 were similar in both groups. Participants with active HCV infection had significantly higher aspartate transaminase (AST) (35 units) and alanine transaminase (46 units) compared to those in the recovered state (P < 0.001). Thus, serum levels of IL10 could be explored in larger prospective cohort study as a predictive marker of recovering from an active HCV infection.

Identifiers:
Authors:
Yotsu, Rie R; Suzuki, Koichi; Simmonds, Rachel E; Bedimo, Roger; Ablordey, Anthony; Yeboah-Manu, Dorothy; Phillips, Richard; Asiedu, Kingsley;
Date:
2018-08-28
Journal:
Current tropical medicine reports
Content:
Identifiers:
Authors:
Woolley, Rebecca J; Velink, Anita; Phillips, Richard O; Thompson, William A; Abass, K Mohammed; van der Werf, Tjip S; de Zeeuw, Janine; Stienstra, Ymkje;
Date:
2016-09-05
Journal:
The American journal of tropical medicine and hygiene
Content:
Identifiers:
Authors:
Marks, Michael; Mitjà, Oriol; Bottomley, Christian; Kwakye, Cynthia; Houinei, Wendy; Bauri, Mathias; Adwere, Paul; Abdulai, Abdul A; Dua, Fredrick; Boateng, Laud;
Date:
2018-05-06
Journal:
The Lancet Global Health
Content:
Identifiers:
Authors:
Amoako YA, Loglo AD, Frimpong M, Agbavor B, Abass MK, Amofa G, Ofori E, Ampadu E, Asiedu K, Stienstra Y, Wansbrough-Jones M, van der Werf T, Phillips RO.
Date:
2021-04-08
Journal:
BMC Infect Dis
Content:
Identifiers:
Authors:
Date:
2021-03-01
Journal:
Int J Tuberc Lung Dis
Content:
Identifiers:
Authors:
Stockdale, Alexander; Phillips, Richard O; Sarfo, Fred S; Appiah, Lambert T; Bonnett, Laura J; Chadwicks, David; Villa, Giovanni; Bhagani, Sanjay; Smith, Colette; Geretti, Anna Maria;
Date:
2016-06-04
Journal:
HEPATOLOGY
Content:
Identifiers:
Authors:
Villa, G; Abdullahi, A; Owusu, D; Smith, C; Azumah, M; Sayeed, L; Austin, H; Awuah, D; Beloukas, A; Chadwick, D;
Date:
2019-07-20
Journal:
HIV MEDICINE
Content:
Identifiers:
Authors:
Villa, G; Phillips, RO; Smith, C; Stockdale, AJ; Beloukas, A; Appiah, LT; Chadwick, D; Ruggiero, A; Sarfo, FS; Post, F;
Date:
2018-06-07
Journal:
Journal of Infection
Content:
Identifiers:
Authors:
Nausch, Norman; Antwi-Berko, Daniel; Mubarik, Yusif; Abass, Kabiru Mohammed; Owusu, Wellington; Owusu-Dabo, Ellis; Debrah, Linda Batsa; Debrah, Alexander Yaw; Jacobsen, Marc; Phillips, Richard O;
Date:
2017-02-27
Journal:
PLoS neglected tropical diseases
Content:
Identifiers:
Authors:
Maaroufi, A; Vince, A; Himatt, SM; Mohamed, R; Fung, J; Opare‐Sem, O; Workneh, A; Njouom, R; Al Ghazzawi, I; Abdulla, M;
Date:
2017-02-04
Journal:
Journal of viral hepatitis
Content:
Identifiers:
Authors:
Neary M, Olagunju A, Sarfo F, Phillips R, Moss D, Owen A, Chadwick D
Date:
2014-02-14
Journal:
Journal of Antimicrobial Chemotherapy.
Content:
Identifiers:
Authors:
Simpson H, Tabah EN, Phillips RO, Frimpong M, Maman I, Ampadu E, Timothy J, Saunderson P, Pullan RL, Cano J
Date:
2021-03-03
Journal:
PLoS Negl Trop Dis
Content:
Identifiers:
Authors:
Frimpong, Michael; Sarfo, Fred Stephen; Duah, Mabel Sarpong; Wansbrough-Jones, Mark; Phillips, Richard O;
Date:
2016-03-07
Journal:
Chronic Wound Care Management and Research
Content:
Identifiers:
Authors:
Awua‑Boateng, Nana Yaa; Mohammed, Aliyu; Aglanu, Leslie Mawuli; Acheampong, Godfred; Amuasi, John Humphrey; Bonsu, Frank Adae; Phillips, Richard Odame; Owusu-Dabo, Ellis;
Date:
2019-09-08
Journal:
International Journal Microbiology
Content:

Background: Despite appropriate prevention and control measures, tuberculosis (TB) remains a significant contributor to maternal morbidity and mortality. Diagnosis of the disease in pregnancy is usually challenging, as the symptoms may be attributed to the pregnancy. Little is known about the true burden of the disease and its associated risk factors among pregnant women. This study sought to assess the prevalence of TB among pregnant women and associated sociodemographic characteristics in Ghana.

Methods: The study used nationally representative data gathered from the national TB project in 2013. A total of 1747 pregnant women were sampled from 56 randomly selected diagnostic health centers across the ten regions of Ghana. TB was confirmed with Ziehl-Neelsen staining technique using morning sputum samples from pregnant women who reported coughing for more than 2 weeks. We assessed how the observed TB prevalence differed by some sociodemographic characteristics and other factors. We further examined the regional spatial distribution of pregnant women with TB in the country.

Results: Up to 11.2% of the pregnant women had a history of cough during pregnancy. Eighteen (1.1%) cases of TB were confirmed among the pregnant women during the 2-year period, with the Eastern region of the country recording the highest (n = 13, 72%), followed by Volta region ( n = 2, 11.1%). No cases were recorded in five regions. The geographical region of residence was the only determinant of TB in pregnancy significantly associated with TB (P = 0.001).

Conclusion: Although the burden of TB was found to be low, appropriate control measures have to be put in place to detect the disease during the early stages of pregnancy to safeguard the health of the expectant mother and the unborn child.

Identifiers:
Authors:
Neary, M; Olagunju, A; Sarfo, F; Phillips, R; Moss, D; Owen, A; Chadwick, D;
Date:
2020-02-14
Journal:
Journal of Antimicrobial Chemotherapy
Content:

To assess associations between polymorphisms within genes encoding proximal tubule transporters implicated in tenofovir renal clearance and kidney tubular dysfunction (KTD), chronic kidney disease (CKD) and individual biochemical parameters. Patients and methods: The study included a cohort of HIV-positive Ghanaians receiving regimens containing tenofovir disoproxil fumarate (n = 66) for at least 6 months prior to study enrolment. SNPs in ABCC10, ABCC2 and ABCC4 were selected for analysis based on previous published associations. All SNPs were genotyped by real-time PCR allelic discrimination. Creatinine clearance (CLCR), serum and urine creatinine concentrations and biochemical measures of KTD were assessed. Statistical significance was determined through univariate linear or binary logistical regression (P ≤ 0.05). Results: None of the SNPs evaluated was associated with CKD or KTD. A trend between body weight and higher incidence of CKD (P = 0.012, OR = 0.9) was observed. ABCC10 2843T>C (rs2125739) was significantly associated with lower log10 baseline creatinine (P = 0.001, β= -0.4), higher baseline CLCR (P = 0.008, β = 65.2) and lower CLCR after 1 year (P = 0.024, β= -26.6). Conclusions: This study demonstrates an association of ABCC10 rs2125739 with indicators of declining renal function and builds on current knowledge of this interaction within a Ghanaian cohort.

Identifiers:
Authors:
Soumya Swaminathan
Date:
2020-11-06
Journal:
Transactions of The Royal Society of Tropical Medicine and Hygiene
Content:

To maximise the likelihood of success, global health programmes need repeated, honest appraisal of their own weaknesses, with research undertaken to address any identified gaps. There is still much to be learned to optimise work against neglected tropical diseases. To facilitate that learning, a comprehensive research and development plan is required. Here, we discuss how such a plan might be developed.

Identifiers:
Authors:
Omansen, Till Frederik; van der Werf, Tjip S; Phillips, Richard Odame;
Date:
2019-04-30
Journal:
Buruli ulcer
Content:

MacCallum and coworkers described Buruli ulcer (BU) as an infectious disease caused by Mycobacterium ulcerans in Victoria, Australia. They first considered the skin lesions in their patients to be caused by tuberculosis or leprosy, when they observed numerous acid-fast bacilli in the biopsy specimens [1]. The typical duration of illness was between 1 and 2 years; treatment was essentially surgical. With the advent of chemotherapy for tuberculosis [2–4], and later for leprosy, doctors made individual attempts to treat the lesions with anti-tuberculosis and anti-leprosy drugs. The anecdotal evidence suggested poor or no response to chemotherapy with rifampicin monotherapy [5], despite the fact that in vitro susceptibility of 33 strains of M. ulcerans was as good as for M. tuberculosis [6]. A randomized clinical trial by the British Medical Research Council in Buruli county (now called Nakasongola; Uganda) failed to show any benefit from clofazimine, a drug then first marketed for leprosy [7]. A small-sized trial with cotrimoxazole (18 participants; 12 evaluable) was inconclusive [8]. A small-sized randomized study in Côte d’Ivoire compared a combination of dapsone and rifampicin with placebo; the follow-up was limited; the ulcer size decreased slightly faster in the intervention group but the baseline characteristics of both groups differed, and the study did not allow to draw any firm conclusions about the effectiveness of these drugs [9]. By the turn of the millennium, the discrepancy between in vitro efficacy of rifampicin [6] or clarithromycin [10] and lack of clinical response prompted to stressing the need for well-designed and well-powered drug trials, but in the meantime, to also improve early detection and surgical treatment [11].

Identifiers:
Authors:
Stockdale, Alexander J; Phillips, Richard Odame; Beloukas, Apostolos; Appiah, Lambert Tetteh; Chadwick, David; Bhagani, Sanjay; Bonnett, Laura; Sarfo, Fred Stephen; Dusheiko, Geoffrey; Geretti, Anna Maria;
Date:
2016-06-01
Journal:
Clinical Infectious Diseases
Content:
Identifiers:
Authors:
Owusu, Michael; Sylverken, Augustina Angelina; Ankrah, Sampson Twumasi; El-Duah, Philip; Ayisi-Boateng, Nana Kwame; Yeboah, Richmond; Gorman, Richmond; Asamoah, Jesse; Binger, Tabea; Acheampong, Godfred;
Date:
2020-12-10
Journal:
PloS one
Content:

Background

Global cases of COVID-19 continue to rise, causing havoc to several economies. So far, Ghana has recorded 48,643 confirmed cases with 320 associated deaths. Although summaries of data are usually provided by the Ministry of Health, detailed epidemiological profile of cases are limited. This study sought to describe the socio-demographic features, pattern of COVID-19 spread and the viral load dynamics among subjects residing in northern, middle and part of the southern belt of Ghana.

Methods

This was a cross-sectional retrospective study that reviewed records of samples collected from February to July, 2020. Respiratory specimens such as sputum, deep-cough saliva and nasopharyngeal swabs were collected from suspected COVID-19 subjects in 12 regions of Ghana for laboratory analysis and confirmation by real-time reverse transcription polymerase chain reaction (RT-PCR).

Results

A total of 72,434 samples were collected during the review period, with majority of the sampled individuals being females (37,464; 51.9%). The prevalence of SARS-CoV-2 identified in the study population was 13.2% [95%CI: 12.9, 13.4). Males were mostly infected (4,897; 51.5%) compared to females. Individuals between the ages 21–30 years recorded the highest number of infections (3,144, 33.4%). Symptomatic subjects had higher viral loads (1479.7 copies/μl; IQR = 40.6–178919) than asymptomatic subjects (49.9; IQR = 5.5–3641.6). There was significant association between gender or age and infection with SARS-CoV-2 (p<0.05). Among all the suspected clinical presentations, anosmia was the strongest predictor of SARS-CoV-2 infection (Adj. OR (95%CI): 24.39 (20.18, 29.49). We observed an average reproductive number of 1.36 with a minimum of 1.28 and maximum of 1.43. The virus trajectory shows a gradual reduction of the virus reproductive number.

Conclusion

This study has described the epidemiological profile of COVID-19 cases in northern, middle and part of the southern belt of Ghana, with males and younger individuals at greater risk of contracting the disease. Health professionals should be conscious of individuals presenting with anosmia since this was seen as the strongest predictor of virus infection.

Identifiers:
Authors:
Chan, HLY; Chen, CJ; Omede, O; Al Qamish, J; Al Naamani, K; Bane, A; Tan, SS; Simonova, M; Cardenas, I; Derbala, M;
Date:
2017-02-04
Journal:
Journal of viral hepatitis
Content:
Identifiers:
Authors:
Sarfo, Fred Stephen; Phillips, Richard; Wansbrough‐Jones, Mark; Simmonds, Rachel E;
Date:
2016-12-01
Journal:
Cellular microbiology
Content:
Identifiers:
Authors:
Debrah, Linda Batsa; Phillips, Richard O; Pfarr, Kenneth; Klarmann-Schulz, Ute; Opoku, Vera Serwaa; Nausch, Norman; Owusu, Wellington; Mubarik, Yusif; Sander, Anna-Lena; Lämmer, Christine;
Date:
2019-07-10
Journal:
The American journal of tropical medicine and hygiene
Content:

Treating Mansonella perstans is challenged by the low efficacy of registered antihelminthics. Wolbachia endobacteria provide an alternative treatment target because depletion results in amicrofilaremia in filarial infections with Wuchereria bancrofti and Onchocerca volvulus infections. This open-label, randomized study sought to confirm that i) Wolbachia are present in M. perstans in Ghana and ii) doxycycline treatment will deplete Wolbachia and cause a slow, sustained decline in microfilariae (MF). Two hundred and two Ghanaians with M. perstans infection were randomized into early (immediate) and delayed (6 months deferred) treatment groups, given doxycycline 200 mg/day for 6 weeks, and monitored for MF and Wolbachia levels at baseline, 4, 12, and 24 months after the study onset (= time of randomization and start of treatment for the early group). Per protocol analysis revealed that the median MF/mL in the early group declined from 138 at baseline to 64 at month 4 and further to 0 at month 12. In the delayed group, MF load did not change from a baseline median of 97 to 102 at month 4 but declined to 42 at month 12, that is, 6 months after receiving treatment, trailing the early group as expected. By month 24, both treatment groups had reached a median MF level of 0. After treatment, Wolbachia were depleted from MF by ≥ 1-log drop compared with baseline levels. We conclude that M. perstans in Ghana harbor Wolbachia that are effectively depleted by doxycycline with subsequent reduction in MF loads, most likely because of interruption of fertility of adult worms.

Identifiers:
Authors:
Phillips, Richard O; Robert, Jérôme; Abass, Kabiru Mohamed; Thompson, William; Sarfo, Fred Stephen; Wilson, Tuah; Sarpong, Godfred; Gateau, Thierry; Chauty, Annick; Omollo, Raymond;
Date:
2020-03-12
Journal:
The 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. Funding: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac.

Identifiers:
Authors:
Geretti, Anna Maria; King, Simon; Adjei-Asante, Kwabena; Appiah, Lambert Tetteh; Owusu, Dorcas Ohui; Sarfo, Fred Stephen; Chadwick, David; Phillips, Richard Odame; Beloukas, Apostolos;
Date:
2017-08-09
Journal:
Journal of Clinical Virology
Content:
Identifiers:
Authors:
Wadagni, Anita C; Steinhorst, Jonathan; Barogui, Yves T; Catraye, PM; Gnimavo, Ronald; Abass, Kabiru M; Amofa, George; Frimpong, Michael; Sarpong, Francisca N; van der Werf, Tjip S;
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:
Di Cristanziano, Veronica; Weimer, Kristina; Böttcher, Sindy; Sarfo, Fred Stephen; Dompreh, Albert; Cesar, Lucio-Garcia; Knops, Elena; Heger, Eva; Wirtz, Maike; Kaiser, Rolf;
Date:
2020-02-16
Journal:
Viruses
Content:

In the post-polio eradication era, increasing attention is given to non-polio enteroviruses. Most of the data about enteroviruses in sub-Saharan Africa are related to acute flaccid paralysis surveillance and target the pediatric population. This study aimed to investigate the presence of enterovirus in PLHIV (people living with HIV) and HIV-negative individuals in Ghana. Stool samples from HIV-positive individuals (n = 250) and healthy blood donors (n = 102) attending the Komfo Anokye Teaching Hospital in Kumasi, Ghana, were screened by real-time PCR for enterovirus. Molecular typing of the VP1 region was performed. Enterovirus-positive samples were tested for norovirus, adenovirus, rotavirus, sapovirus, and cosaviruses. Twenty-six out of 250 HIV-positive subjects (10.4%) and 14 out of 102 HIV-negative individuals (13.7%) were detected enterovirus-positive, not showing a significant different infection rate between the two groups. HIV-negative individuals were infected with Enterovirus C strains only. HIV-positive participants were detected positive for species Enterovirus A, Enterovirus B, and Enterovirus C. Co-infections with other viral enteric pathogens were almost exclusively detected among HIV-positive participants. Overall, the present study provides the first data about enteroviruses within HIV-positive and HIV-negative adults living in Ghana.

Identifiers:
Authors:
Frimpong, Michael; Agbavor, Bernadette; Duah, Mabel Sarpong; Loglo, Aloysius; Sarpong, Francisca N; Boakye-Appiah, Justice; Abass, Kabiru M; Dongyele, Mathias; Amofa, George; Tuah, Wilson;
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:
Boakye-Appiah, Justice K; Steinmetz, Alexis R; Pupulampu, Peter; Ofori-Yirenkyi, Stephen; Tetteh, Ishmael; Frimpong, Michael; Oppong, Patrick; Opare-Sem, Ohene; Norman, Betty R; Stienstra, Ymkje;
Date:
2016-05-02
Journal:
International journal of mycobacteriology
Content:
Identifiers:
Authors:
Adankwah, Ernest; Lundtoft, Christian; Güler, Alptekin; Franken, Kees LMC; Ottenhoff, Tom HM; Mayatepek, Ertan; Owusu-Dabo, Ellis; Phillips, Richard Odame; Nausch, Norman; Jacobsen, Marc;
Date:
2019-07-03
Journal:
Frontiers in immunology
Content:
Identifiers:
Authors:
Kliethermes, Stephanie; Gantenberg, Jason; Mora, Nallely; Phillips, Richard O; Opare-Sem, Ohene; Owusu, Dorcas; Layden, Jennifer E;
Date:
2016-06-03
Journal:
HEPATOLOGY
Content:
Identifiers:
Authors:
Van Der Werf, Tjip S; Barogui, Yves T; Converse, Paul J; Phillips, Richard O; Stienstra, Ymkje;
Date:
2020-04-20
Journal:
Expert review of clinical pharmacology
Content:

Introduction: Pharmacological treatment of Buruli ulcer (Mycobacterium ulcerans infection; BU) is highly effective, as shown in two randomized trials in Africa. Areas covered: We review BU drug treatment–in vitro, in vivo and clinical trials (PubMed: ‘(Buruli OR (Mycobacterium AND ulcerans)) AND (treatment OR therapy).’ We also highlight the pathogenesis of M. ulcerans infection that is dominated by mycolactone, a secreted exotoxin, that causes skin and soft tissue necrosis, and impaired immune response and tissue repair. Healing is slow, due to the delayed wash-out of mycolactone. An array of repurposed tuberculosis and leprosy drugs appears effective in vitro and in animal models. In clinical trials and observational studies, only rifamycins (notably, rifampicin), macrolides (notably, clarithromycin), aminoglycosides (notably, streptomycin) and fluoroquinolones (notably, moxifloxacin, and ciprofloxacin) have been tested. Expert opinion: A combination of rifampicin and clarithromycin is highly effective but lesions still take a long time to heal. Novel drugs like telacebec have the potential to reduce treatment duration but this drug may remain unaffordable in low-resourced settings. Research should address ulcer treatment in general; essays to measure mycolactone over time hold promise to use as a readout for studies to compare drug treatment schedules for larger lesions of Buruli ulcer.

Identifiers:
Authors:
Collinson, Shelui; Frimpong, Venus NB; Agbavor, Bernadette; Montgomery, Bethany; Oppong, Michael; Frimpong, Michael; Amoako, Yaw A; Marks, Michael; Phillips, Richard O;
Date:
2020-05-26
Journal:
PLoS neglected tropical diseases
Content:

Background Buruli ulcer is a chronic ulcerating skin condition, with the highest burden found in Central and West Africa where it disproportionately affects the most vulnerable populations. Treatment is demanding, comprising eight-weeks of daily antibiotics, regular wound care and possible surgical intervention. Treatment completion is key to optimising outcomes, however the degree of and barriers to this are not well understood. Recent change from injectable treatment (SR8) to oral treatment (CR8) has made it feasible to further decentra-lise care, potentially improving treatment access and completion. However, the impact of this and of other demographic and clinical influences on treatment completion must be explored first to ensure appropriate models of care are developed. Methodology/Principal findings A retrospective clinical notes review and secondary data analysis of records from patients diagnosed between 1 January 2006–31 December 2018 at four district hospital clinics in the Ashanti and Central Regions, Ghana. Univariable analyses and multivariable logistic regres-sion were performed to assess the association between explanatory variables and treatment completion. There were 931 patient episodes across the four clinics with overall treatment completion of 84.4%. CR8 was associated with higher treatment completion compared to SR8 (OR 4.1, P = 0.001). There was no statistically significant association found between distance from patient residence to clinic and treatment completion. Conclusions/Significance Improved treatment completion with CR8 supports its use as first line therapy and may enable decentralisation to fully community-based care. We did not find an association between distance to care and treatment completion, though analyses were limited by data availability. However, we did find evidence that distance to care continues to be associated with more severe forms of disease, which may reflect the higher costs of accessing care and lower awareness of the condition the further a patient lives. Decentralised care must therefore also continue to support community engagement and active outreach to identify cases early.

Identifiers:
Authors:
Villa, Giovanni; Phillips, Richard O; Smith, Colette; Stockdale, Alexander J; Ruggiero, Alessandra; Beloukas, Apostolos; Appiah, Lambert T; Chadwick, David; Sarfo, Fred S; Geretti, Anna Maria;
Date:
2018-11-01
Journal:
Journal of Antimicrobial Chemotherapy
Content:
Identifiers:
Authors:
Stienstra, Ymkje; Beeres, Dorien T; Phillips, Richard; Vonk, Machiel; Ravensbergen, Sofanne J;
Date:
2019-07-06
Journal:
The Lancet
Content:

Scabies is a parasitic disease of the skin that disproportionately affects disadvantaged populations. The disease causes considerable morbidity and leads to severe bacterial infection and immune-mediated disease. Scientific advances from the past 5 years suggest that scabies is amenable to population-level control, particularly through mass drug administration. In recognition of these issues, WHO added scabies to the list of neglected tropical diseases in 2017. To develop a global control programme, key operational research questions must now be addressed. Standardised approaches to diagnosis and methods for mapping are required to further understand the burden of disease. The safety of treatments for young children, including with ivermectin and moxidectin, should be investigated. Studies are needed to inform optimum implementation of mass treatment, including the threshold for intervention, target, dosing, and frequency. Frameworks for surveillance, monitoring, and evaluation of control strategies are also necessary.

Identifiers:
Authors:
Blach, Sarah; Zeuzem, Stefan; Manns, Michael; Altraif, Ibrahim; Duberg, Ann-Sofi; Muljono, David H; Waked, Imam; Alavian, Seyed M; Lee, Mei-Hsuan; Negro, Francesco;
Date:
2017-02-03
Journal:
The lancet Gastroenterology & hepatology
Content:
Identifiers:
Authors:
Frimpong, Michael; Ahor, Hubert Senanu; Abd El Wahed, Ahmed; Agbavor, Bernadette; Sarpong, Francisca Naana; Laing, Kenneth; Wansbrough-Jones, Mark; Phillips, Richard Odame;
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:
Abass, Kabiru Mohammed; Van Der Werf, Tjip S; Phillips, Richard O; Sarfo, Fred S; Abotsi, Justice; Mireku, Samuel Osei; Thompson, William N; Asiedu, Kingsley; Stienstra, Ymkje; Klis, Sandor-Adrian;
Date:
2015-02-09
Journal:
The American journal of tropical medicine and hygiene
Content:
Identifiers:
Authors:
Phillips, Richard; Evans, Bethan;
Date:
2018-02-01
Journal:
Urban Studies
Content:
Identifiers:
Authors:
Stockdale, Alexander J; Chaponda, Mas; Beloukas, Apostolos; Phillips, Richard Odame; Matthews, Philippa C; Papadimitropoulos, Athanasios; King, Simon; Bonnett, Laura; Geretti, Anna Maria;
Date:
2017-05-09
Journal:
The Lancet Global health
Content:
Identifiers:
Authors:
Phillips, R.O.
Date:
2019-12-31
Journal:
In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved January 7, 2020, from https://hstalks.com/bs/3962/.
Content:
Identifiers:
Authors:
Adankwah, Ernest; Nausch, Norman; Minadzi, Difery; Abass, Mohammed K; Franken, Kees LMC; Ottenhoff, Tom HM; Mayatepek, Ertan; Phillips, Richard O; Jacobsen, Marc;
Date:
2020-11-08
Journal:
Journal of Infection
Content:

Objectives: IFNγ-release assays (IGRAs) used for diagnosis of Mycobacterium (M.) tuberculosis infection have limited sensitivity. Alternative cytokines and M. tuberculosis latency-associated antigens may improve immune-based tests. Methods: Multiplex cytokine analyses was done in culture supernatants after 6-day in vitro restimulation with M. tuberculosis IGRA and latency-associated antigens (i.e. Rv2628, Rv1733) in tuberculosis patients (n = 22) and asymptomatic contacts (AC)s (n = 20) from Ghana. Results: Four cytokines (i.e. IFNγ, IP-10, IL-22 and IL-6) were significantly increased after IGRA-antigen specific restimulation. IFNγ, IP-10, and IL-22 correlated positively and showed no differences between the study groups whereas IGRA-antigen induced IL-6 was significantly higher in tuberculosis patients. Using adjusted IGRA criteria, IL-6 showed the highest sensitivity for detection of tuberculosis patients (91%) and ACs (85%) as compared to IFNγ, IP-10, and IL-22. Rv2628 and Rv1733 restimulation induced significantly higher IFNγ, IP-10, and IL-22 concentrations in ACs. Combined antigen/cytokine analyses identified study group specific patterns and a combination of Rv2628/Rv1733 induced IFNγ with IGRA-antigen induced IL-6 was optimal for classification of tuberculosis patients and ACs (AUC: 0.92, p<0.0001). Conclusions: We demonstrate the potency of alternative cytokines, especially IL-6, and latency-associated antigens Rv1733/Rv2628 to improve detection of M. tuberculosis infection and to classify tuberculosis patients and healthy contacts.

Identifiers:
Authors:
King, S; Adjei‐Asante, K; Appiah, L; Adinku, D; Beloukas, A; Atkins, M; Sarfo, SF; Chadwick, D; Phillips, RO; Geretti, AM;
Date:
2015-02-02
Journal:
Journal of viral hepatitis
Content:
Identifiers:
Authors:
Ofori, Afua; Steinmetz, Alexis R; Akaasi, John; Frimpong, George A Asafu Adjaye; Norman, Betty R; Obeng-Baah, Joseph; Bedu-Addo, George; Phillips, Richard O;
Date:
2016-05-02
Journal:
International journal of mycobacteriology
Content:
Identifiers:
Authors:
Beeres, Dorien T; Horstman, Jacolien; van der Tak, Pierre; Phillips, Richard O; Abass, Kabiru M; van der Werf, Tjip; Johnson, Roch C; Sopoh, Ghislain E; de Zeeuw, Janine; Dijkstra, Pieter U;
Date:
2019-03-14
Journal:
PLoS neglected tropical diseases
Content:

Background: Buruli Ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. Former BU patients may experience participation restrictions due to physical limitations, stigmatization and other social factors. A scale that measures participation restrictions among children, who represent almost half of the affected population, has not been developed yet. Here, we present the development of a scale that measures participation restrictions in former BU paediatric patients, the psychometric properties of this scale and the scales' results.

Methods: Items were selected and a scale was developed based on interviews with health care workers and former BU patients in and around the BU treatment centre in Lalo, Benin. Construct validity was tested using six a priori formulated hypotheses. Former BU patients under 15 years of age who received treatment in one of the BU treatment centres in Ghana and Benin between 2007-2012 were interviewed.

Results: A feasible 16-item scale that measures the concept of participation among children under 15 years of age was developed. In total, 109 (Ghana) and 90 (Benin) former BU patients were interviewed between 2012-2017. Five construct validity hypotheses were confirmed of which 2 hypotheses related to associations with existing questionnaires were statistically significant (p<0.05). In Ghana 77% of the former patients had a Paediatric Participation (PP) scale score of 0 compared to 22% in Benin. More severe lesions related to BU were seen in Benin. Most of the reported participation problems were related to sports, mainly in playing games with others, going to the playfield and doing sports at school.

Conclusion: The preliminary results of the PP-scale validation are promising but further validation is needed. The developed PP-scale may be valid for use in patients with more severe BU lesions. This is the first research to confirm that former BU patients under 15-year face participation restrictions in important aspects of their lives.

Identifiers:
Authors:
Lundtoft, Christian; Awuah, Anthony Afum-Adjei; Güler, Alptekin; Harling, Kirstin; Schaal, Heiner; Mayatepek, Ertan; Phillips, Richard O; Nausch, Norman; Owusu-Dabo, Ellis; Jacobsen, Marc;
Date:
2019-07-20
Journal:
Genes & Immunity
Content:

Functional interleukin-7 receptor α-chain (IL-7Rα) genetic variants, which affect alternative splicing and expression of the soluble IL-7Rα, are associated with susceptibility to autoimmunity. We previously described aberrant IL-7Rα expression and impaired IL-7-mediated T-cell functions in tuberculosis patients. In the present study, we investigated a possible role of IL7RA gene variants. Six exonic IL7RA polymorphisms were genotyped and two minor alleles were found at lower frequencies in tuberculosis patients as compared to healthy contacts from Ghana (rs11567764, p = 0.002; rs1494558, p = 0.01). The rs11567764 polymorphism tags an IL7RA haplotype exclusively found in African populations and was predicted to affect splicing of exon 5. Reduced mRNA expression of the Δexon_5-6 variant was found in T-cells from carriers of the protective rs11567764 allele. Although we were not able to demonstrate the causative effect of rs11567764, our findings suggested functional implications of genetic variants on IL-7Rα splicing and with potential impact on T-cell protection against tuberculosis.

Identifiers:
Authors:
Chen, DS; Hamoudi, W; Mustapha, B; Layden, J; Nersesov, A; Reic, T; Garcia, V; Rios, C; Mateva, L; Njoya, O;
Date:
2017-04-02
Journal:
Journal of viral hepatitis
Content:
Identifiers:

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