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Assessing and Strengthening African Universities’ Capacity for Doctoral Programmes
(PLoS Medicine, 2011-09) Bates, Imelda; Phillips, Richard Odame; Martin-Peprah, Ruby; Kibiki, Gibson; Gaye, Oumar; et.al
Universities can make a major contribution to good policy-making by generating nationally relevant evidence, but little is known about how to strategically support universities in poorer countries to train and nurture sufficient internationally competitive researchers. N It is difficult for universities to develop a coherent strategy to identify and remedy deficiencies in their doctoral training programmes because there is currently no single process that can be used to evaluate all the components needed to make these programmes successful. N We have developed an evidence-based process for evaluating doctoral programmes from multiple perspectives that comprises an interview guide and a list of corroborating documents and facilities; we refined and validated this process by testing it in five diverse African universities. N The strategy and priority list that emerged from the evaluation process facilitated ‘‘buy-in’’ from internal and external agencies and enabled each university to lead the development, implementation, and monitoring of their own strategy for remedying doctoral programme deficiencies.
Boosting of Cellular Immunity against Mycobacterium tuberculosis and Modulation of Skin Cytokine Responses in Healthy Human Volunteers by Mycobacterium bovis BCG Substrain Moreau Rio de Janeiro Oral Vaccine
(American Society for Microbiology, 2006-01-23) Cosgrove, Catherine A.; Castello-Branco, Luiz R. R.; Hussell, Tracy; Sexton, Amy; Giemza, Rafaela; et.al
Oral immunization of healthy adults with 107 CFU BCG Moreau Rio de Janeiro was well tolerated and significantly boosted gamma interferon responses to purified protein derivative, Ag85, and MPB70 from previous childhood intradermal BCG immunization. Oral BCG offers the possibility of a needle-free tuberculosis vaccine and of boosting the protective immunity from intradermal tuberculosis vaccines.
Buruli ulcer disease: prospects for a vaccine
(Med Microbiol Immunol, 2009-02-07) Huygen, Kris; Phillips, Richard Odame; Adjei, Ohene Adjei; Affolabi, Dissou; Bretzel, Gisela; et.al
Buruli ulcer disease (BUD), caused by Mycobacterium ulcerans, is a neglected bacterial infection of the poor in remote rural areas, mostly affecting children. BUD is a mutilating disease leading to severe disability; it is the third most common mycobacterial infection in immunocompetent people after tuberculosis and leprosy. It is most endemic in West Africa, but cases have been reported from more than 30 countries. Treatment with antibiotics is possible, long-lasting and requires injections; there are cases of treatment failures, and the disease is prone to resistance. A vaccine against M. ulcerans would protect persons at risk in highly endemic areas, and could be used as a therapeutic vaccine to shorten the duration of treatment and prevent relapses. There is considerable evidence supporting the
Candidatus Neoehrlichia mikurensis and Anaplasma phagocytophilum in Urban Hedgehogs
(Emerging Infectious Diseases, 2014-03) Kollie, Karsor; Amoako, Yaw Ampem; Ake, Julien; Mulbah, Tarnue; Phillips, Richard Odame; et.al
Candidatus Neoehrlichia mikurensis is a member of the order Rickettsiales, family Anaplasmataceae (1). Manifestations of infection with these bacteria are atypical and severe and include cough, nausea, vomiting, anemia, headache, pulmonary infiltration, malaise, myalgia, arthralgia, fatigue, recurrent fever for ≤8 months, and/or death (2–5). Candidatus N. mikurensis has been detected in Ixodes ovatus, I. persulcatus, and Haemaphysalis concinna ticks in Asia (1,5). Candidatus N. mikurensis has been identified as one of the most prevalent pathogenic agents in I. ricinus ticks throughout Europe (2,3,6). Rodents of diverse species and geographic origins have been shown to carry these bacteria, but transmission experiments have not been conducted to unambiguously identify natural vertebrate reservoirs (1–3,5–7). This emerging tickborne pathogen has been detected mainly in immunocompromised patients in Sweden (n = 1), Switzerland (n = 3), Germany (n = 2), and the Czech Republic (n = 2) and in immunocompetent patients in China (n = 7) (2–5). Anaplasma phagocytophilum is an obligate, intracellular, tickborne bacterium of the family Anaplasmataceae and causes granulocytic anaplasmosis in humans and domestic animals. In Europe, I. ricinus ticks are its major vector, and red deer, roe deer, rodents, and European hedgehogs (Erinaceus europaeus) are suspected reservoir hosts (8).
Clinical and Bacteriological Efficacy of Rifampin-Streptomycin Combination for Two Weeks followed by Rifampin and Clarithromycin for Six Weeks for Treatment of Mycobacterium ulcerans Disease
(Antimicrobial Agents and Chemotherapy, 2014-02) Phillips, Richard Odame; Sarfo, Fred S.; Abass, Mohammed K.; Abotsi, Justice; Wilson, Tuah; et.al
Buruli ulcer, an ulcerating skin disease caused by Mycobacterium ulcerans infection, is common in tropical areas of western Africa. We determined the clinical and microbiological responses to administration of rifampin and streptomycin for 2 weeks followed by administration of rifampin and clarithromycin for 6 weeks in 43 patients with small laboratory-confirmed Buruli lesions and monitored for recurrence-free healing. Bacterial load in tissue samples before and after treatment for 6 and 12 weeks was monitored by semiquantitative culture. The success rate was 93%, and there was no recurrence after a 12-month follow-up. Eight percent had a positive culture 4 weeks after antibiotic treatment, but their lesions went on to heal. The findings indicate that rifampin and clarithromycin can replace rifampin and streptomycin for the continuation phase after rifampin and streptomycin administration for 2 weeks without any apparent loss of efficacy.
Clinical Efficacy of Combination of Rifampin and Streptomycin for Treatment of Mycobacterium ulcerans Disease
(Antimicrobial Agents and Chemotherapy, 2010-09) Sarfo, Fred Stephen; Phillips, Richard Odame; Asiedu, Kingsley; Ampadu, Edwin; Bobi, Nana; et.al
We have evaluated the clinical efficacy of the combination of oral rifampin at 10 mg/kg of body weight and intramuscular streptomycin at 15 mg/kg for 8 weeks (RS8), as recommended by the WHO, in 160 PCRconfirmed cases of Mycobacterium ulcerans disease. In 152 patients (95%) with all forms of disease from early nodules to large ulcers, with or without edema, the lesions healed without recourse to surgery. Eight patients whose ulcers were healing poorly had skin grafting after completion of antibiotics. There were no recurrences among 158 patients reviewed at the 1-year follow-up. The times to complete healing ranged from 2 to 48 weeks, according to the type and size of the lesion, but the average rate of healing (rate of reduction in ulcer diameter) varied widely. Thirteen subjects had positive cultures for M. ulcerans during or after treatment, but all the lesions healed without further antibiotic treatment. Adverse events were rare. These results confirm the efficacy of RS8 delivered in a community setting.
Cytokine mRNA Expression in Mycobacteriam ulcerans-Infected Human Skin and Correlation with Local Inflammatory Response
(American Society for Microbiology, 2006-05) Phillips, Richard Odame; Horsfield, C.; Mangan, J.; Laing, K.; Etuaful, S.; et.al
Cytokine mRNA expression in biopsies of Mycobacterium ulcerans-infected human tissue was investigated using real-time PCR, and the findings were correlated with the clinical stages of disease and histopathologies. A broad range of cytokine mRNAs were detected in 16 early nodules and 28 late-stage ulcers, including those for the Th1 cytokines tumor necrosis factor alpha (TNF- ) and gamma interferon (IFN- ) and the Th2 cytokine interleukin 10 (IL-10). IFN- was strongly expressed in both nodules and ulcers, suggesting that a Th1 response begins early in the disease. There was a significantly higher expression of IL-8 and other proinflammatory cytokines in results from 32 biopsies with neutrophilia than in those from 12 biopsies without acute inflammation. Ten tissue samples containing granulomas showed high mRNA expression for IFN- , IL-1 , IL-12p35, IL-12p40, IL-15, and TNF- relative to 34 tissue samples without granulomas. These results suggest that the human immune response to M. ulcerans is similar to that seen with some other mycobacteria despite the presence of the toxin mycolactone in the tissues.
Cytokine Response to Antigen Stimulation of Whole Blood from Patients with Mycobacterium ulcerans Disease Compared to That from Patients with Tuberculosis
(American Society for Microbiology, 2006-02) Phillips, Richard Odame; Horsfield, C.; Kuijper, S.; Sarfo, Fred Stephen; Obeng-Baah, J.; et.al
Mycobacterium ulcerans disease (Buruli ulcer) is a skin-ulcerating infection common in some parts of the tropics. We have investigated cytokine secretion after stimulation of whole blood from Buruli ulcer (BU) patients in a region of endemicity in Ghana with M. ulcerans sonicate or culture filtrate antigens to investigate the development of the response over time and its specificity by comparison with the response to Mycobacterium tuberculosis sonicate in human immunodeficiency virus-negative tuberculosis patients. Significant gamma interferon (IFN- ) production in response to whole-blood stimulation with M. ulcerans sonicate was detected in patients with ulcers, which was higher than that in patients with nodules but similar to subjects with healed BU. The mean IFN- response in household contacts of BU patients was not significantly different from that in healthy control subjects from an area of nonendemicity. Results in patients with untreated, smear-positive pulmonary tuberculosis and tuberculosis patients on treatment for more than 2 weeks showed that BU patients responded better to M. ulcerans antigens than tuberculosis patients. In contrast, interleukin-10 results were higher in patients with active M. ulcerans disease than in those with healed lesions, but the pattern of response was similar to that seen in tuberculosis. A similar pattern of cytokine secretion was found using M. tuberculosis sonicate as an antigen. Neither of the two culture filtrate antigens of M. ulcerans appeared to be more specific than M. ulcerans sonicate. In the early stages of M. ulcerans disease there was a mixed Th1 and Th2 cytokine response, but the Th1 response emerged as the dominant type.
Detection of Highly Prevalent Hepatitis B Virus Coinfection among HIV-Seropositive Persons in Ghana
(American Society for Microbiology, 2010-09) Geretti, Anna Maria; Patel, Mauli; Sarfo, Fred Stephen; Phillips, Richard Odame; Chadwick, David; et.al
Simple hepatitis B surface antigen (HBsAg) tests may facilitate ascertainment of hepatitis B virus (HBV) infection in settings with high endemicity but limited infrastructure. We evaluated two rapid HBsAg tests and characterized HBV coinfection in a Ghanaian HIV-positive cohort. Samples from 838 patients were tested by the rapid assays Determine and Vikia and the reference assays Architect, Murex version 3, and Liaison Ultra. The assays were also evaluated using the 2nd International Standard, a seroconversion panel, and two mutant panels. HBsAg-positive samples underwent HBV DNA quantification by real-time PCR and surface and polymerase gene population sequencing. Overall, 140/838 patients (16.7%; 95% confidence interval, 14.2 to 19.2%) were HBsAg positive, and of these, 103/140 (73.6%) were e-antigen negative and 118/140 (84.3%) showed an HBV DNA level of >14 IU/ml (median, 8,279 IU/ml). Assay sensitivities and specificities were as follows: Architect, 97.9 and 99.6%; Liaison, 97.1 and 99.4%; Murex, 98.6 and 99.3%; Determine, 69.3 and 100%; and Vikia, 70.7 and 100%. With Determine, the limit of detection was >1.5 to 3.4 HBsAg IU/ml, and the median HBV DNA loads were 598 and 10,905 IU/ml in Determine-negative and -positive samples, respectively (P 0.0005). Results were similar with the Vikia assay. HBV DNA sequencing indicated infection with genotype E in 82/86 (95.3%) patients. HBsAg mutations affected assay performance, including a T123A mutant that escaped detection by Architect. Major drug resistance mutations were observed in 4/86 patients (4.6%). The prevalence of HBV coinfection was high in this HIV-positive Ghanaian cohort. The two rapid assays identified HBsAg-positive patients at risk for liver disease with high specificity, albeit with only moderate sensitivity.
Dynamics of the Cytokine Response to Mycobacterium ulcerans during Antibiotic Treatment for M. ulcerans Disease (Buruli Ulcer) in Humans
(American Society for Microbiology, 2009-01) Sarfo, Fred Stephen; Phillips, Richard Odame; Ampadu, E.; Sarpong, F.; Adentwe, E.; et.al
We have studied the evolution of the gamma interferon (IFN- ) and interleukin 10 (IL-10) responses after Mycobacterium ulcerans sonicate stimulation of whole blood from patients with early M. ulcerans lesions during treatment with rifampin and streptomycin for 8 weeks. Among the 26 patients, secretion of IFN- increased during treatment, with a significant increase at 4 weeks and a further increase after 8 weeks overall. The increase was more rapid in patients with large or ulcerative lesions, becoming significant by 4 weeks. For small lesions, there was only a minor increase, which did not reach significance. There was no significant change in the median IL-10 response during antibiotic therapy, and there was no inverse correlation between IFN- and IL-10 responses. These results demonstrate that an IFN- secretory response to M. ulcerans developed, independently of IL-10 secretion, in patients whose M. ulcerans disease healed during antibiotic therapy.
Efficacy of the Combination Rifampin-Streptomycin in Preventing Growth of Mycobacterium ulcerans in Early Lesions of Buruli Ulcer in Humans
(American Society for Microbiology, 2005-04-29) Etuaful, S.; Carbonnelle, B.; Phillips, Richard Odame; Evans, M.; Ofori-Adjei, D.; et.al
Mycobacterium ulcerans disease is common in some humid tropical areas, particularly in parts of West Africa, and current management is by surgical excision of skin lesions ranging from early nodules to extensive ulcers (Buruli ulcer). Antibiotic therapy would be more accessible to patients in areas of Buruli ulcer endemicity. We report a study of the efficacy of antibiotics in converting early lesions (nodules and plaques) from culture positive to culture negative. Lesions were excised either immediately or after treatment with rifampin orally at 10 mg/kg of body weight and streptomycin intramuscularly at 15 mg/kg of body weight daily for 2, 4, 8, or 12 weeks and examined by quantitative bacterial culture, PCR, and histopathology for M. ulcerans. Lesions were measured during treatment. Five lesions excised without antibiotic treatment and five lesions treated with antibiotics for 2 weeks were culture positive, whereas three lesions treated for 4 weeks, five treated for 8 weeks, and three treated for 12 weeks were culture negative. No lesions became enlarged during antibiotic treatment, and most became smaller. Treatment with rifampin and streptomycin for 4 weeks or more inhibited growth of M. ulcerans in human tissue, and it provides a basis for proceeding to a trial of antibiotic therapy as an alternative to surgery for early M. ulcerans disease.
Hepatitis C in Sub-Saharan Africa: Urgent Need for Attention
(Oxford University Press, 2014-07) Layden, Jennifer E.; Phillips, Richard Odame; Opare-Sem, Ohene; Akere, Adegboyega; Salako, Babatunde L.; et.al
The hepatitis C virus (HCV), which was not recognized as an infectious agent until the 1980s, is responsible for a worldwide epidemic. The World Health Organization estimates global prevalence at 2.8%, with 185 million persons infected. In contrast to hepatitis B, where successful vaccine campaigns have reduced the disease burden, much less progress has been made toward the control of HCV. Phylogenetic studies suggest that HCV originated in Africa and has been endemic in some regions for at least 500–600 years. However, little is known about the epidemiology, transmission, and clinical course of HCV in Africa. With the advent of highly effective anti- HCV agents, there exists great potential to at least curb the global epidemic. For regions such as sub-Saharan Africa, however, this will require a thorough understanding of the regional population-level epidemiology, risk factors, and transmission mechanisms. Only then can effective treatment and prevention strategies be introduced.
High Frequency of Active HCV Infection Among Seropositive Cases in West Africa and Evidence for Multiple Transmission Pathways
(Oxford University Press, 2014-12-04) Layden, Jennifer E.; Phillips, Richard Odame; Owusu-Ofori, Shirley; Sarfo, Fred Stephen; Kliethermes, Stephanie; et.al
Sub-Saharan Africa (SSA) has one of the highest global hepatitis C virus (HCV) prevalence estimates. However, reports that suggest high rates of serologic false positives and low levels of viremia have led to uncertainty regarding the burden of active infection in this region. Additionally, little is known about the predominant transmission risk factors in SSA.
High prevalence of renal dysfunction and association with risk of death amongst HIV-infected Ghanaians
(Elsevier Ltd., 2013-03-28) Phillips, Richard Odame; Shakoor, Shaid; Appiah, Lambert; Keegan, Rosie; Sarfo, Fred Stephen; et.al
To determine the prevalence of HIV-associated renal dysfunction (RD), identify risk factors for RD and explore the association between baseline renal function and mortality in an HIV-infected population in Ghana. Methods: Creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR) was calculated in patients attending an HIV clinic between 2004 and 2011 using Cockcroft-Gault, MDRD and CKD-EPI formulae. Logistic regression analysis was used to identify risk factors associated with RD and KaplaneMeier/Cox proportional regression analyses to explore associations between baseline CrCl/eGFR and subsequent mortality. Results: In 3137 patients starting antiretroviral therapy (ART) the frequency (95%-CI) of RD, defined by CrCl <60 ml/min/1.73 m2 using Cockroft-Gault formula was 38.8% (37.1e40.5%). RD prevalence in a sub-population of 238 patients, including proteinuria in the definition, was 15.3% (10.3e22.1%) in ART-treated and 43.6% (34.0e53.7%) in ART-na€ıve patients. RD at baseline was associated with increasing age, low CD4 counts, advanced WHO stage and female gender. Cox proportional hazard analysis identified an increased hazard of death with decreasing CrCl, HR 1.46 (1.31e1.63) for each tertile lower than CrCl of 90 ml/min/1.73 m2. Conclusions: RD is very common in HIV-infected ART-na€ıve Ghanaians, and associated with increased risk of mortality. Screening and monitoring of RD is important in this setting, particularly as tenofovir use increases.
Historical epidemiology of hepatitis C virus in select countries—volume 4
(John Wiley & Sons Ltd., 2017-07) Phillips, Richard Odame; Owusu-Ofori, S.; Kaliaskarova, K. S.; Ghazzawi, I. Al; Himatt, S. M.; et.al
Due to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country-specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.
Hypertension and renal failure in Kumasi, Ghana
(Human Hypertension, 1999-01-13) Plange-Rhule, J; Phillips, Richard Odame; Acheampong, JW; Saggar-Malik, AK; Cappuccio, FP; et.al
Hypertension is common in West Africa and likely to become more common as urbanisation increases. There are at present few facilities for the detection and management of hypertension so the influence it has on overall morbidity and mortality in the population is not clear. The objectives of the study were to assess: (a) renal disease and blood pressure related admissions and deaths among acute medical admissions to Komfo Anokye Teaching Hospital, Kumasi, during an 8-month period; and (b) the burden of renal disease among out-patient hypertensives at the same hospital. Ward admission books were examined in the four acute medical wards to ascertain admission diagnosis and cause of death (two 4-month periods in 1995 and 1996). Clinical assessment (blood pressure, plasma creatinine, proteinuria) was also made of 448 consecutive out-patient hypertensives seen between March 1995 and April 1996. Five Keywords: hypertension; renal disease; plasma creatinine; Ghanaians; West Africans Introduction Hypertension is an increasing problem in people of West African descent living in the western world.1,2 Studies in the United States3,4 and Britain5,6 have shown hypertension to be very common and its complications (stroke, heart failure, renal failure) a major cause of morbidity and mortality in black subjects in these countries. There are few data on the prevalence of hypertension in West Africa. Studies suggest that the prevalence of hypertension is higher in urban than rural areas.7–9 Increasing urbanisation in West Africa is associated with an increasing prevalence of hypertension9 so the burden of hypertension and its related complications on morbidity and mortality will rise. Indeed, hypertensive renal damage is the main cause of end-stage renal failure in black populations both in the UK10 and in West Africa.11,12 There is a lack of primary care facilities for the detection of hypertension in West Africa and clinics Correspondence: Dr JB Eastwood, Department of Renal Medicine, St George’s Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK Received 27 March 1998; revised 25 July 1998; accepted 31 July 1998 hundred and ninety-three (17.9%) of 3317 acute medical admissions were ascribable to a cardiovascular cause (hypertension, heart failure, stroke); 171 (28.8%) of these died. One hundred and sixty-six (5.0%) had renal disease of whom 45 (27.1%) died, usually of end-stage renal disease. Among the 448 hypertensive out-patients, 30.2% (110 out of 365) had a plasma creatinine .140 mmol/l (48 > 400 mmol/l) and 25.5% (96 out of 376) had proteinuria. Eighty-nine of the 448 had a diastolic blood pressure >115 mm Hg; in this group 38 (42.7%) had a plasma creatinine of .140 mmol/l (and 18 or 20.2% >400 mmol/l). In conclusion, cardiovascular and renal disease are important contributors to morbidity and mortality among acute medical admissions to a large city hospital in Ghana. Among out-patient hypertensives renal disease is an important complication, especially in those with the more severe hypertension.
Validation of NO2 and NO from the Atmospheric Chemistry Experiment (ACE)
(Atmos. Chem. Phys., 2008-10-08) Kerzenmacher, T.; Wolff, M. A.; Strong, K.; Dupuy, E.; Walker, K. A.; Amekudzi, L. K.; et.al
Vertical profiles of NO2 and NO have been obtained from solar occultation measurements by the Atmospheric Chemistry Experiment (ACE), using an infrared Fourier Transform Spectrometer (ACE-FTS) and (for NO2) an ultraviolet-visible-near-infrared spectrometer, MAESTRO (Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation). In this paper, the quality of the ACE-FTS version 2.2 NO2 and NO and the MAESTRO version 1.2 NO2 data are assessed using other solar occultation measurements (HALOE, SAGE II, SAGE III, POAM III, SCIAMACHY), stellar occultation measurements (GOMOS), limb measurements (MIPAS, OSIRIS), nadir measurements (SCIAMACHY), balloon-borne measurements (SPIRALE, SAOZ) and ground-based measurements (UV-VIS, FTIR). Time differences between the comparison measurements were reduced using either a tight coincidence criterion, or where possible, chemical box models. ACE-FTS NO2 and NO and the MAESTRO NO2 are generally consistent with the correlative data. The ACE-FTS and MAESTRO NO2 volume mixing ratio (VMR) profiles agree with the profiles from other satellite data sets to within about 20% between 25 and 40 km, with the exception of MIPAS ESA (for ACE-FTS) and SAGE II (for ACE-FTS (sunrise) and MAESTRO) and suggest a negative bias between 23 and 40 km of about 10%. MAESTRO reports larger VMR values than the ACE-FTS. In comparisons with HALOE, ACE-FTS NO VMRs typically (on average) agree to ±8% from 22 to 64 km and to +10% from 93 to 105 km, with maxima of 21% and 36%, respectively. Partial column comparisons for NO2 show that there is quite good agreement between the ACE instruments and the FTIRs, with a mean difference of +7.3% for ACEFTS and +12.8% for MAESTRO.

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