Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial.

OBJECTIVE: T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery. METHODS: A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry. RESULTS: Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported. CONCLUSION: Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa

Needs assessment to strengthen capacity in water and sanitation research in Africa:experiences of the African SNOWS consortium

Despite its contribution to global disease burden, diarrhoeal disease is still a relatively neglected area for research funding, especially in low-income country settings. The SNOWS consortium (Scientists Networked for Outcomes from Water and Sanitation) is funded by the Wellcome Trust under an initiative to build the necessary research skills in Africa. This paper focuses on the research training needs of the consortium as identified during the first three years of the project

CD4+ T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa

Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitor-based regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/µl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/µl was 529/µl [95% confidence interval (CI): 517-541] in North America, 494/µl (95% CI: 429-559) in West Africa, 515/µl (95% CI: 508-522) in Southern Africa, 503/µl (95% CI: 478-528) in Asia and 437/µl (95% CI: 425-449) in East Africa. Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional leve

Erysipelothrix rhusiopathiae infection in pigs, pork and raw pork handlers in Kamuli District, Eastern Uganda

Erysipelothrix rhusiopathiae is a zoonotic ubiquitous gram-positive bacterium, which causes erysipelas in swine, mammals, birds and erysipeloid in humans. People in contact with animals, animal products or animal wastes are at greatest risk. From June 2013 to December 2015, a multidisciplinary risk assessment was conducted to identify the risks associated with E. rhusiopathiae along the pig value chain in Kamuli District, Eastern Uganda. Quantitative and qualitative methods of data collection were employed. Serum from 460 pigs and 100 fresh pork samples and human EDTA blood was gathered from 302 raw pork handlers (butchers, abattoir workers and housewives), for microbiology cultures and serology. Six focus group discussions were conducted with 26 butchers/abattoir workers and with 26 housewives. Three key informant interviews were conducted with a health assistant, veterinary officer and a nursing officer. Overall, 308/460 (67%) of the pig sera carried antibodies against E. rhusiopathiae. Forty-five percent (45/100, 45%) of the fresh pork samples were contaminated with E. rhusiopathiae and 30/302 (9.9%) of the raw pork handlers were positive for infection with E. rhusiopathiae. The mean age of the raw pork handlers was 38 years, 21/30 (70%) of men were infected compared to 9/30(30%) of the women. The main risk factor for the infection was the type of raw pork handler. Of the abattoir workers 14/38 (47%) were positive, 9/59 (30%) of the butchers and 7/205 (23.3%) of the housewives were infected with E.rhusiopathiae. This is the first ever report of E. rhusiopathiae in pigs and humans in Uganda and East Africa. Previously, the acute form of swine erysipelas may have been confused for other diseases in pigs reported in Uganda which are characterized acute symptoms such as sudden death (for example, African swine fever). We recommend increasing awareness of the disease among animal and human practitioners as treatment is easy and available and vaccination is possible. However, the disease is still unknown to local veterinarians, clinical doctors, meat inspectors, butchers and laboratory personnel. Proper hygiene, regular pork inspection, use of protective wear among people working/ in contact with animals should be promoted. The study was conducted under the Safe Food, Fair Food project led by the International Livestock Research Institute and carried out with the financial support of the Federal Ministry for Economic Cooperation and Development, Germany, and the CGIAR Research Program on Agriculture for Nutrition and Health, led by the International Food Policy Research Institute

The role of emergency department HIV care in resource-poor settings: lessons learned in western Kenya

The human immunodeficiency virus (HIV) pandemic in sub-Saharan Africa and other high prevalence regions continues to overwhelm health care systems. While there has been a global response to improve the delivery of antiretroviral therapy in these high prevalence regions, there are few models that have developed an adequate plan to deal with HIV specifically in resource-poor emergency department settings. In this manuscript, we report on the experience scaling up HIV care at one emergency department in a large referral hospital located in western Kenya. Specifically, we describe how rapid bedside HIV testing helps to narrow the differential diagnosis of disease processes in acute care patients and how HIV screening of patients discharged from the emergency department can detect HIV-infected individuals

Mentorship needs at academic institutions in resource-limited settings: a survey at makerere university college of health sciences

<p>Abstract</p> <p>Background</p> <p>Mentoring is a core component of medical education and career success. There is increasing global emphasis on mentorship of young scientists in order to train and develop the next leaders in global health. However, mentoring efforts are challenged by the high clinical, research and administrative demands. We evaluated the status and nature of mentoring practices at Makerere University College of Health Sciences (MAKCHS).</p> <p>Methods</p> <p>Pre-tested, self-administered questionnaires were sent by email to all Fogarty alumni at the MAKCHS (mentors) and each of them was requested to complete and email back the questionnaire. In addition to training level and number of mentors, the questionnaires had open-ended questions covering themes such as; status of mentorship, challenges faced by mentors and strategies to improve and sustain mentorship within MAKCHS. Similarly, open-ended questionnaires were sent and received by email from all graduate students (mentees) registered with the Uganda Society for Health Scientists (USHS). Qualitative data from mentors and mentees was analyzed manually according to the pre-determined themes.</p> <p>Results</p> <p>Twenty- two out of 100 mentors responded (14 email and 8 hard copy responses). Up to 77% (17/22) of mentors had Master's-level training and only 18% (4/22) had doctorate-level training. About 40% of the mentors had ≥ two mentees while 27% had none. Qualitative results showed that mentors needed support in terms of training in mentoring skills and logistical/financial support to carry out successful mentorship. Junior scientists and students reported that mentorship is not yet institutionalized and it is currently occurring in an adhoc manner. There was lack of awareness of roles of mentors and mentees. The mentors mentioned the limited number of practicing mentors at the college and thus the need for training courses and guidelines for faculty members in regard to mentorship at academic institutions.</p> <p>Conclusions</p> <p>Both mentors and mentees were willing to improve mentorship practices at MAKCHS. There is need for institutional commitment to uphold and sustain the mentorship best practices. We recommend a collaborative approach by the stakeholders in global health promotion to build local capacity in mentoring African health professionals.</p