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Background: Retention of pregnant and breastfeeding women and their infants in HIV care still remains low in Uganda. Recent literature has shown that the effects of COVID-19 mitigation measures may increase disease burden of common illnesses including HIV, Tuberculosis, Malaria and other key public health outcomes such as maternal mortality. A research program was undertaken to locate disengaged HIV positive women on option B+ and supported them to reengage in care. A 1 year follow up done following the tracing revealed that some women still disengaged from care. We aimed to establish the barriers to and facilitators for reengagement in care among previously traced women on option B+, and how these could have been impacted by the COVID-19 pandemic. Methods: This was a cross sectional qualitative study using individual interviews conducted in June and July, 2020, a period when the COVID-19 response measures such as lockdown and restrictions on transport were being observed in Uganda. Study participants were drawn from nine peri-urban and rural public healthcare facilities. Purposive sampling was used to select women still engaged in and those who disengaged from care approximately after 1 year since they were last contacted. Seventeen participants were included. Data was analysed using the content analysis approach. Results: Women reported various barriers that affected their reengagement and retention in care during the COVID-19 pandemic. These included structural barriers such as transport difficulties and financial constraints; clinical barriers which included unsupportive healthcare workers, short supply of drugs, clinic delays, lack of privacy and medicine side effects; and psychosocial barriers such as perceived or experienced stigma and non-disclosure of HIV sero-status. Supportive structures such as family, community-based medicine distribution models, and a friendly healthcare environment were key facilitators to retention in care among this group. The COVID-19 pandemic was reported to exacerbate the barriers to retention in care. Conclusions: COVID-19 may exacerbate barriers to retention in HIV care among those who have experienced previous disengagement. We recommend community-based models such as drop out centres, peer facilitated distribution and community outreaches as alternative measures for access to ART during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Translational research is a process of applying knowledge from basic biology and clinical trials to techniques and tools that address critical medical needs. Translational research is less explored in the Ugandan health system, yet, it is fundamental in enhancing human health and well-being. With the current high disease burden in Uganda, there are many opportunities for exploring, developing and utilising translational research.Main Body: In this article, we described the current state, barriers and opportunities for translational research in Uganda. We noted that translational research is underutilised and hindered by limited funding, collaborations, laboratory infrastructure, trained personnel, equipment and research diversity. However, with active collaborations and funding, it is possible to set up and develop thriving translational research in Uganda. Researchers need to leverage existing international collaborations to enhance translational research capacity development.Conclusion: Expanding the integration of clinical and translational research in Uganda health care system will improve clinical care. [ABSTRACT FROM AUTHOR]

Background: Cataracts occur earlier among HIV-infected adults and this is attributed to various intraocular inflammatory processes that result in early degeneration. In this study we purposed to investigate whether HIV infected individuals with cataracts develop heightened intraocular inflammatory processes compared to their HIV negative counterparts by determining the concentration of 8 cytokines in the aqueous humour of HIV-positive adults with cataracts and their HIV-negative counterparts.Methods: A cross-sectional study was conducted among consecutive adults with cataracts that were operated in an ophthalmology surgical camp in western Uganda. We determined levels of Granulocyte macrophage stimulating factor (GM-CSF), interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrotic factor alpha (TNF-a), interferon gamma (IFN-g), interleukin 4 (IL-4), interleukin 2 (IL-2), and interleukin (IL-10) in the aqueous fluid using a multiplexed cytokine analysis. Data was entered in the SPSS version 10 and analyzed using STATA statistical software version 7.0. Categorical and continuous variables were compared using the χ2 test, Fisher's exact test and the Student's t-test. Bonferroni correction was used to cater for multiple comparison of p values for the various cytokines.Results: The 50 adults that underwent cataract surgery were outdoor peasants with similar exposure hours to UV radiation. The HIV-positive patients were younger {median age 43 years (SD 11.741)} compared to the HIV -negative patients {median age 66.5 years (SD 21.4)}. The mean CD4+ T cell count of the HIV-positive patients was 161 cells /mm3, and 12(48%) had started anti-retroviral therapy (ART). Pro inflammatory cytokines, GM-CSF, IL-8 and IL-10 were significantly higher among HIV-positive individuals (p = 0.001, 0.030, < 0.001 respectively). HIV-positive individuals on ART also showed significantly higher levels of GM-CSF, IL-8 and IL - 10 (p = 0.002, 0.021, < 0.001 respectively). TNF-a and IL-4 were significantly higher among those with a CD4+ T cell count greater than 200cells/mm3 compared to those with CD4+ T cell count less than 200 cells/mm3 (p = 0.022, 0.032 respectively).Conclusion: Cataracts among HIV-positive adults were associated with higher intraocular inflammation relative to the healthy elderly individuals with cataracts. There is need to explore the potential role of intra-ocular anti-inflammatory agents in the management of cataracts among HIV positive patients. [ABSTRACT FROM AUTHOR]

Background: In the last decade, Makerere University College of Health Sciences (MakCHS) has taken strides in research and training to improve healthcare through collaborative training and research programs. However, there is limited data on the trends of MakCHS faculty contributions to research and on faculty growth to take leading roles in health research. This paper reviews MakCHS faculty research publications over 15.5 years and outlines possible strategies to enhance faculty research outputs.Methods: We used a mixed methods approach. A systematic review of research publications by faculty at MakCHS (PubMed and Google Scholar from January 1, 2000, to June 30, 2015) to quantify the number of research articles, areas researched, authorship contribution by MakCHS faculty, source of funding, as well as affiliated local and international collaborations. Graphs were used to shown trends in publications and leadership of authorship by faculty. Annual individual faculty research productivity was presented as publication per capita. Qualitative data on high priority needs to improve research outputs was collected through focus group discussions (FGDs) with faculty members, and analysed manually into emerging themes.Results: Of 298 faculty at MakCHS at 2015, 89 (30%) were female and 229 (77%) were junior and mid-level faculty (senior lecturer and below). The PubMed and Google Scholar searches yielded 6927 published articles, of which 3399 (49%) full-text articles were downloaded for analysis, 426/3825 (11%) available as titles/abstracts only, and 598/4423 (14%) were excluded. Only 614 articles were published in 2014, giving a publication per capita of 2.1 for any authorship, and 0.3 for first and last authorship positions. MakCHS faculty increasingly contributed as first, second, third, and last authors. Up to 57% of research was in infectious diseases, followed by non-communicable diseases (20%) and non-communicable maternal child health (11%). Priority needs to improve research outputs, as expressed by faculty, were (1) an institutionally led faculty career development program, (2) skills building in research methods and scientific writing, (3) protected time for research related activities, (4) opportunities for collaborative research, and (5) use of individual development plans.Conclusion: Faculty research productivity was low and dominated by infectious diseases and non-communicable disease research. There is a need for structured institutional support to optimise faculty research outputs. Only with increased research productivity will MakCHS and other academic institutions be able to make a significant contribution in addressing national health challenges. [ABSTRACT FROM AUTHOR]

Background: Effective leadership is a cornerstone of successful healthcare delivery in resource limited settings throughout the world. However, few programs in Africa prepare healthcare professionals with the leadership skills vital to the success of the healthcare systems in which they work. One such program, the Afya Bora Consortium Fellowship in Global Health Leadership, has been training health professionals since 2011. The purpose of this study was to assess what career changes, if any, the Afya Bora Fellowship's alumni have experienced since completing the fellowship, and to describe those changes. Methods: The Afya Bora Fellowship is a multidisciplinary, one-year training program that teaches health professionals leadership skills through didactic and experiential learning in four African countries. Between January 2011 and June 2013 the consortium trained 42 nurses and doctors. In November 2013, an electronic survey was sent to all alumni to assess their performance in the workplace post-fellowship. Results: Thirty-one (74%) of 42 alumni completed surveys. Twenty-one (68%) reported changes to their position at work; of those, sixteen (76%) believed the change was due to participation in the fellowship. All alumni reported improved performance at work, and cited the application of a wide range of fellowship skills, including leadership, research, communication, and mentoring. Twenty-six (84%) alumni spearheaded improvements in their workplaces and almost all (97%) remained in contact with colleagues from the fellowship. Among the respondents there were five publications, nine manuscripts in preparation, and three international conference presentations. Conclusions: Afya Bora alumni overwhelmingly reported that the one year fellowship positively influenced both their work and career trajectory. Training health professionals in leadership skills through didactic modules with the opportunity to apply learned skills at attachment sites in the Afya Bora Fellowship has an impact on performance in the workplace and the potential to improve long-term institutional capacity. [ABSTRACT FROM AUTHOR]

Background: Disclosure of parental HIV status is associated with a number of positive outcomes such as improved adherence to clinic appointments, lower levels of parental anxiety and depression, and mutual emotional support between parents and their children. Very few studies in low-resource settings have addressed the issues of parental disclosure of their HIV status to their children.Methods: A cross-sectional study was conducted among adult parents attending HIV/AIDS prevention, care and treatment clinic at Makerere University Infectious Diseases Institute (IDI), Kampala, Uganda. Participants were interviewed using the Parent Disclosure Interview (PDI) questionnaire which is a standard tool developed specifically for HIV infected parents. Data were analyzed using STATA version 13.1.Results: Of 344 participants, only 37 % had told at least one of their children that they were HIV positive. Barriers to disclosure were fear that children may tell other people about the parent's HIV status, desire not to worry or upset children and perceptions that children may not understand. Age of the parent, religion and having someone committed to care of the children were positively associated with parental disclosure of their HIV positives status. Attainment of tertiary level of education was negatively associated with parental disclosure of their HIV status.Conclusions: Parental disclosure of a positive HIVstatus to their children is still low in urban Kampala. There is therefore need to develop locally relevant interventions so as to increase rates of parental disclosure of a positive HIV status to their children and thus promote open and honest discussions about HIV/AIDS at family level. [ABSTRACT FROM AUTHOR]

Introduction: Due to a limited health workforce, many health care providers in Africa must take on health leadership roles with minimal formal training in leadership. Hence, the need to equip health care providers with practical skills required to lead high-impact health care programs. In Uganda, the Afya Bora Global Health Leadership Fellowship is implemented through the Makerere University College of Health Sciences (MakCHS) and her partner institutions. Lessons learned from the program, presented in this paper, may guide development of in-service training opportunities to enhance leadership skills of health workers in resource-limited settings.Methods: The Afya Bora Consortium, a consortium of four African and four U.S. academic institutions, offers 1-year global health leadership-training opportunities for nurses and doctors. Applications are received and vetted internationally by members of the consortium institutions in Botswana, Kenya, Tanzania, Uganda, and the USA. Fellows have 3 months of didactic modules and 9 months of mentored field attachment with 80% time dedicated to fellowship activities. Fellows' projects and experiences, documented during weekly mentor-fellow meetings and monthly mentoring team meetings, were compiled and analyzed manually using pre-determined themes to assess the effect of the program on fellows' daily leadership opportunities.Results: Between January 2011 and January 2015, 15 Ugandan fellows (nine doctors and six nurses) participated in the program. Each fellow received 8 weeks of didactic modules held at one of the African partner institutions and three online modules to enhance fellows' foundation in leadership, communication, monitoring and evaluation, health informatics, research methodology, grant writing, implementation science, and responsible conduct of research. In addition, fellows embarked on innovative projects that covered a wide spectrum of global health challenges including critical analysis of policy formulation and review processes, bottlenecks in implementation of national HIV early infant diagnosis and prevention of mother-to-child HIV-transmission programs, and use of routine laboratory data about antibiotic resistance to guide updates of essential drug lists.Conclusion: In-service leadership training was feasible, with ensured protected time for fellows to generate evidence-based solutions to challenges within their work environment. With structured mentorship, collaborative activities at academic institutions and local health care programs equipped health care providers with leadership skills. [ABSTRACT FROM AUTHOR]

Background: High disease burden and scarcity of healthcare resources present complex ethical dilemmas for nurses working in developing countries. We assessed nurses' knowledge in ethics and their perceptions about Continuous Nurses' Ethics Education (CNEE) for in-service nurses. Methods: Using an anonymous, pre-tested self-administered questionnaire, we assessed nurses' knowledge in basic ethics concepts at three regional hospitals in Uganda. Adequate knowledge was measured by a score ≥50% in the knowledge assessment test. Nurses' perceptions on CNEE were assessed using a six-point Likert scale. Results: Of 114 nurses, 91% were female; with mean age 44.7 (SD 10) years. Half were diploma, 47 (41%) certificates, 6 (5%) bachelors' degrees and one masters' level training. Overall, 18 (16%) scored ≥50% in the ethics knowledge test. Nurses with diploma or higher level of nursing training were less likely to fail the ethics knowledge than certificatelevel nurses (OR 0.14, 95% CI: 0.02-0.7). Only 45% had ever attended at least one CNEE session and up to 93% agreed that CNEE is required to improve nurses' ethics knowledge and practice. Conclusions: Nurses exhibited low knowledge in ethics and positive attitudes towards CNEE. We recommend structured CNEE programs to address basic concepts in nursing ethics and their application in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Sputum smear microscopy for tuberculosis (TB) diagnosis lacks sensitivity in HIV-infected symptomatic patients and increases the likelihood that mycobacterial infections particularly disseminated TB will be missed; delays in diagnosis can be fatal. Given the duration for MTB growth in blood culture, clinical predictors of MTB bacteremia may improve early diagnosis of mycobacteremia. We describe the predictors and mortality outcome of mycobacteremia among HIV-infected sputum smear-negative presumptive TB patients in a high prevalence HIV/TB setting. Methods: Between January and November 2011, all consenting HIV-infected adults suspected to have TB (presumptive TB) were consecutively enrolled. Diagnostic assessment included sputum smear microscopy, urine Determine TB lipoarabinomannan (LAM) antigen test, mycobacterial sputum and blood cultures, chest X-ray, and CD4 cell counts in addition to clinical and socio-demographic data. Patients were followed for 12 months post-enrolment. Results: Of 394 sputum smear-negative participants [female, 63.7%; median age (IQR) 32 (28-39) years], 41/394 (10.4%) had positive mycobacterial blood cultures (mycobacteremia); all isolates were M. tuberculosis (MTB). The median CD4 cell count was significantly lower among patients with mycobacteremia when compared with those without (CD4 31 versus 122 cells/μL, p < 0.001). In a multivariate analysis, male gender [OR 3.4, 95%CI (1.4-7.6), p = 0.005], CD4 count <100 cells/μL [OR 3.1, 95% CI (1.1-8.6), p = 0.030] and a positive lateral flow urine TB LAM antigen test [OR 15.3, 95%CI (5.7-41.1), p < 0.001] were significantly associated with mycobacteremia. At 12 months of follow-up, a trend towards increased mortality was observed in patients that were MTB blood culture positive (35.3%) compared with those that were MTB blood culture negative (23.3%) (p = 0.065). Conclusions: Mycobacteremia occurred in 10% of smear-negative patients and was associated with higher mortality compared with smear-negative patients without mycobacteremia. Advanced HIV disease (CD4 < 100 cells/mm³), male gender and positive lateral flow urine TB LAM test predicted mycobacteremia in HIV-infected smear-negative presumptive TB patients in this high prevalence TB/HIV setting. [ABSTRACT FROM AUTHOR]

Background Good mentoring is a key variable for determining success in completing a doctoral program. We identified prevailing mentoring practices among doctoral students and their mentors, identified common challenges facing doctoral training, and proposed some solutions to enhance the quality of the doctoral training experience for both candidates and mentors at Makerere University College of Health Sciences (MakCHS). Methods This cross-sectional qualitative evaluation was part of the monitoring and evaluation program for doctoral training. All doctoral students and their mentors were invited for a half-day workshop through the MakCHS mailing list. Prevailing doctoral supervision and mentoring guidelines were summarised in a one-hour presentation. Participants were split into two homogenous students' (mentees') and mentors' groups to discuss specific issues using a focus group discussion (FGD) guide, that highlighted four main themes in regard to the doctoral training experience; what was going well, what was not going well, proposed solutions to current challenges and perceived high priority areas for improvement. The two groups came together again and the note-takers from each group presented their data and discussions were recorded by a note-taker. Results Twelve out of 36 invited mentors (33%) and 22 out of 40 invited mentees (55%) attended the workshop. Mentors and mentees noted increasing numbers of doctoral students and mentors, which provided opportunities for peer mentorship. Delays in procurement and research regulatory processes subsequently delayed students' projects. Similarly, mentees mentioned challenges of limited; 1) infrastructure and mentors to support basic science research projects, 2) physical office space for doctoral students and their mentors, 3) skills in budgeting and finance management and 4) communication skills including conflict resolution. As solutions, the team proposed skills' training, induction courses for doctoral students-mentor teams, and a Frequently Asked Questions' document, to better inform mentors', mentees' expectations and experiences. Conclusion Systemic and infrastructural limitations affect the quality of the doctoral training experience at MaKCHS. Clinical and biomedical research infrastructure, in addition to training in research regulatory processes, procurement and finance management, communication skills and information technology, were highlighted as high priority areas for strategic interventions to improve mentoring within doctoral training of clinician scientists. [ABSTRACT FROM AUTHOR]

Background Up to 40% of HIV-infected individuals receiving Highly Active Antiretroviral Therapy (HAART) have poor CD4+ T-cell recovery. The role of natural killer (NK) cells in immune recovery during HAART is not well understood. We described the profiles of NK cell subsets and their expression of activating receptor, NKG2D and cytotoxicity receptor NKp46 among suboptimal immune responders to despite four years of suppressive HAART. Methods A case control study utilized frozen peripheral blood mononuclear cells (PBMC) from a cohort of HIV-infected adults that initiated HAART in 2004/5, at CD4 < 200 cells/μl. Cases were 'suboptimal' responders; patients within the lowest quartile of CD4+ T-cell reconstitution, with a median CD4 count increase of 129 (-43-199) cells/μl (between baseline and after 4 years of HAART) and controls were 'super-optimal' responders; patients within the highest quartile of CD4 T-cell reconstitution with a median CD4 count increase of 528 (416-878) cells/μl). Expression of NK cell lineage markers (CD56+/-CD16+/-) and receptors NKG2D and NKp46, was measured among PBMC from 29 cases of 'suboptimal' responders' and 23 controls of 'super-optimal responders', and compared among 'suboptimal' and 'superoptimal' responders. NK cell populations were compared using the Holm Sidak multiple comparison test and p values < 0.05 were considered statistically significant. Data was analyzed using FLOWJO and GraphPad Prism 6. Results 'Suboptimal responders' had a higher proportion of cytokine producing CD56++CD16+/- (CD56bri) NK cells than the 'super-optimal responders' p = 0.017, and CD56neg NK cells were lower among suboptimal than super-optimal responders (p = 0.007). The largest NK cell subset, CD56dim, was comparable among suboptimal responders and 'super-optimal immune responders'. Expression of NKG2D and NKp46 receptors on NK cell subsets (CD56bri, CD56neg and CD56dim), was comparable among 'suboptimal' and 'super-optimal' immune responders. Conclusions The pro-inflammatory CD56++CD16-- NK cells were higher among 'suboptimal' responders relative to 'super-optimal' responders, despite four years of suppressive HAART. Alteration of NK cell populations could inhibit host immune responses to infections among suboptimal responders. We recommend further analysis of NK cell function among suboptimal immune responders in order to inform targeted interventions to optimize immune recovery among HAART-treated adults. [ABSTRACT FROM AUTHOR]

Background: Most HIV-infected subjects exhibit a progressive rise in CD4 T-cell counts after initiation of highly active antiretroviral therapy (HAART). However, a subset of individuals exhibit very poor CD4 T-cell recovery despite effective control of HIV-RNA viraemia. We evaluated CD4 T-cell proliferation among suboptimal responders and its correlation with CD4 T-cell activation. Methods: The magnitude of CD4 increase (difference between absolute CD4 counts at baseline and absolute CD4 counts at 4 years of ART) was grouped into 4 quartiles for the 211 patients with sustained HIV-RNA viral suppression. Cases of 'Suboptimal immune responders' included patients within the lowest quartile [Median CD4 increase 165 (Range -43-298) cells/μl; n=52] and a comparison group of 'Optimal immune responders' was defined as patients within the highest quartile of CD4 increase [Median CD4 increase 528 (Range 417-878) cells/μl; n=52]. Frozen PBMC were thawed and analysed from a convenient sample of 39 suboptimal responders and 48 optimal responders after 4 years of suppressive antiretroviral therapy. T-cell activation was measured by proportions of T-cells expressing surface marker CD38 and HLADR (CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ cells). T-cell proliferation was determined by the extent of carboxyfluorescein diacetate succinimidyl ester (CFSE) dye dilution on culture day 5 of PBMCs in the presence of antigen (SEB, PPD, CMVpp65, GagA and GagD). Samples were analyzed on a FACS Calibur flow cytometer and flow data was analyzed using FlowJo and GraphPad. Results: Overall, CD4 T-cell proliferation on stimulation with SEB, PPD, CMVpp65, Gag A and Gag D.antigens, was lower among suboptimal than optimal responders; this was significant for SEB (CD4+ p=0.003; CD8+ p=0.048) and PPD antigens (CD8+ p=0.038). Among suboptimal responders, T-cell proliferation decreased with increasing immune activation (Negative correlation; slope = -0.13±-0.11) but not among optimal responders. Conclusion: T-cell immune activation and exhaustion were associated with poor proliferation among suboptimal responders to HAART despite sustained viral suppression. We recommend studies to further understand the mechanisms leading to impaired T-cell function among suboptimal responders as well as the potential role of immune modulation in optimizing CD4 count and functional recovery after HAART. [ABSTRACT FROM AUTHOR]

Background: The AIDS Control Program (ACP) in Uganda has spearheaded the national health sector HIV response for the last three decades. ACP has developed, revised and implemented various HIV prevention, care and treatment policies in order to keep interventions relevant to the changing dynamics of the HIV epidemic. However, the ACP team and partners remain concerned about the lengthy policy development processes. This study documented the policy development and revision processes to identify strengths and weaknesses in order to inform adjustments as Uganda embraces the move to 'zero' HIV infections. Methods: Data was collected through a review of the relevant policy documents and key informant interviews with the five program officers involved in the recently developed Safe Male Circumcision (SMC) policy and the recently revised HIV Counseling and Testing (HCT) policy. Qualitative data was analyzed manually using predetermined themes. Results: Development and revision of the SMC and HCT policies followed similar processes that included a series of meetings between senior management and a selected technical working group. However, the gaps included: i) inadequate awareness of the existence of national policy development and management guidelines; ii) limited engagement of the policy analysis unit in the policy development/revision processes; iii) inadequate tracking and evaluation of the policies before revision or development of new related policies; iv) lack of specific protocols/ standard operating procedures (SOPs); and, v) limited indigenous funding for the entire policy development processes which contributed to non-adherence to the anticipated timelines. Conclusions: Policy development and revision of the SMC and HCT policies followed similar processes. Gaps identified included lack of protocols/SOPs for the processes and limited indigenous funding to support adherence to anticipated timelines. We recommend active involvement of the policy analysis unit in all policy processes. Specific protocols/SOPs for development, analysis, revision, implementation, monitoring, evaluation and impact assessment processes should be developed prior to commencement of the activities. [ABSTRACT FROM AUTHOR]

Background: Malaria case management is a key strategy for malaria control. Effective coverage of parasite-based malaria diagnosis (PMD) remains limited in malaria endemic countries. This study assessed the health system's capacity to absorb PMD at primary health care facilities in Uganda. Methods: In a cross sectional survey, using multi-stage cluster sampling, lower level health facilities (LLHF) in 11 districts in Uganda were assessed for 1) tools, 2) skills, 3) staff and infrastructure, and 4) structures, systems and roles necessary for the implementing of PMD. Results: Tools for PMD (microscopy and/or RDTs) were available at 30 (24%) of the 125 LLHF. All LLHF had patient registers and 15% had functional in-patient facilities. Three months' long stock-out periods were reported for oral and parenteral quinine at 39% and 47% of LLHF respectively. Out of 131 health workers interviewed, 86 (66%) were nursing assistants; 56 (43%) had received on-job training on malaria case management and 47 (36%) had adequate knowledge in malaria case management. Overall, only 18% (131/730) Ministry of Health approved staff positions were filled by qualified personnel and 12% were recruited or transferred within six months preceding the survey. Of 186 patients that received referrals from LLHF, 130(70%) had received pre-referral anti-malarial drugs, none received pre-referral rectal artesunate and 35% had been referred due to poor response to antimalarial drugs. Conclusion: Primary health care facilities had inadequate human and infrastructural capacity to effectively implement universal parasite-based malaria diagnosis. The priority capacity building needs identified were: 1) recruitment and retention of qualified staff, 2) comprehensive training of health workers in fever management, 3) malaria diagnosis quality control systems and 4) strengthening of supply chain, stock management and referral systems. [ABSTRACT FROM AUTHOR]

Background: The training of health workers in the use of malaria rapid diagnostic tests (RDTs) is an important component of a wider strategy to improve parasite-based malaria diagnosis at lower level health care facilities (LLHFs) where microscopy is not readily available for all patients with suspected malaria. This study describes the process and cost of training to attain competence of lower level health workers to perform malaria RDTs in a public health system setting in eastern Uganda. Methods: Health workers from 21 health facilities in Uganda were given a one-day central training on the use of RDTs in malaria case management, including practical skills on how to perform read and interpret the test results. Successful trainees subsequently integrated the use of RDTs into their routine care for febrile patients at their LLHFs and transferred their acquired skills to colleagues (cascade training model). A cross-sectional evaluation of the health workers' competence in performing RDTs was conducted six weeks following the training, incorporating observation, in-depth interviews with health workers and the review of health facility records relating to tests offered and antimalarial drug (AMD) prescriptions pre and post training. The direct costs relating to the training processes were also documented. Results: Overall, 135 health workers were trained including 63 (47%) nursing assistants, a group of care providers without formal medical training. All trainees passed the post-training concordance test with ? 80% except 12 that required re-training. Six weeks after the one-day training, 51/64 (80%) of the health workers accurately performed the critical steps in performing the RDT. The performance was similar among the 10 (16%) participants who were peer-trained by their trained colleagues. Only 9 (14%) did not draw the appropriate amount of blood using pipette. The average cost of the one-day training was US$ 101 (range $92-$112), with the main cost drivers being trainee travel and per-diems. Health workers offered RDTs to 76% of febrile patients and AMD prescriptions reduced by 37% six weeks post-training. Conclusion: One-day training on the use of RDTs successfully provided adequate skill and competency among health workers to perform RDTs in fever case management at LLHF in a Uganda setting. The cost averaged at US $101 per health worker trained, with the main cost drivers being trainee travel and per diems. Given the good peer training noted in this study, there is need to explore the cost-effectiveness of a cascade training model for large scale implementation of RDTs. [ABSTRACT FROM AUTHOR]

Background: Presumptive treatment of malaria is common practice in malaria endemic resource-limited settings. With the changing epidemiology of malaria and the introduction of artemisinin-based combination therapy (ACT), there is increasing need for parasite-based malaria case management to prevent unnecessary use of anti-malarial medicines, improve patient care in parasite-positive patients and identify parasite-negative patients in whom another diagnosis must be sought. Although parasitological confirmation by microscopy or alternatively by malaria rapid diagnostic tests (RDTs) is recommended in all patients suspected of malaria before treatment, gaps remain in the implementation of this policy in resource-limited settings. There is need to evaluate the use of RDTs among highly active anti-retroviral therapy (HAART)-treated people living with HIV (PLHIV). Methods: Within an urban prospective observational research cohort of 559 PLHIV initiated on HAART and cotrimoxazole prophylaxis between April, 2004 and April, 2005, 128 patients with sustained HIV-RNA viral load < 400 copies/ml for four years were evaluated, in a cross-sectional study, for asymptomatic malaria infection using a histidine-rich protein-2 (HRP-2) RDT to detect Plasmodium falciparum antigen in peripheral blood. Patients with positive RDT results had microscopy performed to determine the parasite densities and were followed for clinical signs and symptoms during the subsequent six months. Results: Of the 128 asymptomatic patients screened, only 5 (4%) had asymptomatic P. falciparum antigenaemia. All the patients with positive HRP2 RDT results showed malaria parasites on thick film with parasite densities ranging from 02-15 malaria parasites per high power field. None of the patients with positive RDT results reported signs and symptoms of malaria infection during the subsequent six months. Conclusions: In an urban area of low to moderate stable malaria transmission, there was low HRP2 P. falciparum antigenaemia among PLHIV after long-term HAART and cotrimoxazole prophylaxis. Parasite-based malaria diagnosis (PMD) is recommended among PLHIV that are on long-term anti-retroviral therapy. RDTs should be utilized to expand PMD in similar settings where microscopy is unavailable. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated. Methods: T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30]. Results: Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022]. Conclusion: T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART. [ABSTRACT FROM AUTHOR]

Background: Early and accurate diagnosis of malaria followed by prompt treatment reduces the risk of severe disease in malaria endemic regions. Presumptive treatment of malaria is widely practised where microscopy or rapid diagnostic tests (RDTs) are not readily available. With the introduction of artemisinin-based combination therapy (ACT) for treatment of malaria in many low-resource settings, there is need to target treatment to patients with parasitologically confirmed malaria in order to improve quality of care, reduce over consumption of anti-malarials, reduce drug pressure and in turn delay development and spread of drug resistance. This study evaluated the effect of malaria RDTs on health workers' anti-malarial drug (AMD) prescriptions among outpatients at low level health care facilities (LLHCF) within different malaria epidemiological settings in Uganda. Methods: All health workers (HWs) in 21 selected intervention (where RDTs were deployed) LLHF were invited for training on the use RDTs. All HWs were trained to use RDTs for parasitological diagnosis of all suspected malaria cases irrespective of age. Five LLHCFs with clinical diagnosis (CD only) were included for comparison. Subsequently AMD prescriptions were compared using both a 'pre - post' and 'intervention - control' analysis designs. In-depth interviews of the HWs were conducted to explore any factors that influence AMD prescription practices. Results: A total of 166,131 out-patient attendances (OPD) were evaluated at 21 intervention LLHCFs. Overall use of RDTs resulted in a 38% point reduction in AMD prescriptions. There was a two-fold reduction (RR 0.62, 95% CI 0.55-0.70) in AMD prescription with the greatest reduction in the hypo-endemic setting (RR 0.46 95% CI 0.51-0.53) but no significant change in the urban setting (RR1.01, p-value = 0.820). Over 90% of all eligible OPD patients were offered a test. An average of 30% (range 25%-35%) of the RDT-negative fever patients received AMD prescriptions. When the test result was negative, children under five years of age were two to three times more likely (OR 2.6 p-value <0.001) to receive anti-malarial prescriptions relative to older age group. Of the 63 HWs interviewed 92% believed that a positive RDT result confirmed malaria, while only 49% believed that a negative RDT result excluded malaria infection. Conclusion: Use of RDTs resulted in a 2-fold reduction in anti-malarial drug prescription at LLHCFs. The study demonstrated that RDT use is feasible at LLHCFs, and can lead to better targetting of malaria treatment. Nationwide deployment of RDTs in a systematic manner should be prioritised in order to improve fever case management. The process should include plans to educate HWs about the utility of RDTs in order to maximize acceptance and uptake of the diagnostic tools and thereby leading to the benefits of parasitological diagnosis of malaria. [ABSTRACT FROM AUTHOR]

Background: The estimated number of people living with human immunodeficiency virus (HIV) (PLHIV) in Uganda is 1.5 million (7.3%). As of June 2016, 60% (898,197) of PLHIV were enrolled and receiving antiretroviral therapy (ART). In scientific literature, the effect of HIV and ART on dental caries remains equivocal. At the Prosthetics Clinic of the Department of Dentistry, Makerere University College of Health Sciences, we have seen a number of PLHIV who require replacement of missing teeth with partial or complete dentures as a result of extensive caries. Here we report a case of an HIV positive female patient with extensive dental caries resulting in complete edentulous jaws, associated with psychological stress and stigmatization. Case presentation: A 52-year-old patient, HIV positive for fourteen (14) years and receiving antiretroviral therapy (ART) for the last four years wanted to replace her missing teeth for effective feeding and cosmetic reasons. A diagnosis of partially edentulous maxillary and mandibular arches, cervical caries of tooth # 12, 15, 25, 34 and retained roots of tooth # 11, 13, 22 and 35 was made. Following oral health education and mouth preparation, this patient received a set of removable acrylic full upper and lower dentures. Conclusion: This case may represent the long-term effects of HIV and ART on oral health status especially tooth surfaces in some PLHIV. Further evaluation is required to ascertain if this was an isolated case or it is a common finding among HIV positive adult patients receiving long-term ART in sub-Saharan Africa. Information emerging from these studies would establish the magnitude of dental caries among PLHIV and guide the development of appropriate oral health care guidelines in the management of people living with HIV. [ABSTRACT FROM AUTHOR]

Background: 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)., Methods: 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., Results: 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., Conclusions: 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.

Background: A proportion of individuals who start antiretroviral therapy (ART) fail to achieve adequate CD4 cell reconstitution despite sustained viral suppression. We determined the frequency and clinical significance of suboptimal CD4 reconstitution despite viral suppression (SO-CD4) in an urban HIV research cohort in Kampala, Uganda., Methods: We analyzed data from a prospective research cohort of 559 patients initiating ART between 04/04-04/05. We described the patterns of SO-CD4 both in terms of:- I) magnitude of CD4 cell increase (a CD4 count increase < 50 CD4 cells/microl at 6 months, <100 cells/microl at 12 months; and <200 cells/microl at 24 months of ART) and II) failure to achieve a CD4 cell count above 200 cells/microl at 6,12 and 24 months of ART. Using criteria I) we used logistic regression to determine the predictors of SO-CD4. We compared the cumulative risk of clinical events (death and/or recurrent or new AIDS-defining illnesses) among patients with and without SO-CD4., Results: Of 559 patients initiating ART, 386 (69%) were female. Median (IQR) age and baseline CD4 counts were 38 yrs (33-44) and 98 cells/microl (21-163) respectively; 414 (74%) started a d4T-based regimen (D4T+3TC+NVP) and 145 (26%) a ZDV-based regimen (ZDV+3TC+EFV). After 6, 12 and 24 months of ART, 380 (68%), 339 (61%) and 309 (55%) had attained and sustained HIV-RNA viral suppression. Of these, 78 (21%), 151 (45%) and 166 (54%) respectively had SO-CD4 based on criteria I), and 165(43%), 143(42%) and 58(19%) respectively based on criteria II). With both criteria combined, 56 (15%) and 129 (38%) had SO-CD4 at 6 and 12 months respectively. A high proportion (82% and 58%) of those that had SO-CD4 at 6 months (using criteria I) maintained SO-CD4 at 12 and 24 months respectively. There were no statistically significant differences in the incidence of clinical events among patients with [19/100PYO (12-29)] and without SO-CD4 [23/100PYO (19-28)]., Conclusion: Using criteria I), the frequency of SO-CD4 was 21% at 6 months. Majority of patients with SO-CD4 at 6 months maintained SO-CD4 up to 2 years. We recommend studies of CD4 T-cell functional recovery among patients with SO-CD4.