Showing papers by "Makerere University published in 2015"

Tenofovir-Based Preexposure Prophylaxis for HIV Infection among African Women

Abstract: BackgroundReproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. MethodsWe conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir–emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. ResultsOf 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was −49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), −4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.4...

The 2014 Ebola Outbreak and Mental Health: Current Status and Recommended Response

Abstract: citingsymptomaticpatientsescap-ing from treatment units, families concealing sick rela-tives at home, preferential use of traditional healers,andphysicalcontactwithinfectiouscorpses.Neverthe-less, the Roadmap includes few recommendations toalleviate fear behaviors and address mental healthneedsinEbola-affectedcommunities.InWestAfrica,Ebolavirusdiseasearousesfearbe-haviors, in part because many have witnessed thegraphic hemorrhagic manifestations of those infectedandthebodiesofthosewhohavedied.Thecorpsesandbeddingofpatientswhohavediedposeinfectionhaz-ardstohealthcareworkersandfamilymembers.AsofDecember14,2014,649front-linehealthcareworkershavebecomeilland365havedied.

Count every newborn; a measurement improvement roadmap for coverage data

Abstract: The Every Newborn Action Plan (ENAP), launched in 2014, aims to end preventable newborn deaths and stillbirths, with national targets of ≤12 neonatal deaths per 1000 live births and ≤12 stillbirths per 1000 total births by 2030. This requires ambitious improvement of the data on care at birth and of small and sick newborns, particularly to track coverage, quality and equity. In a multistage process, a matrix of 70 indicators were assessed by the Every Newborn steering group. Indicators were graded based on their availability and importance to ENAP, resulting in 10 core and 10 additional indicators. A consultation process was undertaken to assess the status of each ENAP core indicator definition, data availability and measurement feasibility. Coverage indicators for the specific ENAP treatment interventions were assigned task teams and given priority as they were identified as requiring the most technical work. Consultations were held throughout. ENAP published 10 core indicators plus 10 additional indicators. Three core impact indicators (neonatal mortality rate, maternal mortality ratio, stillbirth rate) are well defined, with future efforts needed to focus on improving data quantity and quality. Three core indicators on coverage of care for all mothers and newborns (intrapartum/skilled birth attendance, early postnatal care, essential newborn care) have defined contact points, but gaps exist in measuring content and quality of the interventions. Four core (antenatal corticosteroids, neonatal resuscitation, treatment of serious neonatal infections, kangaroo mother care) and one additional coverage indicator for newborns at risk or with complications (chlorhexidine cord cleansing) lack indicator definitions or data, especially for denominators (population in need). To address these gaps, feasible coverage indicator definitions are presented for validity testing. Measurable process indicators to help monitor health service readiness are also presented. A major measurement gap exists to monitor care of small and sick babies, yet signal functions could be tracked similarly to emergency obstetric care. The ENAP Measurement Improvement Roadmap (2015-2020) outlines tools to be developed (e.g., improved birth and death registration, audit, and minimum perinatal dataset) and actions to test, validate and institutionalise proposed coverage indicators. The roadmap presents a unique opportunity to strengthen routine health information systems, crosslinking these data with civil registration and vital statistics and population-based surveys. Real measurement change requires intentional transfer of leadership to countries with the greatest disease burden and will be achieved by working with centres of excellence and existing networks.

Transforming health professions’ education through in-country collaboration: examining the consortia among African medical schools catalyzed by the Medical Education Partnership Initiative

Abstract: African medical schools have historically turned to northern partners for technical assistance and resources to strengthen their education and research programmes. In 2010, this paradigm shifted when the United States Government brought forward unprecedented resources to support African medical schools. The grant, entitled the Medical Education Partnership Initiative (MEPI) triggered a number of south-south collaborations between medical schools in Africa. This paper examines the goals of these partnerships and their impact on medical education and health workforce planning. Semi-structured interviews were conducted with the Principal Investigators of the first four MEPI programmes that formed an in-country consortium. These interviews were recorded, transcribed and coded to identify common themes. All of the consortia have prioritized efforts to increase the quality of medical education, support new schools in-country and strengthen relations with government. These in-country partnerships have enabled schools to pool and mobilize limited resources creatively and generate locally-relevant curricula based on best-practices. The established schools are helping new schools by training faculty and using grant funds to purchase learning materials for their students. The consortia have strengthened the dialogue between academia and policy-makers enabling evidence-based health workforce planning. All of the partnerships are expected to last well beyond the MEPI grant as a result of local ownership and institutionalization of collaborative activities. The consortia described in this paper demonstrate a paradigm shift in the relationship between medical schools in four African countries. While schools in Africa have historically worked in silos, competing for limited resources, MEPI funding that was leveraged to form in-country partnerships has created a culture of collaboration, overriding the history of competition. The positive impact on the quality and efficiency of health workforce training suggests that future funding for global health education should prioritize such south-south collaborations.

Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities.

Abstract: Tools to reliably measure Plasmodium falciparum (Pf) exposure in individuals and communities are needed to guide and evaluate malaria control interventions. Serologic assays can potentially produce precise exposure estimates at low cost; however, current approaches based on responses to a few characterized antigens are not designed to estimate exposure in individuals. Pf-specific antibody responses differ by antigen, suggesting that selection of antigens with defined kinetic profiles will improve estimates of Pf exposure. To identify novel serologic biomarkers of malaria exposure, we evaluated responses to 856 Pf antigens by protein microarray in 186 Ugandan children, for whom detailed Pf exposure data were available. Using data-adaptive statistical methods, we identified combinations of antibody responses that maximized information on an individual's recent exposure. Responses to three novel Pf antigens accurately classified whether an individual had been infected within the last 30, 90, or 365 d (cross-validated area under the curve = 0.86-0.93), whereas responses to six antigens accurately estimated an individual's malaria incidence in the prior year. Cross-validated incidence predictions for individuals in different communities provided accurate stratification of exposure between populations and suggest that precise estimates of community exposure can be obtained from sampling a small subset of that community. In addition, serologic incidence predictions from cross-sectional samples characterized heterogeneity within a community similarly to 1 y of continuous passive surveillance. Development of simple ELISA-based assays derived from the successful selection strategy outlined here offers the potential to generate rich epidemiologic surveillance data that will be widely accessible to malaria control programs.

The burden of hypertension in sub-Saharan Africa: a four-country cross sectional study

Abstract: Hypertension, the leading single cause of morbidity and mortality worldwide, is a growing public health problem in sub-Saharan Africa (SSA). Few studies have estimated and compared the burden of hypertension across different SSA populations. We conducted a cross-sectional analysis of blood pressure data collected through a cohort study in four SSA countries, to estimate the prevalence of pre-hypertension, the prevalence of hypertension, and to identify the factors associated with hypertension. Participants were from five different population groups defined by occupation and degree of urbanization, including rural and peri-urban residents in Uganda, school teachers in South Africa and Tanzania, and nurses in Nigeria. We used a standardized questionnaire to collect data on demographic and behavioral characteristics, injuries, and history of diagnoses of chronic diseases and mental health. We also made physical measurements (weight, height and blood pressure), as well as biochemical measurements; which followed standardized protocols across the country sites. Modified Poison regression modelling was used to estimate prevalence ratios (PR) as measures of association between potential risk factors and hypertension. The overall age-standardized prevalence of hypertension among the 1216 participants was 25.9 %. Prevalence was highest among nurses with an age-standardized prevalence (ASP) of 25.8 %, followed by school teachers (ASP = 23.2 %), peri-urban residents (ASP = 20.5 %) and lowest among rural residents (ASP = 8.7 %). Only 50.0 % of participants with hypertension were aware of their raised blood pressure. The overall age-standardized prevalence of pre-hypertension was 21.0 %. Factors found to be associated with hypertension were: population group, older age, higher body mass index, higher fasting plasma glucose level, lower level of education, and tobacco use. The prevalence of hypertension and pre-hypertension are high, and differ by population group defined by occupation and degree of urbanization. Only half of the populations with hypertension are aware of their hypertension, indicating a high burden of undiagnosed and un-controlled high blood pressure in these populations.

Effect of Transfusion of Red Blood Cells With Longer vs Shorter Storage Duration on Elevated Blood Lactate Levels in Children With Severe Anemia: The TOTAL Randomized Clinical Trial

Abstract: Importance Although millions of transfusions are given annually worldwide, the effect of red blood cell (RBC) unit storage duration on oxygen delivery is uncertain. Objective To determine if longer-storage RBC units are not inferior to shorter-storage RBC units for tissue oxygenation as measured by reduction in blood lactate levels and improvement in cerebral tissue oxygen saturation among children with severe anemia. Design, Setting, and Participants Randomized noninferiority trial of 290 children (aged 6-60 months), most with malaria or sickle cell disease, presenting February 2013 through May 2015 to a university-affiliated national referral hospital in Kampala, Uganda, with a hemoglobin level of 5 g/dL or lower and a lactate level of 5 mmol/L or higher. Interventions Patients were randomly assigned to receive RBC units stored 25 to 35 days (longer-storage group; n = 145) vs 1 to 10 days (shorter-storage group; n = 145). All units were leukoreduced prior to storage. All patients received 10 mL/kg of RBCs during hours 0 through 2 and, if indicated per protocol, an additional 10 mL/kg during hours 4 through 6. Main Outcomes and Measures The primary outcome was the proportion of patients with a lactate level of 3 mmol/L or lower at 8 hours using a margin of noninferiority equal to an absolute difference of 25%. Secondary measures included noninvasive cerebral tissue oxygen saturation during the first transfusion, clinical and laboratory changes up to 24 hours, and survival and health at 30 days after transfusion. Adverse events were monitored up to 24 hours. Results In the total population of 290 children, the mean (SD) presenting hemoglobin level was 3.7 g/dL (1.3) and mean lactate level was 9.3 mmol/L (3.4). Median (interquartile range) RBC unit storage was 8 days (7-9) for shorter storage vs 32 days (30-34) for longer storage without overlap. The proportion achieving the primary end point was 0.61 (95% CI, 0.52 to 0.69) in the longer-storage group vs 0.58 (95% CI, 0.49 to 0.66) in the shorter-storage group (between-group difference, 0.03 [95% CI, −0.07 to ∞], P Conclusions and Relevance Among children with lactic acidosis due to severe anemia, transfusion of longer-storage compared with shorter-storage RBC units did not result in inferior reduction of elevated blood lactate levels. These findings have relevance regarding the efficacy of stored RBC transfusion for patients with critical tissue hypoxia and lactic acidosis due to anemia. Trial Registration clinicaltrials.gov Identifier:NCT01586923

Sustainable HIV Treatment in Africa through Viral Load-Informed Differentiated Care

Abstract: There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.

The Epidemiology of Hypertension in Uganda: Findings from the National Non-Communicable Diseases Risk Factor Survey.

Abstract: Background Hypertension is an important contributor to global burden of disease and mortality, and is a growing public health problem in sub-Saharan Africa. However, most sub-Saharan African countries lack detailed countrywide data on hypertension and other non-communicable diseases (NCD) risk factors that would provide benchmark information for design of appropriate interventions. We analyzed blood pressure data from Uganda’s nationwide NCD risk factor survey conducted in 2014, to describe the prevalence and distribution of hypertension in the Ugandan population, and to identify the associated factors.

Increased Antifungal Drug Resistance in Clinical Isolates of Cryptococcus neoformans in Uganda

Abstract: Cryptococcal antigen screening is recommended among people living with AIDS when entering HIV care with a CD4 count of <100 cells/μl, and preemptive fluconazole monotherapy treatment is recommended for those with subclinical cryptococcal antigenemia. Yet, knowledge is limited of current antimicrobial resistance in Africa. We examined antifungal drug susceptibility in 198 clinical isolates collected from Kampala, Uganda, between 2010 and 2014 using the CLSI broth microdilution assay. In comparison with two previous studies from 1998 to 1999 that reported an MIC50 of 4 μg/ml and an MIC90 of 8 μg/ml prior to widespread human fluconazole and agricultural azole fungicide usage, we report an upward shift in the fluconazole MIC50 to 8 μg/ml and an MIC90 value of 32 μg/ml, with 31% of isolates with a fluconazole MIC of ≥ 16 μg/ml. We observed an amphotericin B MIC50 of 0.5 μg/ml and an MIC90 of 1 μg/ml, of which 99.5% of isolates (197 of 198 isolates) were still susceptible. No correlation between MIC and clinical outcome was observed in the context of amphotericin B and fluconazole combination induction therapy. We also analyzed Cryptococcus susceptibility to sertraline, with an MIC50 of 4 μg/ml, suggesting that sertraline is a promising oral, low-cost, available, novel medication and a possible alternative to fluconazole. Although the CLSI broth microdilution assay is ideal to standardize results, limit human bias, and increase assay capacity, such assays are often inaccessible in low-income countries. Thus, we also developed and validated an assay that could easily be implemented in a resource-limited setting, with similar susceptibility results (P = 0.52).

The emergence of sex differences in personality traits in early adolescence: A cross-sectional, cross-cultural study.

Abstract: Although large international studies have found consistent patterns of sex differences in personality traits among adults (i.e., women scoring higher on most facets), less is known about cross-cultural sex differences in adolescent personality and the role of culture and age in shaping them. The present study examines the NEO Personality Inventory-3 (McCrae, Costa, & Martin, 2005) informant ratings of adolescents from 23 cultures (N = 4,850), and investigates culture and age as sources of variability in sex differences of adolescents' personality. The effect for Neuroticism (with females scoring higher than males) begins to take on its adult form around age 14. Girls score higher on Openness to Experience and Conscientiousness at all ages between 12 and 17 years. A more complex pattern emerges for Extraversion and Agreeableness, although by age 17, sex differences for these traits are highly similar to those observed in adulthood. Cross-sectional data suggest that (a) with advancing age, sex differences found in adolescents increasingly converge toward adult patterns with respect to both direction and magnitude; (b) girls display sex-typed personality traits at an earlier age than boys; and (c) the emergence of sex differences was similar across cultures. Practical implications of the present findings are discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Soil Fertility Management in Africa: A Review of Selected Research Trials

Abstract: The increasing recognition of soil fertility depletion as the main biophysical factor limiting crop production in many African smallholder farms has raised interest in using data from past fertilizer studies to identify options for increasing agricultural production. This review of selected fertility research trials in sub-Saharan Africa reveals a pool of information (i) on the principles of fertilizer application for efficient nutrient use and (ii) on potential problems arising with continuous use of fertilizers in intensively cultivated systems. Adequate soil fertility for sustained crop yields can be obtained with combined use of mineral fertilizers and organic materials. Continuous use of N fertilizers can acidify soil, which then requires liming when organic inputs are limiting. Increased deficiencies of N, P, and other nutrients can be expected as a result of intensive cultivation and unbalanced fertilizer use. The use of mineral fertilizers by many smallholder farmers remains low because of socioeconomic constraints. This suggests that locally available organic materials will continue to be used as sources of nutrients. Future soil fertility trials should, therefore, particularly aim at identifying practices for judicious use of organic materials and their combination with mineral fertilizers. Shortcomings of past soil fertility research include limited economic analysis of results and use of trial sites and management that poorly represented those of smallholder farmers. Future research should strive for active participation of farmers, longer time frames to fully evaluate residual effects and rigorous economic analysis of results. Copyright © 1997 American Society of Agronomy and Soil Science Society of America, 677 S. Segoe Rd., Madison, WI53711, USA. Replenishing Soil Fertility in Africa. SSSA Special Publication no. 51.

A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia

Abstract: In sub-Saharan Africans, maternal mortality is unacceptably high, with >400 deaths per 100,000 births compared with <10 deaths per 100,000 births in Europeans. One-third of the deaths are caused by pre-eclampsia, a syndrome arising from defective placentation. Controlling placentation are maternal natural killer (NK) cells that use killer-cell immunoglobulin-like receptor (KIR) to recognize the fetal HLA-C molecules on invading trophoblast. We analyzed genetic polymorphisms of maternal KIR and fetal HLA-C in 484 normal and 254 pre-eclamptic pregnancies at Mulago Hospital, Kampala, Uganda. The combination of maternal KIR AA genotypes and fetal HLA-C alleles encoding the C2 epitope associates with pre-eclampsia [P = 0.0318, odds ratio (OR) = 1.49]. The KIR genes associated with protection are located in centromeric KIR B regions that are unique to sub-Saharan African populations and contain the KIR2DS5 and KIR2DL1 genes (P = 0.0095, OR = 0.59). By contrast, telomeric KIR B genes protect Europeans against pre-eclampsia. Thus, different KIR B regions protect sub-Saharan Africans and Europeans from pre-eclampsia, whereas in both populations, the KIR AA genotype is a risk factor for the syndrome. These results emphasize the importance of undertaking genetic studies of pregnancy disorders in African populations with the potential to provide biological insights not available from studies restricted to European populations.

Adherence to antiretroviral therapy and retention in care for adolescents living with HIV from 10 districts in Uganda

Abstract: Adolescents have gained increased attention because they are the only age group where HIV related mortality is going up. We set out to describe the level and factors associated with adherence to antiretroviral therapy (ART) as well as the 1 year retention in care among adolescents in 10 representative districts in Uganda. In addition, we explored the barriers and facilitators of adherence to ART among adolescents. The study involved 30 health facilities from 10 representative districts in Uganda. We employed both qualitative and quantitative data collection methods in convergent design. The former involved Focus group discussions with adolescents living with HIV, Key informant interviews with various stakeholders and in depth interviews with adolescents. The quantitative involved using retrospective records review to extract the last recorded adherence level from all adolescents who were active in HIV care. Factors associated with adherence were extracted from the ART cards. For the 1 year retention in care, we searched the hospital records of all adolescents in the 30 facilities who had started ART 1 year before the study to find out how many were still in care. Out of 1824 adolescents who were active on ART, 90.4 % (N = 1588) had ≥95 % adherence recorded on their ART cards at their last clinic visit. Only location in rural health facilities was independently associated with poor adherence to ART (P = 0.008, OR 2.64 [1.28 5.43]). Of the 156 adolescents who started ART, 90 % (N = 141) were still active in care 1 year later. Stigma, discrimination and disclosure issues were the most outstanding of all barriers to adherence. Other barriers included poverty, fatigue, side effects, pill burden, depression among others. Facilitators of adherence mainly included peer support groups, counseling, supportive health care workers, short waiting time and provision of food and transport. Adherence to ART was good among adolescents. Being in rural areas was associated with poor adherence to ART and 1 year retention in care was very good among adolescents who were newly started on ART. Stigma and disclosure issues continue to be the main barriers to adherence among adolescents.

Health seeking behaviour and challenges in utilising health facilities in Wakiso district, Uganda

Abstract: Background : The health seeking behaviour of a community determines how they use health services. Utilisation of health facilities can be influenced by the cost of services, distance to health facilities, cultural beliefs, level of education and health facility inadequacies such as stock-out of drugs. Objectives : To assess the health seeking practices and challenges in utilising health facilities in a rural community in Wakiso district, Uganda. Methods : The study was a cross sectional survey that used a structured questionnaire to collect quantitative data among 234 participants. The sample size was obtained using the formula by Leslie Kish. Results : While 89% of the participants were aware that mobile clinics existed in their community, only 28% had received such services in the past month. The majority of participants (84%) did not know whether community health workers existed in their community. The participants’ health seeking behaviour the last time they were sick was associated with age (p = 0.028) and occupation (p = 0.009). The most significant challenges in utilising health services were regular stock-out of drugs, high cost of services and long distance to health facilities. Conclusions : There is potential to increase access to health care in rural areas by increasing the frequency of mobile clinic services and strengthening the community health worker strategy. Key words : Health seeking behaviour, Rural community, Health facilities, Challenges, Uganda

The effect of payment and incentives on motivation and focus of community health workers: five case studies from low- and middle-income countries

Abstract: Community health workers (CHWs) have been proposed as a means for bridging gaps in healthcare delivery in rural communities. Recent CHW programmes have been shown to improve child and neonatal health outcomes, and it is increasingly being suggested that paid CHWs become an integral part of health systems. Remuneration of CHWs can potentially effect their motivation and focus. Broadly, programmes follow a social, monetary or mixed market approach to remuneration. Conscious understanding of the differences, and of what each has to offer, is important in selecting the most appropriate approach according to the context.

FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure.

Abstract: Exposure to Plasmodium falciparum is associated with circulating "atypical" memory B cells (atMBCs), which appear similar to dysfunctional B cells found in HIV-infected individuals. Functional analysis of atMBCs has been limited, with one report suggesting these cells are not dysfunctional but produce protective antibodies. To better understand the function of malaria-associated atMBCs, we performed global transcriptome analysis of these cells, obtained from individuals living in an area of high malaria endemicity in Uganda. Comparison of gene expression data suggested down-modulation of B cell receptor signaling and apoptosis in atMBCs compared to classical MBCs. Additionally, in contrast to previous reports, we found upregulation of Fc receptor-like 5 (FCRL5), but not FCRL4, on atMBCs. Atypical MBCs were poor spontaneous producers of antibody ex vivo, and higher surface expression of FCRL5 defined a distinct subset of atMBCs compromised in its ability to produce antibody upon stimulation. Moreover, higher levels of P. falciparum exposure were associated with increased frequencies of FCRL5+ atMBCs. Together, our findings suggest that FCLR5+ identifies a functionally distinct, and perhaps dysfunctional, subset of MBCs in individuals exposed to P. falciparum.

Global research priorities for infections that affect the nervous system

Abstract: Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries.

Prevalence and Characterization of Carbapenem-Resistant Enterobacteriaceae Isolated from Mulago National Referral Hospital, Uganda.

Abstract: Introduction Carbapenemases have increasingly been reported in enterobacteriaceae worldwide. Most carbapenemases are plasmid encoded hence resistance can easily spread. Carbapenem-resistant enterobacteriaceae are reported to cause mortality in up to 50% of patients who acquire bloodstream infections. We set out to determine the burden of carbapenem resistance as well as establish genes encoding for carbapenemases in enterobacteriaceae clinical isolates obtained from Mulago National Referral Hospital, Uganda. Methods This was a cross-sectional study with a total of 196 clinical isolates previously collected from pus swabs, urine, blood, sputum, tracheal aspirates, cervical swabs, endomentrial aspirates, rectal swabs, Vaginal swabs, ear swabs, products of conception, wound biopsy and amniotic fluid. All isolates were subjected to phenotypic carbapenemase screening using Boronic acid-based inhibition, Modified Hodge and EDTA double combined disk test. In addition, all the isolates were subjected to PCR assay to confirm presence of carbapenemase encoding genes. Results The study found carbapenemase prevalence of 22.4% (44/196) in the isolates using phenotypic tests, with the genotypic prevalence slightly higher at 28.6% (56/196). Over all, the most prevalent gene was blaVIM (21,10.7%), followed by blaOXA-48 (19, 9.7%), blaIMP (12, 6.1%), blaKPC (10, 5.1%) and blaNDM-1 (5, 2.6%). Among 56 isolates positive for 67 carbapenemase encoding genes, Klebsiella pneumonia was the species with the highest number (52.2%). Most 32/67(47.7%) of these resistance genes were in bacteria isolated from pus swabs. Conclusion There is a high prevalence of carbapenemases and carbapenem-resistance encoding genes among third generation cephalosporins resistant Enterobacteriaceae in Uganda, indicating a danger of limited treatment options in this setting in the near future.

Cryptococcal Meningitis: Diagnosis and Management Update

Abstract: Recent advances in the diagnosis and management of cryptococcal meningitis are promising and have been improving long-term survival. Point of care testing has made diagnosing cryptococcal meningitis rapid, practical, and affordable. Targeted screening and treatment programs for cryptococcal antigenemia are a cost effective method for reducing early mortality on antiretroviral therapy (ART). Optimal initial management with amphotericin and flucytosine improves survival against alternative therapies, although amphotericin is difficult to administer and flucytosine is not available in middle or low income countries, where cryptococcal meningitis is most prevalent. Controlling increased intracranial pressure with serial therapeutic lumbar punctures has a proven survival benefit. Delaying ART initiation for 4 weeks after the diagnosis of cryptococcal meningitis is associated with improved survival. Fortunately, new approaches have been leading the way toward improving care for cryptococcal meningitis patients. New trials utilizing different combinations of antifungal therapy are reviewed, and we summarize the efficacy of different regimens.

Stepped wedge randomised controlled trials: systematic review of studies published between 2010 and 2014

Abstract: In a stepped wedge, cluster randomised trial, clusters receive the intervention at different time points, and the order in which they received it is randomised. Previous systematic reviews of stepped wedge trials have documented a steady rise in their use between 1987 and 2010, which was attributed to the design’s perceived logistical and analytical advantages. However, the interventions included in these systematic reviews were often poorly reported and did not adequately describe the analysis and/or methodology used. Since 2010, a number of additional stepped wedge trials have been published. This article aims to update previous systematic reviews, and consider what interventions were tested and the rationale given for using a stepped wedge design. We searched PubMed, PsychINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Web of Science, the Cochrane Library and the Current Controlled Trials Register for articles published between January 2010 and May 2014. We considered stepped wedge randomised controlled trials in all fields of research. We independently extracted data from retrieved articles and reviewed them. Interventions were then coded using the functions specified by the Behaviour Change Wheel, and for behaviour change techniques using a validated taxonomy. Our review identified 37 stepped wedge trials, reported in 10 articles presenting trial results, one conference abstract, 21 protocol or study design articles and five trial registrations. These were mostly conducted in developed countries (n = 30), and within healthcare organisations (n = 28). A total of 33 of the interventions were educationally based, with the most commonly used behaviour change techniques being ‘instruction on how to perform a behaviour’ (n = 32) and ‘persuasive source’ (n = 25). Authors gave a wide range of reasons for the use of the stepped wedge trial design, including ethical considerations, logistical, financial and methodological. The adequacy of reporting varied across studies: many did not provide sufficient detail regarding the methodology or calculation of the required sample size. The popularity of stepped wedge trials has increased since 2010, predominantly in high-income countries. However, there is a need for further guidance on their reporting and analysis.

Predictors of modern contraceptive use during the postpartum period among women in Uganda: a population-based cross sectional study

Abstract: The rationale for promotion of family planning (FP) to delay conception after a recent birth is a best practice that can lead to optimal maternal and child health outcomes. Uptake of postpartum family planning (PPFP) remains low in sub-Saharan Africa. However, little is known about how pregnant women arrive at their decisions to adopt PPFP. We used 3298 women of reproductive ages 15–49 from the 2011 UDHS dataset, who had a birth in the 5 years preceding the survey. We then applied both descriptive analyses comprising Pearson’s chi-square test and later a binary logistic regression model to analyze the relative contribution of the various predictors of uptake of modern contraceptives during the postpartum period. More than a quarter (28%) of the women used modern family planning during the postpartum period in Uganda. PPFP was significantly associated with primary or higher education (OR=1.96; 95% CI=1.43-2.68; OR=2.73; 95% CI=1.88-3.97 respectively); richest wealth status (OR=2.64; 95% CI=1.81-3.86); protestant religion (OR=1.27; 95% CI=1.05-1.54) and age of woman (OR=0.97, 95% CI=0.95-0.99). In addition, PPFP was associated with number of surviving children (OR=1.09; 95 % CI=1.03-1.16); exposure to media (OR=1.30; 95% CI=1.05-1.61); skilled birth attendance (OR=1.39; 95% CI=1.12-1.17); and 1–2 days timing of post-delivery care (OR=1.68; 95% CI=1.14-2.47). Increasing reproductive health education and information among postpartum women especially those who are disadvantaged, those with no education and the poor would significantly improve PPFP in Uganda.