Perceived Quality of Care for Common Childhood Illnesses: Facility versus Community Based Providers in Uganda

Objective

To compare caretakers’ perceived quality of care (PQC) for under-fives treated for malaria, pneumonia and diarrhoea by community health workers (CHWs) and primary health facility workers (PHFWs).

Methods

Caretaker rated PQC for children aged (2-59) months treated by either CHWs or PHFWs for a bought of malaria, pneumonia or diarrhoea was cross-sectionally compared in quality domains of accessibility, continuity, comprehensiveness, integration, clinical interaction, interpersonal treatment and trust. Child samples were randomly drawn from CHW (419) and clinic (399) records from eight Midwestern Uganda districts. An overall PQC score was predicted through factor analysis. PQC scores were compared for CHWs and PHFWs using Wilcoxon rank-sum test. Multinomial logistic regression models were used to specify the association between categorized PQC and service providers for each quality domain. Finally, overall PQC was dichotomized into “high” and “low” based on median score and relative risks (RR) for PQC-service provider association were modeled in a “modified” Poisson regression model.

Results

Mean (SD) overall PQC was significantly higher for CHWs 0.58 (0 .66) compared to PHFWs -0.58 (0.94), p<0.0001. In “modified” Poisson regression, the proportion of caretakers reporting high PQC was higher for CHWS compared to PHFWs, RR=3.1, 95%CI(2.5-3.8). In multinomial models PQC was significantly higher for CHWs compared to PHFWs in all domains except for continuity.

Conclusion

PQC was significantly higher for CHWs compared to PHFWs in this resource constrained setting. CHWs should be tapped human resources for universal health coverage while scaling up basic child intervention as PQC might improve intervention utilization.     

Activation Associated ERK1/2 Signaling Impairments in CD8+ T Cells Co-Localize with Blunted Polyclonal and HIV-1 Specific Effector Functions in Early Untreated HIV-1 Infection

We recently observed that a large proportion of activated (CD38⁺HLA-DR⁺) CD8⁺ T cells from recently HIV-1-infected adults are refractory to phosphorylation of ERK1/2 kinases (p-ERK1/2-refractory). Given that the ERK1/2 pathway mediates intracellular signaling critical for multiple T cell functions, including key effector functions, the loss of ERK1/2 responsiveness may have broad consequences for CD8⁺ T cell function. In the current study, we hypothesized that the p-ERK1/2-refractory population, localized largely within the activated CD38⁺HLA-DR⁺ CD8⁺ T cell population, would display impairments in CD8⁺ T cell effector functions, such as cytokine production and degranulation, compared to CD8⁺ p-ERK1/2-responsive cells. We further hypothesized that the p-ERK1/2-refractory phenotype is persistent over time during untreated infection, and would correlate with poorer virologic control, in a manner independent of CD8⁺ T cell activation level. We performed single-cell resolution, flow cytometric assays of phospho-kinase responses paired to intracellular cytokine staining in one assay to examine IFN-γ, perforin and CD107α responses in CD8⁺ T cells by ERK1/2 signaling profile. On a per cell basis, p-ERK1/2-refractory cells, which fall predominantly within the activated CD8⁺ T cell compartment, produced less IFN-γ in response to polyclonal or HIV-1 antigen-specific stimulation, and expressed lower levels of perforin and CD107α. The p-ERK1/2 refractory cell population displayed minimal overlap with the PD-1 and Tim-3 inhibitory exhaustion markers and predicted high viral load independent of activation, suggesting that ERK1/2 may be a unique marker and point of intervention for improving CD8⁺ T cell function. Blunted effector functions, secondary to ERK1/2 signaling deficits concentrated within activated CD8⁺ T cells, may contribute to immunodeficiency and underlie the predictive capacity of CD8⁺ T cell activation on HIV-1 disease progression. (270/300).     

Validation of the “World Health Organization Disability Assessment Schedule for Children,WHODAS-Child” in Rwanda

Overview

The World Health Organization Disability Assessment Schedule for children (WHODAS-Child) is a disability assessment instrument based on the WHO''s International Classification of Functioning, Disability and Health for children and youth. It is modified from the original adult version specifically for use with children. The aim of this study was to assess the WHODAS-Child structure and metric properties in a community sample of children with and without reported psychosocial problems in rural Rwanda.

Methods

The WHODAS-Child was first translated into Kinyarwanda through a detailed committee translation process and back-translation. Cognitive interviewing was used to assess the comprehension of the translated items. Test-retest reliability was assessed in a group of 64 children. The translated WHODAS-Child was then administered to a final sample of 367 children in southern Kayonza district in rural southeastern Rwanda within a larger psychosocial assessment battery. The latent structure was assessed through confirmatory factor analysis. Reliability was evaluated in terms of internal consistency (Cronbach''s alpha) and test-retest reliability (Pearson''s correlation coefficient). Construct validity was explored by examining convergence between WHODAS-Child scores and mental disorder status, and divergence of WHODAS-Child scores with protective factors and prosocial behaviors. Concordance between parent and child scores was also assessed.

Results

The six-factor structure of the WHODAS-Child was confirmed in a population sample of Rwandan children. Test-retest and inter-rater reliability were high (r = .83 and ICC = .88). WHODAS-Child scores were moderately positively correlated with presence of depression (r = .42, p<.001) and post-traumatic stress disorder (r = .31, p<.001) and moderately negatively correlated with prosocial behaviors (r = .47, p<.001). The Kinyarwanda version of the WHODAS-Child was found to be a reliable and acceptable self-report tool for assessment of functional impairment among children largely referred for psychosocial problems in the study district in rural Rwanda. Further research in low-resource settings and with more general populations is recommended.     

Malaria Prevalence,Spatial Clustering and Risk Factors in a Low Endemic Area of Eastern Rwanda: A Cross Sectional Study

Background

Rwanda reported significant reductions in malaria burden following scale up of control intervention from 2005 to 2010. This study sought to; measure malaria prevalence, describe spatial malaria clustering and investigate for malaria risk factors among health-centre-presumed malaria cases and their household members in Eastern Rwanda.

Methods

A two-stage health centre and household-based survey was conducted in Ruhuha sector, Eastern Rwanda from April to October 2011. At the health centre, data, including malaria diagnosis and individual level malaria risk factors, was collected. At households of these Index cases, a follow-up survey, including malaria screening for all household members and collecting household level malaria risk factor data, was conducted.

Results

Malaria prevalence among health centre attendees was 22.8%. At the household level, 90 households (out of 520) had at least one malaria-infected member and the overall malaria prevalence for the 2634 household members screened was 5.1%. Among health centre attendees, the age group 5–15 years was significantly associated with an increased malaria risk and a reported ownership of ≥4 bednets was significantly associated with a reduced malaria risk. At the household level, age groups 5–15 and >15 years and being associated with a malaria positive index case were associated with an increased malaria risk, while an observed ownership of ≥4 bednets was associated with a malaria risk-protective effect. Significant spatial malaria clustering among household cases with clusters located close to water- based agro-ecosystems was observed.

Conclusions

Malaria prevalence was significantly higher among health centre attendees and their household members in an area with significant household spatial malaria clustering. Circle surveillance involving passive case finding at health centres and proactive case detection in households can be a powerful tool for identifying household level malaria burden, risk factors and clustering.     

A Randomized Pilot Trial of a Moderate Carbohydrate Diet Compared to a Very Low Carbohydrate Diet in Overweight or Obese Individuals with Type 2 Diabetes Mellitus or Prediabetes

We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n = 18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n = 16). We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (−0.6%, 95% CI, −1.1% to −0.03%, p = 0.04). Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p = 0.03); 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p = 0.05). The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p = 0.09). Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications.This clinical trial was registered with ClinicalTrials.gov, number {"type":"clinical-trial","attrs":{"text":"NCT01713764","term_id":"NCT01713764"}}NCT01713764.     

PPARα is essential for retinal lipid metabolism and neuronal survival

Background

Peroxisome proliferator activated receptor-alpha (PPARα) is a ubiquitously expressed nuclear receptor. The role of endogenous PPARα in retinal neuronal homeostasis is unknown. Retinal photoreceptors are the highest energy-consuming cells in the body, requiring abundant energy substrates. PPARα is a known regulator of lipid metabolism, and we hypothesized that it may regulate lipid use for oxidative phosphorylation in energetically demanding retinal neurons.

Results

We found that endogenous PPARα is essential for the maintenance and survival of retinal neurons, with Pparα ^-/- mice developing retinal degeneration first detected at 8 weeks of age. Using extracellular flux analysis, we identified that PPARα mediates retinal utilization of lipids as an energy substrate, and that ablation of PPARα ultimately results in retinal bioenergetic deficiency and neurodegeneration. This may be due to PPARα regulation of lipid transporters, which facilitate the internalization of fatty acids into cell membranes and mitochondria for oxidation and ATP production.

Conclusion

We identify an endogenous role for PPARα in retinal neuronal survival and lipid metabolism, and furthermore underscore the importance of fatty acid oxidation in photoreceptor survival. We also suggest PPARα as a putative therapeutic target for age-related macular degeneration, which may be due in part to decreased mitochondrial efficiency and subsequent energetic deficits.

     

Absence of lower genital tract lesions among women of reproductive age infected with Schistosoma mansoni: A cross-sectional study using a colposcope in Western Kenya

BackgroundFemale genital schistosomiasis (FGS) constitutes four different lesions known to be caused by Schistosoma haematobium ova deposited in the genital tract. Schistosoma mansoni ova may also be found in the genital tract. However, it is not known if S. mansoni causes lower genital tract lesions characteristic of FGS.MethodologyThis study was conducted in 8 villages along the shores of Lake Victoria, western Kenya. Stool and urine samples, collected from women of reproductive age on three consecutive days, were analysed for S. mansoni and S. haematobium infection. S. mansoni positive and S. haematobium negative willing participants, aged 18–50 years were invited to answer a questionnaire (demographics, symptoms), undergo a gynaecological examination and cytology specimen collection by an FGS expert.Principal findingsGynaecologic investigations were conducted in 147 S. mansoni-positive women who had a mean infection intensity of 253.3 epg (95% CI: 194.8–311.9 epg). Nearly 90% of them used Lake Victoria as their main water source. None were found to have cervicovaginal grainy sandy patches or rubbery papules. Homogenous yellow patches were found in 12/147 (8.2%) women. Women with homogenous yellow patches were significantly older (47 years) than the rest (34 years, p = 0.001). No association was found between intensity of S. mansoni infection and homogenous yellow patches (p = 0.70) or abnormal blood vessels (p = 0.14). S. mansoni infection intensity was not associated with genital itch, bloody or malodorous vaginal discharge.ConclusionS. mansoni infection was neither associated with lower genital tract lesions nor symptoms typically found in women with FGS.     

A new carbene based heterobifunctional reagent. Photochemical crosslinking of aldolase

The synthesis of a new photoactivatable heterobifunctional crosslinking reagent, the N-oxysuccinimide ester of 2-carboxy-9-diazofluorene, is described. The ability of the parent chromophore 2-carbomethoxy-9-diazofluorene to insert into cyclohexane and methanol has been established. The reagent has been linked to aldolase and the stoichiometry determined. Photolysis of the probe-linked aldolase indicated that photolysis was very rapid and that the photolysed product was constituted of crosslinked dimer, trimer and tetramer. Increase in concentration of probe linked to aldolase followed by photolysis gave rise to largely tetramer and higher oligomers of aldolase. The use of this carbene-based reagent vis a vis arylazide-based reagent for studying protein crosslinking is discussed.