Building capacity for public and population health research in Africa : the consortium for advanced research training in Africa (CARTA) model

Background: Globally, sub-Saharan Africa bears the greatest burden of disease. Strengthened research capacity to understand the social determinants of health among different African populations is key to addressing the drivers of poor health and developing interventions to improve health outcomes and health systems in the region. Yet, the continent clearly lacks centers of research excellence that can generate a strong evidence base to address the region’s socio-economic and health problems. Objective and program overview: We describe the recently launched Consortium for Advanced Research Training in Africa (CARTA), which brings together a network of nine academic and four research institutions from West, East, Central, and Southern Africa, and select northern universities and training institutes. CARTA’s program of activities comprises two primary, interrelated, and mutually reinforcing objectives: to strengthen research infrastructure and capacity at African universities; and to support doctoral training through the creation of a collaborative doctoral training program in population and public health. The ultimate goal of CARTA is to build local research capacity to understand the determinants of population health and effectively intervene to improve health outcomes and health systems. Conclusions: CARTA’s focus on the local production of networked and high-skilled researchers committed to working in sub-Saharan Africa, and on the concomitant increase in local research and training capacity of African universities and research institutes addresses the inability of existing programs to create a critical mass of well-trained and networked researchers across the continent. The initiative’s goal of strengthening human resources and university-wide systems critical to the success and sustainability of research productivity in public and population health will rejuvenate institutional teaching, research, and administrative systems

Placebo Oral Rabies Vaccine Bait Uptake by Small Indian Mongooses (\u3ci\u3eHerpestes auropunctatus\u3c/i\u3e) in Southwestern Puerto Rico

The small Indian mongoose (Herpestes auropunctatus) is a rabies reservoir in areas of the Caribbean including Puerto Rico, but no rabies vaccination program targeting this host exists. We used two derivatives of iophenoxic acid (IPA) to evaluate placebo oral rabies vaccine bait uptake by mongooses in southwestern Puerto Rico. We hand-distributed baits at an application rate of 200 baits/km2 at three, 400 ha, sites during autumn 2016 and spring 2017. Each site contained 90–100 cage traps in a 100 ha central trapping area. We used ethyl-IPA as a biological marker during the autumn and methyl-IPA during the spring. We live captured mongooses for 10 consecutive days, beginning 1 wk following bait application. We obtained a serum sample from captured mongooses and analyzed the sera for ethyl- and methyl-IPA by liquid chromatography mass spectrometry. During autumn 2016, 63% (55/87) mongooses sampled were positive for ethyl-IPA. In spring 2017, 69% (85/123) of mongooses were positive for methyl-IPA. Pooling seasons, accounting for recaptures between years, and disregarding marker type, 74% (133/179) unique mongooses were positive for IPA biomarker, indicating bait consumption during either the autumn, spring, or both trials. We conclude that distributing baits at an application rate of 200 baits/km2 is sufficient to reach over 60% of the target mongoose population in dry forest habitats of Puerto Rico

Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring.

OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. METHODS: A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. CONCLUSIONS: The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians

Models in the delivery of depression care: A systematic review of randomised and controlled intervention trials

<p>Abstract</p> <p>Background</p> <p>There is still debate as to which features, types or components of primary care interventions are associated with improved depression outcomes. Previous reviews have focused on components of collaborative care models in general practice settings. This paper aims to determine the effective components of depression care in primary care through a systematic examination of both general practice and community based intervention trials.</p> <p>Methods</p> <p>Fifty five randomised and controlled research trials which focused on adults and contained depression outcome measures were identified through PubMed, PsycInfo and the Cochrane Central Register of Controlled Trials databases. Trials were classified according to the components involved in the delivery of treatment, the type of treatment, the primary focus or setting of the study, detailed features of delivery, and the discipline of the professional providing the treatment. The primary outcome measure was significant improvement on the key depression measure.</p> <p>Results</p> <p>Components which were found to significantly predict improvement were the revision of professional roles, the provision of a case manager who provided direct feedback and delivered a psychological therapy, and an intervention that incorporated patient preferences into care. Nurse, psychologist and psychiatrist delivered care were effective, but pharmacist delivery was not. Training directed to general practitioners was significantly less successful than interventions that did not have training as the most important intervention. Community interventions were effective.</p> <p>Conclusion</p> <p>Case management is important in the provision of care in general practice. Certain community models of care (education programs) have potential while others are not successful in their current form (pharmacist monitoring).</p

Multiple Measures Reveal Antiretroviral Adherence Successes and Challenges in HIV-Infected Ugandan Children

Background: Adherence to HIV antiretroviral therapy (ART) among children in developing settings is poorly understood. Methodology/Principal Findings: To understand the level, distribution, and correlates of ART adherence behavior, we prospectively determined monthly ART adherence through multiple measures and six-monthly HIV RNA levels among 121 Ugandan children aged 2–10 years for one year. Median adherence levels were 100% by three-day recall, 97.4% by 30-day visual analog scale, 97.3% by unannounced pill count/liquid formulation weights, and 96.3% by medication event monitors (MEMS). Interruptions in MEMS adherence of $\geq$48 hours were seen in 57.0% of children; 36.3% had detectable HIV RNA at one year. Only MEMS correlated significantly with HIV RNA levels (r = −0.25, p = 0.04). Multivariable regression found the following to be associated with <90% MEMS adherence: hospitalization of child (adjusted odds ratio [AOR] 3.0, 95% confidence interval [CI] 1.6–5.5; p = 0.001), liquid formulation use (AOR 1.4, 95%CI 1.0–2.0; p = 0.04), and caregiver’s alcohol use (AOR 3.1, 95%CI 1.8–5.2; p<0.0001). Child’s use of co-trimoxazole (AOR 0.5, 95%CI 0.4–0.9; p = 0.009), caregiver’s use of ART (AOR 0.6, 95%CI 0.4–0.9; p = 0.03), possible caregiver depression (AOR 0.6, 95%CI 0.4–0.8; p = 0.001), and caregiver feeling ashamed of child’s HIV status (AOR 0.5, 95%CI 0.3–0.6; p<0.0001) were protective against <90% MEMS adherence. Change in drug manufacturer (AOR 4.1, 95%CI 1.5–11.5; p = 0.009) and caregiver’s alcohol use (AOR 5.5, 95%CI 2.8–10.7; p<0.0001) were associated with $\geq$48-hour interruptions by MEMS, while second-line ART (AOR 0.3, 95%CI 0.1–0.99; p = 0.049) and increasing assets (AOR 0.7, 95%CI 0.6–0.9; p = 0.0007) were protective against these interruptions. Conclusions/Significance: Adherence success depends on a well-established medication taking routine, including caregiver support and adequate education on medication changes. Caregiver-reported depression and shame may reflect fear of poor outcomes, functioning as motivation for the child to adhere. Further research is needed to better understand and build on these key influential factors for adherence intervention development

The vaginal microflora in relation to gingivitis

<p>Abstract</p> <p>Background</p> <p>Gingivitis has been linked to adverse pregnancy outcome (APO). Bacterial vaginosis (BV) has been associated with APO. We assessed if bacterial counts in BV is associated with gingivitis suggesting a systemic infectious susceptibilty.</p> <p>Methods</p> <p>Vaginal samples were collected from 180 women (mean age 29.4 years, SD ± 6.8, range: 18 to 46), and at least six months after delivery, and assessed by semi-quantitative DNA-DNA checkerboard hybridization assay (74 bacterial species). BV was defined by Gram stain (Nugent criteria). Gingivitis was defined as bleeding on probing at ≥ 20% of tooth sites.</p> <p>Results</p> <p>A Nugent score of 0–3 (normal vaginal microflora) was found in 83 women (46.1%), and a score of > 7 (BV) in 49 women (27.2%). Gingivitis was diagnosed in 114 women (63.3%). Women with a diagnosis of BV were more likely to have gingivitis (p = 0.01). Independent of gingival conditions, vaginal bacterial counts were higher (p < 0.001) for 38/74 species in BV+ in comparison to BV- women. Counts of four lactobacilli species were higher in BV- women (p < 0.001). Independent of BV diagnosis, women with gingivitis had higher counts of <it>Prevotella bivia </it>(p < 0.001), and <it>Prevotella disiens </it>(p < 0.001). <it>P. bivia, P. disiens, M. curtisii </it>and <it>M. mulieris </it>(all at the p < 0.01 level) were found at higher levels in the BV+/G+ group than in the BV+/G- group. The sum of bacterial load (74 species) was higher in the BV+/G+ group than in the BV+/G- group (p < 0.05). The highest odds ratio for the presence of bacteria in vaginal samples (> 1.0 × 10⁴cells) and a diagnosis of gingivitis was 3.9 for <it>P. bivia </it>(95% CI 1.5–5.7, p < 0.001) and 3.6 for <it>P. disiens </it>(95%CI: 1.8–7.5, p < 0.001), and a diagnosis of BV for <it>P. bivia </it>(odds ratio: 5.3, 95%CI: 2.6 to 10.4, p < 0.001) and <it>P. disiens </it>(odds ratio: 4.4, 95% CI: 2.2 to 8.8, p < 0.001).</p> <p>Conclusion</p> <p>Higher vaginal bacterial counts can be found in women with BV and gingivitis in comparison to women with BV but not gingivitis. <it>P. bivia </it>and <it>P. disiens </it>may be of specific significance in a relationship between vaginal and gingival infections.</p

Characterization of the Poly-T Variant in the TOMM40 Gene in Diverse Populations

We previously discovered that a polymorphic, deoxythymidine-homopolymer (poly-T, rs10524523) in intron 6 of the TOMM40 gene is associated with age-of-onset of Alzheimer's disease and with cognitive performance in elderly. Three allele groups were defined for rs10524523, hereafter ‘523’, based on the number of ‘T’-residues: ‘Short’ (S, T≤19), ‘Long’ (L, 20≤T≤29) and ‘Very Long’ (VL, T≥30). Homopolymers, particularly long homopolymers like ‘523’, are difficult to genotype because ‘slippage’ occurs during PCR-amplification. We initially genotyped this locus by PCR-amplification followed by Sanger-sequencing. However, we recognized the need to develop a higher-throughput genotyping method that is also accurate and reliable. Here we describe a new ‘523’ genotyping assay that is simple and inexpensive to perform in a standard molecular genetics laboratory. The assay is based on the detection of differences in PCR-fragment length using capillary electrophoresis. We discuss technical problems, solutions, and the steps taken for validation. We employed the novel assay to investigate the ‘523’ allele frequencies in different ethnicities. Whites and Hispanics have similar frequencies of S/L/VL alleles (0.45/0.11/0.44 and 0.43/0.09/0.48, respectively). In African-Americans, the frequency of the L-allele (0.10) is similar to Whites and Hispanics; however, the S-allele is more prevalent (0.65) and the VL-allele is concomitantly less frequent (0.25). The allele frequencies determined using the new methodology are compared to previous reports for Ghanaian, Japanese, Korean and Han Chinese cohorts. Finally, we studied the linkage pattern between TOMM40-‘523’ and APOE alleles. In Whites and Hispanics, consistent with previous reports, the L is primarily linked to ε4, while the majority of the VL and S are linked to ε3. Interestingly, in African-Americans, Ghanaians and Japanese, there is an increased frequency of the ‘523’S-APOEε4 haplotype. These data may be used as references for ‘523’ allele and ‘523’-APOE haplotype frequencies in diverse populations for the design of research studies and clinical trials

Ultrasound settings significantly alter arterial lumen and wall thickness measurements

Background. Flow-mediated dilation (FMD) and carotid intima-medial thickness (CIMT), measured by ultrasound, are widely used to test the efficacy of cardioprotective interventions. Although assessment methods vary, automated edge-detecting image analysis software is routinely used to measure changes in FMD and CIMT. We aimed to quantify the effect that commonly adjusted ultrasound settings have on arterial lumen and wall thickness measurements made with CIMT measurement software. Methods. We constructed phantom arteries from a tissue-mimicking agar compound and scanned them in a water bath with a 10 MHz multi-frequency linear-array probe attached to a high-resolution ultrasound machine. B-mode images of the phantoms were recorded with dynamic range (DR) and gain set at five decibel (dB) increments from 40 dB to 60 dB and -10 dB to +10 dB respectively. Lumen diameter and wall-thickness were measured off-line using CIMT measurement software. Results. Lumen measurements: there was a strong linear relationship between DR and gain and measured lumen diameter. For a given gain level, a 5 dB increase in DR reduced the measured lumen diameter by 0.02 ± 0.004 mm (p \u3c 0.001). For a given DR level, a 5 dB increase in gain reduced measured lumen diameter by 0.04 ± 0.004 mm (p \u3c 0.001). A 5 mm increase in distance between the ultrasound probe and the artery reduced measured lumen diameter by 0.04 ± 0.03 mm (p \u3c 0.001). CIMT measurements: For a fixed gain level, a 5 dB increase in DR increased measured wall thickness by 0.003 ± 0.002 mm (p \u3c 0.001). The effects of increasing gain were not consistent and appeared to vary depending on the distance between the artery and the ultrasound probe and the thickness of the artery wall. Conclusion. DR, gain and probe distance significantly alter lumen diameter and CIMT measurements made using image analysis software. When CIMT and FMD are used to test the efficacy of cardioprotective interventions, the DR, gain and probe position used to record baseline scans should be documented and replicated in post-treatment scans in individual trial subjects. If more than one sonographer or imaging centre is used to collect data, the study protocol should document specific DR and gain settings to be used in all subjects

Antimicrobial management and appropriateness of treatment of urinary tract infection in general practice in Ireland

<p>Abstract</p> <p>Background</p> <p>Urinary tract infections (UTIs) are the second most common bacterial infections in general practice and a frequent indication for prescription of antimicrobials. Increasing concern about the association between the use of antimicrobials and acquired antimicrobial resistance has highlighted the need for rational pharmacotherapy of common infections in general practice.</p> <p>Methods</p> <p>Management of urinary tract infections in general practice was studied prospectively over 8 weeks. Patients presenting with suspected UTI submitted a urine sample and were enrolled with an opt-out methodology. Data were collected on demographic variables, previous antimicrobial use and urine samples. Appropriateness of different treatment scenarios was assessed by comparing treatment with the laboratory report of the urine sample.</p> <p>Results</p> <p>A total of 22 practices participated in the study and included 866 patients. Bacteriuria was established for 21% of the patients, pyuria without bacteriuria for 9% and 70% showed no laboratory evidence of UTI. An antimicrobial agent was prescribed to 56% (481) of the patients, of whom 33% had an isolate, 11% with pyuria only and 56% without laboratory evidence of UTI. When taking all patients into account, 14% patients had an isolate identified and were prescribed an antimicrobial to which the isolate was susceptible. The agents most commonly prescribed for UTI were co-amoxyclav (33%), trimethoprim (26%) and fluoroquinolones (17%). Variation between practices in antimicrobial prescribing as well as in their preference for certain antimicrobials, was observed. Treatment as prescribed by the GP was interpreted as appropriate for 55% of the patients. Three different treatment scenarios were simulated, i.e. if all patients who received an antimicrobial were treated with nitrofurantoin, trimethoprim or ciprofloxacin only. Treatment as prescribed by the GP was no more effective than treatment with nitrofurantoin for all patients given an antimicrobial or treatment with ciprofloxacin in all patients. Prescribing cost was lower for nitrofurantoin. Empirical treatment of all patients with trimethoprim only was less effective due to the higher resistance levels.</p> <p>Conclusions</p> <p>There appears to be considerable scope to reduce the frequency and increase the quality of antimicrobial prescribing for patients with suspected UTI.</p

Using Ribosomal Protein Genes as Reference: A Tale of Caution

Background: Housekeeping genes are needed in every tissue as their expression is required for survival, integrity or duplication of every cell. Housekeeping genes commonly have been used as reference genes to normalize gene expression data, the underlying assumption being that they are expressed in every cell type at approximately the same level. Often, the terms "reference genes'' and "housekeeping genes'' are used interchangeably. In this paper, we would like to distinguish between these terms. Consensus is growing that housekeeping genes which have traditionally been used to normalize gene expression data are not good reference genes. Recently, ribosomal protein genes have been suggested as reference genes based on a meta-analysis of publicly available microarray data. Methodology/Principal Findings: We have applied several statistical tools on a dataset of 70 microarrays representing 22 different tissues, to assess and visualize expression stability of ribosomal protein genes. We confirmed the housekeeping status of these genes, but further estimated expression stability across tissues in order to assess their potential as reference genes. One- and two-way ANOVA revealed that all ribosomal protein genes have significant expression variation across tissues and exhibit tissue-dependent expression behavior as a group. Via multidimensional unfolding analysis, we visualized this tissue-dependency. In addition, we explored mechanisms that may cause tissue dependent effects of individual ribosomal protein genes. Conclusions/Significance: Here we provide statistical and biological evidence that ribosomal protein genes exhibit important tissue-dependent variation in mRNA expression. Though these genes are most stably expressed of all investigated genes in a meta-analysis they cannot be considered true reference genes