The Enterics for Global Health (EFGH) Shigella Surveillance Study in Malawi.

Background: Malawi is among 7 countries participating in the Enterics for Global Health (EFGH) Shigella surveillance study, which aims to determine the incidence of medically attended diarrhea attributed to Shigella, a leading bacterial cause of diarrhea in children in low-resource settings. Methods: We describe the EFGH study site in the densely populated informal settlement of Ndirande Township, Blantyre, Malawi. We explore the site's geographical location, demographic characteristics, and the healthcare-seeking behavior of its population, particularly for childhood diarrhea. We also describe the management of childhood diarrhea at the health facility, and the associated challenges to attaining optimum adherence to local and national guidelines at the site. Conclusions: Our overarching aim is to improve global health through understanding and mitigating the impact of diarrhea attributed to Shigella.

Different clinical features in Malawian outpatients presenting with COVID-19 prior to and during Omicron variant dominance: A prospective observational study.

The SARS-CoV-2 Omicron variant has resulted in a high number of cases, but a relatively low incidence of severe disease and deaths, compared to the pre-Omicron variants. Therefore, we assessed the differences in symptom prevalence between Omicron and pre-Omicron infections in a sub-Saharan African population. We collected data from outpatients presenting at two primary healthcare facilities in Blantyre, Malawi, from November 2020 to March 2022. Eligible participants were aged >1month old, with signs suggestive of COVID-19, and those not suspected of COVID-19, from whom we collected nasopharyngeal swabs for SARS-CoV-2 PCR testing, and sequenced positive samples to identify infecting-variants. In addition, we calculated the risk of presenting with a given symptom in individuals testing SARS-CoV-2 PCR positive before and during the Omicron variant-dominated period. Among 5176 participants, 6.4% were under 5, and 77% were aged 18 to 50 years. SARS-CoV-2 infection prevalence peaked in January 2021 (Beta), July 2021 (Delta), and December 2021 (Omicron). We found that cough (risk ratio (RR), 1.50; 95% confidence interval (CI), 1.00 to 2.30), fatigue (RR 2.27; 95% CI, 1.29 to 3.86) and headache (RR 1.64; 95% CI, 1.15 to 2.34) were associated with a high risk of SARS-CoV-2 infection during the pre-Omicron period. In comparison, only headache (RR 1.41; 95% CI, 1.07 to 1.86) did associate with a high risk of SARS-CoV-2 infection during the Omicron-dominated period. In conclusion, clinical symptoms associated with Omicron infection differed from prior variants and were harder to identify clinically with current symptom guidelines. Our findings encourage regular review of case definitions and testing policies to ensure case ascertainment.

Neonatal rotavirus vaccine (RV3-BB) immunogenicity and safety in a neonatal and infant administration schedule in Malawi: a randomised, double-blind, four-arm parallel group dose-ranging study.

BACKGROUND: Rotavirus vaccines reduce rotavirus-related deaths and hospitalisations but are less effective in high child mortality countries. The human RV3-BB neonatal G3P[6] rotavirus vaccine administered in a neonatal schedule was efficacious in reducing severe rotavirus gastroenteritis in Indonesia but had not yet been evaluated in African infants. METHODS: We did a phase 2, randomised, double-blind, parallel group dose-ranging study of three doses of oral RV3-BB rotavirus vaccine in infants in three primary health centres in Blantyre, Malawi. Healthy infants less than 6 days of age with a birthweight 2·5 to 4·0 kg were randomly assigned (1:1:1:1) into one of four treatment groups: neonatal vaccine group, which included high-titre (1·0 × 107 focus-forming unit [FFU] per mL), mid-titre (3·0 × 106 FFU per mL), or low-titre (1·0 × 106 FFU per mL); and infant vaccine group, which included high-titre (1·0 × 107 FFU per mL) using a computer generated code (block size of four), stratified by birth (singleton vs multiple). Neonates received their three doses at 0-5 days to 10 weeks and infants at 6-14 weeks. Investigators, participant families, and laboratory staff were masked to group allocation. Anti-rotavirus IgA seroconversion and vaccine take (IgA seroconversion and stool shedding) were evaluated. Safety was assessed in all participants who received at least one dose of vaccine or placebo. The primary outcome was the cumulative IgA seroconversion 4 weeks after three doses of RV3-BB in the neonatal schedule in the high-titre, mid-titre, and low-titre groups in the per protocol population, with its 95% CI. With the high-titre group as the active control group, we did a non-inferiority analysis of the proportion of participants with IgA seroconversion in the mid-titre and low-titre groups, using a non-inferiority margin of less than 20%. This trial is registered at ClinicalTrials.gov (NCT03483116). FINDINGS: Between Sept 17, 2018, and Jan 27, 2020, 711 participants recruited were randomly assigned into four treatment groups (neonatal schedule high titre n=178, mid titre n=179, low titre n=175, or infant schedule high titre n=179). In the neonatal schedule, cumulative IgA seroconversion 4 weeks after three doses of RV3-BB was observed in 79 (57%) of 139 participants in the high-titre group, 80 (57%) of 141 participants in the mid-titre group, and 57 (41%) of 138 participants in the low-titre group and at 18 weeks in 100 (72%) of 139 participants in the high-titre group, 96 (67%) of 143 participants in the mid-titre group, and 86 (62%) of 138 of participants in the low-titre. No difference in cumulative IgA seroconversion 4 weeks after three doses of RV3-BB was observed between high-titre and mid-titre groups in the neonatal schedule (difference in response rate 0·001 [95%CI -0·115 to 0·117]), fulfilling the criteria for non-inferiority. In the infant schedule group 82 (59%) of 139 participants had a cumulative IgA seroconversion 4 weeks after three doses of RV3-BB at 18 weeks. Cumulative vaccine take was detected in 483 (85%) of 565 participants at 18 weeks. Three doses of RV3-BB were well tolerated with no difference in adverse events among treatment groups: 67 (39%) of 170 participants had at least one adverse event in the high titre group, 68 (40%) of 172 participants had at least one adverse event in the mid titre group, and 69 (41%) of 169 participants had at least one adverse event in the low titre group. INTERPRETATION: RV3-BB was well tolerated and immunogenic when co-administered with Expanded Programme on Immunisation vaccines in a neonatal or infant schedule. A lower titre (mid-titre) vaccine generated similar IgA seroconversion to the high-titre vaccine presenting an opportunity to enhance manufacturing capacity and reduce costs. Neonatal administration of the RV3-BB vaccine has the potential to improve protection against rotavirus disease in children in a high-child mortality country in Africa. FUNDING: Bill & Melinda Gates Foundation, Australian Tropical Medicine Commercialisation Grant.

Dietary Patterns with Healthy and Unhealthy Traits Among Overweight/Obese Hispanic Women with or at High Risk for Type 2 Diabetes.

Hispanic women are at high risk for type 2 diabetes (T2D), with obesity and unhealthy eating being important contributing factors. A cross-sectional design was used in this study to identify dietary patterns and their associations with diabetes risk factors. Participants completed a culturally adapted Food Frequency Questionnaire capturing intake over the prior 3 months. Overweight/obese Hispanic women (n = 191) with or at risk for T2D were recruited from a community clinic into a weight loss intervention. Only baseline data was used for this analysis. Dietary patterns and their association with diabetes risk factors (age, body mass index, abdominal obesity, elevated fasting blood glucose [FBG], and hemoglobin A1c). An exploratory factor analysis of dietary data adjusted for energy intake was used to identify eating patterns, and Pearson correlation coefficient (r) to assess the association of the eating patterns with the diabetes risk factors. Six meaningful patterns with healthful and unhealthful traits emerged: (1) sugar and fat-laden, (2) plant foods and fish, (3) soups and starchy dishes, (4) meats and snacks, (5) beans and grains, and (6) eggs and dairy. Scores for the "sugar and fat-laden" and "meats and snacks" patterns were negatively associated with age (r = - 0.230, p = 0.001 and r = - 0.298, p < 0.001, respectively). Scores for "plant foods and fish" were positively associated with FBG (r = 0.152, p = 0.037). Being younger may be an important risk factor for a diet rich in sugar and fat; this highlights the need to assess dietary patterns among younger Hispanic women to identify traits potentially detrimental for their health.

SHORT-TERM OUTCOMES OF CONSERVATIVE TREATMENT FOR FEMOROACETABULAR IMPINGEMENT: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Femoroacetabular Impingement (FAI) is becoming increasingly more common with noted impairments in physical function, increased pain, and decreased quality of life. Typically, a conservative approach is used through physical therapy or intra-articular injections before an invasive surgical approach is utilized. Identifying the proper course of conservative care by the clinician will aid in improving outcomes. PURPOSE: The purpose of this systematic review and meta-analysis was to investigate short-term effects of conservative physical therapy and intra-articular injections on pain and physical function measures in patients with FAI. STUDY DESIGN: Systematic Review & Meta-Analysis. METHODS: A systematic review and meta-analysis were completed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered with the International Prospective Registry of Systematic Reviews. A literature review was performed in May 2018 using Pubmed, CINAHL, Proquest, and Scopus. Inclusion criteria included humans classified as having femoroacetabular impingement, conservative rehabilitation, and utilization of outcome measures in the domains of pain or function. Exclusion criteria included absence of skilled interaction and study protocols that were not completed. RESULTS: Seven studies were included that summarized physical therapy or intra-articular injection outcomes for femoroacetabular impingement management. Results showed that conservative interventions for short-term periods are effective in reducing pain and improving function for femoroacetabular impingement. Overall, physical therapy revealed moderate to large effect sizes and statistically significant differences in both pain (SMD, 0.91, CI: 0.07, 1.76, p=0.030) and function (SMD, 0.80, CI: 0.34, 1.28, p=0.001) for femoroacetabular impingement. Intra-articular injection demonstrated small effect sizes for pain outcomes (SMD, 0.29, CI: -1.25, 1.83, p = 0.710) and small to moderate effect size for improvement in function (SMD, 0.49, CI: 0.03, 0.96, p = 0.040). CONCLUSIONS: Physical therapy demonstrated positive results to self-reported pain and function and may hold more promise than intra-articular injection alone. Common treatments that were associated with improved outcomes were patient education, activity modification, manual therapy, and strengthening. There are a limited number of high-quality articles on this topic, which should be addressed in future research. LEVEL OF EVIDENCE: 1a.

High Prevalence of Undiagnosed Hyperglycemia in Low-Income Overweight and Obese Hispanic Women in Oregon.

BACKGROUND: Overweight Hispanic women are at high risk for type 2 diabetes. A clinical diagnosis of hyperglycemia is often necessary to access interventions. We examined the prevalence of undiagnosed hyperglycemia among a group of low-income overweight or obese Hispanic women, who were receiving care at a Federally Qualified Health Center (FQHC). METHODS: Among 196 overweight or obese Hispanic women (mean age 44 ± 10 years, mean weight 86.8 ± 16.5 kg, mean body mass index [BMI] 36.5 ± 6.4 kg/m2) enrolled in a randomized clinical weight-loss trial, we compared A1C and fasting blood glucose (FBG) obtained at baseline with women's existing diabetes and prediabetes diagnoses in the medical record. RESULTS: According to the information in participants' medical records, 36% (70/196) had diagnosed diabetes, 20% (39/196) had a diagnosis of prediabetes, and the remaining 44% (87/196) had neither diagnosis. Among participants without a diagnosis of diabetes or prediabetes during the baseline screening for our study, 63% (55/87) had at least one test in the prediabetes range (baseline A1C and FBG were in prediabetes range for 39 and 55 participants, respectively), and 13% (11/87) had at least one test in the diabetic range (baseline A1C and FBG values in diabetes range for 3 and 11 participants, respectively). DISCUSSION: We found substantial prevalence of undiagnosed hyperglycemia among a sample of overweight and obese Hispanic women. It is possible that limited awareness of diabetes risk may be a barrier to patient compliance with screening recommendations.

Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS,S/AS01E Malaria Vaccine Integrated Within an Expanded Program on Immunization Regimen: A Phase II, Single-Center, Open, Controlled Trial in Infants in Malawi.

BACKGROUND: In a phase III trial, the RTS,S/AS01 malaria vaccine produced lower anti-circumsporozoite (CS) antibody titers when co-administered with Expanded Programme on Immunization vaccines (0-, 1- and 2-month schedule) at 6 to 12 weeks compared with 5 to 17 months at first vaccination. Alternative infant immunization schedules within the Expanded Programme on Immunization were investigated. METHODS: This phase II, open, single-site (Blantyre, Malawi) trial was conducted in infants 1 to 7 days of age. Subjects were equally randomized across 7 groups to receive 3 doses of RTS,S/AS01E at time points that included ≤7 days, 6, 10, 14 and 26 weeks, and 9 months. All RTS,S/AS01E groups plus a control group (without RTS,S/AS01E) received Bacillus Calmette-Guérin + oral poliovirus vaccine at ≤7 days, diphtheria, tetanus, whole-cell pertussis, hepatitis B and Haemophilus influenzae type b vaccine + oral poliovirus vaccine at 6, 10, and 14 weeks and measles vaccine at 9 months; one RTS,S/AS01E group and the control additionally received hepatitis B vaccination at ≤7 days. Serum anti-CS antibody geometric mean concentration (GMC; enzyme-linked immunosorbent assay) and safety were assessed up to age 18 months. RESULTS: Of the 480 infants enrolled, 391 completed the study. No causally related serious adverse event was reported. A higher frequency of fever within 7 days of RTS,S/AS01E vaccination compared with control was observed. Compared with the standard 6-, 10-, 14-week schedule, anti-CS antibody GMC ratios post-dose 3 were significantly higher in the 10-, 14- and 26-week group only (ratio 1.80; 95% confidence interval, 1.24-2.60); RTS,S/AS01E vaccination at ≤7 days and 10 and 14 weeks produced significantly lower anti-CS GMCs (ratio 0.59; 95% confidence interval, 0.38-0.92). CONCLUSIONS: Initiation of RTS,S/AS01E vaccination above 6 weeks of age tended to improve anti-CS antibody responses. Neonatal vaccination was well tolerated but produced a comparatively lower immune response.

Creating a World-Class Program through Training and Certification.

The animal research field has gotten more sophisticated with the use of genetically engineered animals, biohazardous agents, and advanced technologies. Trained and competent personnel are a cornerstone of any animal care and use program. Individual career success is a combination of education, experience, continuing competence, professional development, and personal commitment. Integration of training and certification into programs demonstrate institutional commitment to quality research and enhance the program by providing staff with knowledge and training to address problems and situation that arise and to perform their job in a professional and effective manner. Professional development programs offered through the American Association for Laboratory Animal Science-including the AALAS Learning Library and the AALAS certification process-will be presented.

Timeliness of Colonoscopy After Abnormal Fecal Test Results in a Safety Net Practice.

Fecal testing can only reduce colorectal cancer mortality if patients with an abnormal test result receive a follow-up colonoscopy. As part of the Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC) project, we examined factors associated with adherence to follow-up colonoscopy among patients with abnormal fecal test results. As part of STOP CRC outreach, Virginia Garcia Memorial Health Center staff distributed 1753 fecal immunochemical tests (FIT), of which 677 (39 %) were completed, and 56 had an abnormal result (8 %). Project staff used logistic regression analyses to examine factors associated with colonoscopy referral and completion. Of the 56 patients with abnormal FIT results; 45 (80 %) had evidence of a referral for colonoscopy, 32 (57 %) had evidence of a completed colonoscopy within 18 months, and 14 (25 %) within 60 days of an abnormal fecal test result. In adjusted analysis, Hispanics had lower odds of completing follow-up colonoscopy within 60 days than non-Hispanic whites (adjusted OR 0.20; 95 % CI 0.04, 0.92). Colonoscopy within 60 days trended lower for women than for men (adjusted OR 0.25; 95 % CI 0.06-1.04). Among the 24 patients lacking medical record evidence of a colonoscopy, 19 (79 %) had a documented reason, including clinician did not pursue, patient refused, and colonoscopy not indicated. No reason was found for 21 %. Improvements are needed to increase rates of follow-up colonoscopy completion, especially among female and Hispanic patients.

Feasibility and impact of implementing a private care system's diabetes quality improvement intervention in the safety net: a cluster-randomized trial.

BACKGROUND: Integrated health care delivery systems devote considerable resources to developing quality improvement (QI) interventions. Clinics serving vulnerable populations rarely have the resources for such development but might benefit greatly from implementing approaches shown to be effective in other settings. Little trial-based research has assessed the feasibility and impact of such cross-setting translation and implementation in community health centers (CHCs). We hypothesized that it would be feasible to implement successful QI interventions from integrated care settings in CHCs and would positively impact the CHCs. METHODS: We adapted Kaiser Permanente's successful intervention, which targets guideline-based cardioprotective prescribing for patients with diabetes mellitus (DM), through an iterative, stakeholder-driven process. We then conducted a cluster-randomized pragmatic trial in 11 CHCs in a staggered process with six "early" CHCs implementing the intervention one year before five "'late" CHCs. We measured monthly rates of patients with DM currently prescribed angiotensin converting enzyme (ACE)-inhibitors/statins, if clinically indicated. Through segmented regression analysis, we evaluated the intervention's effects in June 2011-May 2013. Participants included ~6500 adult CHC patients with DM who were indicated for statins/ACE-inhibitors per national guidelines. RESULTS: Implementation of the intervention in the CHCs was feasible, with setting-specific adaptations. One year post-implementation, in the early clinics, there were estimated relative increases in guideline-concordant prescribing of 37.6 % (95 % confidence interval (CI); 29.0-46.2 %) among patients indicated for both ACE-inhibitors and statins and 38.7 % (95 % CI; 23.2-54.2 %) among patients indicated for statins. No such increases were seen in the late (control) clinics in that period. CONCLUSIONS: To our knowledge, this was the first clinical trial testing the translation and implementation of a successful QI initiative from a private, integrated care setting into CHCs. This proved feasible and had significant impact but required considerable adaptation and implementation support. These results suggest the feasibility of adapting diverse strategies developed in integrated care settings for implementation in under-resourced clinics, with important implications for efficiently improving care quality in such settings. CLINICALTRIALS.gov: NCT02299791 .

HOMER2, a stereociliary scaffolding protein, is essential for normal hearing in humans and mice.

Hereditary hearing loss is a clinically and genetically heterogeneous disorder. More than 80 genes have been implicated to date, and with the advent of targeted genomic enrichment and massively parallel sequencing (TGE+MPS) the rate of novel deafness-gene identification has accelerated. Here we report a family segregating post-lingual progressive autosomal dominant non-syndromic hearing loss (ADNSHL). After first excluding plausible variants in known deafness-causing genes using TGE+MPS, we completed whole exome sequencing in three hearing-impaired family members. Only a single variant, p.Arg185Pro in HOMER2, segregated with the hearing-loss phenotype in the extended family. This amino acid change alters a highly conserved residue in the coiled-coil domain of HOMER2 that is essential for protein multimerization and the HOMER2-CDC42 interaction. As a scaffolding protein, HOMER2 is involved in intracellular calcium homeostasis and cytoskeletal organization. Consistent with this function, we found robust expression in stereocilia of hair cells in the murine inner ear and observed that over-expression of mutant p.Pro185 HOMER2 mRNA causes anatomical changes of the inner ear and neuromasts in zebrafish embryos. Furthermore, mouse mutants homozygous for the targeted deletion of Homer2 present with early-onset rapidly progressive hearing loss. These data provide compelling evidence that HOMER2 is required for normal hearing and that its sequence alteration in humans leads to ADNSHL through a dominant-negative mode of action.

Strategies and opportunities to STOP colon cancer in priority populations: pragmatic pilot study design and outcomes.

BACKGROUND: Colorectal-cancer is a leading cause of cancer death in the United States, and Latinos have particularly low rates of screening. Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC) is a partnership among two research institutions and a network of safety net clinics to promote colorectal cancer screening among populations served by these clinics. This paper reports on results of a pilot study conducted in a safety net organization that serves primarily Latinos. METHODS: The study assessed two clinic-based approaches to raise rates of colorectal-cancer screening among selected age-eligible patients not up-to-date with colorectal-cancer screening guidelines. One clinic each was assigned to: (1) an automated data-driven Electronic Health Record (EHR)-embedded program for mailing Fecal Immunochemical Test (FIT) kits (Auto Intervention); or (2) a higher-intensity program consisting of a mailed FIT kit plus linguistically and culturally tailored interventions delivered at the clinic level (Auto Plus Intervention). A third clinic within the safety-net organization was selected to serve as a passive control (Usual Care). Two simple measurements of feasibility were: 1) ability to use real-time EHR data to identify patients eligible for each intervention step, and 2) ability to offer affordable testing and follow-up care for uninsured patients. RESULTS: The study was successful at both measurements of feasibility. A total of 112 patients in the Auto clinic and 101 in the Auto Plus clinic met study inclusion criteria and were mailed an introductory letter. Reach was high for the mailed component (92.5% of kits were successfully mailed), and moderate for the telephone component (53% of calls were successful completed). After exclusions for invalid address and other factors, 206 (109 in the Auto clinic and 97 in the Auto Plus clinic) were mailed a FIT kit. At 6 months, fecal test completion rates were higher in the Auto (39.3%) and Auto Plus (36.6%) clinics compared to the usual-care clinic (1.1%). CONCLUSIONS: Findings showed that the trial interventions delivered in a safety-net setting were both feasible and raised rates of colorectal-cancer screening, compared to usual care. Findings from this pilot will inform a larger pragmatic study involving multiple clinics. TRIAL REGISTRATION: ClinicalTrial.gov: NCT01742065.

Surveillance of rotavirus gastro-enteritis in children in Blantyre, Malawi.

BACKGROUND: Rotavirus is a leading cause of acute gastro-enteritis in infants and young children worldwide. Previous studies of rotavirus gastro-enteritis in Malawi have documented a high disease burden with an extensive diversity of circulating rotavirus strains. METHODS: In anticipation of the introduction of national rotavirus vaccination, a 2-year surveillance study was undertaken in 2008 and 2009 of children in Blantyre seeking hospital care for acute gastro-enteritis. Rotavirus was detected in faecal specimens by ELISA. Rotavirus G and P types were determined by RT-PCR. RESULTS: Rotavirus, which circulated throughout the year, was detected in 220/720 (31%) children. Over 85% of patients with rotavirus gastro-enteritis were <1 year of age. A total of 13 rotavirus G/P types were identified, the most common strains being G1P[8] (39·5%), G12P[6] (23·2%), G2P[4] (9·5%), G9P[8] (6·8%) and G8P[4] (6·4%). CONCLUSIONS: The data confirm the importance of rotavirus infection in young Malawian children and highlight the continuing diversity of circulating rotavirus strains in Blantyre. Together with previous observations, the findings contribute to a baseline of data against which the impact of future rotavirus vaccination in Malawi can be assessed.

Association between caffeine citrate exposure and necrotizing enterocolitis in preterm infants.

PURPOSE: The results of a case-control study of the potential role of caffeine citrate therapy in the development of necrotizing enterocolitis (NEC) are presented. METHODS: Patient records for a 10-year period were reviewed to collect sufficient data to test the hypothesis that newborns treated in a hospital's perinatal intensive care unit for NEC might have had a higher cumulative exposure to caffeine citrate relative to that of neonates of similar postconceptional and postnatal age who did not develop NEC. Ninety-five cases of NEC were identified; each case was matched to a control case by gestational age and birth weight. To enable comparative analyses, each control was assigned an index date according to the number of days from birth to NEC diagnosis in the paired case. Data collected for analysis included patient demographics, information on caffeine citrate and concomitant medication use, and potential confounding factors. RESULTS: Analysis of aggregated data for the entire seven-day NEC event timeframe indicated no significant differences between cases and controls with regard to average caffeine citrate loading doses (p = 0.5), cumulative exposure (p = 0.2), and trough serum concentrations (p = 0.5); mean cumulative exposure values differed significantly at one time point (four days prior to NEC diagnosis (p = 0.04). CONCLUSION: Cumulative exposure to caffeine citrate among infants who developed NEC and infants who did not develop NEC differed significantly at only one of six evaluated time points during the seven days before NEC development or the index date. There was no significant difference between groups in the proportions of patients who received caffeine citrate or in mean serum caffeine concentrations.

Collaborative development of a randomized study to adapt a diabetes quality improvement initiative for federally qualified health centers.

This case study describes how we are translating a diabetes care quality improvement initiative from an insured (HMO) setting into federally qualified health centers (FQHCs). We outline the innovative collaborative processes whereby researchers and FQHC providers adapted this initiative, which includes health information technology tools, to meet the FQHCs' needs.

Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: a randomized, double-blind, placebo controlled trial.

Rotavirus gastroenteritis is a major cause of morbidity and mortality among African infants and young children. A phase III, placebo-controlled, multi-centre clinical trial of a live, oral G1P[8] human rotavirus vaccine (RIX4414) undertaken in Malawi and South Africa significantly reduced the incidence of severe rotavirus gastroenteritis in the first year of life. We now report on vaccine efficacy in the Malawi cohort of children who were followed into the second year of life. A total of 1773 healthy infants were enrolled in Blantyre, Malawi into three groups. Two groups received three doses of RIX4414 or placebo at age 6, 10, and 14 weeks and the third group received placebo at 6 weeks and RIX4414 at age 10 and 14 weeks. Subjects were followed by weekly home visits for episodes of gastroenteritis until 1 year of age, and were then re-consented for further follow-up to 18-24 months of age. Severity of gastroenteritis episodes was graded according to the Vesikari scoring system. Seroconversion for anti-rotavirus IgA was determined on a subset of children by using ELISA on pre- and post-vaccine blood samples. Rotavirus VP7 (G) and VP4 (P) genotypes were determined by RT-PCR. A total of 70/1030 (6.8%, 95% CI 5.3-8.5) subjects in the pooled (2 dose plus 3 dose) RIX4414 group compared with 53/483 (11.0%, 8.3-14.1) subjects in the placebo group developed severe rotavirus gastroenteritis in the entire follow-up period (vaccine efficacy 38.1% (9.8-57.3)). The point estimate of efficacy in the second year of life (17.6%; -59.2 to 56.0) was lower than in the first year of life (49.4%; 19.2-68.3). There were non-significant trends towards a higher efficacy in the second year of life among children who received the three-dose schedule compared with the two-dose schedule, and a higher anti-rotavirus IgA seroresponse rate in the three-dose RIX4414 group. Rotavirus strains detected included genotype G12 (31%); G9 (23%); and G8 (18%); only 18% of strains belonged to the G1P[8] genotype. While the optimal dosing schedule of RIX4414 in African infants requires further investigation, vaccination with RIX4414 significantly reduced the incidence of severe gastroenteritis caused by diverse rotavirus strains in an impoverished African population with high rotavirus disease burden in the first two years of life.

Developing a network of community health centers with a common electronic health record: description of the Safety Net West Practice-based Research Network (SNW-PBRN).

In 2001, community health center (CHC) leaders in Oregon established an organization to facilitate the integration of health information technology, including a shared electronic health record (EHR), into safety net clinics. The Oregon Community Health Information Network (shortened to OCHIN as other states joined) became a CHC information technology hub, supporting a network-wide EHR with one master patient index, now linked across >40 safety net organizations serving >900,000 patients with nearly 800,000 distinct CHC visits. Recognizing the potential of OCHIN's multiclinic network and comprehensive EHR database for conducting safety net-based research, OCHIN leaders and local researchers formed the Safety Net West practice-based research network (PBRN). The Safety Net West "community- based laboratory," based at OCHIN, is positioned to become an important resource for many studies including: evaluation of the real-time impact of health care reform on uninsured populations; development of new models of primary care delivery; dissemination and translation of interventions from other EHR-based systems (e.g., Kaiser Permanente) into the community health setting; and analyses of factors influencing disparities in health and health care access. We describe the founding of Safety Net West, its infrastructure development, current projects, and the future goals of this community-based PBRN with a common EHR.

Epidemiology of rotavirus infection in children in Blantyre, Malawi, 1997-2007.

Acute gastroenteritis caused by rotavirus infection is an important cause of morbidity and mortality among infants and young children in Africa. From 1997 through 2007, we enrolled 3740 children <5 years of age with acute gastroenteritis who received hospital care at the Queen Elizabeth Central Hospital in Blantyre, Malawi. Group A rotavirus was detected in fecal specimens by enzyme immunoassay. Rotavirus strains were characterized for VP7 (G) and VP4 (P) types with use of reverse-transcription polymerase chain reaction. Overall, rotavirus was detected in one-third of children. The median age of children with rotavirus gastroenteritis was 7.8 months, compared with 10.9 months for those without rotavirus in stool specimens (P > .001). Rotavirus circulated throughout the year, with the detection proportion greatest during the dry season (from May through October). A total of 15 single rotavirus strain types were detected during the study period, with genotypes P[8]G1, P[6]G8, P[4]G8, P[6]G1, P[8]G3, and P[6]G9 comprising 83% of all strains characterized. Serotype G12 was detected for the first time in Blantyre during the final 2 years of study. Zoonotic transmission and viral reassortment contributed to the rich diversity of strains identified. Current rotavirus vaccines have the potential to greatly reduce the rotavirus disease burden in Malawi, but they will be required to protect against a broad range of rotavirus serotypes in a young population with year-round rotavirus exposure.