Neeta Shenvi

Controlling Endemic Cholera with Oral Vaccines

Background Although advances in rehydration therapy have made cholera a treatable disease with low case-fatality in settings with appropriate medical care, cholera continues to impose considerable mortality in the worlds most impoverished populations. Internationally licensed, killed whole-cell based oral cholera vaccines (OCVs) have been available for over a decade, but have not been used for the control of cholera. Recently, these vaccines were shown to confer significant levels of herd protection, suggesting that the protective potential of these vaccines has been underestimated and that these vaccines may be highly effective in cholera control when deployed in mass immunization programs. We used a large-scale stochastic simulation model to investigate the possibility of controlling endemic cholera with OCVs. Methods and Findings We construct a large-scale, stochastic cholera transmission model of Matlab, Bangladesh. We find that cholera transmission could be controlled in endemic areas with 50% coverage with OCVs. At this level of coverage, the model predicts that there would be an 89% (95% confidence interval [CI] 72%–98%) reduction in cholera cases among the unvaccinated, and a 93% (95% CI 82%–99%) reduction overall in the entire population. Even a more modest coverage of 30% would result in a 76% (95% CI 44%–95%) reduction in cholera incidence for the population area covered. For populations that have less natural immunity than the population of Matlab, 70% coverage would probably be necessary for cholera control, i.e., an annual incidence rate of ≤ 1 case per 1,000 people in the population. Conclusions Endemic cholera could be reduced to an annual incidence rate of ≤ 1 case per 1,000 people in endemic areas with biennial vaccination with OCVs if coverage could reach 50%–70% depending on the level of prior immunity in the population. These vaccination efforts could be targeted with careful use of ecological data.

The Movement Imagery Questionnaire-Revised, Second Edition (MIQ-RS) Is a Reliable and Valid Tool for Evaluating Motor Imagery in Stroke Populations

Mental imagery can improve motor performance in stroke populations when combined with physical therapy. Valid and reliable instruments to evaluate the imagery ability of stroke survivors are needed to maximize the benefits of mental imagery therapy. The purposes of this study were to: examine and compare the test-retest intra-rate reliability of the Movement Imagery Questionnaire-Revised, Second Edition (MIQ-RS) in stroke survivors and able-bodied controls, examine internal consistency of the visual and kinesthetic items of the MIQ-RS, determine if the MIQ-RS includes both the visual and kinesthetic dimensions of mental imagery, correlate impairment and motor imagery scores, and investigate the criterion validity of the MIQ-RS in stroke survivors by comparing the results to the KVIQ-10. Test-retest analysis indicated good levels of reliability (ICC range: .83–.99) and internal consistency (Cronbach α: .95–.98) of the visual and kinesthetic subscales in both groups. The two-factor structure of the MIQ-RS was supported by factor analysis, with the visual and kinesthetic components accounting for 88.6% and 83.4% of the total variance in the able-bodied and stroke groups, respectively. The MIQ-RS is a valid and reliable instrument in the stroke population examined and able-bodied populations and therefore useful as an outcome measure for motor imagery ability.

Association of Red Blood Cell Transfusion, Anemia, and Necrotizing Enterocolitis in Very Low-Birth-Weight Infants

IMPORTANCE Data regarding the contribution of red blood cell (RBC) transfusion and anemia to necrotizing enterocolitis (NEC) are conflicting. These associations have not been prospectively evaluated, accounting for repeated, time-varying exposures. OBJECTIVE To determine the relationship between RBC transfusion, severe anemia, and NEC. DESIGN, SETTING, AND PARTICIPANTS In a secondary, prospective, multicenter observational cohort study from January 2010 to February 2014, very low-birth-weight (VLBW, ≤1500 g) infants, within 5 days of birth, were enrolled at 3 level III neonatal intensive care units in Atlanta, Georgia. Two hospitals were academically affiliated and 1 was a community hospital. Infants received follow-up until 90 days, hospital discharge, transfer to a non-study-affiliated hospital, or death (whichever came first). Multivariable competing-risks Cox regression was used, including adjustment for birth weight, center, breastfeeding, illness severity, and duration of initial antibiotic treatment, to evaluate the association between RBC transfusion, severe anemia, and NEC. EXPOSURES The primary exposure was RBC transfusion. The secondary exposure was severe anemia, defined a priori as a hemoglobin level of 8 g/dL or less. Both exposures were evaluated as time-varying covariates at weekly intervals. MAIN OUTCOMES AND MEASURES Necrotizing enterocolitis, defined as Bell stage 2 or greater by preplanned adjudication. Mortality was evaluated as a competing risk. RESULTS Of 600 VLBW infants enrolled, 598 were evaluated. Forty-four (7.4%) infants developed NEC. Thirty-two (5.4%) infants died (all cause). Fifty-three percent of infants (319) received a total of 1430 RBC transfusion exposures. The unadjusted cumulative incidence of NEC at week 8 among RBC transfusion-exposed infants was 9.9% (95% CI, 6.9%-14.2%) vs 4.6% (95% CI, 2.6%-8.0%) among those who were unexposed. In multivariable analysis, RBC transfusion in a given week was not significantly related to the rate of NEC (adjusted cause-specific hazard ratio, 0.44 [95% CI, 0.17-1.12]; P = .09). Based on evaluation of 4565 longitudinal measurements of hemoglobin (median, 7 per infant), the rate of NEC was significantly increased among VLBW infants with severe anemia in a given week compared with those who did not have severe anemia (adjusted cause-specific hazard ratio, 5.99 [95% CI, 2.00-18.0]; P = .001). CONCLUSIONS AND RELEVANCE Among VLBW infants, severe anemia, but not RBC transfusion, was associated with an increased risk of NEC. Further studies are needed to evaluate whether preventing severe anemia is more important than minimizing RBC transfusion.

Blood Transfusion and Breast Milk Transmission of Cytomegalovirus in Very Low-Birth-Weight Infants : A Prospective Cohort Study

IMPORTANCE Postnatal cytomegalovirus (CMV) infection can cause serious morbidity and mortality in very low-birth-weight (VLBW) infants. The primary sources of postnatal CMV infection in this population are breast milk and blood transfusion. The current risks attributable to these vectors, as well as the efficacy of approaches to prevent CMV transmission, are poorly characterized. OBJECTIVE To estimate the risk of postnatal CMV transmission from 2 sources: (1) transfusion of CMV-seronegative and leukoreduced blood and (2) maternal breast milk. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter birth-cohort study was conducted from January 2010 to June 2013 at 3 neonatal intensive care units (2 academically affiliated and 1 private) in Atlanta, Georgia. Cytomegalovirus serologic testing of enrolled mothers was performed to determine their status. Cytomegalovirus nucleic acid testing (NAT) of transfused blood components and breast milk was performed to identify sources of CMV transmission. A total of 539 VLBW infants (birth weight, ≤ 1500 g) who had not received a blood transfusion were enrolled, with their mothers (n = 462), within 5 days of birth. The infants underwent serum and urine CMV NAT at birth to evaluate congenital infection and surveillance CMV NAT at 5 additional intervals between birth and 90 days, discharge, or death. EXPOSURES Blood transfusion and breast milk feeding. MAIN OUTCOMES AND MEASURES Cumulative incidence of postnatal CMV infection, detected by serum or urine NAT. RESULTS The seroprevalence of CMV among the 462 enrolled mothers was 76.2% (n = 352). Among the 539 VLBW infants, the cumulative incidence of postnatal CMV infection at 12 weeks was 6.9% (95% CI, 4.2%-9.2%); 5 of 29 infants (17.2%) with postnatal CMV infection developed symptomatic disease or died. A total of 2061 transfusions were administered among 57.5% (n = 310) of the infants; none of the CMV infections was linked to transfusion, resulting in a CMV infection incidence of 0.0% (95% CI, 0.0%-0.3%) per unit of CMV-seronegative and leukoreduced blood. Twenty-seven of 28 postnatal infections occurred among infants fed CMV-positive breast milk (12-week incidence, 15.3%; 95% CI, 9.3%-20.2%). CONCLUSIONS AND RELEVANCE Transfusion of CMV-seronegative and leukoreduced blood products effectively prevents transmission of CMV to VLBW infants. Among infants whose care is managed with this transfusion approach, maternal breast milk is the primary source of postnatal CMV infection. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00907686.

High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial.

BACKGROUND Tuberculosis, including multidrug-resistant tuberculosis (MDR-TB), is a major global health problem. Individuals with tuberculosis disease commonly exhibit vitamin D deficiency, which may adversely affect immunity and the response to therapy. OBJECTIVE We determined whether adjunctive high-dose vitamin D3 supplementation improves outcomes in individuals with pulmonary tuberculosis disease. DESIGN The study was a double-blind, randomized, placebo-controlled, intent-to-treat trial in 199 individuals with pulmonary tuberculosis disease in Tbilisi, Georgia. Subjects were randomly assigned to receive oral vitamin D3 [50,000 IUs (1.25 mg) thrice weekly for 8 wk and 50,000 IU every other week for 8 wk] or a placebo concomitant with standard first-line antituberculosis drugs. The primary outcome was the time for the conversion of a Mycobacterium tuberculosis (Mtb) sputum culture to negative. RESULTS Baseline characteristics between groups were similar. Most subjects (74%) were vitamin D deficient (plasma 25-hydroxyvitamin D [25(OH)D] concentration <50 nmol/L). With vitamin D3, plasma 25(OH)D concentrations peaked at ∼250 nmol/L by 8 wk and decreased to ∼125 nmol/L at week 16. Adverse events and plasma calcium concentrations were similar between groups. In 192 subjects with culture-confirmed tuberculosis, an adjusted efficacy analysis showed similar median culture-conversion times between vitamin D3 and placebo groups [29 and 27 d, respectively; HR: 0.86; 95% CI: 0.63, 1.18; P = 0.33). Eight-week culture-conversion rates were also similar (84.0% and 82.1% for vitamin D3 and placebo, respectively; P = 0.99). CONCLUSION A high-dose vitamin D3 regimen safely corrected vitamin D deficiency but did not improve the rate of sputum Mtb clearance over 16 wk in this pulmonary tuberculosis cohort. This trial was registered at clinicaltrials.gov at NCT00918086.

Further Assessment to Determine the Additive Effect of Botulinum Toxin Type A on an Upper Extremity Exercise Program to Enhance Function Among Individuals With Chronic Stroke but Extensor Capability

OBJECTIVE To determine whether dose-specified botulinum toxin type A (BTX-A) and a standardized exercise protocol produce better upper extremity function than placebo and the same exercise program. DESIGN Double-blind randomized trial. SETTING A rehabilitation research center. PARTICIPANTS A convenience sample of patients (N=25, age range, 23-76 y) who sustained a stroke 3 to 24 months previously but could initiate wrist extension. INTERVENTIONS Participants were randomly selected to receive either BTX-A (maximum 300 U) or saline, followed by 12 to 16 exercise sessions. MAIN OUTCOME MEASURES The primary outcome was the Wolf Motor Function Test (WMFT). Secondary outcome measures included the Modified Ashworth Scale (MAS), active range of motion, and the Stroke Impact Scale (SIS; quality of life). RESULTS There were no group-by-time interactions for changes in the WMFT and no treatment difference (P=.86), although the BTX-A group could complete more tasks governing proximal joint motions. MAS scores improved for the BTX-A group and worsened for the control group after injection (P=.02), as did the SIS emotion domain (P=.035). CONCLUSIONS Among chronic stroke survivors, BTX-A did not impact function, movement, or tone more than a standardized exercise program.

A 7% Decrease in the Differential Renal Uptake of MAG3 Implies a Loss in Renal Function

OBJECTIVES To address the fact that a decrease in the relative renal uptake of 99mTc-mercaptoacetyltriglycine (MAG3) on serial MAG3 scans may indicate a loss of function and require a change in management by providing guidance as to what constitutes a meaningful change in serial relative function measurements as well determining the normal variation of other common MAG3 renogram parameters. METHODS A prospective study was conducted in 24 male urology patients with stable renal function. The mean age was 66.5 ± 7.9 (SD) years; the mean serum creatinine was 1.38 ± 0.57 (SD) mg/dL, and the MAG3 renal scans were performed a mean of 11 ± 8 days apart. Each MAG3 scan included a measurement of relative function as well as the time to maximum counts and 20 minutes to maximum count ratios for both cortical and whole kidney regions of interest. RESULTS The Pearson and intraclass correlations for the baseline and repeat measurements of relative renal function were both 0.98. Bland-Altman plots showed no bias between the baseline and repeat relative uptake measurements. The mean difference between 2 repeated measurements of the relative MAG3 uptake was 0.04 ± 2.88% (SD) for the left kidney and 0.08 ± 3.07% (SD) for the right kidney. Comparable results were obtained for the other renogram parameters. CONCLUSIONS Measurements of relative renal uptake of MAG3 and common renogram parameters are highly reproducible; a decrease in relative uptake ≥7% (ie, 50%-43%) implies a loss in renal function.

Reference Values for Renal Size Obtained From MAG3 Scintigraphy

Purpose The purposes of this study were to establish reference values for renal size determined from 99mTc-MAG3 renal scintigraphy and to derive regression equations to predict normal limits. Methods The study population consisted of 106 subjects evaluated for kidney donation who underwent 99mTc-MAG3 renal scintigraphy. Renal length, width, and area were determined from the pixel length and area of whole-kidney regions of interest and correlated with patient sex, height, weight, body mass index, and body surface area (BSA). Reference values were obtained based on estimation of the lower and upper percentiles via quantile regression. Results The mean (SD) left and right kidney lengths was 12.2 (1.0) and 12.1 (1.0) in male and 11.9 (0.9) and 11.8 (0.9) in female patients, respectively. Sex was not a significant factor in the quantile regression models. Regression equations defining the lower and upper limits of renal length (cm) and area (cm2) are as follows: left kidney length (5th percentile), 8.2 + 1.3 × BSA; left kidney length (95th percentile), 9.1 + 2.3 × BSA; right kidney length (5th percentile), 8.8 + 1.0 × BSA; right kidney length (95th percentile), 11.1 + 1.4 × BSA; left kidney area (5th percentile), 32.5 + 9.6 × BSA; left kidney area (95th percentile), 12.6 + 31.7 × BSA; right kidney area (5th percentile), 16.1 + 18.5 × BSA; right kidney area (95th percentile), 32.6 + 22.2 × BSA. Conclusions Regression equations have been developed, which define the upper and lower limits of renal size from 99mTc-MAG3 images and may assist in the detection of unsuspected bilateral increases or decreases in renal size.

A culture-specific nutrient intake assessment instrument in patients with pulmonary tuberculosis

BACKGROUND & AIM To develop and evaluate a culture-specific nutrient intake assessment tool for use in adults with pulmonary tuberculosis (TB) in Tbilisi, Georgia. METHODS We developed an instrument to measure food intake over 3 consecutive days using a questionnaire format. The tool was then compared to 24 h food recalls. Food intake data from 31 subjects with TB were analyzed using the Nutrient Database System for Research (NDS-R) dietary analysis program. Paired t-tests, Pearson correlations and intraclass correlation coefficients (ICC) were used to assess the agreement between the two methods of dietary intake for calculated nutrient intakes. RESULTS The Pearson correlation coefficient for mean daily caloric intake between the 2 methods was 0.37 (P = 0.04) with a mean difference of 171 kcals/day (p = 0.34). The ICC was 0.38 (95% CI: 0.03-0.64) suggesting the within-patient variability may be larger than between-patient variability. Results for mean daily intake of total fat, total carbohydrate, total protein, retinol, vitamins D and E, thiamine, calcium, sodium, iron, selenium, copper, and zinc between the two assessment methods were also similar. CONCLUSIONS This novel nutrient intake assessment tool provided quantitative nutrient intake data from TB patients. These pilot data can inform larger studies in similar populations.

The impact of diabetes on CD4 recovery in persons with HIV in an urban clinic in the United States

The purpose of this study was to exam the impact of type 2 diabetes mellitus (T2DM) on CD4 cell count trends in adults with HIV. In a longitudinal retrospective study in an urban primary care HIV clinic in the southeastern United States from 2010 to 2012, patients with HIV medical charts were audited to obtain their CD4 cell count, diabetes status, weight, and demographic information. Rates of increase of CD4 T cell count (i.e. slopes) were obtained using a linear mixed-effects model. Most of the HIV–T2DM cohort (n = 262) and HIV-only cohort (n = 2399) were African American (76%) and male (77%). The CD4 T cell counts were consistently higher in the HIV–T2DM cohort (p < .0001). The mean rate of CD4 T cell count increase (mean ± SE) was 63 ± 9 cells/µl/year in HIV–T2DM African American women and 28 ± 7 cells/µl/year in HIV–T2DM African American men (p = 0.003). In the multivariable slope analysis, the CD4 T cell count increase was significantly faster for HIV–T2DM African American women than for all other patients (mean difference = 30/cells/µl/year, 95% CI: 13–47; p < 0.001). Gender, race/ethnicity, and the diagnosis of diabetes influenced the recovery of CD4 cell counts.