IMPORTANCE: Although intraocular lenses (IOLs) are often implanted in children, little is known whether primary IOL implantation or aphakia and contact lens correction results in better long-term ...visual outcomes after unilateral cataract surgery during infancy. OBJECTIVE: To compare long-term visual outcomes with contact lens vs IOL correction following unilateral cataract surgery during infancy. DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial enrolled 114 infants with a unilateral congenital cataract who underwent cataract surgery with or without primary IOL implantation between 1 and 6 months of age. Data on long-term visual outcomes were collected when the children were age 10.5 years (July 14, 2015, to July 12, 2019) and analyzed from March 30 through August 6, 2019. INTERVENTIONS: Intraocular lens implantation at the time of cataract surgery. MAIN OUTCOMES AND MEASURES: Best-corrected visual acuity using the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) testing protocol. Analysis was performed on an intention-to-treat basis. RESULTS: Best-corrected visual acuity was measured at age 10.5 years for 110 of the 114 patients (96%) enrolled as infants. The participants included 58 girls (53%) and 52 boys (47%). Overall, 27 of the children (25%) had good (logMAR 0.30 Snellen equivalent, 20/40 or better) visual acuity in the treated eye (12 22% in the IOL group and 15 27% in the aphakia group), but 50 children (44%) had a visual acuity of logMAR 1.00 (Snellen equivalent, 20/200) or worse (25 44% in the IOL group and 25 44% in the aphakia group). The median logMAR acuity in the treated eye was similar in children randomized to receive an IOL at the time of cataract extraction (0.89; interquartile range IQR, 0.33-1.43 Snellen equivalent, 20/159) and those who remained aphakic (0.86; IQR, 0.30-1.46 Snellen equivalent, 20/145) (IQR, 0.30-1.46; P = .82). Although the overall difference in median visual acuity between the 2 groups was small, the estimate was imprecise (99% CI for the difference in medians was −0.54 to 0.47). CONCLUSIONS AND RELEVANCE: As in previous phases of the study, visual acuity outcomes were highly variable with only 27 children (25%) achieving excellent visual acuity in their treated eye and 50 children (44%) having poor vision in the treated eye. Implanting an IOL at the time of cataract extraction was neither beneficial nor detrimental to the visual outcome. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00212134
Containing Pandemic Influenza at the Source Longini, Ira M; Nizam, Azhar; Xu, Shufu ...
Science (American Association for the Advancement of Science),
08/2005, Volume:
309, Issue:
5737
Journal Article
Peer reviewed
Highly pathogenic avian influenza A (subtype H5N1) is threatening to cause a human pandemic of potentially devastating proportions. We used a stochastic influenza simulation model for rural Southeast ...Asia to investigate the effectiveness of targeted antiviral prophylaxis, quarantine, and pre-vaccination in containing an emerging influenza strain at the source. If the basic reproductive number (R₀) was below 1.60, our simulations showed that a prepared response with targeted antivirals would have a high probability of containing the disease. In that case, an antiviral agent stockpile on the order of 100,000 to 1 million courses for treatment and prophylaxis would be sufficient. If pre-vaccination occurred, then targeted antiviral prophylaxis could be effective for containing strains with an R₀ as high as 2.1. Combinations of targeted antiviral prophylaxis, pre-vaccination, and quarantine could contain strains with an R₀ as high as 2.4.
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3.
Environmental signatures associated with cholera epidemics Constantin de Magny, Guillaume; Murtugudde, Raghu; Sapiano, Mathew R.P ...
Proceedings of the National Academy of Sciences - PNAS,
11/2008, Volume:
105, Issue:
46
Journal Article
Peer reviewed
Open access
The causative agent of cholera, Vibrio cholerae, has been shown to be autochthonous to riverine, estuarine, and coastal waters along with its host, the copepod, a significant member of the ...zooplankton community. Temperature, salinity, rainfall and plankton have proven to be important factors in the ecology of V. cholerae, influencing the transmission of the disease in those regions of the world where the human population relies on untreated water as a source of drinking water. In this study, the pattern of cholera outbreaks during 1998-2006 in Kolkata, India, and Matlab, Bangladesh, and the earth observation data were analyzed with the objective of developing a prediction model for cholera. Satellite sensors were used to measure chlorophyll a concentration (CHL) and sea surface temperature (SST). In addition, rainfall data were obtained from both satellite and in situ gauge measurements. From the analyses, a statistically significant relationship between the time series for cholera in Kolkata, India, and CHL and rainfall anomalies was determined. A statistically significant one month lag was observed between CHL anomaly and number of cholera cases in Matlab, Bangladesh. From the results of the study, it is concluded that ocean and climate patterns are useful predictors of cholera epidemics, with the dynamics of endemic cholera being related to climate and/or changes in the aquatic ecosystem. When the ecology of V. cholerae is considered in predictive models, a robust early warning system for cholera in endemic regions of the world can be developed for public health planning and decision making.
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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 world's 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.
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 < or = 1 case per 1,000 people in the population.
Endemic cholera could be reduced to an annual incidence rate of < or = 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.
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Though the Rwandan Ministry of Health (MOH) prioritizes the scale-up of postpartum family planning (PPFP) programs, uptake and sustainability of PPFP services in Rwanda are low. Furthermore, highly ...effective long-acting reversible contraceptive method use (LARC), key in effective PPFP programs, is specifically low in Rwanda. We previously pilot tested a supply-demand intervention which significantly increased the use of postpartum LARC (PPLARC) in Rwandan government clinics. In this protocol, we use an implementation science framework to test whether our intervention is adaptable to large-scale implementation, cost-effective, and sustainable.
In a type 2 effectiveness-implementation hybrid study, we will evaluate the impact of our PPFP intervention on postpartum LARC (PPLARC) uptake in a clinic-randomized trial in 12 high-volume health facilities in Kigali, Rwanda. We will evaluate this hybrid study using the RE-AIM framework. The independent effectiveness of each PPFP demand creation strategy on PPLARC uptake among antenatal clinic attendees who later deliver in a study facility will be estimated. To assess sustainability, we will assess the intervention adoption, implementation, and maintenance. Finally, we will evaluate intervention cost-effectiveness and develop a national costed implementation plan.
Adaptability and sustainability within government facilities are critical aspects of our proposal, and the MOH and other local stakeholders will be engaged from the outset. We expect to deliver PPFP counseling to over 21,000 women/couples during the project period. We hypothesize that the intervention will significantly increase the number of stakeholders engaged, PPFP providers and promoters trained, couples/clients receiving information about PPFP, and PPLARC uptake comparing intervention versus standard of care. We expect PPFP client satisfaction will be high. Finally, we also hypothesize that the intervention will be cost-saving relative to the standard of care. This intervention could dramatically reduce unintended pregnancy and abortion, as well as improve maternal and newborn health. Our PPFP implementation model is designed to be replicable and expandable to other countries in the region which similarly have a high unmet need for PPFP.
ClinicalTrials.gov NCT05056545 . Registered on 31 March 2022.
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6.
Containing Bioterrorist Smallpox Halloran, M. Elizabeth; Longini, Ira M.; Nizam, Azhar ...
Science (American Association for the Advancement of Science),
11/2002, Volume:
298, Issue:
5597
Journal Article
Peer reviewed
The need for a planned response to a deliberate introduction of smallpox has recently become urgent. We constructed a stochastic simulator of the spread of smallpox in structured communities to ...compare the effectiveness of mass vaccination versus targeted vaccination of close contacts of cases. Mass vaccination before smallpox introduction or immediately after the first cases was more effective than targeted vaccination in preventing and containing epidemics if there was no prior herd immunity (that is, no prior immunologic protection within the population). The effectiveness of postrelease targeted and mass vaccinations increased if we assumed that there was residual immunity in adults vaccinated before 1972, but the effectiveness of targeted vaccination increased more than that of mass vaccination. Under all scenarios, targeted vaccination prevented more cases per dose of vaccine than did mass vaccination. Although further research with larger-scale structured models is needed, our results suggest that increasing herd immunity, perhaps with a combination of preemptive voluntary vaccination and vaccination of first responders, could enhance the effectiveness of postattack intervention. It could also help targeted vaccination be more competitive with mass vaccination at both preventing and containing a deliberate introduction of smallpox.
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The occurrence of outbreaks of cholera in Africa in 1970 and in Latin America in 1991, mainly in coastal communities, and the appearance of the new serotype Vibrio cholerae O139 in India and ...subsequently in Bangladesh have stimulated efforts to understand environmental factors influencing the growth and geographic distribution of epidemic Vibrio cholerae serotypes. Because of the severity of recent epidemics, cholera is now being considered by some infectious disease investigators as a "reemerging" disease, prompting new work on the ecology of vibrios. Epidemiological and ecological surveillance for cholera has been under way in four rural, geographically separated locations in Bangladesh for the past 4 years, during which both clinical and environmental samples were collected at biweekly intervals. The clinical epidemiology portion of the research has been published (Sack et al., J. Infect. Dis. 187:96-101, 2003). The results of environmental sampling and analysis of the environmental and clinical data have revealed significant correlations of water temperature, water depth, rainfall, conductivity, and copepod counts with the occurrence of cholera toxin-producing bacteria (presumably V. cholerae). The lag periods between increases or decreases in units of factors, such as temperature and salinity, and occurrence of cholera correlate with biological parameters, e.g., plankton population blooms. The new information on the ecology of V. cholerae is proving useful in developing environmental models for the prediction of cholera epidemics.
While much is known about recurrent clinical events in patients with intracranial atherosclerotic disease (ICAD), there is limited data on characteristics of recurrent infarcts.
The NIH-funded MyRIAD ...prospective, observational study was designed to identify mechanisms of ischemia and predictors of recurrence in ICAD. Recurrent infarction was assessed on MRI at 6-8 weeks. We reviewed the DWI/ADC and FLAIR sequences in patients with recurrent stroke and characterized the number of infarcts, infarct location, size, and patterns based on whether they were borderzone (BZ), perforator (SC/P), cortical or territorial (C/T), and mixed. Temporal characteristics were delineated by ADC/FLAIR correlation.
Of the 89 patients with 6-8 weeks MRI, 22 (24.7%) had recurrent infarcts in the territory of the symptomatic artery. Recurrent infarcts were evident on DWI in 63.6% and single infarcts in 54.5%. The median recurrent infarct volume was 2.0 cm
compared to median index infarct volumes of 2.5 cm
. A mixed infarct pattern was most common (40.9%), followed by borderzone (22.7%), cortical or territorial (27.3%), while only 9.1% were in a perforator artery distribution. Amongst those with a mixed pattern, 8/9 had a borderzone distribution infarct as part of their mixed infarct pattern.
These findings provide novel data on the characteristics of early recurrent infarcts in patients with symptomatic ICAD.
, an estuarine bacterium, is the causative agent of cholera, a severe diarrheal disease that demonstrates seasonal incidence in Bangladesh. In an extensive study of
occurrence in a natural aquatic ...environment, water and plankton samples were collected biweekly between December 2005 and November 2006 from Mathbaria, an estuarine village of Bangladesh near the mangrove forests of the Sundarbans. Toxigenic
exhibited two seasonal growth peaks, one in spring (March to May) and another in autumn (September to November), corresponding to the two annual seasonal outbreaks of cholera in this region. The total numbers of bacteria determined by heterotrophic plate count (HPC), representing culturable bacteria, accounted for 1% to 2.7% of the total numbers obtained using acridine orange direct counting (AODC). The highest bacterial culture counts, including toxigenic
, were recorded in the spring. The direct fluorescent antibody (DFA) assay was used to detect
O1 cells throughout the year, as free-living cells, within clusters, or in association with plankton.
O1 varied significantly in morphology, appearing as distinctly rod-shaped cells in the spring months, while small coccoid cells within thick clusters of biofilm were observed during interepidemic periods of the year, notably during the winter months. Toxigenic
O1 was culturable in natural water during the spring when the temperature rose sharply. The results of this study confirmed biofilms to be a means of persistence for bacteria and an integral component of the annual life cycle of toxigenic
in the estuarine environment of Bangladesh.
, the causative agent of cholera, is autochthonous in the estuarine aquatic environment. This study describes morphological changes in naturally occurring
O1 in the estuarine environment of Mathbaria, where the bacterium is culturable when the water temperature rises and is observable predominantly as distinct rods and dividing cells. In the spring and fall, these morphological changes coincide with the two seasonal peaks of endemic cholera in Bangladesh.
O1 cells are predominantly coccoid within biofilms but are rod shaped as free-living cells and when attached to plankton or to particulate matter in interepidemic periods of the year. It is concluded that biofilms represent a stage of the annual life cycle of
O1, the causative agent of cholera in Bangladesh.
Antigen-specific CD4 and CD8 T cells are important components of the immune response to
, yet little information is currently known regarding how the breadth, specificity, phenotype, and function of
...-specific T cells correlate with
infection outcome in humans. To facilitate evaluation of human
-specific T cell responses targeting multiple different Ags, we sought to develop a high throughput and reproducible T cell response spectrum assay requiring low blood sample volumes. We describe here the optimization and standardization of a microtiter plate-based, diluted whole blood stimulation assay utilizing overlapping peptide pools corresponding to a functionally diverse panel of 60
Ags. Using IFN-γ production as a readout of Ag specificity, the assay can be conducted using 50 μl of blood per test condition and can be expanded to accommodate additional Ags. We evaluated the intra- and interassay variability, and implemented testing of the assay in diverse cohorts of
-unexposed healthy adults, foreign-born adults with latent
infection residing in the United States, and tuberculosis household contacts with latent
infection in a tuberculosis-endemic setting in Kenya. The
-specific T cell response spectrum assay further enhances the immunological toolkit available for evaluating
-specific T cell responses across different states of
infection, and can be readily implemented in resource-limited settings. Moreover, application of the assay to longitudinal cohorts will facilitate evaluation of treatment- or vaccine-induced changes in the breadth and specificity of Ag-specific T cell responses, as well as identification of
-specific T cell responses associated with
infection outcomes.
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