Francisco J. Luquero

Measuring the Performance of Vaccination Programs Using Cross-Sectional Surveys: A Likelihood Framework and Retrospective Analysis

Justin Lessler and colleagues describe a method that estimates the fraction of a population accessible to vaccination activities, and they apply it to measles vaccination in three African countries: Ghana, Madagascar, and Sierra Leone.

Urban Cholera Transmission Hotspots and Their Implications for Reactive Vaccination: Evidence from Bissau City, Guinea Bissau

Background Use of cholera vaccines in response to epidemics (reactive vaccination) may provide an effective supplement to traditional control measures. In Haiti, reactive vaccination was considered but, until recently, rejected in part due to limited global supply of vaccine. Using Bissau City, Guinea-Bissau as a case study, we explore neighborhood-level transmission dynamics to understand if, with limited vaccine and likely delays, reactive vaccination can significantly change the course of a cholera epidemic. Methods and Findings We fit a spatially explicit meta-population model of cholera transmission within Bissau City to data from 7,551 suspected cholera cases from a 2008 epidemic. We estimated the effect reactive vaccination campaigns would have had on the epidemic under different levels of vaccine coverage and campaign start dates. We compared highly focused and diffuse strategies for distributing vaccine throughout the city. We found wide variation in the efficiency of cholera transmission both within and between areas of the city. “Hotspots”, where transmission was most efficient, appear to drive the epidemic. In particular one area, Bandim, was a necessary driver of the 2008 epidemic in Bissau City. If vaccine supply were limited but could have been distributed within the first 80 days of the epidemic, targeting vaccination at Bandim would have averted the most cases both within this area and throughout the city. Regardless of the distribution strategy used, timely distribution of vaccine in response to an ongoing cholera epidemic can prevent cases and save lives. Conclusions Reactive vaccination can be a useful tool for controlling cholera epidemics, especially in urban areas like Bissau City. Particular neighborhoods may be responsible for driving a citys cholera epidemic; timely and targeted reactive vaccination at such neighborhoods may be the most effective way to prevent cholera cases both within that neighborhood and throughout the city.

Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study

BACKGROUNDnOral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention.nnnMETHODSnWe did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India).nnnFINDINGSnBetween Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0).nnnINTERPRETATIONnOne dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings.nnnFUNDINGnMédecins Sans Frontières.

The First Use of the Global Oral Cholera Vaccine Emergency Stockpile: Lessons from South Sudan

Andrew Azman and colleagues describe their experience of deploying >250,000 doses of oral cholera vaccine in South Sudan in 2014

Protection against cholera from killed whole-cell oral cholera vaccines: a systematic review and meta-analysis

Summary Background Killed whole-cell oral cholera vaccines (kOCVs) are becoming a standard cholera control and prevention tool. However, vaccine efficacy and direct effectiveness estimates have varied, with differences in study design, location, follow-up duration, and vaccine composition posing challenges for public health decision making. We did a systematic review and meta-analysis to generate average estimates of kOCV efficacy and direct effectiveness from the available literature. Methods For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Review Library on July 9, 2016, and ISI Web of Science on July 11, 2016, for randomised controlled trials and observational studies that reported estimates of direct protection against medically attended confirmed cholera conferred by kOCVs. We included studies published on any date in English, Spanish, French, or Chinese. We extracted from the published reports the primary efficacy and effectiveness estimates from each study and also estimates according to number of vaccine doses, duration, and age group. The main study outcome was average efficacy and direct effectiveness of two kOCV doses, which we estimated with random-effect models. This study is registered with PROSPERO, number CRD42016048232. Findings Seven trials (with 695 patients with cholera) and six observational studies (217 patients with cholera) met the inclusion criteria, with an average two-dose efficacy of 58% (95% CI 42–69, I2=58%) and effectiveness of 76% (62–85, I2=0). Average two-dose efficacy in children younger than 5 years (30% [95% CI 15–42], I2=0%) was lower than in those 5 years or older (64% [58–70], I2=0%; p<0·0001). Two-dose efficacy estimates of kOCV were similar during the first 2 years after vaccination, with estimates of 56% (95% CI 42–66, I2=45%) in the first year and 59% (49–67, I2=0) in the second year. The efficacy reduced to 39% (13 to 57, I2=48%) in the third year, and 26% (−46 to 63, I2=74%) in the fourth year. Interpretation Two kOCV doses provide protection against cholera for at least 3 years. One kOCV dose provides at least short-term protection, which has important implications for outbreak management. kOCVs are effective tools for cholera control. Funding The Bill & Melinda Gates Foundation.

Evaluación de las estancias inadecuadas en un servicio de cardiología

Una medida esencial en la busqueda de la eficiencia hospitalaria es evitar estancias inadecuadas. No se ha publicado ningun estudio en este sentido realizado en un servicio de cardiologia de nuestro pais. Para conocer la tasa de inadecuacion de estancias hospitalarias, hemos realizado un estudio observacional analitico retrospectivo. La recogida de datos se realizo conforme al Appropriateness Evaluation Protocol (AEP). La tasa de inadecuacion fue de 27 estancias cada 100 pacientes-dia. En el analisis multivariable, los factores relacionados con estancias inadecuadas fueron los grupos de mayor edad, las estancias mayores de 7 dias y los dias correspondientes a los ultimos tercios de estancia. Las causas mas frecuentes de estancias inadecuadas estuvieron relacionadas con el retraso en procedimientos diagnosticos o terapeuticos y con que estos procedimientos podrian haberse hecho sin ingreso.

Adapting to the global shortage of cholera vaccines: targeted single dose cholera vaccine in response to an outbreak in South Sudan

Shortages of vaccines for epidemic diseases, such as cholera, meningitis, and yellow fever, have become common over the past decade, hampering efforts to control outbreaks through mass reactive vaccination campaigns. Additionally, various epidemiological, political, and logistical challenges, which are poorly documented in the literature, often lead to delays in reactive campaigns, ultimately reducing the effect of vaccination. In June 2015, a cholera outbreak occurred in Juba, South Sudan, and because of the global shortage of oral cholera vaccine, authorities were unable to secure sufficient doses to vaccinate the entire at-risk population-approximately 1 million people. In this Personal View, we document the first public health use of a reduced, single-dose regimen of oral cholera vaccine, and show the details of the decision-making process and timeline. We also make recommendations to help improve reactive vaccination campaigns against cholera, and discuss the importance of new and flexible context-specific dose regimens and vaccination strategies.

Potential for Controlling Cholera Using a Ring Vaccination Strategy: Re-analysis of Data from a Cluster-Randomized Clinical Trial

Introduction Vaccinating a buffer of individuals around a case (ring vaccination) has the potential to target those who are at highest risk of infection, reducing the number of doses needed to control a disease. We explored the potential vaccine effectiveness (VE) of oral cholera vaccines (OCVs) for such a strategy. Methods and Findings This analysis uses existing data from a cluster-randomized clinical trial in which OCV or placebo was given to 71,900 participants in Kolkata, India, from 27 July to 10 September 2006. Cholera surveillance was then conducted on 144,106 individuals living in the study area, including trial participants, for 5 y following vaccination. First, we explored the risk of cholera among contacts of cholera patients, and, second, we measured VE among individuals living within 25 m of cholera cases between 8 and 28 d after onset of the index case. For the first analysis, individuals living around each index case identified during the 5-y period were assembled using a ring to define cohorts of individuals exposed to cholera index cases. An index control without cholera was randomly selected for each index case from the same population, matched by age group, and individuals living around each index control were assembled using a ring to define cohorts not exposed to cholera cases. Cholera attack rates among the exposed and non-exposed cohorts were compared using different distances from the index case/control to define the rings and different time frames to define the period at risk. For the VE analysis, the exposed cohorts were further stratified according to the level of vaccine coverage into high and low coverage strata. Overall VE was assessed by comparing the attack rates between high and low vaccine coverage strata irrespective of individuals’ vaccination status, and indirect VE was assessed by comparing the attack rates among unvaccinated members between high and low vaccine coverage strata. Cholera risk among the cohort exposed to cholera cases was 5–11 times higher than that among the cohort not exposed to cholera cases. The risk gradually diminished with an increase in distance and time. The overall and indirect VE measured between 8 and 28 d after exposure to a cholera index case during the first 2 y was 91% (95% CI 62%–98%) and 93% (95% CI 44%–99%), respectively. VE persisted for 5 y after vaccination and was similar whether the index case was a young child (<5 y) or was older. Of note, this study was a reanalysis of a cholera vaccine trial that used two doses; thus, a limitation of the study relates to the assumption that a single dose, if administered quickly, will induce a similar level of total and indirect protection over the short term as did two doses. Conclusions These findings suggest that high-level protection can be achieved if individuals living close to cholera cases are living in a high coverage ring. Since this was an observational study including participants who had received two doses of vaccine (or placebo) in the clinical trial, further studies are needed to determine whether a ring vaccination strategy, in which vaccine is given quickly to those living close to a case, is feasible and effective. Trial registration ClinicalTrials.gov NCT00289224

Cholera Rapid Test with Enrichment Step Has Diagnostic Performance Equivalent to Culture

Cholera rapid diagnostic tests (RDT) could play a central role in outbreak detection and surveillance in low-resource settings, but their modest performance has hindered their broad adoption. The addition of an enrichment step may improve test specificity. We describe the results of a prospective diagnostic evaluation of the Crystal VC RDT (Span Diagnostics, India) with enrichment step and of culture, each compared to polymerase chain reaction (PCR), during a cholera outbreak in South Sudan. RDTs were performed on alkaline peptone water inoculated with stool and incubated for 4–6 hours at ambient temperature. Cholera culture was performed from wet filter paper inoculated with stool. Molecular detection of Vibrio cholerae O1 by PCR was done from dry Whatman 903 filter papers inoculated with stool, and from wet filter paper supernatant. In August and September 2015, 101 consecutive suspected cholera cases were enrolled, of which 36 were confirmed by PCR. The enriched RDT had 86.1% (95% CI: 70.5–95.3) sensitivity and 100% (95% CI: 94.4–100) specificity compared to PCR as the reference standard. The sensitivity of culture versus PCR was 83.3% (95% CI: 67.2–93.6) for culture performed on site and 72.2% (95% CI: 54.8–85.8) at the international reference laboratory, where samples were tested after an average delay of two months after sample collection, and specificity was 98.5% (95% CI: 91.7–100) and 100% (95% CI: 94.5–100), respectively. The RDT with enrichment showed performance comparable to that of culture and could be a sustainable alternative to culture confirmation where laboratory capacity is limited.

Pregnancy Outcomes after a Mass Vaccination Campaign with an Oral Cholera Vaccine in Guinea: A Retrospective Cohort Study

Introduction Since 2010, WHO has recommended oral cholera vaccines as an additional strategy for cholera control. During a cholera episode, pregnant women are at high risk of complications, and the risk of fetal death has been reported to be 2–36%. Due to a lack of safety data, pregnant women have been excluded from most cholera vaccination campaigns. In 2012, reactive campaigns using the bivalent killed whole-cell oral cholera vaccine (BivWC), included all people living in the targeted areas aged ≥1 year regardless of pregnancy status, were implemented in Guinea. We aimed to determine whether there was a difference in pregnancy outcomes between vaccinated and non-vaccinated pregnant women. Methods and Findings From 11 November to 4 December 2013, we conducted a retrospective cohort study in Boffa prefecture among women who were pregnant in 2012 during or after the vaccination campaign. The primary outcome was pregnancy loss, as reported by the mother, and fetal malformations, after clinical examination. Primary exposure was the intake of the BivWC vaccine (Shanchol) during pregnancy, as determined by a vaccination card or oral history. We compared the risk of pregnancy loss between vaccinated and non-vaccinated women through binomial regression analysis. A total of 2,494 pregnancies were included in the analysis. The crude incidence of pregnancy loss was 3.7% (95%CI 2.7–4.8) for fetuses exposed to BivWC vaccine and 2.6% (0.7–4.5) for non-exposed fetuses. The incidence of malformation was 0.6% (0.1–1.0) and 1.2% (0.0–2.5) in BivWC-exposed and non-exposed fetuses, respectively. In both crude and adjusted analyses, fetal exposure to BivWC was not significantly associated with pregnancy loss (adjusted risk ratio (aRR = 1.09 [95%CI: 0.5–2.25], p = 0.818) or malformations (aRR = 0.50 [95%CI: 0.13–1.91], p = 0.314). Conclusions In this large retrospective cohort study, we found no association between fetal exposure to BivWC and risk of pregnancy loss or malformation. Despite the weaknesses of a retrospective design, we can conclude that if a risk exists, it is very low. Additional prospective studies are warranted to add to the evidence base on OCV use during pregnancy. Pregnant women are particularly vulnerable during cholera episodes and should be included in vaccination campaigns when the risk of cholera is high, such as during outbreaks.