The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study

BackgroundIn 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both.ConclusionsReactive vaccination campaigns using a single dose of OCV may avert more cases and deaths than a standard two-dose campaign when vaccine supplies are limited, while at the same time reducing logistical complexity. These findings should motivate consideration of the trade-offs between one- and two-dose campaigns in resource-constrained settings, though further field efficacy data are needed and should be a priority in any one-dose campaign.     

Reactive vaccination in the presence of disease hotspots

Reactive vaccination has recently been adopted as an outbreak response tool for cholera and other infectious diseases. Owing to the global shortage of oral cholera vaccine, health officials must quickly decide who and where to distribute limited vaccine. Targeted vaccination in transmission hotspots (i.e. areas with high transmission efficiency) may be a potential approach to efficiently allocate vaccine, however its effectiveness will likely be context-dependent. We compared strategies for allocating vaccine across multiple areas with heterogeneous transmission efficiency. We constructed metapopulation models of a cholera-like disease and compared simulated epidemics where: vaccine is targeted at areas of high or low transmission efficiency, where vaccine is distributed across the population, and where no vaccine is used. We find that connectivity between populations, transmission efficiency, vaccination timing and the amount of vaccine available all shape the performance of different allocation strategies. In highly connected settings (e.g. cities) when vaccinating early in the epidemic, targeting limited vaccine at transmission hotspots is often optimal. Once vaccination is delayed, targeting the hotspot is rarely optimal, and strategies that either spread vaccine between areas or those targeted at non-hotspots will avert more cases. Although hotspots may be an intuitive outbreak control target, we show that, in many situations, the hotspot-epidemic proceeds so fast that hotspot-targeted reactive vaccination will prevent relatively few cases, and vaccination shared across areas where transmission can be sustained is often best.     

Flexibility of Oral Cholera Vaccine Dosing—A Randomized Controlled Trial Measuring Immune Responses Following Alternative Vaccination Schedules in a Cholera Hyper-Endemic Zone

BackgroundA bivalent killed whole cell oral cholera vaccine has been found to be safe and efficacious for five years in the cholera endemic setting of Kolkata, India, when given in a two dose schedule, two weeks apart. A randomized controlled trial revealed that the immune response was not significantly increased following the second dose compared to that after the first dose. We aimed to evaluate the impact of an extended four week dosing schedule on vibriocidal response.Conclusions/SignificanceComparable immune responses and safety profiles between the two dosing schedules support the option for increased flexibility of current OCV dosing. Further operational research using a longer dosing regimen will provide answers to improve implementation and delivery of cholera vaccination in endemic and epidemic outbreak scenarios.     

The case for reactive mass oral cholera vaccinations

Introduction

The outbreak of cholera in Zimbabwe intensified interest in the control and prevention of cholera. While there is agreement that safe water, sanitation, and personal hygiene are ideal for the long term control of cholera, there is controversy about the role of newer approaches such as oral cholera vaccines (OCVs). In October 2009 the Strategic Advisory Group of Experts advised the World Health Organization to consider reactive vaccination campaigns in response to large cholera outbreaks. To evaluate the potential benefit of this pivotal change in WHO policy, we used existing data from cholera outbreaks to simulate the number of cholera cases preventable by reactive mass vaccination.

Methods

Datasets of cholera outbreaks from three sites with varying cholera endemicity—Zimbabwe, Kolkata (India), and Zanzibar (Tanzania)—were analysed to estimate the number of cholera cases preventable under differing response times, vaccine coverage, and vaccine doses.

Findings

The large cholera outbreak in Zimbabwe started in mid August 2008 and by July 2009, 98,591 cholera cases had been reported with 4,288 deaths attributed to cholera. If a rapid response had taken place and half of the population had been vaccinated once the first 400 cases had occurred, as many as 34,900 (40%) cholera cases and 1,695 deaths (40%) could have been prevented. In the sites with endemic cholera, Kolkata and Zanzibar, a significant number of cases could have been prevented but the impact would have been less dramatic. A brisk response is required for outbreaks with the majority of cases occurring during the early weeks. Even a delayed response can save a substantial number of cases and deaths in long, drawn-out outbreaks. If circumstances prevent a rapid response there are good reasons to roll out cholera mass vaccination campaigns well into the outbreak. Once a substantial proportion of a population is vaccinated, outbreaks in subsequent years may be reduced if not prevented. A single dose vaccine would be of advantage in short, small outbreaks.

Conclusions

We show that reactive vaccine use can prevent cholera cases and is a rational response to cholera outbreaks in endemic and non-endemic settings. In large and long outbreaks a reactive vaccination with a two-dose vaccine can prevent a substantial proportion of cases. To make mass vaccination campaigns successful, it would be essential to agree when to implement reactive vaccination campaigns and to have a dynamic and determined response team that is familiar with the logistic challenges on standby. Most importantly, the decision makers in donor and recipient countries have to be convinced of the benefit of reactive cholera vaccinations.     

Assessing the best time interval between doses in a two-dose vaccination regimen to reduce the number of deaths in an ongoing epidemic of SARS-CoV-2

The SARS-CoV-2 pandemic is a major concern all over the world and, as vaccines became available at the end of 2020, optimal vaccination strategies were subjected to intense investigation. Considering their critical role in reducing disease burden, the increasing demand outpacing production, and that most currently approved vaccines follow a two-dose regimen, the cost-effectiveness of delaying the second dose to increment the coverage of the population receiving the first dose is often debated. Finding the best solution is complex due to the trade-off between vaccinating more people with lower level of protection and guaranteeing higher protection to a fewer number of individuals. Here we present a novel extended age-structured SEIR mathematical model that includes a two-dose vaccination schedule with a between-doses delay modelled through delay differential equations and linear optimization of vaccination rates. By maintaining the minimum stock of vaccines under a given production rate, we evaluate the dose interval that minimizes the number of deaths. We found that the best strategy depends on an interplay between the vaccine production rate and the relative efficacy of the first dose. In the scenario of low first-dose efficacy, it is always better to vaccinate the second dose as soon as possible, while for high first-dose efficacy, the best strategy of time window depends on the production rate and also on second-dose efficacy provided by each type of vaccine. We also found that the rate of spread of the infection does not affect significantly the thresholds of the best window, but is an important factor in the absolute number of total deaths. These conclusions point to the need to carefully take into account both vaccine characteristics and roll-out speed to optimize the outcome of vaccination strategies.     

Knowledge,Attitudes, and Practices regarding Diarrhea and Cholera following an Oral Cholera Vaccination Campaign in the Solomon Islands

BackgroundIn response to a 2011 cholera outbreak in Papua New Guinea, the Government of the Solomon Islands initiated a cholera prevention program which included cholera disease prevention and treatment messaging, community meetings, and a pre-emptive cholera vaccination campaign targeting 11,000 children aged 1–15 years in selected communities in Choiseul and Western Provinces.ConclusionsThis pre-emptive OCV campaign in a cholera-naïve community provided a unique opportunity to assess household-level knowledge, attitudes, and practices regarding diarrhea, cholera, and water, sanitation, and hygiene (WASH). Our findings suggest that education provided during the vaccination campaign may have reinforced earlier mass messaging about cholera and diarrheal disease in vaccinated communities.     

Using Mobile Health (mHealth) and Geospatial Mapping Technology in a Mass Campaign for Reactive Oral Cholera Vaccination in Rural Haiti

Background

In mass vaccination campaigns, large volumes of data must be managed efficiently and accurately. In a reactive oral cholera vaccination (OCV) campaign in rural Haiti during an ongoing epidemic, we used a mobile health (mHealth) system to manage data on 50,000 participants in two isolated communities.

Methods

Data were collected using 7-inch tablets. Teams pre-registered and distributed vaccine cards with unique barcodes to vaccine-eligible residents during a census in February 2012. First stored on devices, data were uploaded nightly via Wi-fi to a web-hosted database. During the vaccination campaign between April and June 2012, residents presented their cards at vaccination posts and their barcodes were scanned. Vaccinee data from the census were pre-loaded on tablets to autopopulate the electronic form. Nightly analysis of the day''s community coverage informed the following day''s vaccination strategy. We generated case-finding reports allowing us to identify those who had not yet been vaccinated.

Results

During 40 days of vaccination, we collected approximately 1.9 million pieces of data. A total of 45,417 people received at least one OCV dose; of those, 90.8% were documented to have received 2 doses. Though mHealth required up-front financial investment and training, it reduced the need for paper registries and manual data entry, which would have been costly, time-consuming, and is known to increase error. Using Global Positioning System coordinates, we mapped vaccine posts, population size, and vaccine coverage to understand the reach of the campaign. The hardware and software were usable by high school-educated staff.

Conclusion

The use of mHealth technology in an OCV campaign in rural Haiti allowed timely creation of an electronic registry with population-level census data, and a targeted vaccination strategy in a dispersed rural population receiving a two-dose vaccine regimen. The use of mHealth should be strongly considered in mass vaccination campaigns in future initiatives.     

Use of oral cholera vaccines in an outbreak in Vietnam: a case control study

Background

Killed oral cholera vaccines (OCVs) are available but not used routinely for cholera control except in Vietnam, which produces its own vaccine. In 2007–2008, unprecedented cholera outbreaks occurred in the capital, Hanoi, prompting immunization in two districts. In an outbreak investigation, we assessed the effectiveness of killed OCV use after a cholera outbreak began.

Methodology/Principal Findings

From 16 to 28 January 2008, vaccination campaigns with the Vietnamese killed OCV were held in two districts of Hanoi. No cholera cases were detected from 5 February to 4 March 2008, after which cases were again identified. Beginning 8 April 2008, residents of four districts of Hanoi admitted to one of five hospitals for acute diarrhea with onset after 5 March 2008 were recruited for a matched, hospital-based, case-control outbreak investigation. Cases were matched by hospital, admission date, district, gender, and age to controls admitted for non-diarrheal conditions. Subjects from the two vaccinated districts were evaluated to determine vaccine effectiveness. 54 case-control pairs from the vaccinated districts were included in the analysis. There were 8 (15%) and 16 (30%) vaccine recipients among cases and controls, respectively. The vaccine was 76% protective against cholera in this setting (95% CI 5% to 94%, P = 0.042) after adjusting for intake of dog meat or raw vegetables and not drinking boiled or bottled water most of the time.

Conclusions/Significance

This is the first study to explore the effectiveness of the reactive use of killed OCVs during a cholera outbreak. Our findings suggest that killed OCVs may have a role in controlling cholera outbreaks.     

Mass Vaccination with a New,Less Expensive Oral Cholera Vaccine Using Public Health Infrastructure in India: The Odisha Model

Introduction

The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model.

Methods

All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel.

Results

The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25% between the two doses. Higher coverage was observed among females and among 6–17 year-olds. Vaccine cost at market price (about US$1.85/dose) was the costliest item. The vaccine delivery cost was $0.49 per dose or $1.13 per fully vaccinated person.

Discussion

This is the first undertaken project to collect empirical evidence on the use of Shanchol within a mass vaccination campaign using existing public health program resources. Our findings suggest that mass vaccination is feasible but requires detailed micro-planning. The vaccine and delivery cost is affordable for resource poor countries. Given that the vaccine is now WHO pre-qualified, evidence from this study should encourage oral cholera vaccine use in countries where cholera remains a public health problem.     

Safety and immunogenicity of a monovalent MF59®-adjuvanted A/H1N1 vaccine in HIV-infected children and young adults

BackgroundThis Phase IV study evaluated the safety and immunogenicity of a two-dose, MF59^®-adjuvanted (Novartis Vaccines, Marburg, Germany), monovalent, A/H1N1 pandemic influenza vaccination schedule in Human Immunodeficiency Virus (HIV) positive children and young adults.MethodsA total of 83 children infected with HIV-1, and 37 non-immunocompromised, age-matched controls were enrolled. All participants received two vaccine doses administered three weeks apart. Antibody responses were assessed by haemagglutination assay at baseline, three weeks after each vaccine dose, and six months after immunization. Vaccines were evaluated according to European influenza vaccine licensure criteria.ResultsThe investigational vaccine was well tolerated. After the first vaccine dose, seroconversion rates were significantly lower in HIV-positive patients (60%) than controls (82%), with GMTs of 419 and 600, respectively. No significant differences in seroconversion rates were observed between the two study groups in response to the second vaccine dose. Persisting antibody titers were similar for both HIV-positive and non-infected controls, six months after immunization.ConclusionOne dose of MF59-adjuvanted vaccine was sufficient to provide adequate levels of seroprotection against A/H1N1 influenza disease in HIV-positive children. However, a two-dose vaccination schedule may be optimal for this population.     

Comparative Effectiveness of Different Strategies of Oral Cholera Vaccination in Bangladesh: A Modeling Study

Background

Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies.

Methods & Findings

We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh. We used the model to predict the effectiveness of different cholera vaccination strategies over a period of 20 years. We explored vaccination programs that targeted one of three increasingly focused age groups (the entire vaccine-eligible population of age one year and older, children of ages 1 to 14 years, or preschoolers of ages 1 to 4 years) and that could occur either as campaigns recurring every five years or as continuous ongoing vaccination efforts. Our modeling results suggest that vaccinating 70% of the population would avert 90% of cholera cases in the first year but that campaign and continuous vaccination strategies differ in effectiveness over 20 years. Maintaining 70% coverage of the population would be sufficient to prevent sustained transmission of endemic cholera in Matlab, while vaccinating periodically every five years is less effective. Selectively vaccinating children 1–14 years old would prevent the most cholera cases per vaccine administered in both campaign and continuous strategies.

Conclusions

We conclude that continuous mass vaccination would be more effective against endemic cholera than periodic campaigns. Vaccinating children averts more cases per dose than vaccinating all age groups, although vaccinating only children is unlikely to control endemic cholera in Bangladesh. Careful consideration must be made before generalizing these results to other regions.     

Evaluation of COVID-19 vaccination strategies with a delayed second dose

Two of the Coronavirus Disease 2019 (COVID-19) vaccines currently approved in the United States require 2 doses, administered 3 to 4 weeks apart. Constraints in vaccine supply and distribution capacity, together with a deadly wave of COVID-19 from November 2020 to January 2021 and the emergence of highly contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose or to continue with the recommended 2-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these 2 vaccination strategies, while varying the temporal waning of vaccine efficacy following the first dose and the level of preexisting immunity in the population. Our results show that for Moderna vaccines, a delay of at least 9 weeks could maximize vaccination program effectiveness and avert at least an additional 17.3 (95% credible interval [CrI]: 7.8–29.7) infections, 0.69 (95% CrI: 0.52–0.97) hospitalizations, and 0.34 (95% CrI: 0.25–0.44) deaths per 10,000 population compared to the recommended 4-week interval between the 2 doses. Pfizer-BioNTech vaccines also averted an additional 0.60 (95% CrI: 0.37–0.89) hospitalizations and 0.32 (95% CrI: 0.23–0.45) deaths per 10,000 population in a 9-week delayed second dose (DSD) strategy compared to the 3-week recommended schedule between doses. However, there was no clear advantage of delaying the second dose with Pfizer-BioNTech vaccines in reducing infections, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the characteristics and durability of vaccine-induced protection after the first dose in order to determine the optimal time interval between the 2 doses.

There are two widely used COVID-19 vaccination strategies; administering the two doses three to four weeks apart or delaying the administration of the second dose. A modelling study calibrated to COVID-19 spread and vaccination in the US shows that delaying the second dose can maximize the benefits of vaccination programs under certain conditions.     

An Estimation of Private Household Costs to Receive Free Oral Cholera Vaccine in Odisha,India

BackgroundService provider costs for vaccine delivery have been well documented; however, vaccine recipients’ costs have drawn less attention. This research explores the private household out-of-pocket and opportunity costs incurred to receive free oral cholera vaccine during a mass vaccination campaign in rural Odisha, India.MethodsFollowing a government-driven oral cholera mass vaccination campaign targeting population over one year of age, a questionnaire-based cross-sectional survey was conducted to estimate private household costs among vaccine recipients. The questionnaire captured travel costs as well as time and wage loss for self and accompanying persons. The productivity loss was estimated using three methods: self-reported, government defined minimum daily wages and gross domestic product per capita in Odisha.FindingsOn average, families were located 282.7 (SD = 254.5) meters from the nearest vaccination booths. Most family members either walked or bicycled to the vaccination sites and spent on average 26.5 minutes on travel and 15.7 minutes on waiting. Depending upon the methodology, the estimated productivity loss due to potential foregone income ranged from $0.15 to $0.29 per dose of cholera vaccine received. The private household cost of receiving oral cholera vaccine constituted 24.6% to 38.0% of overall vaccine delivery costs.InterpretationThe private household costs resulting from productivity loss for receiving a free oral cholera vaccine is a substantial proportion of overall vaccine delivery cost and may influence vaccine uptake. Policy makers and program managers need to recognize the importance of private costs and consider how to balance programmatic delivery costs with private household costs to receive vaccines.     

Costs of Illness Due to Cholera, Costs of Immunization and Cost-Effectiveness of an Oral Cholera Mass Vaccination Campaign in Zanzibar

Background

The World Health Organization (WHO) recommends oral cholera vaccines (OCVs) as a supplementary tool to conventional prevention of cholera. Dukoral, a killed whole-cell two-dose OCV, was used in a mass vaccination campaign in 2009 in Zanzibar. Public and private costs of illness (COI) due to endemic cholera and costs of the mass vaccination campaign were estimated to assess the cost-effectiveness of OCV for this particular campaign from both the health care provider and the societal perspective.

Methodology/Principal Findings

Public and private COI were obtained from interviews with local experts, with patients from three outbreaks and from reports and record review. Cost data for the vaccination campaign were collected based on actual expenditure and planned budget data. A static cohort of 50,000 individuals was examined, including herd protection. Primary outcome measures were incremental cost-effectiveness ratios (ICER) per death, per case and per disability-adjusted life-year (DALY) averted. One-way sensitivity and threshold analyses were conducted. The ICER was evaluated with regard to WHO criteria for cost-effectiveness. Base-case ICERs were USD 750,000 per death averted, USD 6,000 per case averted and USD 30,000 per DALY averted, without differences between the health care provider and the societal perspective. Threshold analyses using Shanchol and assuming high incidence and case-fatality rate indicated that the purchase price per course would have to be as low as USD 1.2 to render the mass vaccination campaign cost-effective from a health care provider perspective (societal perspective: USD 1.3).

Conclusions/Significance

Based on empirical and site-specific cost and effectiveness data from Zanzibar, the 2009 mass vaccination campaign was cost-ineffective mainly due to the relatively high OCV purchase price and a relatively low incidence. However, mass vaccination campaigns in Zanzibar to control endemic cholera may meet criteria for cost-effectiveness under certain circumstances, especially in high-incidence areas and at OCV prices below USD 1.3.     

The impact of spatial arrangements on epidemic disease dynamics and intervention strategies

The role of spatial arrangements on the spread and management strategies of a cholera epidemic is investigated. We consider the effect of human and pathogen movement on optimal vaccination strategies. A metapopulation model is used, incorporating a susceptible–infected–recovered system of differential equations coupled with an equation modelling the concentration of Vibrio cholerae in an aquatic reservoir. The model compared spatial arrangements and varying scenarios to draw conclusions on how to effectively manage outbreaks. The work is motivated by the 2010 cholera outbreak in Haiti. Results give guidance for vaccination strategies in response to an outbreak.     

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 city''s 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.     

First Outbreak Response Using an Oral Cholera Vaccine in Africa: Vaccine Coverage,Acceptability and Surveillance of Adverse Events,Guinea, 2012

Background

Despite World Health Organization (WHO) prequalification of two safe and effective oral cholera vaccines (OCV), concerns about the acceptability, potential diversion of resources, cost and feasibility of implementing timely campaigns has discouraged their use. In 2012, the Ministry of Health of Guinea, with the support of Médecins Sans Frontières organized the first mass vaccination campaign using a two-dose OCV (Shanchol) as an additional control measure to respond to the on-going nationwide epidemic. Overall, 316,250 vaccines were delivered. Here, we present the results of vaccination coverage, acceptability and surveillance of adverse events.

Methodology/Principal Findings

We performed a cross-sectional cluster survey and implemented adverse event surveillance. The study population included individuals older than 12 months, eligible for vaccination, and residing in the areas targeted for vaccination (Forécariah and Boffa, Guinea). Data sources were household interviews with verification by vaccination card and notifications of adverse events from surveillance at vaccination posts and health centres. In total 5,248 people were included in the survey, 3,993 in Boffa and 1,255 in Forécariah. Overall, 89.4% [95%CI:86.4–91.8%] and 87.7% [95%CI:84.2–90.6%] were vaccinated during the first round and 79.8% [95%CI:75.6–83.4%] and 82.9% [95%CI:76.6–87.7%] during the second round in Boffa and Forécariah respectively. The two dose vaccine coverage (including card and oral reporting) was 75.8% [95%CI: 71.2–75.9%] in Boffa and 75.9% [95%CI: 69.8–80.9%] in Forécariah respectively. Vaccination coverage was higher in children. The main reason for non-vaccination was absence. No severe adverse events were notified.

Conclusions/Significance

The well-accepted mass vaccination campaign reached high coverage in a remote area with a mobile population. Although OCV should not be foreseen as the long-term solution for global cholera control, they should be integrated as an additional tool into the response.     

Modelling optimal vaccination strategy for SARS-CoV-2 in the UK

The COVID-19 outbreak has highlighted our vulnerability to novel infections.Faced with this threat and no effective treatment, in line with many other countries, the UK adopted enforced social distancing (lockdown) to reduce transmission—successfully reducing the reproductive number R below one. However, given the large pool of susceptible individuals that remain, complete relaxation of controls is likely to generate a substantial further outbreak. Vaccination remains the only foreseeable means of both containing the infection and returning to normal interactions and behaviour. Here, we consider the optimal targeting of vaccination within the UK, with the aim of minimising future deaths or quality adjusted life year (QALY) losses. We show that, for a range of assumptions on the action and efficacy of the vaccine, targeting older age groups first is optimal and may be sufficient to stem the epidemic if the vaccine prevents transmission as well as disease.     

Optimizing global COVID-19 vaccine allocation: An agent-based computational model of 148 countries

BackgroundBased on the principles of equity and effectiveness, the World Health Organization and COVAX formulate vaccine allocation as a mathematical optimization problem. This study aims to solve the optimization problem using agent-based simulations.MethodsWe built open-sourced agent-based models to simulate virus transition among a demographically representative sample of 198 million people in 148 countries using advanced computational services. All countries continuing their current vaccine progress is defined as the baseline scenario. Comparison scenarios include achieving minimum vaccination rates and allocating vaccines based on pandemic levels.FindingsThe simulations are fitted using the pandemic data from 148 countries from January 2020 to June 2021. Under the baseline scenario, the world will add 24.36 million cases and 468,945 deaths during the projection period of three months. Inoculating at least 10%, 20%, and 26% of populations in all countries requires 1.12, 3.31, and 5.00 million additional vaccine doses every day, respectively. Achieving these benchmarks reduces new cases by 0.56, 2.74, and 3.32 million, respectively. If allocated by the current global distribution, 5.00 million additional vaccine doses will only avert 1.45 million new cases. If those 5.00 million vaccines are allocated based on projected cases in each country, the averted cases will increase more than six-fold to 9.20 million. Similar differences between allocation methods are observed in averted deaths.ConclusionThe global distribution of COVID-19 vaccines can be optimized to achieve better outcomes in terms of both equity and effectiveness. Alternative vaccine allocation methods may avert several times more cases and deaths than the current global distribution. With reasonable requirements on additional vaccines, COVAX could adopt alternative allocation strategies that reduce cross-country inequity and save more lives.     

Optimizing reactive responses to outbreaks of immunizing infections: balancing case management and vaccination

For vaccine-preventable infections, immunization generally needs to be supplemented by palliative care of individuals missed by the vaccination. Costs and availability of vaccine doses and palliative care vary by disease and by region. In many situations, resources for delivery of palliative care are independent of resources required for vaccination; however we also need to consider the conservative scenario where there is some trade-off between efforts, which is of potential relevance for resource-poor settings. We formulate an SEIR model that includes those two control strategies - vaccination and palliative care. We consider their relative merit and optimal allocation in the context of a highly efficacious vaccine, and under the assumption that palliative care may reduce transmission. We investigate the utility of a range of mixed or pure strategies that can be implemented after an epidemic has started, and look for rule-of-thumb principles of how best to reduce the burden of disease during an acute outbreak over a spectrum of vaccine-preventable infections. Intuitively, we expect the best strategy to initially focus on vaccination, and enhanced palliative care after the infection has peaked, but a number of plausible realistic constraints for control result in important qualifications on the intervention strategy. The time in the epidemic when one should switch strategy depends sensitively on the relative cost of vaccine to palliative care, the available budget, and [Formula: see text]. Crucially, outbreak response vaccination may be more effective in managing low-[Formula: see text] diseases, while high [Formula: see text] scenarios enhance the importance of routine vaccination and case management.