Module9 – version2 (20Feb2017)_Eng

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DENGUE OUTBREAK AND EVALUATION

INFORMATION FOR STAKEHOLDERS

The purpose of this document is to summarize, for decision makers and program planners, key accessible information on dengue outbreak detection and response, and discuss the use of the new dengue vaccine, CYD-TDV, in the context of dengue outbreaks

TABLE OF CONTENTS

1. REFERENCES

2. INTRODUCTORY REMARKS

3. OUTBREAK DEFINITION 3.1. The endemic channel method 3.2. Other outbreak signals

4. OUTBREAK DETECTION

4.1. Type of surveillance Passive or Active Surveillance

Comprehensive or Sentinel Surveillance

Syndromic or Laboratory-Based Surveillance

Indicator-Based or Event-Based Surveillance

Entomological Surveillance

Monitoring of Environmental and Social Risks

4.2. Surveillance procedures Case-definition

Notification procedures

4.3. Type of signal Alert signal

Outbreak signal

5. EMEGENCY PREPAREDNESS 5.1. Establishment of a Multisectoral

Dengue Action Committee 5.2. Development of the Emergency

Response Plan 5.3. Risk assessment 5.4. Communication for Behavioral

Impact (COMBI - community sensitization)

5.5. Preparedness of Health Sector

6. OUTBREAK RESPONSE 6.1. Appropriate clinical case management 6.2. Reinforcement of vector control

activities 6.3. Risk communication

7. DENGUE VACCINATION IN THE

CONTEXT OF OUTBREAK 7.1. Phase III efficacy trial data 7.2. Vaccine introduction in an outbreak 7.3. Programmatic challenges

8. MONITORING AND EVALUATION 8.1. Evaluation of the vaccine if an outbreak

occurs in the introduction area 8.2. Evaluation of the vaccine if used as part

of the outbreak response

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1. REFERENCES

A panel of resources and publications is suggested, available online from the following websites World Health Organization, 2016: “Technical

handbook for dengue surveillance, outbreak prediction / detection and outbreak response”. This evidence-based handbook proposes a “model contingency plan to assist programme managers and planners in developing a national, context-specific, dengue outbreak response plan. It is downloadable at: http://www.who.int/tdr/publications/year/2016/tech_handbook_dengue/en/

World Health Organization (WHO) and the Special Programme for Research and Training in Tropical Diseases, 2009 “Dengue Guidelines for Diagnosis, Treatment, Prevention, and Control”. This document serves an authoritative reference source to assist in the development of national or regional guidelines. Chapter 5 gives guidance to countries at risk of dengue outbreak and suggests strategies for preparedness, alert and response at local, national and international levels. The handbook is downloadable at: http://www.who.int/tdr/publications/documents/dengue-diagnosis.pdf

World Health Organization, 2004 “Planning social mobilization and communication for dengue fever prevention and control: a step-by-step guide”. This document presents the basic steps and underlying principles of Communication for behavioral impact (COMBI) for dengue, including dengue outbreaks, and offers a comprehensive and innovative managerial insight to planning social mobilization and communication or behavioral impact: http://apps.who.int/iris/handle/10665/42832?mode=full

The WHO vaccine position paper, outlining WHO recommendations for the dengue vaccine, was published 29 July 2016: No 30, 2016, 91, 349–364, available at

http://www.who.int/wer/2016/wer9130.pdf?ua=1

The Dengue Vaccine Initiative (DVI) published a series of statements on CYD-TDV, including on SAGE Dengue Vaccine recommendations. They are available at: http://www.denguevaccines.org/resource_library

Brady et al, “Dengue disease outbreak definitions are implicitly variable”. Epidemics 11 (2015) 92–102” DOI: 10.1016/j.epidem.2015.03.002. This article discusses a range of outbreak definitions

based on various endemic channels. It is downloadable at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429239/

Pilger et al, “Dengue outbreak response: documented effective interventions and evidence gaps. TropIKA.net. (2010) vol.1, n.1, pp. 0-0. ISSN 2078-8606”. This article reviews the effectiveness of interventions employed during dengue outbreak and recommends a multidisciplinary approach combined with monitoring and evaluation. It can be downloaded at: http://journal.tropika.net/pdf/tropika/v1n1/a02v1n1.pdf

Badurdeen et al, “Sharing experiences: towards an evidence based model of dengue surveillance and outbreak response in Latin America and Asia”. BMC Public Health (2013) 13:607DOI: 10.1186/1471-2458-13-607. This article identifies strengths and limitations in dengue surveillance, outbreak preparedness, detection and response. It is available at: http://bmcpublichealth.biomedcentral.com/articles/10.1186/1471-2458-13-607

Harrington et al, “Detecting and Responding to a Dengue Outbreak: Evaluation of Existing Strategies in Country Outbreak Response Planning” This article is available at: https://www.hindawi.com/journals/jtm/2013/756832/

Pan American Health Organization (PAHO) “Dengue: guidelines for patient care in the Region of the Americas. Washington, D.C. PAHO, 2016. http://iris.paho.org/xmlui/bitstream/handle/123456789/31207/9789275118900-eng.pdf?sequence=1&isAllowed=y

2. INTRODUCTORY REMARKS

Dengue disease has established itself globally in both endemic and epidemic transmission cycles. Epidemic dengue is an increasing public health problem affect in g tropical and sub-tropical countries, and is facilitated by urbanization, modern transportation, lack of effective vector control interventions and globalization.

Dengue outbreaks may vary in its magnitude, duration and seasons. Depending on the wide range of dengue virus transmission settings, dynamics can be dominated by:

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o Rare large outbreak with global cyclical variations

o Seasonal patterns determined by peak transmission of the disease and influenced by characteristics of the host, the vector and the agent

o Small outbreaks occurring only once every few years in densely populated, and concentrating most of the case burden

While predominantly reported among urban and peri-urban populations, outbreaks have recently been also reported in rural areas.

Various factors might influence the occurrence of an outbreak, including:

o Demographic risk factors (e.g. population distribution and density, individual susceptibility and contacts, migrations, education, socio-economic characteristics)

o National and local public health context (surveillance, contingency plan, health services performances, communication plan, community programs)

o Geographical and ecological risk factors (rainfall, temperature, artificial and natural breeding sites)

3. OUTBREAK DEFINITION

Early detection of outbreaks is essential for timely response, and the signals which are triggering the response need to be carefully established. A seasonal increase in dengue cases has to be distinguished from an unexpected sudden increase of cases above a defined threshold defining an outbreak. The dengue outbreak definition must allow early and accurate detection.

There is no standard definition of a dengue outbreak, and consequently, there is a variety of thresholds for triggering an outbreak response.

3.1. The endemic channel method Many countries (including Columbia, Dominican

Republic, Brazil, Mexico, Vietnam and Malaysia) are using the “endemic channel” approach to define an outbreak. This may be referred to as the “classic” definition of a dengue outbreak

The principle is to track deviation from seasonal profiles, by collecting the current surveillance data (number of cases or incidence rate per week or month) and comparing them to the endemic channel. The endemic channel is defined as the

reference baseline value (average number of cases by week or by month) for the preceding 5-7 years.

Outbreak/epidemic thresholds are defined as the level of variation above the endemic channel which triggers the outbreak/epidemic signal. It is arbitrarily set at two standard deviations (2SD, 95% threshold) above the mean of the preceding 5 years (classic method), but some countries use the median and the third quartile (75% threshold, a lower threshold than 2SD)

The area between the lines of the mean (upper bound of the yellow area) and +2 SD (upper bound of the red area) is called the “alert zone” or the “alarm zone”. The area above the +2 SD line is called the “outbreak/epidemic zone” (Figure 1)

Figure1. Example of dengue endemic channel: the number of dengue cases (blue line) cross the +2D line several times, before the case numbers rise definitively into the outbreak/epidemic zone.

The thresholds for alert/alarm and outbreak /

epidemic will vary according to the administrative level affected (district, state / province, national), and to the endemicity level

There are several advantages of using the endemic channel method for the dengue outbreak definition:

o This is a simple instrument and the crossing of the upper threshold line is easy to assess using surveillance data

o This is a standard definition of dengue outbreak that can be used to inform the mass media and the public about the ongoing situation

o It is possible to determine the size of an outbreak in term of duration, total number of cases, and case fatality rate during the outbreak, thereby facilitating in-country and cross-country comparisons

Mean or median

+ 2 SD or 3rd quartile

- 2 SD or 1st quartile

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Time (months)

Success zoneSecurity zoneAlert zoneEpidemic zone

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o It helps to assess the effect of response mechanisms and to define “stopping rules” (i.e. when the intensified response can be terminated)

The challenges of this method mostly relate to the quality of available data for determining the alarm/alert and epidemic thresholds

3.2. Other outbreak definitions Below are examples of alert signals already used in countries:

Incidence threshold: e.g. > 300 cases per 100,000 population (Brazil)

Clustering of cases, e.g.:

> 10 cases per week in a local area (Sri Lanka)

Increased case number at “commune” level within 2 weeks: 2 – 20 cases = mild outbreak, 20 – 100 = moderate outbreak, > 100 case = severe outbreak (Vietnam)

≥2 connected cases at local level (Malaysia and Mexico)

≥2dengue cases in 28 days in one village or neighborhood (Singapore)

Increase in the weekly number of cases compared to the previous year: e.g. 25% increase (Dominican Republic) or 50% increase (Indonesia)

Elevated entomological indices (Peru, Sri Lanka, Vietnam, Brazil)

Change of serotype or increase in dengue incidence during the dry season (Peru)

Other alert signals were proposed during WHO/TDR expert meeting (2012):

Change in age group distribution

Increased number of hospitalized cases / probable dengue

Increase in vector presence

Climate changes: increase in rainfall / temperature / humidity

Increase internal displacement / population mobility

Occurrence of outbreak in a neighboring geographical unit

4. OUTBREAK DETECTION

The capacity to detect outbreak depends on the performances of the surveillance system. The overall objectives of public health surveillance which are the most applicable to dengue are as follows:

Detect outbreaks quickly for early intervention

Measure the burden of disease and provide data for the assessment of the social and economic impact of dengue on the affected community

Monitor trends in the distribution and spread of dengue over time and geographically

Assess the magnitude of outbreaks

Evaluate the effectiveness of the dengue prevention and control programs

Facilitate planning and resource allocation on the basis of lessons learned from program evaluation

4.1. Type of surveillance The epidemiological surveillance system should be able to differentiate between transient and seasonal increases in disease incidence and increases observed at the beginning of outbreaks. Passive or Active Surveillance

“Passive surveillance” is the backbone of diseases routine reporting, in which the notification of dengue-like syndromes is usually initiated by health care providers. A particular challenge of passive surveillance systems is continuously to motivate health care providers to report cases in accordance with standardized case definitions; the local physicians may not consider dengue in their differential diagnosis and/or fail to report cases quickly and routinely. As a result, an outbreak has often reached or passed its peak before it is recognized, and opportunities for control are missed. Designating dengue as a (mandatory) notifiable disease that is covered by public health legislation is one way to improve compliance with reporting

In “active surveillance”, the disease report is initiated by the health authority which systematically asks health care providers about the notification of the disease of interest. This involves outreach by public health authorities to stimulate reporting; examples include regular telephone calls or visits to laboratories and hospital to collect data in a timely fashion

Comprehensive or Sentinel Surveillance

In a “comprehensive routine surveillance” system, all identified sources are required to report. This “exhaustive” approach is better suited to diseases under elimination or eradication, and to disease requiring immediate public health interventions. Mandatory notification is part of comprehensive surveillance and the occurrence of a single case, if confirmed, is sufficient to trigger public health

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intervention. This type of surveillance is resource intensive.

In “sentinel surveillance” system, only a fraction of health care structures (generally major hospitals in the case of dengue) are required to report. This approach is more suited for endemic countries with limited resources where dengue case notifications do not require immediate public health action. Sentinel surveillance may be very effective at determining diseases trend locally, but because sentinel sites may not represent the general population or the general incidence of dengue, they may have limited value in determining national disease patterns and trends.

Syndromic or Laboratory-Based Surveillance

In “syndromic surveillance” systems, dengue case definitions are made of association of symptoms without etiological confirmation; they have been developed as an additional tool for early warning of abnormal signals. Generally it uses sensitive, simple and stable case definitions and permits immediate reporting, and above all, wider surveillance coverage, for early detection of dengue outbreaks. Particularly useful in low-resources settings, it however provides lower levels of specificity and requires more efforts for the verification of alerts.

Sentinel “laboratory surveillance” corresponds to the “conventional disease-specific surveillance”; it can complement effectively syndromic surveillance systems. Biologically-based surveillance is essential for the monitoring of the dynamic of events and their potential risks, as well as case management. It is widely applied to discriminate between diseases with similar symptoms (dengue, Zika, Chikungunya), to generate information on dengue virus sero/genotype and to establish epidemiological links between events occurring in different locations. This type of surveillance is resource intensive, but provides validated information that reduces the risk of verifying too many “fake alerts”.

Indicator-Based or Event-Based Surveillance

“Indicator-based surveillance (IBS) corresponds to the conventional component of surveillance system. It is defined as the systematic collection, monitoring, analysis and interpretation of structured data (i.e. indicators) produced by a number of well-identified, predominantly health-based formal sources (e.g. health-care structures, health professional, laboratories), but might also

include non-human health sources such as entomological or meteorological data when these are regularly collected and organized for human health purposes.

“Event-based surveillance” (EBS) is defined as the organized collection, monitoring, assessment of mainly unstructured ad-hoc information regarding health events or risks. The information collected for EBS is diverse in nature and originate from multiple, often non-predetermined sources both official and unofficial, including rumors reported by the media or ad-hoc report from informal networks.

Box 1 - Examples of EBS Ad-hoc detection by country X that locally acquired

dengue fever has been diagnosed in neighboring country Y through the consultation of country Y MOH’s website

National meteorological center reports unusual rainfalls are expected in the country in the coming weeks

Vector-control services report abnormal density or introduction of Aedes aegypti in a region

Educational establishments are reporting an expected level of absenteeism among pupils

Local newspapers or radio report abnormal number of febrile cases occurring during a short period of time

Over-the-counter medications sales (from pharmacies)

Internet-based illness reporting (social networks)

Entomological Surveillance

Entomological surveillance is used for operational purposes to determine changes in geographical distribution of vectors, for monitoring and evaluating control programs, for obtaining measurements of the vector population over time, and for facilitating appropriate and timely decisions regarding interventions. Most common method used remains the sampling of mosquito larvae and pupae.

The basic sampling unit is the house or premise, which is systematically searched for water-holding containers. Containers are examined for the presence of mosquito larvae and pupae. Three indices are commonly computed: the house index

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(proportion of houses infected with larvae or pupae), the container index (proportion of water-holding containers infested with larvae or pupae), and the Breteau index (number of positive container per 100 houses visited)

Monitoring of Environmental and Social Risks

Various factors have been determined to influence a community’s vulnerability to dengue outbreaks, including the density and distribution of human population, the settlement characteristics; the housing style, education and socio-economic status. Knowledge of status and change in the distribution of water supply services, domestic water storage practices and solid waste disposal services, are of particular relevance. Meteorological data (especially rainfall patterns) are generally a good predictive value of the short term fluctuation of the vector population.

4.2. Surveillance procedures Case-definition

WHO dengue case definition may be applied to all suspect cases to decide how they should be classified. Using standard case definitions ensures that every case is diagnosed in the same way, regardless of where or when it occurred, or who identified it.

During outbreak, efforts should be made to find additional cases from health institutions and community-based investigation and to determine whether clustering exists. Standard case definition should be available in all health facilities and known from all health personnel in charge of triage and case management.

Box 2 presents the 2009 WHO revised classification, and the 2016 dengue case classification proposed by PAHO.

Notification procedures

They may vary depending on:

Whether dengue case notification is mandatory or not

Whether there is a zero-reporting procedure or not

Whether the data are cased-based or aggregated

Frequency of reporting: immediate, daily, weekly or monthly

Procedure for data transmission: porter, regular courier, telephone, fax, VHF radio or newer technologies using computerized system and mobile technologies: SMS, internet-based

including web-based interfaces and android / IOS-based applications.

4.3. Type of signals Alert signal

An alert signal for early responses may be defined in different ways:

o Case number/incidence enter the alarm zone

o Syndromic indicators above thresholds (outbreak in neighboring geographical area, increase in % positive serology, increase in hospitalized or outpatient fever cases, favorable climate, new serotype detected, sudden school or work absenteeism, vector proliferation, etc

o Specific alarms for the dry (low) season

Outbreak signal

Following the alert signal, an investigation is recommended to confirm the outbreak.

It can be conducted though analysis of epidemiological data and epidemic channel, obtaining travel history of the index case, investigating epi-links amongst cases, analyzing data from syndromic, EBS or IBS surveillance (clusters, households, co-workers, schools, etc), conducting vector surveillance data, an /or active case finding.

5. EMERGENCY PREPAREDNESS During the interepidemic period, a number of activities needs to be organized to prepare for an efficient outbreak response:

5.1. Establishment of a Multisectoral Dengue Action Committee

If the prevention and control of dengue are to be affective and sustainable, a multisectoral, multidisciplinary and multilevel approach is required. The committee must have solid funding and a designated national coordinator with the political mandate to make policy and financial decisions and to coordinate the multisectoral preparedness and response strategy at local and national levels.

A major responsibility of the dengue action committee is to develop the dengue emergency response plan, review it regularly, and update it as necessary on the basis of the lessons learned from

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its implementation and simulation. Members of the committee should communicate regularly with their stakeholders.

5.2. Development of the Emergency Response Plan

The dengue emergency plan should clearly articulate its aims, objectives and scope, the lead coordinating institution and the organizational link with other agencies. Each agency should be assigned specific roles and responsibilities under the plan, and costs and resources should be identified. Hard copies of the plan should be distributed to all response and supportive agencies. The plan should ideally include a monitoring and evaluation framework with performance indicators for each of the response and support agencies as well as overall indicators of the plan’s effectiveness.

Once the plan has been drafted and approved by participating groups, it is important to conduct simulations and table top exercises.

Human, financial and logistic resources should be ensured, including equipment and supplies needed for rapid assessment and emergency response.

The outbreak responses messages and material should be ideally prepared in advance (for example: radio/TV spots, messages to release via social media, pamphlets, posters, school-based activities, work-based activities, etc.) for the implementation of risk communication and dengue-risk reduction activities.

5.3. Risk assessment It is important to:

Identify, characterize and map high-risk areas by environmental, socioeconomic and epidemiologic indicators (based on current epidemiological metrics, high-risk locations such as cemeteries and construction sites, and areas that experiences recurrent or recent outbreaks, or are bordering another area highly endemic for dengue.

Conduct baseline entomological assessment to identify and map the distribution of potentially competent dengue vectors.

Define the specific groups who require special attention because on their dependence of others, their vulnerability and their immediate surroundings.

5.4. Communication for Behavioral Impact (COMBI - community sensitization)

It may be necessary to conduct a baseline study on knowledge of and attitude towards dengue. An intensive COMBI program that ensures accurate and timely information for the public should be implemented concurrently with vector control activities in order to engage the community in practices that reduce dengue transmission.

Public education must continue to reinforce how important it is for people to seek medical attention if they have dengue symptoms; it should also stress the need to reduce larval habitats and explore the feasible options for personal protections.

5.5. Preparedness of Health Sector The training of all relevant health workers should

be ensured, including officers in state and private hospitals - In endemic areas, physicians, nurses and laboratory staff should receive regular clinical training in the management of dengue patients; it is important to raise the clinicians’ awareness on the spectrum of disease, the case definition and disease classification, the use of rapid diagnostic tests, and the essential and complexities of treatment. It is important to emphasize that treatment of dengue consist of appropriate hydration and the administration of Paracetamol to control pain and fever. Physicians must be able to distinguish between typical and atypical (as well as between minor and severe) dengue syndromes. Contact should be made with national and regional reference laboratories.

National Guidelines on clinical management of dengue should be circulated

Engagement of private sector should obtained

Dengue triage and treatment areas in major hospital and high risk areas should be organized

Adequate supplies should be supplied for laboratory analysis and case management (IV fluids, etc.) and identification of resources for back up stock (urinary bladder catheters, bed pans, fluid measuring containers for oral fluids and urine, blood pressure sets, pulse oxymeters, etc.)

6. OUTBREAK RESPONSE

Outbreak response activities are initiated according to the different levels of alert. The

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implementation of “staged response” strategy allows a timely and adapted response.

The type of signals and the scope of the response vary between countries. An example of staged response is given in Figure 2.

Outbreak response includes a wide range of activities, such as:

o Outbreak investigations o Mobilization of resources, including the

dengue task force and local committees o Enhancement of surveillance activities o Strengthening of laboratory capacities o Intensification of routine activities, such as

vector control activities o Community-level risk communication and

social mobilization o Training of relevant workforce

Dengue outbreak response has been defined as the sum of measures specifically addressing a dengue outbreak aimed at reducing case fatality rates, numbers of cases and entomological parameters. Successful outbreak management strategies combine actions from different sectors and involve active community participation. For the dengue outbreak response, the following apply:

6.1. Appropriate clinical case management A case of severe dengue requires careful

observation and repeated laboratory tests throughout the illness. It is imperative that medical and nursing staff understand the rationale and priorities for patient care under outbreak conditions.

The principal burden that dengue outbreaks create for affected countries is not the number of deaths but the enormous number of hospitalizations and days of illness. Providing care for an elevated number of dengue cases requires criteria for triage, trained physicians and nursing personnel, beds, supplies and equipment, and training guidelines for treatment and patient isolation. Planning for sufficient provisions during a dengue outbreak can be guided by hospitalization rates in previous outbreaks.

After an outbreak in a given area, decisions on the need for laboratory confirmation of all suspected dengue virus cases should be based on available

resources (e.g. only 10–30% of suspected cases may be tested), surveillance should be focused on severe disease.

It is essential to train health professionals in the early detection of cases and to educate the community to seek medical attention when dengue symptoms appear. During this initial contact with health care professionals, the patients and their household members should be given orientation in eliminating adult mosquitoes and water-holding containers in and around their residence to avoid mosquito bites.

6.2. Reinforcement of vector control activities

Risk-reduction activities (e.g., reduce mosquito breeding potential of water-holding containers) should be implemented in priority areas through community outreach teams, vector control field personnel, and other interventions

Intensity vector control by source reduction and fogging activities should be reinforced in prioritized high risk areas while ensuring quality of interventions (ideally impact assessment) and community support. Messages should be disseminated to residents with clear steps on how to collaborate with fogging activities: e.g. leave windows and doors open during fogging sessions; close the house once the fogging has been completed; and do not enter the house for two or

four hours after fogging).

6.3. Risk communication The risk needs to be declared and communicated:

the dengue national committee in collaboration with the health promotion and communication team will ensure communication of consistent risk messages to national, regional and local authorities, public and private health systems, local dengue committees and the private sector (safety officers at construction sites, factories, office buildings, etc.)

A community level risk communication should be implemented in priority areas through community outreach teams, health care providers, etc.

Regular updates on outbreak status should be communicated

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Figure 2. Example of a staged response (adapted from Harrington et al, 2013)

7. DENGUE VACCINATION IN THE CONTEXT OF OUTBREAK

The first dengue vaccine (CYD-TDV, brand name Dengvaxia®) has been registered in more than 13 Latin America and Asia Pacific countries since December 2015, and has been introduced in large-scale public sector programs in Brazil and the Philippines. CYD-TDV is a tetravalent, live attenuated viral vaccine indicated in individuals over 9 years of age living in endemic countries. The indicated CYD-TDV schedule is three doses administered 6 months apart.

7.1. Phase III efficacy trial data Due to high completion of the 3-dose series in the

trials, it was not possible to estimate long term VE and duration of protection after dose 1 and after dose 2, and additional protection conferred by dose 2 and dose 3. Those remain research questions to be addressed.

However, in vaccinees ≥9 years, analysis of pooled data over a period of 6 months following each dose, shows that CYD-TDV efficacy is observed from the first dose: VE equals 70.8% (95%CI 58.1-

79.6) between doses 1 and 2, 66.6% (95%CI 54.5-75.5) between doses 2 and 3, and 62.4% (95%CI 51.4-70.9) between dose 3 and 6 months post-dose 3

Kaplan-Meier curves on trial data show that the protective effect of 1 dose is rapid.

7.2. Vaccine introduction during an outbreak

CYD-TDV is not currently indicated for outbreak response since the immunization requires the administration of three doses over a period of 12 months, and given the absence of studies assessing the impact of vaccine during an outbreak.

However, there is no restriction in vaccine use during epidemics since outbreak can signal the potential utility of a public health preventative vaccination program.

The duration of efficacy and safety from an incomplete schedule and in subsequent outbreaks is not known. Benefit-risk of vaccination at the individual level in a non-dengue endemic area experiencing an outbreak is not known

Surv

eill

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ata

Epidemic zone

Alert zone

Secure /Success

zone

Outbreak response• Outbreak investigation, if required• Mobilization of the multi-sectoral outbreak committee• Deployment of vector control• Risk communication & Social mobilization• Health service management and emergency reinforcement• Reinforcement/re-allocation of human resources• Dengue vaccination ?

Early response • Outbreak investigation• Surveillance enhancement (active, sentinel, mortality, SD)• Support laboratory diagnostic for case confirmation• Increase of routine vector control activities• Risk communication & community mobilization• Emergency training of health staff and other stakeholders• Dengue vaccination ?

Interepidemic activities• Active surveillance• Confirmation of hospital admission data, incl. mortality rate• Syndromic surveillance• Routine staff training• Dengue vaccination ?

Alertsignal

Outbreak signal

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Commencing the three dose vaccination schedule during an outbreak may offer the individual some protection from dengue over the duration of the outbreak.

At the population level, the impact of CYD-TDV on an outbreak was modeled using the Thailand trial data. The results of this analysis indicate that the impact of vaccination on an outbreak increases when the vaccine is given early at the beginning of the outbreak, and as a greater percent of the target population is vaccinated.

Consequently, if the decision to use dengue vaccine is accelerated as a result of an outbreak, vaccination should start as soon as possible with the goal of vaccinating as many catch-up cohorts as is feasible using mass vaccination campaigns.

If the outbreak occurs in an area or population age groups where dengue vaccination has not been introduced, vaccine introduction (routine + introductory catch-up cohorts) should be considered.

If the outbreak includes an area and population age groups where dengue vaccination has already been introduced, an assessment should be made of how the routine program can be strengthened and catch-up campaigns should be considered

7.3. Programmatic challenges Vaccination campaign should be organized in a

timely way in order to target a meaningful impact on mortality and morbidity. Considering the time-lag in outbreak detection and the time needed to organize the campaign, it is possible that while a decision to vaccinate is taken during the outbreak, the actual vaccination campaign will take place after the outbreak has begun to decline or has passed.

The strategy to vaccinate during an outbreak has to be discussed beforehand. Several criteria should be carefully considered:

o Timing of vaccination introduction, from the alert signal or from the outbreak signal?

o Is the vaccine stockpile sufficient for administrating all 3 doses to the target population?

o Is the system ready for an emergency vaccine introduction: health staff training, logistics, social mobilization, etc?

Apart from the potential or perceived benefit of outbreak response vaccination, the risks of improperly planned and implemented vaccination campaigns should be considered. In the case the vaccine is introduced as part of an outbreak

response strategy, the process of registration, program policy, procurement, implementation should not be circumvented but rather accelerated

To ensure longer-term protection beyond the duration of the outbreak, the population should be given all three doses of CYD-TDV at 6 months interval

Outbreak response includes a wide range of interventions, among the most important are assuring timely access to appropriate clinical care in addition to vector control, environmental management, personnel protection measures, advocacy, communication, surveillance (i.e. IMS-Dengue strategies). Vaccination must complement but not replace the traditional package of interventions implemented during outbreak. Proper consideration should be given to the opportunity cost of committing technical and financial resources to outbreak response immunization.

Consideration should be given to how coverage and compliance with the recommended three dose schedule can be optimized if vaccination is launched during an outbreak

8. MONITORING AND EVALUATION

Similarly to the deployment of all novel vaccines, a comprehensive package of monitoring and evaluation (M&E) activities should be conducted with the objective to track vaccine implementation, to assess program outcomes, and to evaluate vaccine impact. This M&E package should encompass epidemiological assessments, programmatic evaluations, and economical analyses.

8.1. Evaluation of the vaccine if an outbreak occurs in the introduction area

At the time of the phase 3 clinical trials, several outbreaks occurred in the trial areas, but neither the vaccine performance nor the programmatic issues were evaluated.

When an outbreak occurs in the vaccine introduction area, all vaccine assessment activities already in place should be continued and enhanced, with a special attention to the documentation of vaccination status of dengue cases including number of doses, date of vaccination, and age at vaccination.

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Several situations might contribute to the occurrence of an epidemic in a vaccinated area: o Vaccine failure. In some vaccinees, the vaccine

failed to mount a sufficient protective immunity. This is more likely to happen in populations where dengue was not prevalent in the past, and when serotype 2, for which the vaccine has the lowest efficacy, is the predominant serotype in the area. It is strongly recommended to undertake pre/post vaccine introduction routine surveillance of dengue serotypes in vaccine introduction areas.

o Programmatic failure. It happens when immunization program failed to efficiently vaccinate the target populations. This should be evaluated through vaccine coverage surveys (with stratification by age, areas and doses).

o Restricted vaccination program. When these programs are targeting a small number of birth cohorts (e.g. 9 years old), with no catch up cohorts of broader age group at introduction. If only a small fraction of the population is immunized, the number of susceptible individuals is not reduced and the population remains at risk.

o Incomplete vaccination series. Individuals receiving only one or two doses of the vaccine should not be considered as fully immunized, and the occurrence of dengue cases in this group should not be considered as a vaccine failure. An outbreak might occur, especially when these cases are clustering with unvaccinated individuals. The definition of vaccine failure should be limited to subjects that have completed the vaccination series and have a failure-defining event more than a specified number of days after the final third dose. Surveillance data on number of doses, dates at vaccination, and date of diagnosis, should help evaluating whether the vaccine has failed or the series was incomplete.

All vaccine failures (as defined) and any other breakthrough cases should be investigated in detail to determine whether they might have failed to mount a response due to host-related factors

8.2. Evaluation of the vaccine if used as part of the outbreak response

Although this is not in the scope of its current indication, the dengue vaccine may be used in an effort to control an ongoing outbreak. Alternatively, if an outbreak occurs in an area where routine

dengue vaccination has been implemented, catch-up campaigns might be implemented as an emergency approach for managing a dengue epidemic. This strategy may include immunizing adolescents and adults in addition to children.

When vaccine is introduced as part of an outbreak response, a comprehensive evaluation should be implemented. The evaluation should include the assessment of vaccine coverage, data quality, the documentation of reasons for vaccine refusals as well as the monitoring of vaccine wastage, AEFI, and human resource adequacy. Good vaccination coverage data requires maintaining detailed and complete dengue vaccine register that includes data on eligibility, refusal or consent, vaccination date and vaccine dose.

Because the first dose of the vaccine is given in the context of the outbreak, the completion of the 3-dose vaccination series should be closely followed up after the outbreak response.

Due to delays in detecting the outbreak and implementing vaccine, impact may be lower than expected. Vaccination should be implemented as early as possible to maximize the impact of the intervention.

At risk population should be identified and prioritized for vaccination. In this respect, the eventuality of cases clustering should be evaluated based on available information (e.g. places of residence and work, name of school, university, kinder garden). Specific areas and population groups will be targeted for immunization and more globally for the implementation of other outbreak response interventions (enhanced vector control activities, optimization of case management including strengthening of the laboratory capacity, community communication and social mobilization). Vaccination should be preferentially given to family contacts, neighbors, colleagues, or schoolmates. Lists of vaccine-eligible individuals should be available to evaluate the vaccination program and the compliance to public health recommendations.

The methods used in the assessment of the effectiveness and the impact of the vaccination program when it is used in response of an outbreak include: o Case control study: allow calculating the vaccine

effectiveness (VE) through the comparison of vaccine status between incident dengue cases and persons sharing the same opportunity for exposure and for vaccination but without the disease.

o Monitoring of changes in surveillance data

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Box 2 - Dengue case definition A.WHO revised case definition (WHO, 2009.“Dengue Guidelines for Diagnosis, Treatment, Prevention, and Control”)

B. Dengue case definition (PAHO, 2016. “Dengue: guidelines for patient care in the Region of the Americas”)