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FIELD GUIDE

Yellow fever

Investigation of

yellow fever epidemics in Africa

WHO/HSE/EPR/2008.5

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EPR publications are available on the Internet at the following address:

www.who.int/csr/resources/publications/

© World Health Organization 2008

All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857;

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The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.

The mention of speciﬁc companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned.

Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.

All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use.

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Acknowledgements

WHO would like to thank for their support GAVI, UNICEF and all those who have contributed to preparing, drafting and revising this document Investigation of Yellow Fever Epidemics in Africa: a Field Guide:

Institut Pasteur, Dakar Laurence Marrama Amadou Sall Diène Sarr

WHO/HQ

Sylvie Briand Sergio Yactayo William Perea

Agence de Médecine Préventive Dorothy Leab

The ERI (Epidemic Readiness and Intervention, WHO) team, and in particular Sergio Yactayo who coordinated the production of this ﬁeld guide, which was prepared and written by Laurence Marrama, Amadou Sall and Diène Sarr. Sylvie Briand made a valuable contribution to revising it, and Dorothy Leab provided advice on educational aspects of the layout.

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Foreword

This ﬁeld guide is intended for health professionals working at the central and peripheral levels (physicians, health workers and decision-makers) who have to deal with a case of yellow fever in Africa.

Its main objective is to help standardize investigations of yellow fever epidemics. At the national level, this should improve management of epidemics and at the international level facilitate comparative analyses of outbreaks of this disease.

Its speciﬁc objectives are the following:

to provide basic practical information on yellow fever.

to go over the different steps of epidemiological, entomological and virological investigation.

to present an analytical method that makes it possible to bring together the information essential for taking decisions.

The document provides a framework for users, who will be able to adapt it to local conditions.

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Introduction to yellow fever epidemics

Yellow fever is a viral haemorrhagic fever. Since the 1980s, yellow fever has been on the rise in Africa, with an increase both in the number of cases notiﬁed and in the number of countries notifying cases (1).

This rise is probably partly attributable both to improved systems of surveillance and to better access to laboratory services. However, the situation is particularly disturbing in West Africa, where the increase in the circulation of the yellow-fever virus within insufﬁciently immunized populations, in conjunction with rampant urbanization, sets the conditions for the outbreak of devastating epidemics. West Africa has already experienced ﬁve urban epidemics, three of them in capital cities: Abidjan (Côte d’Ivoire, 2001), Conakry (Guinea, 2002), Dakar and Touba (Senegal, 2002) and Bobo-Dioulasso (Burkina Faso, 2004) (1).

These urban epidemics had a limited impact thanks to mass immunization campaigns urgently organized to protect the populations. Although these urban populations are now immunized, the epidemic risk persists in smaller towns and in semi urban areas whose populations are not yet protected.

The yellow fever virus is transmitted by the bite of certain mosquitoes of the genus Aedes.

It infects primates (humans and monkeys) who, after a short period of viraemia (2 to 9 days) then acquire lasting, in all appearances lifelong immunity. After they have been infected by the yellow fever virus, monkeys become resistant to infection. This is why circulation of the virus in the forest is assured by the renewal of the monkey population thanks to the birth of non-immune monkeys (2).

An epidemic of yellow fever requires infecting mosquitoes and non-immunized and thus receptive individuals.

In humans, clinical diagnosis of yellow fever is difﬁcult as there are numerous differential diagnoses (annexes 1&2). This makes laboratory conﬁrmation essential.

Figure 1: Clinical diagnosis of yellow fever

Adapted from © Gentillini M. Médicine Tropicale. Ed Flammarion, Paris, 1993 with the kind permission of the BIOLOGICAL SIGNS

x Cytolysis: SGOT SGPT x Liver cell failure

Cholesterol TP x Proteinuria Cylindruria Haematuria Uraemia x Normal blood count Isolation of the virus

Serology: TSP (late stage) Speciﬁc IgM (early stage)

CLINICAL SIGNS Fever

Pain

Change in overall state of health Congestion of the conjunctiva (red phase) Jaundice

Haemorrhagic syndrome Hepatic coma

Kidney failure:

oliguria or oliguria-anuria Liver

Kidney

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There is no speciﬁc curative treatment; however, the disease is vaccine-preventable.

Yellow-fever vaccine is harmless and side effects are rare. Ten days after vaccination, it provides immunity that last ten years and probably even for life. An emergency vaccination campaign must be organized as soon as a yellow-fever epidemic is conﬁrmed.

The yellow-fever control strategy advocated by WHO is built on 4 pillars:

Routine yellow-fever vaccination for children after 9 months under the expanded programme on immunization (EPI)

Catch-up campaigns for populations with a low level of vaccination coverage Enhanced disease surveillance

Rapid epidemic response

Thanks to GAVI and other donors, countries now have support for the purchase of vaccine for routine immunization campaigns. There is also a global vaccine stock for the response to yellow-fever epidemics. (Contact: yellow fever focal point WHO - Geneva or e-mail outbreak@who.int).

Why conduct an investigation into a yellow-fever epidemic?

To conﬁrm that we are actually dealing with a case of yellow fever;

In order better to understand transmission of the disease and to analyse the risk of dissemination;

To prepare an appropriate response; in particular, to guide decisions by the authorities:

when should we vaccinate, what is the target population, how many people need to be vaccinated and what complementary measures are required?

The procedure for this investigation involves four steps:

checking information,

organizing the investigation, carrying out the ﬁeld investigation,

making recommendations for the response.

This ﬁeld guide will address these steps, with the objective of informing health professionals who are not specialized in yellow fever by taking them through the preparation and implementation of an investigation into a yellow fever epidemic in the ﬁeld:

By setting out in detail the main stages of the investigation;

By offering practical advice and tools at each stage;

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By summarizing the technical knowledge required for a satisfactory analysis of the situation.

Standardization of yellow-fever investigations thanks to this ﬁeld guide should permit:

(i) better control of epidemics of yellow fever in countries regularly affected and (ii) comparative analysis of outbreaks in different countries.

This document takes up notions contained in various WHO documents, scientiﬁc articles and reference texts and examines them with this objective in mind.

REFERENCES

1. Progress in the control of yellow fever in Africa. Weekly Epidemiological Record, N° 6, 2005, (80):49–60 2. Vainio J., Cutts F. Yellow fever, 1998. World Health Organization (WHO/EPI/GEN) 98.11.

http://www.who.int/csr/resources/publications/yellowfev/WHO_CDS_CSR_EDC_2000_1_EN/en/

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Investigation of a yellow fever

epidemic: PROCEDURE

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Instructions

This ﬁrst part of the ﬁeld guide follows a chronological pattern corresponding to the progress of the different stages in the investigation of a yellow fever epidemic.

It provides a comprehensive and step by step overview of the information available on:

Activities, durations, reference cards and additional information.

The information is broken down into these categories at the top of each page.

Different icons are used for each particular type of information:



: the objectives of each stage and a description of the activities to be carried out.



: important considerations to be borne in mind.



: key messages to be retained from each stage.

Summary of the stages

Figure 2: Breakdown of the stages, objectives and activities

Stages Objectives Activities

1. Checking

information  Conduct as exhaustive as possible an analysis of the situation when one or more cases of yellow fever have been notiﬁed

Respond, by answering the following questions:

Is it a suspected case of yellow fever?

Has the person been vaccinated against yellow fever, and if so when?

Has the case been conﬁrmed by a laboratory?

Where was the case infected?

•

• 2. Preparing the

investigation  to deal with administrative (permits) and logistic (human, material and ﬁnancial resources) aspects of the ﬁeld investigation

 to complete the required information

 this may be done simultaneously with checking the information.

Forming a team Obtaining permits

Preparing the ﬁeld mission

Preparing laboratory analysis of the specimens

•

3. Field

investigation  Describe the situation among the population

 Describe the type of transmission:

identify the vectors involved in transmission

 Evaluate the risks of the disease spreading

Evaluation mission on the site of the epidemic

•

4. Preparing the

response  Disseminate information

 Recommendations for the response

Communication

•

Activities Reference cards Further information

Days

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Stage 1: Checking information

OBJECTIVES



To conduct as exhaustive as possible an analysis of the situation

One or more cases of yellow fever have been notiﬁed. What should be done?

Before organizing the investigation of the epidemic and sending a team to the site, it is important to conduct as exhaustive an analysis as possible of the situation in order to assess it.

The available information must be gathered and checked. The purpose of this stage is to determine (i) that the case is indeed a case of yellow fever and (ii) how certain we are of this.

Is it a suspected case of yellow fever?

What were the clinical signs of the case or cases?

Check:

Symptoms: fever, jaundice (and/or haemorrhage) The course of the disease: in succession fever then

jaundice over a few days

Do the clinical signs correspond to the deﬁnition of a suspected case of yellow fever proposed by WHO for issuing an alert:

« Any case presenting with acute onset of fever, with jaundice appearing within 14 days of onset of the ﬁrst symptoms » (1).

Has the person been vaccinated against yellow fever, and if so when?

Check:

The date of vaccination on the vaccination card.

If there is no document certifying that a person has been vaccinated against yellow fever, they are to be

RC 1/ Table of signs and symptoms of yellow fever RC 5/

Differential diagnosis of haemorrhagic fevers and jaundice RC 3/ Alert form: suspected yellow fever

A 1/ Diagnosis of yellow fever:

clinical signs A 2/ Diagnosis of YF:

Differential diagnosis

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Has the case been conﬁrmed by a laboratory?

Check:

Virological criterion: at least one of the ﬁve criteria in annex 3 is met. Presence of yellow fever speciﬁc viral IgM is the commonest criterion

That laboratory results are compatible with the date of onset of the clinical signs and of the sample That the patient has not recently been vaccinated

against yellow fever (certiﬁed, by a document, in most cases a vaccination card)

Where was the case infected?

Check:

Where has the person been during the fortnight prior to onset of symptoms: Does the person live in or have they travelled to an endemic zone (ﬁg. 3) or a zone in which an epidemic is under way (specify place, date and duration)?

Contacts with persons likely to be infected: has the case been in contact with people, whether sick or not, from areas recently affected by yellow fever?

RC 2/ Table of laboratory tests RC 4/ Form to be sent to the laboratory RC 6/ List of notiﬁcation centres

A 3/ Diagnosis of YF:

Conﬁrmation by the laboratory A 5/ Yellow fever endemic zone

A 6/ Basic epidemiological patterns in Africa

Days

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15°

10°

TOGOBENIN

BURUNDI

ERITREA

ETHIOPIA

KENYA

MADAGASCAR MALAWI

MOZAMBIQUE RWANDA

SOMALIA

UNITED REPUBLIC OF TANZAN

IA UGANDA

ZAMBIA ANGOLA CAMEROON

CENTRAL AFRICAN REPUBLIC

CHAD

CONGO DEMOCRATIC REPUBLIC OF THE CONGO EQUATORIAL

GUINEA

GABON SAO TOME AND PRINCIPE

ALGERIA

EGYPT LIBYAN ARAB

JAMAHIRIYA MOROCCO

SUDAN

TUNISIA

BOTSWANA

LESOTHO NAMIBIA

SOUTH AFRICA

SWAZILAND BURKINA

FASO

COTE D'IVOIRE GAMBIA

GHANA

GUINEA GUINEA-BISSAU

LIBERIA

MAURITANIA MALI

NIGER

NIGERIA SENEGAL

SIERRA LEONE

ZIMBABWE

Figure 3: Map of the yellow fever endemic zone in Africa (ref 15)

IMPORTANT :



A case of yellow fever detected on the basis of clinical signs, must be conﬁrmed by a

laboratory.



A single conﬁrmed case of yellow fever should be grounds for giving the alert. In isolated areas with a scattered population and poor access to the health system, many cases may go unnoticed.



Places where conﬁrmed cases have stayed during the fortnight before the onset of clinical signs must be considered as zones of infection and investigated.

At this stage, it is possible to analyse the risk of an epidemic using three African transmission contexts:

endemic areas, zones of emergence and epidemic areas.

Endemic areas: in the dense forests and gallery forests in which the sylvatic cycle of yellow fever circulates. Human cases are sporadic and linked to work in the forest.

YELLOW FEVER ENDEMIC AREA

Days

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Zones of emergence: in interfaces between the forest galleries and the savanna, where vectors that reproduce in natural sites and sites around homes come into contact with hosts; these proliferate during the rainy season and spend the dry season in hardy egg form. Rural epidemics occur during the rainy season in more or less remote villages and hamlets and may affect a large number of people of all ages.

Epidemic Areas: these comprise more or less urbanized areas in which the urban cycle develops thanks to A. aegypti. Frequently, urban epidemics are hardly affected by rainfall, because domestic habitats are under water throughout the year.

They are associated with the introduction into the urban environment of individuals carrying the virus and may develop very rapidly if the population is unvaccinated.

If this information as a whole is available and makes it possible to assert that there is a yellow fever epidemic, the response must be organized without delay.

However, a ﬁeld investigation is always necessary to complete the information and determine where and how to respond.

KEY MESSAGES



Clinical diagnosis is uncertain  This makes conﬁrmation by a laboratory essential.



The vaccine is safe and effective.



Importance of the ecological context.

REFERENCES

1. Progress in the control of yellow fever in Africa. Weekly Epidemiological Record, N° 6, 2005, (80):49–60

RC 6/ List of centres for notiﬁcation

Days

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Stage 2: Preparing the investigation

OBJECTIVES



To deal with administrative (permits) and logistic (human, material and ﬁnancial resources) details necessary for the ﬁeld investigation.



To complete the required information

 this may be done simultaneously with checking the information.

The purpose of an investigation into an epidemic is to gather and analyse information in the ﬁeld in order to take decisions and guide the response.

It often calls for travel to remote rural areas. Sound preparation is thus crucial to assuring the success of the mission.

Form a team

The ﬁeld investigation team must be multidisciplinary and include health personnel from the peripheral and central levels because they have thorough knowledge of conditions in the ﬁeld and will be responsible for implementing the response. It is also important for representatives of the community and of the authorities to be involved as they make the team’s work easier. If there is a national epidemic control committee, it should also be involved in the investigation.

The team thus comprises several essential members supplemented, as needed, by persons with additional skills.

What skills?

The following areas of expertise will need to be pooled:

Epidemiology:

Drafting the epidemiological investigation protocol

Counting and analysing case distribution by time, place and person

RC 10/ Terms of reference of the investigation team

RC 12/ Role of each level of the health system for prevention of YF

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Days

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Analysing epidemic risks in neighbouring areas

Evaluating the capacity of the surveillance system to detect cases and monitor the epidemic

Setting up a warning system in neighbouring districts

Establishing a surveillance system for

adverse evnets following immunization (AEFI) if it is decided to conduct a mass vaccination campaign.

Entomology:

Developing the entomological investigation protocol

Identiﬁcation of vector species Evaluation of entomological risk

indicators

Determination of the modes of transmission

Recommending vector-control measures adapted to the situation

Laboratory:

Development of a protocol for analysis of specimens

Collection of specimens and transport to the laboratory

Analysis of specimens

Looking for the virus in captured mosquitoes (possibly)

Evaluating new diagnostic tools (possibly)

Response:

Management of mass vaccination in compliance with safety instructions

RC 11/ Role of each level of the health system for surveillance of yellow fever and support for the laboratory

A 6/ Principal epidemiological patterns of yellow fever in Africa

A 4/ YF vaccine and vaccination against yellow fever

Days Days Activities Reference cards Further information

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Control of transmission (control of vector larvae and adults).

Social mobilization

What’s to be done if the required skills are unavailable on the spot?

Request ad hoc support from WHO by e-mail:

outbreak@who.int

Request support from regional structures who possess expertise (WHO collaborating centres) Use this ﬁeld guide

Distribution of tasks

Designate a coordinator from the start of the investigation;

Clearly deﬁne the terms of reference of the permanent members of the team;

From the outset, share responsibility for drafting the ﬁnal report among the team members in accordance with a predetermined plan.

Precautions necessary

All the members of the team must provide proof that they have been vaccinated against yellow fever at least 10 days before the start of the ﬁeld investigation.

The coordinator must be aware of the appropriate procedure in case of security problems or health evacuation. if the team travels to an insecure zone, the members of the international team must have insurance cover for the trip and have been trained in the WHO security rules (interactive CD- ROM training mandatory for international ofﬁcials, determined by the security phase in force in the country).

A 5/ Areas endemic for yellow fever

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Obtaining permits

Obtain administrative permits for the investigation mission from the supervisory authorities (mission order, travel permit …).

In countries in which a complex emergency is in force, before departure check that the roads are safe (mines, armed gangs, check points, etc.) by contacting the United Nations security ofﬁcial.

Gather additional information During the information veriﬁcation stage, it is worthwhile gathering the following additional information:

General background information:

Existence, operation and evaluation of a yellow fever surveillance system

Systematic surveillance data gathered over the previous years and months

Yellow fever control measures (routine or ad hoc) in the country

Data on vaccination coverage in the country and region to be investigated

Availability of stocks of yellow fever vaccine and syringes in the region affected

Data on yellow fever epidemics in the country This information is available in the country (from the Ministry of Health or national committee for epidemic control). Additional information may be found on the following WHO web sites (1).

Information on the epidemic alert to be investigated:

New information available since notiﬁcation of the ﬁrst suspected case (new suspected cases,

response measures …)

Information on the background situation to the epidemic: population movements or gatherings, NGOs working in the sector, means of

communication in the district, etc.

RC 7/ Contact details of ofﬁcials at district and country level RC 13/

Check-list of administrative, ﬁnancial and logistic elements of the investigation

RC 15/

Evaluation of yellow-fever vaccination coverage

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Prepare the necessary equipment for the investigation

For the epidemiological survey;

To collect laboratory specimens;

To carry out the entomological surveys;

For travel, food, accommodation and

communication, taking into account local conditions Caution, it may be an outbreak of a viral haemorrhagic fever other than yellow fever; consequently, personal protective equipment may be of use.

For further information, contact: outbreak@who.int

Estimate the required budget for the investigation

Estimate the budget required for the operation (personnel, per-diem, insurance, equipment, communication and transport) and take enough money to cover these needs if the site of the investigation is remote.

Contact the national laboratory Inform it that specimens will shortly be sent.

Check methods of taking and transporting specimens

Prepare the analysis of the specimens at the laboratory

Determine the methods of communication

Determine who is to receive information and when it is to be sent. What type of information is needed?

Hold a daily brieﬁng for the investigation team Transmit data from the investigation once or twice a

week to the central level

Find out about the policy adopted by the national authorities for communicating with the media (2).

RC 8/ Check list of equipment required in the laboratory to conﬁrm diagnosis of yellow fever

RC 9/ Safety procedure for packing and transport of specimens

A 7/ Equipment for investigating a epidemic

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Contact the Ministry of Health’s International Health Regulations focal point to inform it of the state of progress of the investigation, as yellow fever is one of the epidemic diseases subject to international surveillance.

KEY MESSAGES



A multidisciplinary team with precise terms of reference.



Designation of a coordinator.



^Permits.



Check the team’s vaccinations.



An adequate budget.



Communication.

REFERENCES AND WEB SITES

1. http://www.who.int/csr/disease/yellowfev/en/

http://afro.who.int/yellowfever

2. WHO, 2005, WHO outbreak communication guidelines

http://who.int/csr/resources/publications/WHO_CDS_2005_28/en/

index1.html

Days

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Stage 3: Field investigation

OBJECTIVES



Describe the situation among the population



Conﬁrm whether or not there is a yellow fever epidemic



Describe the mode of transmission: identify the vectors involved in transmission



Evaluate the risks of the disease spreading The key questions which the investigation must answer.

Is there an epidemic of yellow fever, or just isolated cases?

What is the scale of the epidemic (zone affected, number of cases …)?

What is the risk of the epidemic spreading (factors affecting disease transmission and propagation)?

What is the best strategy to control the epidemic?

For reasons of teaching methodology, the different elements of epidemic investigation and response are addressed separately. However, they interact throughout the process. Each discipline provides speciﬁc answers to the key questions (Fig. 4).

A 10/

Epidemiological survey method

3-7

Days

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Figure 4: Analytical matrix for key questions, by discipline

Clinical

epidemiology Response

managementVirology Entomology DESCRIBE THE SITUATION

Is it a yellow fever

epidemic? X X X

What is the scale of the

epidemic? X X X

EVALUATE THE RISK OF THE DISEASE SPREADING What factors affect

transmission and dissemination?

X X X

ORGANIZE THE RESPONSE What populations need

to be vaccinated? X X X X

Are human and material resources available both to implement the campaign and provide follow-up?

X X

What vector-control interventions are necessary?

X

Describe the situation among the population

A.1 Deﬁne cases Reminder:

Not all yellow fever virus infections produce clinical signs and symptoms

Although typically, yellow fever evolves through 4 phases, WHO estimates that only 15% of cases will develop a toxic phase during the disease (1).

There are atypical cases of YF: For every one or few typical cases identiﬁed, there may be numerous atypical cases which may go unnoticed. For this reason, it is important to be familiar with the different types of clinical signs and symptoms of yellow fever.

Other diseases with identical clinical signs and symptoms to yellow fever

RC 5/

Differential diagnosis of haemorrhagic fevers and jaundice

A 8/

Epidemiological and clinical data A 1/ Yellow fever diagnosis:

clinical signs A 2/ Yellow fever diagnosis:

Differential diagnosis A 9/

Comparison of deﬁnitions of suspected cases, for alert and for investigation

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As far as possible, ALL suspected yellow fever cases must be conﬁrmed by laboratory (i.e., specimens taken).

However, it will not be possible to obtain laboratory conﬁrmation for certain cases (suspect deaths, persons absent during the survey …), expanding the case deﬁnition will make it possible to include them as « suspected cases » and thus better to estimate the scale of the epidemic among the population.

As soon as the first case has been confirmed, the definition of «suspected case» used for the investigation will be more comprehensive than that used for the alert; this is because:

It has to be an operational deﬁnition. It must specify the zone and period of investigation It must make it possible to identify the largest

possible number of cases in order, if possible, to ﬁnd the 1^st case (origin of the epidemic), and to evaluate its scale and the risks of dissemination.

This means that it has to be more sensitive

Reporting « suspected cases »

The « suspected case » deﬁnition used for the alert will be supplemented by:

a criterion of space: « any person having stayed in the zone of … » (suspect zone)

a criterion of time: « since … » (outside an urban area: the beginning of the rainy season; in an urban area: in the last two months)

broader clinical criteria:

either fever + jaundice or fever + haemorrhages

or death within two weeks of the onset of the ﬁrst clinical signs

or fever + contact with a conﬁrmed case

Conﬁrmed case

Any suspected case (cf. definition above) confirmed by the laboratory and without recent vaccination (less than 2 years ago) certified by a yellow-fever vaccination card.

RC 14/

Analysis of epidemiological data in terms of time, place and person

A 3/ Yellow fever diagnosis:

Conﬁrmation by the laboratory A 10/ Method used in epidemiological investigation

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How to request laboratory conﬁrmation?

Specimens must be taken from any suspected case for yellow fever conﬁrmation. The specimens must be sent to the national reference laboratory. The laboratory tests carried out vary depending on the date of appearance of the clinical signs.

A.2 Detecting cases

These case deﬁnitions will enable investigators to count the number of cases using a standardized method. A data-collection sheet is then completed (ﬁg. 5) and a sample taken from each patient.

Which data are indispensable?

The survey form (fig. 5) is in 2 parts: a part for the epidemiological data collected in the field and a part for the laboratory results, which is filled in when they have been received.

When the results are entered into a data base or tabulator, it is important carefully to number the forms.

Figure 5: Survey form for essential data

Information requested on the form

Reason, or analytical value Name and forename of case Identiﬁes patient and avoids

duplicates, to be coded later to preserve anonymity

Age, sex, precise address

and phone number Analysis in terms of place and person

Date of onset of disease Epidemic curve Clinical signs motivating

consultation (fever, jaundice or haemorrhage) and date of appearance

Checking diagnosis Differential diagnosis

Course of disease (alive, deceased, with date of decease)

Counting cases and deaths, calculating case fatality rate Yellow fever vaccination and

source of information (card, register, other)

Interpretation of laboratory results

Movements: places, contact with suspected cases

Point of contamination, epidemic dynamics

Profession Hypotheses regarding risk

groups and/or modes of contamination

Date form completed and

name of investigator Checking consistency with other data, question the investigator again if data missing

RC 4/ Form for transmittal to the

laboratory for deﬁnitive case classiﬁcation

RC 3/ Alert form: suspected yellow fever

A 11/

Collection, packing and transport of human specimens

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A.3 Count cases

The epidemiological survey makes it possible to gather data not only on cases but also demographic statistics on the population in which they have emerged (see ﬁgure 6).

The data concerning cases make it possible to describe the epidemic in terms of the number of cases.

IMPORTANT:



Using demographic statistics, it is possible to calculate rates, and thus make comparisons between two different populations during the same epidemic or during two different

epidemics.

Figure 6: Data organization

Case data Population data per

geographical zone Indicator Calculation of indicator N° of cases Case incidence = N° of cases

N° of deaths Mortality = N° of deaths

N° of cases Size Incidence rate = N° of cases/size N° of deaths Size Mortality rate = N° of deaths/size N° of cases Case fatality = N° of deaths/n° of cases N° of deaths

A.4 Analyse data in terms of time-place- person (TPP)

So as to be able to describe distribution of the epidemic in terms of time, place and individual case characteristics, data concerning cases and demographic statistics must be organized in terms of TIME, PLACE and PERSON.

Evolution of the epidemic over time

The NUMBER of cases and/or the NUMBER of deaths are represented by a histogram known as the EPIDEMIC CURVE: the horizontal axis shows the unit of time (hours, days, weeks …) and the vertical axis the number of cases/deaths (ﬁg. 7). Cases are positioned in time using the date of onset of the clinical signs.

RC 16/ Yellow fever epidemic curve

RC 14/

Analysis of epidemiological data in terms of time, place and person.

A 12/ Practical example for calculating rates

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This curve, which may be produced in the ﬁeld, makes it possible to deﬁne:

the probable date of outbreak of the epidemic, the possible origin of the virus, on the basis of the

origin of the ﬁrst case,

the speed at which the epidemic is spreading, the scale of the epidemic.

This curve may be produced in the ﬁeld. Incidence and mortality rates may also be represented by linear graphs.

Figure 7: Epidemic curve representing the number of conﬁrmed cases and of deceased suspected cases, identiﬁed over time during the investigation into the yellow fever epidemic (September to December 2001, Bambey department, Senegal). (2)

orange square = 1 case conﬁrmed by the laboratory (IgM+), black square = 1 deceased suspected case.

What should be done if the health centres’ registers do not mention the date of onset of the symptoms?

If we know the date of onset of the disease it is possible to determine the epidemic curve. If this date is not indicated, it may be estimated by backdating from the appearance of jaundice, because a patient with jaundice probably caught the disease 7 days before the appearance of the ﬁrst symptoms.

Spatial evolution of the epidemic

Data analysis in terms of units of space makes it possible to identify areas at risk and to track the areas affected by the disease. These data may be represented on a bar chart, although it is often more useful to show them on a map in the form of areas or points (ﬁg. 8).

5 4 3 2 1

36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 N° of cases

Weeks

September October November December Months

(33)

Figure 8: Map showing health areas where suspected cases were identiﬁed during the investigation into the yellow fever epidemic in Kita circle, from 02 to 11 January 2005 (3).

Figure 9: Conﬁrmed cases, map showing sites visited and geographical distribution of carriers of yellow- fever speciﬁc IgM (Investigation into the yellow fever epidemic in Diourbel department in 2001) (2).

Individual case characteristics

Individual characteristics, especially age and sex, may inﬂuence mortality and morbidity.

The speciﬁc indicators calculated are useful in

deﬁning vaccination strategy: how many people need vaccinating and what is the target population?

Bafoulabé cercle Kayes region

Kéniéba cercle Kayes region

Koulikoro region District boundary Boundary of health area Health areas investigated and in which suspected cases are present

Bamako Sébékoro

Sirakoro Senko Koféba Séféto Dioungouté

Kita

Sagabari

Ndiane

Keur Samba Kane

Khombole

Lambaye Ndiabi

Baba Garage

Taïba Kassé

Thieppe Darou NDiaye

MBoussou Santhié Keur MBaar Ndème Ngokaré3

Keur Daour

BAMBEY

DIOURBEL Tiourkheime

Pagui Lagnar Khandiar

Peye Ngoye Ngoye Bari Ndondol

N

S

W E Village investigated, IgM detected

Village investigated, IgM not detected Health post visited Track Road

10 km

Map of Diourbel region: results of screening for yellow-fever specific IgM (December 2001)

(34)

It should be noted that cases are often found among children. This may be linked to:

inadequate EPI coverage

mass immunization campaigns having taken place some time ago (from which children born later did not beneﬁt)

immunity acquired by adults as a result of previous infection by yellow fever virus or by a heterologous ﬂavivirus.

In addition, epidemics may particularly concern:

certain professional groups (forestry workers in the case of sylvatic transmission)

nomadic groups who it is difﬁcult to cover by mass immunization campaigns (EPI, mass campaigns) (4).

This makes the speciﬁc indicators calculated using these data very important in deﬁning vaccination strategy: how many people need vaccinating and what is the target population?

Deontological and ethical aspects

It is essential for patients to be informed of the results of their tests. The results are given to the attending physician or to the investigating team, who must as far as possible conceal the identity of cases to protect them from being stigmatized by their community.

Peoples’ anonymity and the security of their personal data are assured, outside the medical sphere, by a coding system. Everyone who uses the information is bound by professional secrecy.

Describe mode of transmission:

Identify the vectors implicated in transmission

It is crucial to identify the vectors implicated in transmission. The method used to collect specimens for investigation purposes depends on the vector’s stage of development and activity.

RC 18/ African yellow fever vectors

A 12/ Practical example for calculating rates

(35)

B.1 Capturing active adult vectors

Although there are several methods of capturing active adult forms of vectors (on humans, on animals, with traps), capture on humans is the method that provides the best data as it is speciﬁc to human-vector contact. However, for obvious ethical reasons this method is no longer recommended by WHO.

B.2 Collection of resting adult vectors

Collection of « residual fauna » in homes is valuable if the vector is indoor dwelling, and tends to rest indoors.

Specimens are collected using a special aspirator. It is also possible to collect adults by spraying insecticides and collecting the mosquitoes on sheets previously spread out on the ﬂoor.

B.3 Collection of immature forms (larvae and eggs)

Immature forms may be collected at the larval

(identiﬁcation of breeding sites) or egg stage (ovitraps).

B.4 Time for prospecting

If there is an epidemic, it is important to go to the spot as quickly as possible to determine the size and nature of the vector populations responsible (5).

However, it should be noted that the vectors do not all emerge at the same time, for example:

A. aegypti may be found throughout the year.

A. vittatus is present essentially during the 1^st half of the rainy season.

the other vectors are generally present during the 2^nd half of the rainy season.

Moreover, collecting « lasting » Aedes eggs makes it possible to detect a species’ presence even though adults and larvae are no longer detectable.

A 13/ Collection of immature vectors A 14/

Calculation of indices for stegomyia index

(36)

B.5 Identiﬁcation and transport of vectors to the laboratory

As soon as they have been collected, the adult mosquitoes must be placed, if possible on a

refrigerated table. They are then immediately frozen, in speciﬁc batches, in dry ice or liquid nitrogen for transport to the laboratory, where the virus will be isolated.

The larvae may (i) be kept alive until the adult stage, identiﬁed and then frozen or (ii) transported to the laboratory in a tube with alcohol for identiﬁcation.

In the case of the eggs laid on the walls of the ovitraps, simply empty the water from the trap and take it to the laboratory. After water has been added, the larvae will be raised until the adult stage. If the eggs have been laid on sticks or paper (placed on the walls), they may be stored for long periods and easily sent to a specialized laboratory for identiﬁcation.

B.6 Registration of the results

If investigations are to produce viable conclusions, not only the results, but also the operating conditions should be registered. A form containing the following information will be prepared for each capture and collection:

name of the place (and, if possible map coordinates).

precise place of capture or collection (village, gallery forest, etc.).

date.

time of capture, in the case of adults and number of capturers.

for residual fauna, type and number of homes visited.

type and number of breeding sites prospected for larval collection and egg harvesting.

number of homes corresponding to the intra- and extra-domiciliary breeding sites prospected.

RC 19/ Rapid assessment monitoring form RC 15/

(37)

Evaluate the risks of the disease spreading

It is important carefully to analyse the risks of

dissemination during an epidemic as well as the future risk of outbreak of other epidemics if appropriate control measures are not introduced.

C.1 Human Migrations

There are four ways in which yellow fever epidemics can spread:

Migration of infected monkeys, especially in the areas of gallery forest: e.g. the 1983 epidemic in Burkina Faso (6).

Movement of adult vectors.

Transport of infected immature forms in water reservoirs.

Human migration, a predominant factor.

This means that analysis of the risk of dissemination must take stock of the different types of population movement: migration by nomads, travel by traders, religious gatherings (e.g. pilgrimages), receiving refugees, etc.

C.2 Vector density and mosquito infection Vector density is evaluated, for both adult vectors and immature forms, using indices known as stegomyia indices.

Batches of mosquitoes preserved in liquid nitrogen or dry ice may also occasionally be examined for the virus.

C.3 Population immunity

The rate at which the epidemic spreads will depend on what proportion of the population is already immunized. It is generally considered that when at least 60-80 % of the population is immunized, the risk of an epidemic is considerably reduced (7).

RC 20/ Risk of yellow fever spreading

RC 15/

A 14/

Calculation of indices for stegomyia index

(38)

In determining what proportion of the population is immunized, the following should be taken into account:

Vaccination coverage by the Expanded Programme on Evaluation (EPI) in previous years (evaluated, if possible, by a vaccination coverage survey)

EPI catch-up campaigns

Vaccination campaigns carried out during epidemics.

By compiling these three sets of information, it is possible to obtain an idea of the proportion of the population already protected by vaccination.

If the region has already experienced an epidemic, the attack rate is considered to be 1/1000. This means that for every case identiﬁed, we may estimated that 1000 persons have been in contact with the virus and have developed natural immunity against the disease.

These calculations are merely approximate. If sufﬁcient quantities of the vaccine are available, it is preferable to protect the population as extensively as possible.

KEY MESSAGES



Objectively evaluate the rumour or the scale of the epidemic.



Suspected cases must be conﬁrmed by the laboratory.



Then apply the operational case deﬁnition in terms of Time, Place and Person.



Then carry out an evaluation of the epidemic on the basis of the number of cases.



An entomological evaluation may be required.



Analyse other risks of dissemination of the disease.

REFERENCES

1. Vainio J, Cutts F. Yellow fever, 1998. World Health Organization, (WHO/EPI/GEN/98.11).

http://www.who.int/csr/resources/publications/yellowfev/WHO_CDS_CSR_

EDC_2000_1_EN/en/

2. Institut Pasteur de Dakar. La Fièvre Jaune dans la région de Diourbel, Sénégal: Rapport de la mission effectuée du 18 au 23 décembre 2001.

3. Institut Pasteur de Dakar. La Fièvre Jaune dans la région de Kita, Mali: in 2004. Rapport de la mission effectuée du 2 au 11 January 2005.

4. The yellow fever situation in Africa and South America in 2005. Weekly Epidemiological Record, 2006, 81:317-324.

5. Dabis F, Drucker J, Moren A. Epidémiologie d’intervention, éd. Arnette, Paris, France, 1992.

6. Baudon D, Robert V, Roux J, Stanghellini A, Gazin P, Molez JF, Lhuillier M, Sartholi JL, Saluzzo JF, Cornet M, et al. Epidemic yellow fever in Upper Volta. Lancet. 1984, 2(8393):42

7. Cordelier H, Germain M, Hervy JP & Mouchet J. Guide pratique pour l’étude des vecteurs de la ﬁèvre jaune en Afrique et méthodes de lutte , ed.

Orstom, Paris, 1977.

Days

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Stage 4: Preparing the response

OBJECTIVES



Inform the authorities of the results and recommendations



Decide what type of response strategy is most appropriate



Identify post-investigation and response activities

Disseminating information

The investigation team is responsible for transmitting the relevant information to the authorities throughout the investigation and on its completion to allow the appropriate decisions to be taken.

A.1 How should the authorities be debriefed?

As a rule, it takes some time to draft a complete report. This makes it important rapidly to inform the authorities orally of the most important ﬁndings of the investigation.

Description of the epidemic: number of cases, indicators for the human and vector population Analysis of risk of dissemination or re-emergence Explanations of the cause of the epidemic

Recommendations for the response

This presentation must be clear and demonstrative.

A.2 How should the report be drafted?

Although each member of the multidisciplinary team must write their speciﬁc section of the report, a summary containing the different elements of information will have to be produced. A preliminary written report summarizing the main features of the epidemic must be submitted to the Ministry of Health by the investigation team within a few days of its having completed the mission, pending submission of the ﬁnal report.

RC 24/ Outline for an oral presentation of a report on an investigation

RC 23/ Outline for a written report on an investigation into a yellow fever epidemic

7-10

Days

One injection, ten year's protection...

FIELD GUIDE

Yellow fever

Investigation of

yellow fever epidemics in Africa

Contents

Acknowledgements

Foreword

Introduction to yellow fever epidemics

Investigation of a yellow fever

epidemic: PROCEDURE

Instructions







Summary of the stages

Stage 1: Checking information

OBJECTIVES



IMPORTANT :







KEY MESSAGES







Stage 2: Preparing the investigation

OBJECTIVES





KEY MESSAGES













Stage 3: Field investigation

OBJECTIVES









IMPORTANT:



KEY MESSAGES













Stage 4: Preparing the response

OBJECTIVES





