Rapid Health Assessment in Outbreaks of VHF

a) General characteristics

Viral haemorrhagic fevers (VHF) are caused by a number of viruses, some associated with insects or rodents, which may infect humans. These diseases cause special problems for public health services because of their epidemic potential, high case-fatality rates and the unusual difficulties arising in their treatment and prevention. Although the specific clinical profile of each viral illness may vary, there are two prominent features that may occur in all types of VHF during the most critical stage of the illness:

a tendency to bleed, with the risk of severe haemorrhage from both cutaneous and internal sites
the development of shock which may be irreversible

The existence of a specific virus in a community tends to reflect the geographic distribution of its natural host. Nonetheless, human and natural environments are changing quickly: in this perspective, research should be considered an integral part of emergency preparedness against these epidemics.

Several viral infections also have the potential for extensive nosocomial spread (spread within a health care facility), especially when safe barrier nursing procedures are not observed. In these conditions, case-fatality rates can often exceed 50%, and may reach 80% for several days.

The table below lists the major VHFs which cause epidemics and their distribution.

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VHFs Causing Epidemics

VHF	Distribution	Natural Host/Vector
Lassa Fever	Central/West Africa	rodents
Junin/Machupo/Guanarito/Sabia	South America	rodents
Ebola/Marburg	Africa	unknown
Crimean-Congo haemorrhagic fever (CCHF)	Africa/Asia	ticks
Rift Valley fever	Africa	mosquitoes
Dengue haemorrhagic fever	Africa/Americas/Pacific/ Middle East/Australasia/ Caribbean/India	mosquitoes
Yellow fever	Africa/South America	mosquitoes
Haemorrhagic Fever with Renal Syndrome (HFRS)	Asia/Europe	rodents

b) The special concerns of yellow fever

In Africa and South America, yellow fever has caused many serious epidemics, with high attack rates and mortality. However, while the clinical presentation of yellow fever may resemble other types of VHF, it is unique with respect to emergency preparedness and containment. Unlike other VHFs, timely vaccination against yellow fever, combined with vector control measures, interrupt transmission and prevent unnecessary cases and deaths.

There are many examples in which the first recognition of a yellow fever epidemic occurred several months after the actual epidemic onset. The consequences of such late detection (e.g. delayed initiation of control efforts) underscore the need to consider yellow fever in a rapid assessment when an outbreak of VHF is reported or rumoured.

An epidemic alert for an outbreak of VHF with yellow fever as a possible cause should be given when one of the following occurs:

one case is confirmed in a community with abundant vector mosquitoes;
a single case of yellow fever is diagnosed by serology or virus isolation, or suggested by histopathology, or
reports are made of abortion or deaths among domestic animals may indicate Rift Valley fever activity.

Early warning procedures should be established for early detection of VHFs. Routine health surveillance, and rapid reporting from hospitals are essential for detecting VHF outbreaks at an early stage.

Hospital reports of increased incidence of fatal hepatitis, suspected cases of yellow fever and of VHF, deserve to be considered as early warning indicators. Ask:

Where are the high risk areas for past and potential VHF and yellow fever epidemics? At-risk populations? Based on past experience, when are the high-risk seasons?
What is the likely health impact of an epidemic of VHF or yellow fever? (number of cases, hospitalizations, deaths?)
What are the early signs that would signal a VHF or yellow fever ‘epidemic alert’? Can or could they be detected earlier through improved epidemic surveillance and reporting?

Because VHF outbreaks frequently occur in rural areas, their early detection is often missed by routine health surveillance. However when reported, such outbreaks assume high visibility with the media, often in a context of panic expressed by the medical and local communities affected.

Therefore, the rapid assessment provides a valuable opportunity to allay anxiety at the community level and to give basic information on protective measures to prevent further spread. Top

2. Preparedness for the Rapid Assessment

Develop locally-adapted working case-definitions for VHFs and yellow fever, as well as guidelines that help health workers at all levels recognize suspicious trends and/or trigger an epidemic alert.

The prompt diagnosis of the cause of a VHF outbreak requires analysis of a representative sample of specimens by a competent laboratory. Epidemic preparedness should give this utmost priority, as well as assessing capacity of national laboratories; identifying reference laboratories, and ensuring methods of diagnostic specimen transport.

Most of the viruses (excluding dengue haemorrhagic fever) causing VHF are classified as ‘Biosafety Level 4’ pathogens. This biohazard requires analysis at special facilities which provide maximum containment.

Attempts to isolate the virus should be undertaken only at approved high containment laboratories. Therefore, these should be identified in advance and contacts established with the nearest specialist laboratory to obtain details of precautions necessary for packing and transport of specimens.

Serology can be carried out in standard laboratories only if it is possible to inactivate specimens and reagents.

It is also necessary to:

identify qualified local team members in advance, (e.g. an epidemiologist, clinician/entomologist, virologist, and veterinarian) skilled in assessing VHF outbreaks;
put in place advance provisions for obtaining rapid outside specialist support if qualified personnel are not locally available;
obtain advice from a virologist on the specimens needed, precautions required for collection, the equipment necessary, and procedures for shipment (consider International Air Transport Association (IATA) shipping restrictions);
identify channels and means for rapid communication between peripheral areas and sub-national/central levels - satellite telephone and facsimile may be required;
identify a knowledgeable individual to communicate with the press; develop a strategy to effectively deal with press inquiries.

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3. Conducting the Rapid Assessment

The rapid assessment consists of confirming an outbreak of VHF and estimating its geographic distribution, assessing the impact on health, assessing the existing response capacity and immediate needs.

3.1 Confirming an Outbreak of VHF and estimating its geographic distribution

a) Initial case-definition

As for all potential epidemics, this is best determined in advance, as part of emergency preparedness. Simple, workable case-definitions should be defined for suspect, probable and confirmed cases of VHF.

Examples of case-definitions for VHF are:

Suspect Case
"acute fever with either jaundice, or cutaneous and internal bleeding, accompanied by shock"; in the case of dengue the rash should also be mentioned.
Probable Case
"a suspect case with at least two of the following signs: severe myalgia and headache, conjunctivitis, rash, shock, proteinuria, death, where the case has had contact with a possible source of transmission".
Confirmed case
"a suspect or probable case with one of the following: virus isolation from blood or tissue; detection of viral antigen or genome in blood, tissue or other body fluid; presence of specific IgM antibody in titer high enough to indicate recent infection".

Yellow fever

In a rapid assessment, it may be difficult to distinguish yellow fever from other haemorrhagic illnesses, or diseases such as malaria. However, to maximize case-detection at this early stage, it is often necessary to use a broad case-definition such as ‘jaundice, fatal or non-fatal’ to identify suspected cases.

b) Confirm the increase in the number of cases.
(See Rapid Health Assessment in Epidemics of Infectious Origin.)

c) Case-finding and estimating geographic distribution
(See Rapid Health Assessment in Epidemics of Infectious Origin.)

It is important to recognize that there could be many asymptomatic or mild cases who are hospitalized with a non-specific febrile illness. In order to be thorough, case-finding efforts for VHF and yellow fever should not be limited to infectious wards but should include other hospital departments and health facilities.
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d) Collection of appropriate specimens for laboratory analysis and confirmation

Because the definitive diagnosis of a VHF can only be made by serology or virus isolation, it is essential that appropriate specimens are collected during the rapid assessment.

Key considerations in specimen collection are as follows.

Essential information should be included with specimens (locality, name of patient, age, sex, date of sampling, date of disease onset, summary of clinical and epidemiological findings).
All specimens should be collected in sterile containers.
All specimens must be considered potentially infectious and dangerous. Therefore, stringent safety precautions should be observed.
For every patient, a specimen of whole blood should be collected without anticoagulant for virus isolation or antibody detection.
Do not freeze whole blood nor liver specimen: separate sera if specimen is to be frozen.
All sera/cerebrospinal fluid (CSF) specimens should be frozen for preservation during transport. For virus isolation, specifically, specimens should be ideally stored on liquid nitrogen or dry ice
Specimens are best hand-carried from peripheral areas to the central level.
Use non-breakable container (plastic, screw-cap) with absorbent material to contain any leakage, and double outer container. Follow International Air Transport Association (IATA) regulations for air transport of specimen.

Specimens required:

Whole blood from patients who have been sick less than 7 days. Do not separate sera from blood clots unless laboratory workers can be protected against infectious aerosols.
Convalescent sera from patients at least 14 days after onset. Sera should be carefully separated from blood clots.
For suspect yellow fever cases, liver specimens taken at postmortem with a biopsy needle. These should be divided in two - one placed in 10% buffered formalin, and the other treated in the same way as a whole blood specimen: not frozen without anticoa
Skin snips from fatal cases of suspect VHF preserved in formalin
To verify the clinical diagnosis and identify the causative virus, it is advisable to transport specimens to WHO collaborating centres for urgent analysis.

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3.2 Assessing Impact on Health

a) Collect information on a representative sample of cases

When the cause of a VHF outbreak is not known, careful interviewing and physical examination of suspect, probable and confirmed cases is extremely important. These early clinical findings provide clues as to type of virus and source of infection. As a minimum, gather information on:

name, age, sex, residence, date of onset and of reporting.
signs and symptoms, severity of illness, outcome treatment given and response to treatment.
presence of risk-factors, e.g. history of contact.

Useful information on the mode of transmission can be gained by investigating the contacts of identified index cases. It is also important to ask about exposures to infected animal hosts (e.g. contact while slaughtering livestock).

The definition of a ‘primary’ or ‘close’ contact is one or more of:

has shared the same place (for working or traveling), the same room or meals, had occasional face-to-face contact during the period of communicability of a severe, classical or mild form of the disease.
has given care, handled the patient's belongings, participated in autopsy or burial preparations without special protection; or
has traveled from an area where VHF transmission is endemic.

The definition of a "possible" contact is:

Was a close contact of a case during a period in which (s)he was possibly not yet contagious (e.g. persons hospitalized in the same ward).

Whatever the method chosen, the characterization of the contact should include a clarification on the index case: Was he or she suspect, probable or confirmed?

b) Analyze the information gathered

(Refer to Rapid Health Assessment in Epidemics of Infectious Origin.)
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c) Assess vectors present

One rapid assessment priority is to identify whether vectors are present in the affected area that may transmit VHF or yellow fever. It is not the purpose of a rapid assessment to carry out a detailed entomological survey - but rather to ask the following questions.

Are there vectors present in the affected area? If so, what?
Are they known to be human biters?
Are there breeding sites? If so, how extensive?

The answers to these preliminary questions are critical for deciding on the need for further entomological studies and control measures for vectors and natural hosts.

d) Assess disease in other vertebrate hosts

Are there unexplained deaths in monkeys in the affected area? If so, where and when did they occur?
Are there unexplained deaths or abortions in livestock? If so, where and when did they occur? (Particularly relevant for Rift Valley fever.)

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3.3 Assessing Existing Response Capacity and Immediate Needs

a) Assess local response capacity

Local epidemic surveillance

Are there sufficient trained personnel, vehicles and communications support to maintain adequate surveillance? Is outside technical help needed?
Is there a need for animal studies (e.g. sentinel herd surveillance) or further entomological investigations?

Response capacity of existing health services

What steps have local health officials taken to organize epidemic response? Is there a plan of action, standardized reporting procedures, trained staff?
Are hospitals equipped to carry out safe barrier nursing measures? (Check bed nets, gloves, disinfectants, masks, gowns.)
What is local cold chain capacity? Trained vaccinators? Jet injectors? Vehicles? Stocks of syringes? Yellow fever vaccine stocks in country?
Do medical, nursing and laboratory personnel need further training on case-detection and safe patient management?
What links have been established with key community members (e.g. for allaying panic, health education and improved case-detection)?
What vector control equipment, pesticides and larvicides are available?
Has a strategy been developed for dealing with press inquiries?

3.4 Deciding on immediate needs

To decide on immediate needs, ask:

is there an outbreak of VHF which has or could lead to a large number of cases?
if so, are external resources needed to contain it?

If the answer to both questions is "yes", then an emergency response is needed.
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State the following:

Is there an outbreak of some type of VHF?
If so, how many cases and deaths so far?
What is the geographic distribution?
Does it appear to be spreading?
What are the trends?
What is the clinical presentation?
Are signs and symptoms indicative of any specific type of VHF?
Where should specimens be sent for rapid analysis?
Is the etiologic agent responsible for the outbreak identified?
Have specimens being sent to reference laboratories?
What are the estimated geographic magnitude, size of population at risk and health impact in numbers of projected cases and deaths?

Describe immediate needs
Are outside resources such as the following needed

Drugs
Other supplies
Equipment
Manpower
Expert assistance
Logistics
Funding
Other

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Table of contents

1. Assessment Purpose and Background

1.2 Background

2. Preparedness for the Rapid Assessment

3. Conducting the Rapid Assessment