Lecturer:

Tigran Ugujyan
Epidemiologist,
Master of Public Health

Zoonoses
 Viral
•Rabies
•Yellow fever
•Nipah virus infection
•Japanese encephalitis
•KFD
 Bacterial
•Chikungunya fever
•Brucellosis
•Leptospirosis
•Plague
•Human salmonellosis
 Rickettsial diseases
•Rickettsial zoonoses
•Scrub typhus
•Murine typhus
•Tick typhus
•Q Fever
 Parasitic zoonoses
•Taeniasis
•Hydatid disease
•Leishmaniasis
Yellow fever
Yellow fever is a zoonotic disease caused by an arbovirus.
It affects principally monkeys and other vertebrates in
tropical America and Africa and is transmitted to man by
certain culicine mosquitoes. It shares clinical features with
other viral haemorrhagic fevers (e.g., dengue HF, Lassa
fever) but is characterized by more severe hepatic and renal
involvement.
Yellow fever
The spectrum of disease varies from clinically
indeterminate to severe cases. Severe cases develop
jaundice with haemorrhagic manifestations (black vomit,
epistaxis, melena) and albuminuria or anuria, shock,
agitation, stupor and coma (1). In general death occurs
between the fifth and tenth day of illness. The case fatality
rate may reach 80 per cent in severe cases. Survivors exhibit
long-lasting immunity.
Problem statement
47 countries in Africa and Latin America, with a
combined population of more than 900 million, are at risk of
yellow fever. In Africa, an estimated 508 million people live
in 32 countries at risk. The remaining are in 13 countries of
Latin America, with Bolivia, Brazil. Colombia, Ecuador and
Peru at greatest risk (2).
Problem statement
There were an estimated 84,000-170,000 cases and
29,000-60,000 deaths worldwide in the year 2013. Small
number of imported cases occur in countries free of yellow
fever. Although disease has never been reported in Asia, the
region is at risk because the conditions required for
transmission are present there (2) .
Epidemiological
determinants
Agent factors
(a) AGENT : The causative agent, Flavivirus fibricus
formerly classified as a group B arbovirus, is a member of
the togavirus family. It shares group-specific antigens with
other members of the genus (e.g., West Nile, dengue). Under
natural conditions, the virus is pantropic but after continued
culture in tissues, as in chick embryo, it loses all its
pathogenic properties but retains its antigenicity.
Agent factors
(b) RESERVOIR OF INFECTION : In forest areas, the
reservoir of infection is mainly monkeys and forest
mosquitoes. In urban areas, the reservoir is man (subclinical
and clinical cases) besides Aedes aegypti mosquitoes.
Agent factors
(c) PERIOD OF COMMUNICABILITY : (I) MAN : Blood of
patients is infective during the first 3 to 4 days of illness.
(II) MOSQUITOES : After an "extrinsic incubation period" of
8 to 12 days, the mosquito becomes infective . The virus
multiplies in the insect vector. After becoming infective, the
mosquito remains so for life . Transovarian transmission of
the virus in mosquitoes has been shown to occur in adverse
conditions (e.g. , during extended dry seasons), in the
absence of susceptible hosts (1).
Host factors
(a) AGE AND SEX : All ages and both sexes are
susceptible to yellow fever in the absence of immunity
(b) OCCUPATION : Persons whose occupation brings them
in contact with forests (wood cutters, hunters) where yellow
fever is endemic are exposed to the risk of infection
(c) IMMUNITY : One attack of yellow fever gives lifelong
immunity; second attacks are unknown. Infants born of
immune mothers have antibodies up to 6 months of life.
Environmental factors
(a) CLIMATE : A temperature of 24 deg.C or over is
required for the multiplication of the virus in the mosquito. It
should be accompanied by a relative humidity of over 60 per
cent for the mosquitoes to live long enough to convey the
disease.
Environmental factors
(b) SOCIAL FACTORS : In Africa, urbanization is
leading to the extension of yellow fever. In addition, the
expanding population is encroaching on areas that were
previously sparsely populated, thereby bringing man closer to
the jungle cycles of yellow fever. The increasing number of
people who travel and the greater speed with which they are
transported from endemic areas to receptive areas, also gives
a cause for concern (3).
Modes of transmission
There are three known cycles of transmission, the jungle,
intermediate and the urban cycles (2).
Sylvatic (or jungle) yellow fever.
In tropical rainforests, yellow fever occurs in monkeys that are infected
by wild mosquitoes. The infected monkeys then pass the virus to
other mosquitoes that feed on them. The infected
mosquitoes bite humans entering the forest, resulting in
occasional cases of yellow fever. The majority of
infections occur in young men working in the forest (e.g.
for logging).
Intermediate yellow fever
In humid or semi-humid parts of Africa, small-scale epidemics occur, Semi-
domestic mosquitoes (that breed in the wild and around
households) infect both monkeys and humans. Increased
contact between people and infected mosquitoes leads to
transmission. Many separate villages in an area can suffer
cases simultaneously. This is the most common type of
outbreak in Africa. An outbreak can become a more severe
epidemic if the infection is carried into an area populated
with both domestic mosquitoes and unvaccinated people.
Urban yellow fever
Large epidemics occur when infected people introduce the virus into
densely populated areas with a high number of non-immune
people and Aedes mosquitoes. Infected mosquitoes
transmit the virus from person to person.
Treatment
There is no specific treatment for yellow fever, only
supportive care to treat dehydration and fever. Associated
bacterial infections can be treated with antibiotics.
Supportive care may improve outcomes for seriously ill
patients, but it is rarely available in poorer areas.
Incubation period
3 to 6 days (6 days recognized under International Health
Regulations) .
CONTROL OF YELLOW FEVER
Jungle yellow fever
Jungle yellow fever continues to be an uncontrollable
disease. The virus maintains itself in the animal kingdom.
Mosquito control is difficult and can be considered only in
restricted areas. Vaccination of humans with 17D vaccine is
the only control measure.
Urban yellow fever
(1) VACCINATION: Rapid immunization of the
population at risk is the most effective control strategy for
yellow fever. For international use, the approved vaccine is
the 17D vaccine. It is a live attenuated vaccine prepared
from a non-virulent strain (17D strain), which is grown in
chick embryo and subsequently freeze-dried.
Urban yellow fever
The sensitivity of the lyophilized 17D vaccine to heat is a
major drawback to the use of this vaccine, in mass campaigns
in tropical countries. It has to be stored between +5 and
- 30 deg.C, preferably below zero deg. C until reconstituted
with the sterile, cold physiological saline diluent provided.
Reconstituted vaccine should be kept on ice, away from
sunlight, and discarded if not used within half an hour.
Urban yellow fever
The vaccine is administered subcutaneously at the
insertion of deltoid in a single dose of 0.5 ml irrespective of
age. Immunity begins to appear on the 7th day and lasts
possibly for life (2) .
The risk of death from yellow fever is much higher than
the risks related to the vaccine. People who should not be
vaccinated include (2) :
Urban yellow fever
(a) children aged under 9 months for routine immunization
(or under 6 months during an epidemic);
(b) pregnant women - except during a yellow fever outbreak
when the risk of infection is high;
(c) people with severe allergies to egg protein; and
(d) people with severe immunodeficiency caused by
symptomatic HIV/AIDS or other causes, or in the
presence of thymus disorder.
Urban yellow fever
Mild post-vaccinial reactions (e.g., myalgia , headache ,
low-grade fever) may occur in 2-5 per cent of vaccinees,
5 to 10 days after vaccination. Anaphylaxis is very rare,
occurring mainly in those allergic to eggs (4) .
Cholera and yellow fever vaccines together or within
3 weeks interfere with each other, so whenever possible,
they should be given 3 weeks or more apart (5) .
Urban yellow fever
(2) VECTOR CONTROL : The other principal method of
preventing yellow fever is through intensive vector control.
The objective of vector control is to reduce rapidly the
vector population to the lowest possible level and thereby
stop or reduce transmission quickly. This approach has
proved successful in the Americas to prevent urban
epidemics.
Urban yellow fever
The vector, Aedes mosquito is peti-domestic in habits. It
can be controlled by vigorous anti-adult and anti-larval
measures. The long-term policy should be based on
organized "source reduction" methods (e.g. , elimination of
breeding places) supported by health education aimed at
securing community participation.
Urban yellow fever
Personal protection against contact with insects is of
major importance in integrated vector control. Such
protection may include the use of repellents, mosquito nets,
mosquito coils and fumigation mats (7).
Urban yellow fever
(3) SURVEILLANCE : A programme of surveillance
(clinical, serological, histopathological and entomological)
should be instituted in countries where the disease is
endemic, for the early detection of the presence of the virus
in human populations or in animals that may contribute to
its dissemination.
Urban yellow fever
For the surveillance of Aedes mosquitoes, the WHO uses
an index known as Aedes aegypti index. This is a house
index and is defined as "the percentage of houses and their
premises, in a limited well-defined area, showing actual
breeding of Aedes aegypti larvae" (8) . This index should not
be more than 1 per cent in towns and seaports in endemic
areas to ensure freedom from yellow fever (9) .
International measures
India is a yellow fever "receptive" area, that is, "an area
in which yellow fever does not exist, but where conditions
would permit its development if introduced". The
population of India is unvaccinated and susceptible to
yellow fever. The vector, Aedes aegypti is found in
abundance. The climatic conditions are favourable in most
parts of India for its transmission. The common monkey of
India (Macacus spp) is susceptible to yellow fever. The
missing link in the chain of transmission is the virus of yellow
fever which does not seem to occur in India.
International measures
The virus of yellow fever could get imported into India in
two ways: (I) through infected travellers (clinical and
subclinical cases), and (II) through infected mosquitoes.
Measures designed to restrict the spread of yellow fever are
specified in the "International Health Regulations" of
WHO (8) . These are implemented by the Government of India
through stringent aerial and maritime traffic regulations.
Broadly these comprise :
International measures
(I) TRAVELLERS : All travellers (including infants)
exposed to the risk of yellow fever or passing through
endemic zones of yellow fever must possess a valid
international certificate of vaccination against yellow fever
before they are allowed to enter yellow fever "receptive"
areas. If no such certificate is available, the traveller is placed
on quarantine, in a mosquito-proof ward, for 6 days from
the date of leaving an infected area. If the traveller arrives
before the certificate becomes "valid", he is isolated till the
certificate becomes valid.
International measures
(II) MOSQUITOES : The aircraft and ships arriving from
endemic areas are subjected to aerosol spraying with
prescribed insecticides on arrival for destruction of insect
vectors. Further, airports and seaports are kept free from the
breeding of insect vectors over an area extending at least
400 metres around their perimeters. The "aedes aegypti
index" is kept below 1.
International certificate of vaccination (10)
India and most other countries require a valid certificate
of vaccination against yellow fever from travellers coming
from infected areas. A few countries (including India) require
this even if the traveller has been in transit. It rests with each
country to decide whether a certificate of vaccination against
yellow fever shall be required for infants under one year of
age, after weighing the risk of importation of yellow fever by
unvaccinated infants against the risk to the infant arising
from vaccination.
International certificate of vaccination (10)
In this regard, India requires vaccination of
infants (≥ 9 months of age) too. The validity of the certificate
begins 10 days after the date of vaccination. For the purpose
of international travel, the vaccination must be given at an
officially designated centre, and the certificate must be
validated with the official stamp of the Ministry of Health,
Government of India.
International certificate of vaccination (10)
The certificate is valid only if it conforms with the model prescribed
under the International Health Regulations. On the other hand, for
their own protection, travellers who enter endemic areas should
receive vaccination against yellow fever (10).
New yellow fever vaccination requirement
for
travellers
In May 2014, the World Health Assembly adopted an
amendment of International Health Regulations (2005) ,
which stipulates that the period of protection afforded by
yellow fever vaccination , and the term of validity of the
certificate will change from 10 years to the duration of the life
of the person vaccinated . On 11th July 2016, the amendment
entered into force and is legally binding upon all IHR states.
New yellow fever vaccination requirement
for
travellers
This lifetime valid ity applies automatically to all existing and
new certificates, beginning 10 days after the date of
vaccination. Accordingly, as of 11th July 2016, revaccination
or a booster dose of yellow fever vaccine will not be required
for international travellers as a condition of entry into a State
Party, regardless of the date that their international certificate
of vaccination was initially issued (11).
New yellow fever vaccination requirement
for
travellers
In India, the lifetime validity of yellow fever vaccination
applies automatically. The list of yellow fever endemic
countries are as follows:
In Africa : Angola, Benin, Burkina Faso, Burundi,
Cameroon, Central African Republic, Chad, Congo, Cote
d' Ivoire, Democratic Republic of the Congo, Equatorial
Guinea, Ethiopia, Gabon, Gambia, Ghana, Guinea,
Guinea-Bissau, Kenya, Liberia, Mali, Mauritania, Niger,
Nigeria, Rwanda, Senegal, Sierra Leone, Sudan, South
Sudan, Togo and Uganda;
New yellow fever vaccination requirement
for
travellers
and in the Americas:
Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana,
Panama, Paraguay, Peru, Suriname, Trinidad and Tobago
(Trinidad only) , and Venezuela (Bolivarian Republic of).
Note : -When a case of yellow fever is reported from any
country, that country is regarded by the Government of
India as a country with risk of yellow fever transmission and
is added to the above list (10).
Epidemic preparedness and response
WHO recommends that every at-risk country have at
least one national laboratory where basic yellow fever blood
tests can be performed. A confirmed case of yellow fever in
an unvaccinated population is considered as an outbreak. A
confirmed case in any context must be fully investigated.
Investigation teams must assess and respond to the outbreak
with both emergency vaccination campaigns and longerterm
immunization plans (2).
The Elimination Yellow Fever Epidemic (EYE)
Strategy (2)
The EYE Strategy was developed by WHO, UNICEF and
GAVI, in response to increased threat of yellow fever urban
outbreaks with international spread. It is guided by three
strategic objectives :
1. Protect at-risk populations :
2. Prevent international spread of yellow fever; and
3. Contain outbreaks rapidly.
These objectives are underpinned by five
competencies of success:
1. Affordable vaccines and sustained vaccine market;
2. Strong political commitment at global, regional and
country levels ;
3. High-level governance with long-term partnerships;
4. Synergies with other health programmes and sectors;
and
5. Research and development for better tools and practices.
References
1. WHO (1986). Bull WH064 (4) 511-524.
2. WHO (2018). Fact Sheet Yellow Feuer, 1st May 2018.
3. WHO (1972). WHO. Chr., 26 (2) 60- 65.
4 WHO (2010), Weekly Epidemiological Record, No. 5, 29th Jan., 2010.
5. Immunization Practices. Advisory Committee, US countries for
Disease Control (1984) Ann. Int. Med., 100 : 540 42.
6. Med Digest (1985) Feb. P.29.
7. WHO (1985) Tech. Rep. Ser., No. 720 P.31.
References
8. WHO (2005). International Health Regulations, Second Annotated
Edition.
9. WHO (1971). Tech. Rep. Ser., No.479.
10. Govt. of India (2013), Bureau of Immigration, Health Regulation,
Ministry of Home Affairs, Immigration Visa - Foreigners Registration
and Tracking.
11. WHO (2016). International Trauel and Health, New Yellow Fever
Vaccination Requirements for Travellers.