Medicine for Africa - Medical Information Service

ELLOW FEVER

Definition:

Yellow fever is an acute viral disease that also used to be called ‘yellow jack’, ‘black vomit’ or ‘vomito negro’, or sometimes ‘American Plague’.  The term yellow refers to the symptoms of jaundice that occur in some patients.

Yellow fever is caused by a virus of the genus Flavivirus, a single-stranded enveloped RNA arbovirus.  The disease is transmitted to humans by the bite of a mosquito of the so-called Aedes mosquito family, and its deposition of viral particles via its infected saliva.  Aedes (Ae.) simpsaloni, Ae. africanus and Ae. aegypti are the main vectors in Africa, and the Haemagogus genus in South America, the two regions of its prevalence.  Ae. aegypti is also the transmitting mosquito vector for dengue fever in Africa.

There are three types of yellow fever – ‘sylvatic (or jungle) yellow fever’, ‘intermediate yellow fever’, and ‘urban yellow fever’.

Jungle yellow fever, also called sylvatic yellow fever, is spread via wild infected mosquitoes to monkeys in the tropical rain forests. As the mosquito feeds on an infected monkey, it engulfs the virus, and then transmits it to the next, yet uninfected monkey. This form of the disease is mainly a disease of monkeys, however, humans can become infected if they enter this cycle and are bitten by mosquitoes that have previously become infected by the monkeys. Thus, this form of yellow fever is rare, and limited to people who go to the tropical rain forests.    

The second type, intermediate yellow fever, is prevalent in humid and semi-humid savannah areas of Africa, where small scale epidemics may occur.  The semi-domestic mosquitoes can infect both monkeys and humans, thus, this area is termed the ‘zone of emergence’, where humans are more and more exposed to the infected mosquitoes.  In Africa, this form of yellow fever is the most common type seen in outbreaks, and it can shift to the more severe form of urban outbreaks as the infection is carried into this kind of environment.

And finally, urban yellow fever is the major form of human disease, transmitted among humans by the bite of the mosquito Ae. aegypti, and can cause large epidemics over wide areas and regions.  This mosquito exclusively transmits the disease from person to person as it loves to live near human residents, and is particularly active during the daytime.   Ae. aegypti has well adapted to human habitation, and preferably breeds in standing waters, especially artificial water containers, such as flower vases or pots, cisterns, standing water in uncovered barrels, cisterns and even the interior of discarded tires. 

All three forms of yellow fever exist in Africa, while only the jungle yellow fever and urban yellow fever are present in South America.

Following infection, the virus replicates locally at the bite site before spreading via the lymphatic system throughout the body.  Finally, it settles in various organ systems, including the heart, kidneys, liver and adrenal glands.  High viral loads can be present in the blood, and so-called Councilman bodies (dead liver cells) can be found in the parenchyma of the liver.

            Historic review

The occurrence of yellow fever has been known for over 400 years, and it has caused a number of large epidemics in both Africa and the Americas.  During the revolt for freedom on the island of Santo Domingo in 1802, almost the entire French army was ‘attacked’ by the disease and perished, resulting in the independence of Haiti from Napoleon’s France.  Periodic outbreaks followed in other countries, claiming thousands of victims in the Western Hemisphere, from South America to as far north as Boston in Massachusetts.  The last epidemic in the USA struck New Orleans in 1905.

It was not until 1928 that the viral cause of the disease was discovered, followed by the development of an attenuated 17D strain vaccine by Max Theiler, a South African born physician. This vaccine is still being used worldwide and considered the mainstay of fighting the disease.  For his work, Dr. Theiler received the Nobel Prize for Medicine in 1951.

Symptoms:

Symptoms usually occur three to six days after inoculation of the virus by way of a bite of an infected mosquito.   In most cases, the disease is a self-limited illness that proceeds relatively mild, and is often difficult to differentiate from any other fever causing illness.

However, in about 15% of cases, the illness progresses into its severe form, resulting in high fever, chills, muscles aches and pains, as well as lower backache pain, usually accompanied by headaches, nausea and vomiting, and an occasional skin rash on the chest.  This phase of yellow fever lasts for about three to four days, followed by an (erroneous) remission phase before entering its second phase.  Now, the infection also involves the liver and kidneys, resulting in kidney and liver failure with subsequent jaundice (yellow discoloration of the skin and eyes, which gave the disease its name), bleeding and shock.  In this phase, the disease carries a fatality rate ranging from 15% to over 50%.

 
Diagnosis:

At first, a preliminary diagnosis can be made, based upon the patient’s clinical picture and symptoms.   

A definite diagnosis of yellow fever requires the detection of specific IgM and neutralizing antibodies in the serum of blood or in cerebrospinal fluid (CSF).  In addition, during the acute infection stage, nucleic acid amplification by way of ELISA (Enzyme Linked ImmunoSorbent Assay), or immunohistochemical staining of liver biopsies, or autopsy tissue can be useful.

Aspartate aminotransferase (AST) is often increased in blood tests, as are prothrombin time (PT), activated partial thromboplastin time (aPTT), and the internationally recognized summary of those two values, the ‘international rationalized ratio’ (INR).  Clotting times will be prolonged, as levels of blood coagulation factor VII, fibrinogen and platelets will be diminished, increasing the risk of disseminated intravascular coagulation (DIC).  Often, albuminuria (increase of albumin levels in the urine) is associated with an increase in BUN (blood urine nitrogen).  Due to the abnormalities in blood coagulation factors, hemorrhagic lesions in multiple organ systems, as well as necrosis of the median lobe of the liver, are characteristics of the severe form of yellow fever.

The differential diagnosis includes other viral hemorrhagic fevers, malaria, viral hepatitis, and even leptospirosis, all of which may confuse the final diagnosis of yellow fever.

 
Treatment:

There is no specific treatment for yellow fever. As it is usually a self-limited disease, the mainstay of treatment consists of supportive therapy, including oral and intravenous fluid intakes, in order to prevent dehydration and to maintain an adequate blood pressure, and to prevent dehydration and subsequent concentration of the blood.

To manage the febrile episodes, acetaminophen containing drugs are preferred over aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids, which should be avoided.  Any superimposed bacterial infections should be treated with an appropriate specific antibiotic.

 
Prevention:

While there is no immediate therapy available for yellow fever, there is a very effective vaccine available, preventing the infection with the yellow fever virus within one week in over 95% of cases.  One dose of vaccination provides for at least 10 years of protection, and probably even life-long.

Vaccination programs in developing countries can be performed in mass campaigns, providing for wide-ranging vaccination coverage in high risk areas. While childhood vaccination is strongly recommended by the World Health Organization (WHO), it should not be administered to children younger than six months of age, in order to prevent most of the known side effects.  Ideally, it should be administered in conjunction with other routine vaccinations, such as against measles at age nine months.

Travelers to and from countries with known potentials of yellow fever infectivity, should also be vaccinated.  International regulations require the proof of a yellow fever vaccination for travels to and from those countries.  

Another way of preventing a mosquito bite consists of taking appropriate preventive measures while in exposed regions, including:

• Wearing long-sleeved shirts/blouses and long pants, preferably pre-treated with an insecticide such as permethrin;
• Using DEET- (N,N-diethyl-3-methylbenzamide), Picaridin (KBR 3023), or PMD (p-Methane 3,8-diole), or oil of lemon eucalyptus;
• Remain in air-conditioned or well-screened places, especially during the day;
• Use indoor sprays to eliminate the mosquito;
• Prevent the mosquito from finding breeding places by eliminating sources of stagnant water around human habitats (such as [flower] pots, old tires or any other kind of potentially water-holding containers.

In order to prevent an epidemic in a potentially diseased country, requires that at least 80% of the population must have been immunized or be immune to yellow fever.  this high level of protection can only be achieved, if yellow fever vaccinations are incorporated in country-wide childhood immunization programs and mass catch-up campaigns are successfully implemented.  Unfortunately, only few African countries have achieved this level of protection to-date.  

             Community Education

In endemic or potentially endemic areas, the community needs to be educated to seek protective vaccination, to learn of the potential sources of the disease, and how to prevent the mosquito from breeding. 

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