Yellow fever is an acute
viralA virus is an infectious agent too small to be seen directly with a light microscope. They are not made of cells and can only replicate inside the cells of another organism . Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
disease. The virus, a 40 to 50 nm enveloped
RNA virusAn RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...
of the family of
FlaviviridaeThe Flaviviridae are a family of viruses that are primarily spread through arthropod vectors . The family gets its name from Yellow Fever virus, a type virus of Flaviviridae; flavus means yellow in Latin...
is transmitted by the bite of mosquitoes (the yellow fever mosquito,
Aedes aegyptiThe yellow fever mosquito, Aedes aegypti , is a mosquito that can spread the dengue fever, Chikungunya and yellow fever viruses, and other diseases. The mosquito can be recognized by white markings on legs and a marking of the form of a lyre on the thorax...
, and other species). Yellow fever is an important cause of hemorrhagic illness in tropical and subtropical areas of African and South American despite existence of an effective
vaccineA vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains a small amount of an agent that resembles a microorganism...
. The
yellow refers to the
jaundiceJaundice, also known as icterus , is a yellowish discoloration of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia...
symptoms that affect some patients.
Since the 17th century, yellow fever has been a source of many devastating
epidemics in America, Africa and Europe. , the
World Health OrganizationThe World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health...
(WHO) estimates that yellow fever causes 200,000 illnesses and 30,000 deaths every year in unvaccinated populations.
Cause
Yellow fever is caused by the
yellow fever virusYellow fever virus is a flavivirus of the family Flaviviridae. It is a positive sense single-stranded RNA virus.It is the agent of yellow fever....
, a 40 to 50 nm big enveloped
RNA virusAn RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...
belonging to the family
FlaviviridaeThe Flaviviridae are a family of viruses that are primarily spread through arthropod vectors . The family gets its name from Yellow Fever virus, a type virus of Flaviviridae; flavus means yellow in Latin...
. The positive
senseSense, when applied in a molecular biology context, is a general concept used to compare the polarity of nucleic acid molecules, such as DNA or RNA, to other nucleic acid molecules...
single-stranded
RNARibonucleic acid is a biologically important type of molecule that consists of a long chain of nucleotide units. Each nucleotide consists of a nitrogenous base, a ribose sugar, and a phosphate...
is approximately 11.000
nucleotideNucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides play central roles in metabolism...
s long and has a single
open reading frameIn molecular genetics, an open reading frame is a portion of an organism's genome which contains a sequence of bases that could potentially encode a protein. The start-points and end-points of a given ORF are not equivalent to the ends of the messenger RNA , but the ends of the ORF are usually...
encoding a polyprotein.
HostHost or hosts may refer to:* Host or sacramental bread* Host — organism harboring another organism on or in itself* Host — "personality" emphasized in treating dissociative identity disorder...
proteaseA protease breaks down proteins. A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein...
s cut this polyprotein into 3 structural (C, prM, E) and 7 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5); the enumeration corresponds to the arrangement of the protein coding
geneA gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cells and pass genetic traits to offspring...
s in the
genomeIn modern molecular biology the genome refers to all of its hereditary information encoded in DNA .The genome includes both the genes and the non-coding sequences of the DNA. The term was adapted in 1920 by Hans Winkler, Professor of Botany at the University of Hamburg, Germany...
.
The viruses infect amongst others
monocyteMonocyte is a type of white blood cell, part of the human body's immune system. Monocytes have two main functions in the immune system: replenish resident macrophages and dendritic cells under normal states, and in response to inflammation signals, monocytes can move quickly Monocyte is a type of...
s,
macrophageMacrophages are white blood cells within tissues, produced by the division of monocytes. Human macrophages are about in diameter...
s and
dendritic cellDendritic cells are immune cells that form part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system, thus functioning as antigen-presenting cells....
s. They attach to the cell surface via specific
receptorIn biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach...
s and are taken up by an endosomal
vesicleA vesicle is a bubble of liquid within a cell. More technically, a vesicle is a small, intracellular, membrane-enclosed sac that stores or transports substances within a cell. Vesicles form naturally because of the properties of lipid membranes ...
. Inside the
endosomeIn biology, an endosome is a membrane-bound compartment inside cells, roughly 500 nm in diameter when fully mature.-Function:Many endocytotic vesicles, derived from the plasma membrane, are either transported to a pre-existing endosome and fuse with it or are acidified via proton pump to become an...
, the dropping
pHpH is a measure of the acidity or basicity of a solution. It is defined as the cologarithm of the activity of dissolved hydrogen ions . Hydrogen ion activity coefficients cannot be measured experimentally, so they are based on theoretical calculations...
induces the fusion of the endosomal membrane with the virus envelope. Thus, the
capsidA capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
reaches the
cytosolThe cytosol or intracellular fluid is the liquid found inside cells. In eukaryotes this liquid is separated by cell membranes from the contents of the organelles suspended in the cytosol, such as the mitochondrial matrix inside the mitochondrion...
, decays and releases the genome. Receptor binding as well as membrane fusion are
catalyzedCatalysis is the process in which the rate of a chemical reaction is either increased or decreased by means of a chemical substance known as a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. The catalyst may participate...
by the protein E, which changes its conformation at low pH, which causes a rearrangement of the 90 homo
dimerA dimer is a chemical or biological entity consisting of two structurally similar subunits called monomers, which are joined by bonds, which can be strong or weak.- Organic chemistry :...
s to 60 homo
trimerTrimer might refer to:* trimer , a reaction product composed of three identical molecules* Protein trimer, a compound of three macromolecules non-covalently bound* Trimer, Ille-et-Vilaine, a commune in France-See also:...
s.
After entering the host cell, the viral genome is replicated in the rough
ERThe endoplasmic reticulum is an eukaryotic organelle that forms an interconnected network of tubules, vesicles, and cisternae within cells. The lacey membranes of the endoplasmic reticulum were first seen by Keith R. Porter, Albert Claude, and Ernest F...
and in the so-called
vesicle packetsThe Golgi apparatus is an organelle found in most eukaryotic cells...
. At first, an immature form of the virus particle is produced inside the ER, whose M-protein is not yet cleaved to its mature form and is therefore denoted as prM (
precursor M) and forms a complex with protein E. The immature particles are processed in the
Golgi apparatusThe Golgi apparatus is an organelle found in most eukaryotic cells...
by the host protein
furinFurin is a protein that in humans is encoded by the FURIN gene. It was named furin because it was in the upstream region of an oncogene known as FES. The gene was known as FUR and therefore the protein was named furin...
, which cleaves prM to M. This releases E from the complex which can now take its place in the mature, infectious virion.
Transmission
The yellow fever virus is mainly transmitted through the bite of the yellow fever mosquito
Aedes aegyptiThe yellow fever mosquito, Aedes aegypti , is a mosquito that can spread the dengue fever, Chikungunya and yellow fever viruses, and other diseases. The mosquito can be recognized by white markings on legs and a marking of the form of a lyre on the thorax...
, but other mosquitos can also serve as a
vectorIn biology, the term vector may be used in different contexts:*Vector , an organism, often an invertebrate arthropod, that transmits a pathogen from reservoir to host...
for the virus. Like other
ArbovirusArbovirus is a shortened name given to viruses that are transmitted by arthropods, or arthropod-borne viruses .Some Arboviruses are able to cause emergent disease. Arthropods are able to transmit the virus upon biting allowing the virus to enter the bloodstream which can cause viraemia.The majority...
es which are transmitted via mosquitos, the yellow fever virus is taken up by a female mosquito which sucks the blood of an infected person. Viruses thus reach the stomach of the mosquito, and if the virus concentration is high enough, the virions can infect epithelial cells and replicate there. From there they reach the haemocoel (the blood system of mosquitos) and from there the
salivary glandThe salivary glands in mammals are exocrine glands, glands with ducts, that produce saliva. They also secrete amylase, an enzyme that breaks down starch into glucose...
s. When the mosquito sucks blood the next time, it injects its saliva into the wound, and thus the virus reaches the blood of the bitten person. There are also indications for a vertical infection of the yellow fever virus with
A. aegypti, i.e. the transmission from a female mosquito to her clutch and thus the larva. This infection of vectors without a previous blood meal seems to play a role in single, sudden breakouts of the disease.
There are three epidemiologically different infectious cycles, in which the virus is transmitted from mosquitos to humans or other primates. In the urban cycle, only the yellow fever mosquito
Aedes aegyptiThe yellow fever mosquito, Aedes aegypti , is a mosquito that can spread the dengue fever, Chikungunya and yellow fever viruses, and other diseases. The mosquito can be recognized by white markings on legs and a marking of the form of a lyre on the thorax...
is involved, which is well adapted to urban centres and can, besides yellow fever, also transmit other diseases such as Dengue and
ChikungunyaChikungunya virus is an insect-borne virus, of the genus Alphavirus, that is transmitted to humans by virus-carrying Aedes mosquitoes. There have been recent outbreaks of CHIKV associated with severe illness. CHIKV causes an illness with symptoms similar to dengue fever...
. The urban cycle is responsible for the major outbreaks of yellow fever, as they occur in Africa. Except an outbreak in Bolivia 1999, this urban cycle no longer exists in South America and is only observed in Africa.
Besides the urban cycle there exists, both in Africa and South America, a silvatic cycle (Forest cycle or
JungleA jungle is usually a dense forest in a hot climate, such as a tropical rainforest. The word jungle originates from the Sanskrit word jangala which refers to uncultivated land, among other meanings. The term is prevalent in many languages of the Indian subcontinent and particularly Urdu and Hindi...
cycle), where
Aedes africanus (in Africa) or mosquitos of the
genusIn biology, a genus is a taxonomic unit used in the classification of living and fossil organisms. The term comes from Latin genus "descent, family, type, gender" , cognate with – genos, "race, stock, kin" ..In addition, genus is a taxonomic rank in the hierarchy In biology, a genus (plural:...
Haemagoggus and
Sabethes (in South America) serve as a vector. In the jungle it is mainly non-human primates that are infected; the disease in African primates is mainly asymptomatic. In South America this is at the moment the only way of infection for humans, which explains the low incidence of yellow fever cases on this continent. People who become infected in the jungle can carry the virus to urban centres, where
Ae. aegyptiThe yellow fever mosquito, Aedes aegypti , is a mosquito that can spread the dengue fever, Chikungunya and yellow fever viruses, and other diseases. The mosquito can be recognized by white markings on legs and a marking of the form of a lyre on the thorax...
occurs as a vector. It is due to this silvatic cycle that yellow fever cannot be eradicated..
In Africa there is a third infectious cycle, also known as
savannahSavannah or savanna is a type of grassland.It can also mean:-Software:* GNU Savannah, an aggregation of software development projects affiliated with the GNU project-Places in the USA:...
cycle or intermediate cycle, which occurs between the jungle and urban cycle. Different mosquitos of the genus
AedesAedes is a genus of mosquito originally found in tropical and subtropical zones, but has spread by human activity to all continents excluding Antarctica. Several of the species transmit important human diseases and one species, Aedes albopictus, is the most invasive mosquito in the world...
are involved.
Prevalence
Yellow fever is
endemicIn epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
in tropical and subtropical areas of South America and Africa. Even though the main vector
Aedes aegyptiThe yellow fever mosquito, Aedes aegypti , is a mosquito that can spread the dengue fever, Chikungunya and yellow fever viruses, and other diseases. The mosquito can be recognized by white markings on legs and a marking of the form of a lyre on the thorax...
also occurs in Asia, in the pacific and the
middle eastThe Middle East is a region that spans southwestern Asia, southeastern Europe, and northeastern Africa. It has no clear boundaries, often used as a synonym to Near East, in opposition to Far East...
, yellow fever does not occur in these areas; the reason for this is unknown.
Worldwide there are about 600 million people living in endemic areas and the official estimations of the
WHOThe World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health...
amount to 200.000 cases of disease and 30.000 deaths a year; the number of officially reported cases is far lower. Estimated 90 % of the infections occur on the African continent.
Phylogenetic analysis identified seven
genotypeThe genotype is the genetic constitution of a cell, an organism, or an individual usually with reference to a specific character under consideration...
s of yellow fever viruses, and it is assumed that they are differently adapted to humans and to the vector
Ae. aegyptiThe yellow fever mosquito, Aedes aegypti , is a mosquito that can spread the dengue fever, Chikungunya and yellow fever viruses, and other diseases. The mosquito can be recognized by white markings on legs and a marking of the form of a lyre on the thorax...
. Five genotypes occure solely in Africa, and it can be assumed that the Westafrica-genotype I is especially virulent or infectious, because it is this type that is often associated with major outbreaks of yellow fever. In South America there are two genotypes identified.
Signs and symptoms
Yellow fever begins suddenly after an incubation period of three to six days. Most of the cases cause only a mild infection with fever, headache, chills, back pain, loss of appetite, nausea and vomiting. In these cases the infection abates after three to four days.
15 % of the cases enter a second phase (the toxic phase) of the disease with recurring fever, this time accompanied by
jaundiceJaundice, also known as icterus , is a yellowish discoloration of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia...
due to
liver damageHepatitis implies injury to the liver characterized by the presence of inflammatory cells in the tissue of the organ. The name is from ancient Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
, as well as abdominal pain. Bleedings in the mouth, the eyes and in the
gastrointestinal tractThe human gastrointestinal tract , digestive tract, guts or gut is the system of organs within humans that takes in food, digests it to extract energy and nutrients, and expels the remaining matter...
can cause vomitus containing blood (thus the name "vómito negro").
This toxic phase is fatal in approximately 20 % of cases.
Surviving the infection causes life-long
immunityImmunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...
and normally there are no remaining organ damages.
Pathogenesis
After transmission of the virus from a mosquito the viruses replicate in the lymph nodes and infect in particular
dendritic cellDendritic cells are immune cells that form part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system, thus functioning as antigen-presenting cells....
s. From there they reach the liver and infect
hepatocyteHepatocytes make up 70-80% of the cytoplasmic mass of the liver.These cells are involved in protein synthesis, protein storage and transformation of carbohydrates, synthesis of cholesterol, bile salts and phospholipids, and detoxification, modification and excretion of exogenous and endogenous...
s (probably indirectly via
Kupffer cellKupffer cells, also known as Browicz-Kupffer cells, are specialized macrophages located in the liver that form part of the reticuloendothelial system .-History:...
s), which leads to
eosinophilic degradationEosinophil granulocytes, usually called eosinophils , are white blood cells that are one of the immune system components responsible for combating infection and parasites in vertebrates. Along with mast cells, they also control mechanisms associated with allergy and asthma...
of these cells and to the release of
cytokineCytokines are any of a number of substances that are secreted by specific cells of the immune system which carry signals locally between cells, and thus have an effect on other cells. They are a category of signaling molecules that are used extensively in cellular communication. They are proteins,...
s. Necrotic masses (
Councilman bodiesIn pathology, a Councilman body, also known as Councilman hyaline body, is an eosinophilic globule often found in the liver of individuals suffering from yellow fever...
) appear in the
cytoplasmThe cytoplasm is the part of a cell that is enclosed within the cell membrane. In eukaryotic cells, the cytoplasm contains organelles, such as mitochondria, which are filled with liquid that is kept separate from the rest of the cytoplasm by biological membranes. The contents of the cell nucleus...
of
hepatocyteHepatocytes make up 70-80% of the cytoplasmic mass of the liver.These cells are involved in protein synthesis, protein storage and transformation of carbohydrates, synthesis of cholesterol, bile salts and phospholipids, and detoxification, modification and excretion of exogenous and endogenous...
s.
When the disease takes a deadly course, a cardiovascular shock and
multi organ failureMultiple organ dysfunction syndrome ', previously known as multiple organ failure , is altered organ function in an acutely ill patient requiring medical intervention to achieve homeostasis...
with strongly increased cytokine levels (
cytokine stormA cytokine storm, or hypercytokinemia is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells, with highly elevated levels of various cytokines.-Symptoms:...
) follow.
Diagnosis
Yellow fever is a clinical
diagnosisDiagnosis is the identification of the nature of anything, either by process of elimination or other analytical methods...
, which often relies on the whereabouts of the diseased person during the incubation time. Liver
biopsyA biopsy is a medical test involving the removal of cells or tissues for examination. It is the removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
can verify
inflammationInflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a...
and
necrosisNecrosis is the premature death of cells and living tissue. Necrosis is caused by external factors, such as infection, toxins , or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
of hepatocytes and detect viral
antigenAn antigen is a substance that prompts the generation of antibodies and can cause an immune response. "Self" antigens are usually tolerated by the immune system; whereas "Non-self" antigens are identified as intruders and attacked by the immune system...
s. Serologically an
enzyme linked immunosorbent assayEnzyme-linked immunosorbent assay, also called ELISA, enzyme immunoassay or EIA, is a biochemical technique used mainly in immunology to detect the presence of an antibody or an antigen in a sample. The ELISA has been used as a diagnostic tool in medicine and plant pathology, as well as a quality...
confirm
IgMIGM might be an acronym or abbreviation for:* The polymeric immunoglobulin, IgM* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium* IG Metall - the dominant German metalworkers' union...
during the acute phase of the disease, or an increase in
titerA titer is a measure of concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positive or negative. The titer corresponds to the highest dilution factor that still yields a positive reading...
as compared to the healthy condition. Further, a
reverse transcription polymerase chain reactionReverse transcription polymerase chain reaction is a variant of polymerase chain reaction , a laboratory technique commonly used in molecular biology to generate many copies of a DNA sequence, a process termed "amplification"...
can amplify and demonstrate viral genetic information, this can also help distinguish between different
flavivirusFlavivirus is a genus of the family Flaviviridae. This genus includes the West Nile virus, dengue virus, Tick-borne Encephalitis Virus, Yellow Fever Virus, and several other viruses which may cause encephalitis....
es. This is essential for the
differential diagnosisA differential diagnosis is a systematic method used to identify unknowns. This method, essentially a process of elimination, is used by taxonomists to identify living organisms, and by physicians or other clinicians to diagnose the specific disease in a patient.Not all medical diagnoses are...
, because other viral infections can cause similar symptoms.
Treatment
For yellow fever there is, like for all diseases caused by
FlavivirusFlavivirus is a genus of the family Flaviviridae. This genus includes the West Nile virus, dengue virus, Tick-borne Encephalitis Virus, Yellow Fever Virus, and several other viruses which may cause encephalitis....
es, no causative cure. Hospitalisation is advisable and intensive care may be necessary due to in some cases rapid deterioration in state of health.
Different methods for acute treatment of the disease were shown to be not very successful, for example is passive immunisation after emergence of symptoms probably without effect. Also did
RibavirinRibavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides...
and other antiviral drugs as well as treatment with
interferonInterferons are natural cell-signaling proteins produced by the cells of the immune system of most vertebrates in response to challenges such as viruses, parasites and tumor cells. They belong to the large class of glycoproteins known as cytokines and are produced by a wide variety of cells in...
s not have a positive effect on the patient
A symptomatic treatment includes rehydration and pain relief with drugs like
ParacetamolParacetamol or acetaminophen is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of fever, headaches, and other minor aches and pains, and is a major ingredient in numerous cold and flu remedies...
.
Acetlysalicylic acidAspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication....
(for example
Aspirin®) should not be given due to its haemodiluting effect, which can be devastating in the case of inner bleeding that can occur with yellow fever.
Prevention
Personal prevention of yellow fever includes vaccination as well as prevention of mosquito bites in areas where yellow fever is endemic. Institutional measures for prevention of yellow fever include vaccination programmes and measures of controlling tiger mosquitos.
Vaccination
For journeys into affected areas vaccination is highly recommended. The protective effect is established after 10 days after vaccination in 95% of the vaccinated people and lasts for at least 10 years.
The attenuated live
vaccineVaccination is the administration of antigenic material to produce immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by a pathogen. Vaccination is generally considered to be the most effective and cost-effective method of preventing infectious diseases...
(stem 17D) was developed in 1937 by
Max TheilerMax Theiler was a South African/American virologist. He was awarded the Nobel Prize in Physiology or Medicine in 1951 for developing a vaccine against yellow fever.-Career development:...
and is produced in chicken eggs.
WHO recommends to vaccinate people living in endemic areas routinely between the 9th and 12th month after birth..
In a few cases (less than one in 200,000 to 300,000), the vaccination can cause YEL-AVD (
yellow fever vaccine-associated viscerotropic disease), which is fatal in 60% of all cases. It is probably due to a genetic defect in the immune system. Age is an important risk factor; in children the complication rate is less than one case per 10 million vaccinations.
Further an infection of the nervous system can occur in one in 200,000 to 300,000, causing YEL-AND (
yellow fever vaccine-associated neurotropic disease), which can cause
meningoencephalitisMeningoencephalitis is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain.-Causes:Causative organisms include protozoans, viral and bacterial...
and is in less than 5% fatal.
Compulsory vaccination
Some countries in Asia are theoretically in danger of yellow fever epidemics (responsible mosquitos and infectable monkeys), even though the disease does not yet occur there. To prevent introduction of the virus, some counties demand previous vaccination of foreign visitors, if they had passed through yellow fever areas. Vaccination has to be proven in a vaccination certificate which is valid 10 days after the vaccination and lasts for 10 years. A list of the countries which require yellow fever vaccination was published by the WHO.
If vaccination is for some reasons not possible, dispensation is possible. In this case an exemption certificate of WHO standard is required.
Even though 32 of 44 countries where yellow fever occurs endemically do have vaccination programmes, many of these countries have less than 50 % of their population vaccinated..
Vector control
Besides vaccination, control of the yellow fever mosquito
Aedes aegyptiThe yellow fever mosquito, Aedes aegypti , is a mosquito that can spread the dengue fever, Chikungunya and yellow fever viruses, and other diseases. The mosquito can be recognized by white markings on legs and a marking of the form of a lyre on the thorax...
is of major importance, especially because the same mosquito can, besides yellow fever, transmit Dengue and
ChikungunyaChikungunya virus is an insect-borne virus, of the genus Alphavirus, that is transmitted to humans by virus-carrying Aedes mosquitoes. There have been recent outbreaks of CHIKV associated with severe illness. CHIKV causes an illness with symptoms similar to dengue fever...
disease.
Ae. aegyptiThe yellow fever mosquito, Aedes aegypti , is a mosquito that can spread the dengue fever, Chikungunya and yellow fever viruses, and other diseases. The mosquito can be recognized by white markings on legs and a marking of the form of a lyre on the thorax...
breeds preferentially in water, for example in installations by inhabitants of areas with precarious drinking water supply, or in civilising rubbish; especially tires, cans and plastic bottles. Especially in proximity to urban centres of developing countries these conditions are very frequent and present a perfect habitat for
Ae. aegyptiThe yellow fever mosquito, Aedes aegypti , is a mosquito that can spread the dengue fever, Chikungunya and yellow fever viruses, and other diseases. The mosquito can be recognized by white markings on legs and a marking of the form of a lyre on the thorax...
. Two strategies are used fighting the mosquito:
One approach is to deaden the developing larva. Measures are taken to reduce water build-ups (the habitats of the larva), and
larvicideA larvicide is an insecticide that is specifically targeted against the larval life stage of an insect. Their most common use is against mosquitoes...
s are used as well as larva-eating fish and
copepodCopepods are a group of small crustaceans found in the sea and nearly every freshwater habitat. Many species are planktonic , but more are benthic , and some continental species may live in limno-terrestrial habitats and other wet terrestrial places, such as swamps, under leaf fall in wet forests,...
s, which reduce the number of larva and thus indirectly the number of disease-transmitting mosquitos.
For many years, copepods of the genus
MesocyclopsMesocyclops is a genus of copepod crustaceans in the family Cyclopidae.Species include:* * Mesocyclops annulatus* * * Mesocyclops brevisetosus* * * * Mesocyclops insulensis* Mesocyclops longisetus* * Mesocyclops ogunnus...
have been used in
VietnamVietnam , officially the Socialist Republic of Vietnam , is the easternmost country on the Indochina Peninsula in Southeast Asia. It is bordered by China to the north, Laos to the northwest, Cambodia to the southwest, and the South China Sea to the east...
for fighting Dengue fever (yellow fever does not occur in Asia), with the effect that in the affected areas no cases of Dengue fever occurred since 2001. Similar mechanisms are probably also effective against yellow fever.
As a chemical larvicide mainly
pyriproxyfenPyriproxyfen is a pyridine based pesticide which is found to be effective against a variety of arthropoda. It was introduced to the US in 1996 to protect cotton crops against whitefly...
is recommended, because it is safe for humans and effective even in small doses.
Besides larva, also the adult yellow fever mosquitos are targeted. Curtains and lids of water tanks are sprayed with
insecticideAn insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...
s. Spraying insecticides inside houses is not recommended by the WHO. Similar to the
malariaMalaria is a vector-borne infectious disease caused by a eukaryotic protist of the genus Plasmodium. It is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. Each year, there are approximately 350–500 million cases of malaria, killing between one and...
carrier, the
AnophelesAnopheles, , is a genus of mosquito. There are approximately 460 recognised species: while over 100 can transmit human malaria, only 30-40 commonly transmit parasites of the genus Plasmodium that cause malaria which affects humans in endemic areas...
mosquito, insecticide treated
mosquito netA mosquito net offers protection against mosquitos, flies, and other insects, and thus against diseases such as malaria. Its fine, see-through, mesh construction stops many insects from biting and disturbing the person using the net...
s are used successfully against
Ae. aegyptiThe yellow fever mosquito, Aedes aegypti , is a mosquito that can spread the dengue fever, Chikungunya and yellow fever viruses, and other diseases. The mosquito can be recognized by white markings on legs and a marking of the form of a lyre on the thorax...
.
History
West AfricaWest Africa or Western Africa is the westernmost region of the African continent. Geopolitically, the UN definition of Western Africa includes the following 16 countries distributed over an area of approximately 5 million square km:*Benin...
has long been regarded as the home of yellow fever. Yellow fever has had an important role in the history of Africa, the
AmericasThe Americas, or America, are lands in the Western hemisphere or New World, comprising the continents of North America and South America with their associated islands and regions. America may be ambiguous in English, as it is more commonly used to refer to the United States of America...
, Europe, and the
CaribbeanThe Caribbean is a region consisting of the Caribbean Sea, its islands , and the surrounding coasts...
.
Cuba: 1762–1763
British and American colonial troops died by the thousands in the
British expedition against CubaThe Battle of Havana was a military action from March to August 1762, as part of the Seven Years' War. British forces besieged and captured the city of Havana, which at the time was an important Spanish naval base in the Caribbean, and dealt a serious blow to the Spanish navy...
between 1762 and 1763. Epidemics struck coastal and island communities throughout the area during the next 140 years, with 10% of the population dying as a result.
Philadelphia, Pennsylvania: 1793
The
Yellow Fever Epidemic of 1793The Yellow Fever Epidemic of 1793 is believed to have killed several thousand people in Philadelphia, Pennsylvania, United States. The Yellow fever epidemic struck the city when it was the capital of the United States and a major seaport....
killed as many as 10,000 people in
Philadelphia, PennsylvaniaPhiladelphia is the largest city in Pennsylvania and the sixth-most-populous city in the United States.In 2008, the population of the city proper was estimated to be over 1.4 million, while the metropolitan area's population of 5.8 million made it the country's fifth-largest...
. Thousands, including President
George WashingtonGeorge Washington was the commander of the Continental Army in the American Revolutionary War and served as the first President of the United States of America...
, fled the city, including most members of the Federal (Philadelphia was the capital of the United States at this time) and city governments. As a result, civil services collapsed and almost vanished. However, the mayor remained and eventually, with the help of a "Committee of Twenty" composed of volunteer residents drawn from all walks of life, order and civil services were restored. Members of the
Free African SocietyThe Free African Society was a non-denominational community formed in 1787 in Philadelphia by Richard Allen, Absalom Jones and others for the benefit of African Americans released from slavery...
, a charitable organization of African-Americans originally founded as a self-help group, were instrumental in this regard. They served as nurses and home-care attendants, often for no pay, and Mayor William Clarkson later praised their work when racist claims of price-gouging and theft were raised.
Although many other well-to-do citizens chose to leave the city,
Stephen GirardStephen Girard was a French-born, naturalized American, philanthropist and banker. He personally saved the U.S...
stayed to care for the sick and dying. He supervised the conversion of a mansion outside the city limits into a hospital and recruited volunteers to nurse victims, and personally cared for patients. For his efforts, Girard was feted as a hero by the City Hall after the outbreak subsided.
The first family of
Dolley MadisonDolley Payne Todd Madison was the spouse of the fourth President of the United States, James Madison, and was First Lady of the United States from 1809 to 1817...
, née Dolley Payne, who would later become
First Lady of the United StatesFirst Lady of the United States is the title of the hostess of the White House. Because this position is traditionally filled by the wife of the President of the United States, the title is most often applied to the wife of a sitting president...
during
James MadisonJames Madison was an American politician and political philosopher who served as the fourth President of the United States , and was one of the Founding Fathers of the United States....
's administration, was stricken in this epidemic. John Todd, Dolley's husband, was a Quaker and a lawyer. He felt it was his duty to remain in Philadelphia and provide legal services (wills, probate, etc.) to those who were dying or the families of those who died. However, he moved his family across the river. One day on a visit to his family, he collapsed into his wife's arms on the doorstep of their house and died soon after. Dolley and her eldest son, John Payne Todd, contracted yellow fever but survived. Dolley's youngest son William Temple Todd and John's parents also perished in the 1793 epidemic.
Alexander HamiltonAlexander Hamilton was the first United States Secretary of the Treasury, a Founding Father, economist, and political philosopher...
and his wife,
Elizabeth SchuylerElizabeth Hamilton was the wife of Alexander Hamilton, the founder of the Federalist party and first Secretary of the Treasury of the United States of America...
, contracted yellow fever but survived.
Dr.
Benjamin RushBenjamin Rush was a Founding Father of the United States. Rush lived in the state of Pennsylvania and was a physician, writer, educator, humanitarian and a devout Christian, as well as the founder of Dickinson College in Carlisle, PennsylvaniaRush was a signatory of the Declaration of...
also contracted yellow fever, but survived. His fame, as a signer of the
Declaration of IndependenceA declaration of independence is an assertion of the independence of an aspiring state or states. Such places are usually declared from part or all of the territory of another nation or failed nation, or are breakaway territories from within the larger state...
and as head medical doctor for the American army in the middle Atlantic states region during the
American RevolutionThe American Revolution is the political upheaval during the last half of the 18th century in which thirteen of Britain's colonies in North America at first rejected the governance of the Parliament of Great Britain, and later the British monarchy itself, to become the sovereign United States of...
, brought him hundreds, perhaps thousands, of patients during this epidemic. His methods were severe and split the medical community at that time, resulting in an ongoing letter-writing war in the press both during and after the epidemic. Some contemporaries, notably
William CobbettWilliam Cobbett was an English pamphleteer, farmer and journalist, who was born in Farnham, Surrey. He believed that reforming Parliament and abolishing the rotten boroughs would help to end the poverty of farm labourers, and he attacked the borough-mongers, sinecurists and "tax-eaters" relentlessly...
, objected to Rush's extreme use of bloodletting. Cobbett accused Rush of killing more patients than he had saved. Rush sued Cobbett for libel, winning a judgment of $500. However, unlike a number of other doctors, he remained in Philadelphia and did his best to help the residents who were struck down by the disease.
At the time of the Philadelphia epidemic, the most widespread belief was that the disease spread via contaminated water. A "Watering Committee" was appointed and recommended a
municipal water supplyThe Fairmount Water Works in Philadelphia, Pennsylvania was the first municipal waterworks in the United States. Designed in 1812 by Frederick Graff and built between 1819 and 1822 it operated until 1909, winning praise for its design and becoming a popular tourist attraction...
, which came into use in 1801. The initial installation, by
Benjamin LatrobeBenjamin Henry Boneval Latrobe was a British-born American architect best known for his design of the United States Capitol, as well as his design of the Baltimore Basilica, the first Catholic Cathedral built in the United States...
, was inefficient and unreliable, and was replaced in 1812-1815. Of course the water system did nothing directly to alleviate yellow fever, but it allowed city residents to remove their makeshift arrangements of wells and cisterns, which had provided breeding places for mosquitoes. Thus, the desired effect was actually achieved.
Haiti: 1802
In 1802, an army of forty thousand sent by First Consul Napoleon Bonaparte of France to
HaitiHaiti , officially the Republic of Haiti , is a Creole- and French-speaking Caribbean country. Along with the Dominican Republic, it occupies the island of Hispaniola, in the Greater Antillean archipelago...
to suppress the
Haitian RevolutionThe Haitian Revolution is, as historian C.L.R. James affirms, "the only successful slave revolt in history." It established Haiti as the first republic ruled by blacks. At the time of the revolution, Haiti was known as Saint-Domingue and was a colony of France...
was decimated by an epidemic of yellow fever (including the expedition's commander and Bonaparte's brother-in-law,
Charles LeclercCharles Victor Emmanuel Leclerc was a French Army general and husband to Pauline Bonaparte, sister to Napoleon Bonaparte.-To 1801:...
). Some historians believe Haiti was to be a staging point for an invasion of the United States through
LouisianaThe Louisiana Purchase was the acquisition by the United States of America of of the French territory Louisiana in 1803. The U.S...
(then still under French control).
New Orleans, Louisiana: 1853
This outbreak claimed 7,849 residents of New Orleans. The press and the medical profession did not alert citizens of the outbreak until the middle of July, after over a thousand had already died. The reason for this silence was that the New Orleans business community feared that word of an epidemic would cause a quarantine to be placed on the city, and commerce would thus be hurt.
Norfolk, Virginia: 1855
A ship carrying persons infected with the virus arrived in
Hampton RoadsHampton Roads is the name of both a body of water and the region of land areas which surround it in southeastern Virginia. Hampton Roads is notable for its year-round ice-free harbor, for United States Navy, Coast Guard, Air Force, NASA, Marines, and Army facilities, shipyards, coal piers, and...
in southeastern
VirginiaThe Commonwealth of Virginia is a U.S. state on the Atlantic Coast of the Southern United States. Virginia is nicknamed the "Old Dominion" and sometimes the "Mother of Presidents" because it is the birthplace of eight U.S. presidents. The geography and climate of the state are shaped by the Blue...
in June 1855. The disease spread quickly through the community, eventually killing over 3,000 people, mostly residents of
NorfolkNorfolk is an independent city in the Commonwealth of Virginia in the United States. With a population of 234,403 as of the 2000 census, it is Virginia's second-largest incorporated city behind its eastern neighbor, Virginia Beach....
and
PortsmouthPortsmouth is an independent city located in the U.S. Commonwealth of Virginia. As of the 2000 census, the city had a total population of 100,565, but a 2006 Census estimate showed the city's population had increased to 101,377....
. The
Howard AssociationHoward Association, a benevolent organization, was formed in Norfolk, Virginia during the 1855 Yellow Fever Epidemic which killed 1 in 3 residents of Norfolk and sister city Portsmouth in Hampton Roads. Contributions were used to set up a hospital and an orphanage, to feed the hungry and to bury...
, a benevolent organization, was formed to help coordinate assistance in the form of funds, supplies, and medical professionals and volunteers which poured in from many other areas, particularly the
AtlanticThe Atlantic Ocean is the second-largest of the world's oceanic divisions. With a total area of about 106.4 million square kilometres , it covers approximately one-fifth of the Earth's surface and about one-quarter of its water surface area. The first part of its name refers to the Atlas of Greek...
and
Gulf CoastThe Gulf of Mexico is the ninth largest body of water in the world. Considered a smaller part of the Atlantic Ocean, it is an ocean basin largely surrounded by the North American continent and the island of Cuba. It is bounded on the northeast, north and northwest by the Gulf Coast of the United...
areas of the United States.
Memphis, Tennessee: 1878
There were several outbreaks of yellow fever in
MemphisMemphis is a city in the southwest corner of the U.S. state of Tennessee, and the county seat of Shelby County. Memphis rises above the Mississippi River on the 4
th Chickasaw Bluff just south of the mouth of the Wolf River....
during the 1870s, culminating in the devastating 1878 epidemic, with over 5,000 fatalities in the city itself and 20,000 along the whole of the Mississippi River Valley. It has been claimed that the large death toll was due to commercial interests taking precedence over reporting the outbreak of yellow fever.
The French Panama Canal Effort: 1882–1889
The French effort to build a
Panama CanalThe Panama Canal is a ship canal which joins the Caribbean Sea to the Pacific ocean. One of the largest and most difficult engineering projects ever undertaken, it had an enormous impact on shipping between the two oceans, replacing the long and treacherous route via the Drake Passage and Cape Horn...
was fatally damaged by the prevalence of endemic tropical diseases in the Isthmus. Although
malariaMalaria is a vector-borne infectious disease caused by a eukaryotic protist of the genus Plasmodium. It is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. Each year, there are approximately 350–500 million cases of malaria, killing between one and...
was also a serious problem for the French canal builders, the numerous yellow fever fatalities and the fear they engendered made it difficult for the French company to retain sufficient technical staff to sustain the effort. Since the mode of transmission of the disease was unknown, the French response to the disease was limited to care of the sick. Unfortunately, the French hospitals contained many pools of stagnant water, such as basins underneath potted plants, in which mosquitoes could breed. The eventual failure, as a result of the deaths, of the French company licensed to build the canal resulted in a massive financial crisis in France.
Carlos Finlay and Walter Reed
Carlos FinlayCarlos Juan Finlay was a Cuban physician and scientist, recognized as a pioneer in yellow fever research.- Early life and education :...
, a Cuban doctor and scientist, first proposed proofs in 1881 that yellow fever is transmitted by
mosquitoMosquito is a common insect in the family Culicidae...
es rather than direct human contact.
Walter ReedMajor Walter Reed, M.D., was a U.S. Army physician who in 1900 led the team which postulated and confirmed the theory that yellow fever is transmitted by mosquitoes, rather than by direct contact...
, M.D., (1851–1902) was an
American ArmyThe United States Army is the branch of the United States Military responsible for land-based military operations. It is the largest and oldest established branch of the U.S. military and is one of seven uniformed services...
surgeon who led a team that confirmed Finlay's theory. This risky but fruitful research work was done with human volunteers, including some of the medical personnel, such as
Clara MaassClara Louise Maass was an American nurse who died as a result of volunteering for medical experiments to study yellow fever. -Early life:...
and
Walter Reed MedalThe Walter Reed Medal is a military decoration of the United States Army which was created by an act of the United States Congress on February 28, 1929...
winner surgeon
Jesse William LazearJesse William Lazear was an American physician.He was the son of William and Charlotte née Pettigrew...
, who allowed themselves to be deliberately infected and died of the virus. Although Dr. Reed received much of the credit in history books for "beating" yellow fever, Reed himself credited Dr. Finlay with the discovery of the yellow fever vector, and thus how it might be controlled. Dr. Reed often cited Finlay's papers in his own articles and gave him credit for the discovery, even in his personal correspondence. The acceptance of Finlay's work was one of the most important and far-reaching effects of the Walter Reed Commission of 1900. Applying methods first suggested by Finlay, the elimination of yellow fever from Cuba was completed, as well as the completion of the
Panama CanalThe Panama Canal is a ship canal which joins the Caribbean Sea to the Pacific ocean. One of the largest and most difficult engineering projects ever undertaken, it had an enormous impact on shipping between the two oceans, replacing the long and treacherous route via the Drake Passage and Cape Horn...
. Lamentably, almost 20 years had passed before Reed and his Board began their efforts, twenty years during which most of the scientific community ignored Finlay's theory of mosquito transmission.
Finlay and Reed's work was put to the test for the first time in the United States when a yellow fever epidemic struck New Orleans in 1905, although efforts had been successful in Havana since 1901. A conference organized in New Orleans in 1905 by Dr. A. L. Metz resulted in
President RooseveltTheodore Roosevelt was the 26th President of the United States. He is well remembered for his energetic persona, his range of interests and achievements, his model of masculinity, and his "cowboy" image. He was a leader of the Republican Party and founder of the short-lived Bull Moose Party...
directing the United States' Government to take control of the matter. The United States Public Health Service put into effect a mosquito control campaign, this included, fumigating houses, inspecting cisterns for drinking water, and treating pools of standing water with
keroseneKerosene, sometimes spelled kerosine in scientific and industrial usage, also known as paraffin, is a combustible hydrocarbon liquid. The name is derived from Greek keros...
. The result was that the death toll from the epidemic was much lower than that from previous yellow fever epidemics, and that there has not been a major outbreak of the disease in the United States since. Although no cure has yet been discovered, an effective vaccine has been developed, which can prevent and help people recover from the disease.Yellow fever can turn into a deadly disease if it is not treated properly.
Current research
In the hamster model of yellow fever, early administration of the antiviral
ribavirinRibavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides...
is an effective early treatment of many pathological features of the disease. Ribavirin treatment during the first five days after virus infection improved survival rates, reduced tissue damage in target organs (liver and spleen), prevented hepatocellular
steatosisIn cellular pathology, steatosis is the process describing the abnormal retention of lipids within a cell. It reflects an impairment of the normal processes of synthesis and elimination of triglyceride fat. Excess lipid accumulates in vesicles that displace the cytoplasm...
, and normalized alanine aminotransferase (a liver damage marker) levels. The results of this study suggest that ribavirin may be effective in the early treatment of yellow fever, and that its mechanism of action in reducing liver pathology in yellow fever virus infection may be similar to that observed with ribavirin in the treatment of
hepatitis CHepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but once established, chronic infection can progress to scarring of the liver , and advanced scarring which is generally apparent after many years...
, a virus related to yellow fever. Because ribavirin had failed to improve survival in a virulent primate (rhesus) model of yellow fever infection, it had been previously discounted as a possible therapy.
In the past, yellow fever has been researched by several countries as a potential biological weapon.