Yellow fever

from Wikipedia, the free encyclopedia
Classification according to ICD-10
A95 Yellow fever
ICD-10 online (WHO version 2019)

The yellow fever , also Ochropyra or black vomit (in older texts also Siamese illness and jungle fever called) is an infectious disease caused by the yellow fever virus is caused. The virus is a 40 to 50  nanometer large, enveloped RNA virus with positive polarity from the flavivirus family .

The virus is transmitted as a vector by mosquitoes and is widespread in tropical and subtropical areas of South America and Africa . The only known hosts for the virus are primates and various mosquito species . The origin of the disease is believed to be in Africa, from where it was spread through the slave trade and transatlantic traffic from the 16th century in South America. Several major disease outbreaks have occurred in America, Africa, and Europe since the 17th century. Yellow fever was considered one of the most dangerous infectious diseases in the 19th century.

The disease manifests itself in most cases with fever, nausea and pain and subsides after a few days. Sometimes it comes to severe, sometimes fatal courses with liver damage, development of jaundice (as an expression of hepatitis , hence the name of the disease) and blood clotting disorders (increased bleeding tendency, hemorrhagic diathesis ). The yellow fever is therefore one of the so-called hemorrhagic fevers . The WHO estimates that 200,000 people fall ill and 30,000 people die of yellow fever each year; an estimated 90% of the infections occur on the African continent.

There is a very safe and effective vaccination against yellow fever, which was developed in the 1930s / 1940s by the South African virologist Max Theiler . In some countries there is a compulsory vaccination for people entering the country. Since no causal therapy for yellow fever is known, in addition to vaccination programs, measures to control the transmitting yellow fever mosquito are of great importance in the affected countries. Since the 1980s, cases of yellow fever have been increasing again, which is why yellow fever is often referred to as a reemerging disease .

Pathogen

Yellow fever viruses (shown in TEM)

Yellow fever is caused by the yellow fever virus , a round virus 40 to 50 nm in diameter  belonging to the flavivirus family . The viral genome is around 11,000 nucleotides long and consists of positive-stranded ribonucleic acid (RNA), so it can be read directly from ribosomes and thus used to synthesize an amino acid chain ( protein ) without any further intermediate steps . The genome comprises only one open reading frame that codes for a polyprotein (a long amino acid chain that has to be broken down into the individual functional proteins after synthesis).

During an infection, the viruses attach to the cell surface of a host cell via specific receptors and are taken up by a developing endosome vesicle . These vesicles are normally used to digest substances , but the virus uses them as a means of transport to get inside the cell. Inside the endosome, the acidic pH induces the fusion of the endosome membrane and the virus envelope , so that the internal structures ( capsid and genome) are released into the cytosol . After that, the viral genome using viral is RNA polymerases and a negative-strand RNA as an intermediate step replicated . The positive strands that are increased in this way are used for the synthesis of the viral structural proteins (envelope proteins and capsid proteins) in the rough ER and in so-called vesicle packets . After maturation in the Golgi apparatus , infectious virus particles develop. These leave the cell and infect other host cells.

transmission

Stegomyia aegypti

The yellow fever virus is mainly transmitted by the bite of the yellow fever mosquito ( Stegomyia aegypti ), but other mosquitoes can also serve as vectors . As with other mosquito-borne arboviruses , the yellow fever virus is ingested by a female mosquito who suckles the blood of an infected person. The viruses get into the mosquito's stomach and if the virus concentration is high enough, the viruses can attack the stomach epithelial cells and multiply there. From there they get into the haemocoil (the mosquito's blood system) and on to the salivary glands . The next time the mosquito sucks blood, it injects its saliva into the wound, bringing the virus into the person's bloodstream. There is also evidence of a vertical infection of the yellow fever virus in A. aegypti , i.e. the transmission from the female mosquito to her clutch and thus the larvae. This infection of the vectors without a previous blood meal appears to play a role in individual, sudden outbreaks.

There are three epidemiologically distinguishable infection cycles in which the virus is transmitted from mosquitoes to humans or other primates. On the urban cycle , the yellow fever mosquito is involved, which is well adapted to large urban centers and there next to yellow fever and other diseases such as dengue and chikungunya transfers. The urban cycle is primarily responsible for major yellow fever outbreaks such as those occurring in Africa. With the exception of an outbreak in Bolivia in 1999, this urban cycle no longer exists in South America and is only observed in Africa.

In addition to the urban cycle, there is a silvatic cycle (forest cycle or jungle cycle) in both Africa and South America , in which Aedes africanus (in Africa) or mosquitoes of the genus Haemagoggus and Sabethes (in South America) serve as vectors. Mainly non-human primates are infected in the jungle. While the disease is mostly asymptomatic in these primates in Africa, it is often fatal in South America. In South America, the silvatic cycle is currently the only route of infection for humans, which explains, among other things, the lower incidence of yellow fever cases on this continent. People infected this way in the jungle can bring the virus to urban centers, where the yellow fever mosquito acts as a vector. Because of this silvatic cycle, yellow fever cannot be completely eradicated either.

In Africa there is a third infection cycle , also known as the savannah cycle or intermediate cycle , which occurs between the jungle and urban cycle. Different mosquito species of the genus Aedes are involved.

distribution

Risk of transmission of the yellow fever virus according to estimates by the CDC 2011
Endemic areas Africa:
AngolaAngola Angola
BeninBenin Benin
BurundiBurundi Burundi
CameroonCameroon Cameroon
Central African RepublicCentral African Republic Central African Republic
ChadChad Chad
Congo Democratic RepublicDemocratic Republic of Congo Democratic Republic of Congo
Congo RepublicRepublic of the Congo Republic of the Congo
Ivory CoastIvory Coast Ivory Coast
Equatorial GuineaEquatorial Guinea Equatorial Guinea
EthiopiaEthiopia Ethiopia
GabonGabon Gabon
GambiaGambia Gambia
GhanaGhana Ghana
Guinea-aGuinea Guinea
Guinea-BissauGuinea-Bissau Guinea-Bissau
KenyaKenya Kenya
LiberiaLiberia Liberia
MaliMali Mali
MauritaniaMauritania Mauritania
NigerNiger Niger
NigeriaNigeria Nigeria
RwandaRwanda Rwanda
SenegalSenegal Senegal
Sierra LeoneSierra Leone Sierra Leone
SudanSudan Sudan
South SudanSouth Sudan South Sudan
TogoTogo Togo
UgandaUganda Uganda
Lower risk Africa:
EritreaEritrea Eritrea
Sao Tome and PrincipeSao Tome and Principe Sao Tome and Principe
SomaliaSomalia Somalia
TanzaniaTanzania Tanzania
ZambiaZambia Zambia
Endemic areas of South America:
ArgentinaArgentina Argentina
BoliviaBolivia Bolivia
BrazilBrazil Brazil
ColombiaColombia Colombia
EcuadorEcuador Ecuador
French GuianaFrench Guiana French Guiana
GuyanaGuyana Guyana
PanamaPanama Panama
ParaguayParaguay Paraguay
PeruPeru Peru
SurinameSuriname Suriname
Trinidad and TobagoTrinidad and Tobago Trinidad and Tobago
VenezuelaVenezuela Venezuela

Yellow fever is found in tropical and subtropical areas in South America and Africa are endemic . Although the main vector - the yellow fever mosquito - is also found in Asia, the Pacific and the Middle East , yellow fever does not occur in these regions; the reason for this is unknown. There are approximately 600 million people in endemic areas worldwide , and WHO official estimates are 200,000 diseases and 30,000 deaths per year worldwide; the number of reported cases is far lower. An estimated 90% of infections occur on the African continent.

  • Transmission risk for yellow fever according to data from the CDC (2010)

  • Distribution of yellow fever in South America

  • Distribution of yellow fever in Africa

Phylogenetic analyzes identified seven genotypes of yellow fever viruses that are believed to be differently adapted to humans and to the yellow fever mosquito. Five genotypes occur exclusively in Africa, whereby it is assumed that the West Africa genotype I is particularly virulent or infectious, as it is often found in larger outbreaks of yellow fever. Two genotypes have been identified in South America.

Symptoms of illness

Yellow fever has an incubation period of three to six days, after which the fever suddenly rises to over 39 ° C (and sometimes over 40 ° C). Most cases are mild, the infection then only manifests itself in a brief febrile illness with headache , chills , back pain, loss of appetite, nausea and vomiting. In mild cases, the infection can subside after three to four days.

In about 15% of the cases a second phase of the disease manifests itself with a return of the fever, during which a short-term improvement of the state of health is possible. Similar to z. B. in typhus abdominalis a so-called "relative bradycardia " can be observed during this renewed increase in fever . Normally, if the core body temperature increases by 1 ° C, the heartbeat increases by about 10 beats per minute. The absence of this increase is known as the "Faget sign" in yellow fever.

The second phase is accompanied by jaundice due to liver damage and pain in the lower abdomen. As a sign of increased bleeding tendency and sensitivity of the capillaries , the phenomenon of the " Spanish flag " occurs when the skin is subjected to pressure . Bleeding of the oral mucosa, the conjunctiva and the nasal mucosa ( nosebleeds ) are characteristic. Massive bleeding in the gastrointestinal tract can lead to bloody stool and vomiting , whereby the blood is colored black from contact with stomach acid; hence the historical name "Vomito negro" ( black vomiting ) and the division into hemorrhagic fever . This second phase, also called the toxic phase , ends fatally in 20% of all cases. If the infection survives, there is lifelong immunity and there is usually no permanent organ damage.

Pathogenesis

An infection with the yellow fever virus primarily leads to damage to epithelial cells ( mucous membranes , blood vessels) and muscle cells of the heart . After the pathogen has been transmitted by a mosquito, the viruses initially multiply in lymph nodes and infect dendritic cells in particular . From there, the viruses spread via viraemia to the entire organism and thus also reach the liver. Here the viruses infect the liver cells , most likely indirectly via Kupffer cells , which leads to the eosinophilic degradation of these cells and the release of cytokines . The microscopically visible accumulations of pigment in Kupffer's cells in yellow fever are also known as “Villela corpuscles”. A fatal outcome is followed by cardiovascular shock and multiple organ failure with greatly increased cytokine levels (a so-called cytokine storm ). Histologically, eosinophilic inclusion bodies (" Councilman bodies ") are visible in liver cells , and occasionally inclusions in the cell nucleus (" Torres bodies ").

diagnosis

Yellow fever is mostly a clinical diagnosis , often based on the location of the sick person during the incubation period. Sporadic and only mild courses can only be reliably recognized by a virological examination. Since the mild course of regional outbreaks also play a major role and these patients also contribute to the spread of the virus, any fever with pain, nausea and vomiting that occurs within six to ten days at the most after leaving the endemic area is suspected of being yellow fever.

If an infection is suspected, the yellow fever virus can be detected up to about 6-10 days after the onset of the disease. This can be done by means of reverse transcriptase-polymerase chain reaction , in which the genetic material of the virus is multiplied and thus directly detected. The direct detection of the pathogen can also be carried out via virus isolation by culturing in cell culture, whereby this process can take one to four weeks. Both procedures are carried out with blood plasma (heparin blood ). Serologically , an enzyme-linked immunosorbent assay in the acute phase of the disease yellow fever specific IgM detected or an increase in specific IgG - titer detected compared to a preliminary test. Together with clear clinical symptoms, detection of IgM or a four-fold increase in IgG are considered reliable indicators. Since the serological test methods often cross-react with other flaviviruses, for example the dengue virus , these indirect methods are never proof of an infection.

The histological changes in the liver also occur in other viral, hemorrhagic virus infections with liver involvement, so they are not signs of disease. A post-mortem liver biopsy can confirm inclusion bodies and necrosis of hepatocytes and can be used to detect specific, viral antigen . Typical signs of inflammation are often missing in the histological picture, especially in the case of fulminant courses. Due to the increased tendency to bleed, a liver biopsy is not indicated in the patient and only serves to confirm the diagnosis after death.

The handling of all examination material of the patient, especially blood and biopsies, is subject to strict safety regulations and may only be carried out in laboratories of protection level 3 .

Differential diagnosis

Sudden fever with jaundice and bleeding tendencies with corresponding stay in the affected areas can be the beginning of a yellow fever infection in the differential diagnosis and to a malaria think. Other infections associated with jaundice must be ruled out, such as all classic viral hepatitis , leptospirosis or relapsing fever . Other viral infections with haemorrhagic fever must be differentiated, such as infection with Ebola virus , the Lassa virus , Marburg virus or Junin virus . The bleeding tendency (“Spanish flag” as a skin symptom) occurring very early in the course of the disease is more typical of yellow fever. Generalized, septic courses of herpes simplex infections or herpes B can show symptoms very similar to yellow fever. Non-infectious causes can also be associated with jaundice and an increased tendency to bleed, for example various forms of poisoning with substances that are toxic to the liver .

treatment

As for all diseases caused by flaviviruses , there is no causal therapy for yellow fever . If possible, you should be admitted to a hospital (hospitalization) and, due to the rapidly deteriorating condition of the disease in some cases, intensive medical supervision is advisable. Various methods for the acute treatment of the disease have shown little success in studies, so passive immunization after the onset of symptoms is likely to be ineffective. Also, ribavirin and other antiviral drugs showed just as treatments with interferons no positive effects in the yellow fever patients. Symptomatic treatment includes rehydration and drugs such as paracetamol to relieve pain. On acetylsalicylic acid (eg. As aspirin ) should be avoided due to its anticoagulant activity, as this in the case of internal bleeding, which can occur in yellow fever, is devastating.

prevention

Personal preventive measures against yellow fever include vaccination and avoiding mosquito bites in areas where yellow fever is endemic. Institutional measures to prevent yellow fever include vaccination programs and measures to control the disease-carrying mosquitoes.

vaccination

A vaccination involving injection of the vaccine into the deltoid muscle

When traveling to affected areas, a vaccination is strongly recommended, as non-native people who have traveled to the country are particularly affected by severe disease. The vaccination protection starts in 95% of the vaccinated after 10 days and lasts for life. The attenuated live vaccine (strain 17D) was isolated by Max Theiler in 1937 from a deceased patient from Ghana and is obtained by propagation in incubated chicken eggs . The WHO recommends that vaccination be carried out routinely in endemic areas between 9 and 12 months of age.

Quite often (in about 20% of all cases) the vaccination leads to mild, flu-like symptoms. Very rarely, in fewer than one case for every 200,000 to 300,000 vaccinations, YEL-AVD ( yellow fever vaccine-associated viscerotropic disease ) can occur, which leads to death in 60% of all cases. This is very likely due to a genetic defect in the immune system, but a 20-fold higher incidence rate has also been observed in certain vaccination campaigns . Age is a major risk factor; in children the complication rate is roughly one case in 10 million vaccine doses. A second serious side effect is an infection of the nervous system, a so-called YEL-AND ( yellow fever vaccine-associated neurotropic disease ). This complication can occur in one case for every 200,000 to 300,000 vaccinations, which can cause meningoencephalitis and lead to death in less than 5% of cases.

According to the manufacturer, the vaccine is not suitable for babies under six months of age, and according to the WHO, not under nine months. In people over 60 years of age, the indication for the first vaccination must be made strictly because of an increased risk of serious side effects . Pregnant women should only be given the vaccine after careful risk-benefit assessment, as no data on safety are available. Vaccination is contraindicated in immunosuppressed people; In the case of HIV infection, vaccination should only be carried out if the patient is immune. Furthermore, vaccination is not indicated in people with a thymic disease . Due to the manufacturing method, the live vaccine must not be inoculated in people who are allergic to egg white. Prior to the previous administration of immunoglobulins (passive vaccination), an interval of at least three months must generally be observed for vaccinations. Other live vaccines ( mumps , measles , rubella ) should be given either at the same time or four weeks apart. In order not to pass the vaccine virus on to the transfusion recipient, no blood should be donated after the vaccination (the recommended waiting time is 2 to 4 weeks). The yellow fever vaccination may only be administered by specially trained doctors (so-called “yellow fever vaccination center”). This is due to the danger of yellow fever, the previously very complicated handling of the vaccine and the will to be able to guarantee maximum safety for those affected. The executing authorities in Germany are the relevant ministries of the federal states .

Compulsory vaccination

Some countries in Asia are at least theoretically threatened by yellow fever (vector mosquitoes and infectable monkeys have been proven), without the disease occurring there so far. In order to avoid that the virus is introduced and can settle permanently, these and other countries require foreign visitors to be vaccinated beforehand if they have traveled through yellow fever areas (including transit ). It must be proven by a vaccination certificate, which becomes valid 10 days after the vaccination and is valid for life. A list of all countries that require yellow fever vaccination is published by the WHO. If the vaccination cannot be carried out for one of the reasons described above, an exemption from the obligation to vaccinate is possible. The vaccination exemption certificate required in this case is issued by a vaccination center recognized by the WHO.

Although 32 of the 44 countries where yellow fever is endemic have vaccination programs, in many of these countries less than 50% of all people are vaccinated.

Vector control

Information campaign on the prevention of dengue and yellow fever in Paraguay

In addition to vaccinations, the control of the yellow fever mosquito ( Aedes aegypti ) is of great importance, especially since the same mosquito can transmit other diseases such as dengue and chikungunya in addition to yellow fever . The yellow fever mosquito breeds preferentially in pools of water that were created by residents in areas with a precarious drinking water supply or that accumulate in household waste; especially in tires , but also in old cans and plastic containers. These conditions are particularly common near the urban centers of developing countries and form an excellent habitat for the yellow fever mosquito. Two strategies are followed in combating the mosquito:

On the one hand, measures are taken to kill the developing larvae. In addition to measures to reduce larval waters, larvicides , larva-eating fish and copepods are used, which directly reduce the number of larvae and thus indirectly the number of mosquitoes that transmit disease. In Vietnam, copepods of the genus Mesocyclops have been used to combat dengue fever for several years (yellow fever does not occur in Asia), and the implementation of the measures is checked monthly. As a result, there has been no case of dengue fever in the affected areas since 2001; a similar measure is likely to be effective against yellow fever because both measures target the same organism. Pyriproxyfen is mainly recommended as a chemical larvicide , as it is harmless to humans and is effective even in small amounts.

On the other hand, in addition to the larvae, the adult yellow fever mosquitoes are also combated. Curtains and covers of water tanks are treated with insecticide and insecticide can be sprayed in the interior, but this is not recommended by the WHO. As against the carrier of malaria , the Anopheles mosquito, mosquito nets treated with insecticide are also used successfully against yellow fever mosquitoes .

history

Carlos Finlay
Walter Reed

The evolutionary origins of the yellow fever virus are very likely in Africa. It is believed that the virus originally came from East or Central Africa and from there spread to West Africa. Both the yellow fever mosquito and the virus itself reached South America probably through shipping that started after 1492 . The first likely outbreak of the disease took place in 1648 in Yucatan , where the disease was known as xekik (black vomiting). At least 25 major outbreaks followed, for example in Philadelphia in 1793, in which several thousand people died and the American government, including then President George Washington, was forced to leave the city. Occasional outbreaks were also recorded in Europe, for example in Barcelona in 1821 with several thousand deaths. In 1878, 20,000 people died in an eruption in the Mississippi Valley, and the last outbreak in the United States occurred in New Orleans in 1905 .

As early as 1881, the Cuban doctor and scientist Carlos Juan Finlay put forward the hypothesis that mosquitoes transmit yellow fever. After the American invasion of Cuba in the 1890s had claimed 13 times as many deaths from yellow fever as from military operations, further experiments were carried out on the "mosquito hypothesis" and doctor Walter Reed proved that yellow fever was indeed transmitted by mosquitoes . In fact, as early as 1848, Josiah Clark Nott had published a remarkable article in which he wrote about yellow fever and "the reasons for the assumption that its cause is to be found in an insect life form". While Nott's arguments were still vague and imprecise , the discussion published by Louis Daniel Beauperthuy in 1853, in which he described yellow fever and other diseases as caused by mosquitos, could only be called explicit.

Yellow fever was thus the first virus that mosquito-borne transmission was proven. The American army doctor William C. Gorgas applied this knowledge consistently and thus achieved a complete elimination of yellow fever in Havana and was also able to successfully take action against yellow fever during the construction of the Panama Canal - after a French attempt to build the canal failed due to yellow fever and malaria, among other things .

In 1927 the yellow fever virus was isolated in West Africa ( Adrian Stokes succeeded in proving its transferability to monkeys), which led to the development of two vaccines against yellow fever in the 1930s. The vaccine 17D was around 1937 from which South Africa originating microbiologist Max Theiler developed at the Rockefeller Institute. He won the vaccine from chicken eggs and received the Nobel Prize in Medicine in 1951 for this achievement . A French research team developed the vaccine FNV ( french neurotropic vaccine ), which they obtained from the brains of mice - but since it was associated with a higher incidence of encephalitis in children, its use was no longer recommended from 1961. 17D, on the other hand, is still needed today and has so far delivered over 400 million individual doses. Since then, however, little has been invested in the development of new vaccines, which means that the technology, which is more than 60 years old, cannot adapt vaccine production quickly enough to the needs of a yellow fever outbreak. Newer vaccines based on Vero cells are in development and should replace the 17D vaccine in the future.

A policy of vector control and consistent vaccination programs brought the urban yellow fever cycle in South America under control and, apart from an urban outbreak in Santa Cruz de la Sierra ( Bolivia ), no yellow fever transmitted by the yellow fever mosquito has been detected since 1943 . Since the 1980s, however, the number of yellow fever cases in South America has increased again and the yellow fever mosquito has returned to the urban centers in South America, partly because the vector control programs have been abandoned again. Even if an urban cycle has not yet established itself, there are fears that this could take place again. When an outbreak in Paraguay in 2008 was originally feared it was an urban outbreak, this did not come true.

In Africa, on the other hand, vaccination programs were mostly carried out to eradicate the virus. However, this did not succeed because the silvatic cycle was retained. The disease began to spread again, especially after measures to combat yellow fever were abandoned and only a few countries included yellow fever vaccination in their regular vaccination program.

Potential biological weapon

Yellow fever has been studied as a potential biological weapon by various governments, including the US and possibly North Korean governments . The American government's program officially ended in 1969. During the Second World War , an attempt was made to vaccinate all American military personnel against yellow fever, as the Japanese army wanted to obtain yellow fever viruses in 1939, which the American secret services knew about. At this point in time, no yellow fever vaccine had been cleared by the FDA in the US and an unrecognized vaccine was being used, resulting in 330,000 people being infected with the hepatitis B virus (this is the largest outbreak of this) Viral disease at all). Furthermore, in 1975 a major WHO experiment in India, which was carried out with American money and in which the control of the yellow fever mosquito should have been investigated, was stopped by the Indian government because Indian scientists had feared that the American government was actually investigating the possibility of yellow fever as a to use biological weapon. It is also feared that terrorists could use the yellow fever virus as a biological weapon.

Reporting requirement

Yellow fever is notifiable in Austria in accordance with Section 1, Paragraph 1, Number 1 of the 1950 Epidemic Act in the event of suspicion, illness or death . Doctors and laboratories, among others, are obliged to report this ( Section 3 Epidemics Act).

In Switzerland there is an obligation to report clinical suspicion, death and positive and negative evidence of infection for the pathogen yellow fever virus by the attending physician or the examining laboratory. This results from the Epidemics Act (EpG) in conjunction with the Epidemics Ordinance and Annex 1 or Annex 3 of the Ordinance of the FDHA on the reporting of observations of communicable diseases in humans .

In Germany, yellow fever, according to § 6 Infection Protection Act (IfSG) on suspicion of a virus hemorrhagic fever conditional or according to § 7 IfSG upon detection of the pathogen yellow fever virus on the part of the physician or lab name reportable . It is primarily the heads of the laboratories that are required to report ( Section 8 IfSG).

literature

  • Yellow fever. Leaflet for doctors . Robert Koch Institute. As of October 29, 2010 .
  • Jari Vainio, Felicity Cutts: Yellow Fever ( Memento from 23 August 2000 in the Internet Archive ) (PDF, 86 pp., 400 kB), WHO, London School of Hygiene and Tropical Medicine, 1998.
  • W. Lang, Th. Löscher: Tropical medicine in clinic and practice. Thieme, Stuttgart 2000, ISBN 3-13-785803-8 , pp. 350-355.
  • Gordon C. Cook, Alimuddin I. Zumla (Eds.): Manson's Tropical Diseases. Saunders, London 2002, ISBN 0-7020-2640-9 , pp. 755-758.
  • Th. Mertens, O. Haller, H.-D. Klenk (Hrsg.): Diagnosis and therapy of viral diseases - guidelines of the society for virology. 2nd ed., Elsevier, Munich 2004, ISBN 3-437-21971-5 , pp. 77-82.
  • ED Barnett: Yellow fever: epidemiology and prevention. In: Clinical Infectious Diseases . Volume 44, Number 6, March 2007, pp. 850-856, ISSN  1537-6591 . doi: 10.1086 / 511869 , PMID 17304460 . (Review).
  • Paul de Kruif : Walter Reed. The scare away of yellow fever. In: Paul de Kruif: Microbe hunters. (Original edition: Microbe Hunters. Harcourt, Brace & Co., New York 1926) Orell Füssli Verlag, Zurich / Leipzig 1927; 8th edition, ibid. 1940, pp. 301–322.

Web links

Wiktionary: Yellow fever  - explanations of meanings, word origins, synonyms, translations
Commons : Yellow Fever  - Collection of pictures, videos and audio files

Individual evidence

  1. ↑ Michael BA Oldstone: Viruses, Plagues, and History , 1st edition. 2nd edition, Oxford University Press, 2000, ISBN 0-19-513422-2 , p. 45.
  2. ↑ a b c d e f Barrett AD, Higgs S: Yellow fever: a disease that has yet to be conquered . In: Annu. Rev. Entomol. . 52, 2007, pp. 209-229. doi : 10.1146 / annurev.ento.52.110405.091454 . PMID 16913829 .
  3. ↑ a b Sampath A, Padmanabhan R: Molecular targets for drug discovery flavivirus . In: Antiviral Research . 81, No. 1, January 2009, pp. 6-15. doi : 10.1016 / j.antiviral.2008.08.004 . PMID 18796313 .
  4. ^ D. Fontenille et al .: First evidence of natural vertical transmission of yellow fever virus in Aedes aegypti, its epidemic vector . Trans R Soc Trop Med Hyg. (1997) 91 (5): pp. 533-535 PMID 9463659
  5. ↑ Jentes ES. Poumerol G, Gershman MD, et al. The revised global yellow fever risk map and recommendations for vaccination, 2010: consensus of the Informal WHO Working Group on Geographic Risk for Yellow Fever. Lancet Infect Dis. 2011; 11: 622-32
  6. ↑ a b c d e f g h i j Tolle MA: Mosquito-borne diseases . In: Curr Probl Pediatr Adolesc Health Care . 39, No. 4, April 2009, pp. 97-140. doi : 10.1016 / j.cppeds.2009.01.001 . PMID 19327647 .
  7. ↑ a b WHO | Yellow fever . Retrieved August 13, 2009.
  8. ↑ RKI leaflet on yellow fever, accessed on March 15, 2015: http://www.rki.de/DE/Content/Infekt/EpidBull/Merkblaetter/Ratgeber_Gelbfieber.html
  9. ↑ Chastel C: Centenary of the discovery of yellow fever virus and its transmission by a mosquito (Cuba 1900-1901) . In: Bull Soc Pathol Exot . 96, No. 3, August 2003, pp. 250-6. PMID 14582304 .
  10. ↑ a b c d Monath TP: Treatment of yellow fever . In: Antiviral Res . 78, No. 1, April 2008, pp. 116-124. doi : 10.1016 / j.antiviral.2007.10.009 . PMID 18061688 .
  11. ↑ Susanne Modrow, Dietrich Falke, Uwe Truyen: Molecular Virology - An Introduction for Biologists and Physicians , 2nd Edition, Spektrum Akademischer Verlag, 2002, ISBN 3-8274-1086-X , p. 182.
  12. ↑ a b c d e Barrett AD, Teuwen DE: Yellow fever vaccine - how does it work and why do rare cases of serious adverse events take place? . In: Current Opinion in Immunology . 21, No. 3, June 2009, pp. 308-313. doi : 10.1016 / j.coi.2009.05.018 . PMID 19520559 .
  13. ↑ Yellow fever vaccination booster not needed . Retrieved June 7, 2013.
  14. ^ Supplementary information on vaccine safety . Archived from the original on April 26, 2003. Retrieved October 11, 2009.
  15. ^ Message from the Standing Vaccination Commission (STIKO) at the RKI: On side effects and isolated complications after yellow fever vaccination . In: Epidemiological Bulletin . No. 44 , 2001 ( rki.de [PDF; accessed on February 28, 2013]).
  16. ↑ Donating Blood: Eligibility Criteria by Topic . Retrieved February 28, 2013.
  17. ↑ BLOOD DONATION AFTER VACCINATION . Archived from the original on November 3, 2013. Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. Retrieved October 11, 2009. @1@ 2Template: Webachiv / IABot / www.reiseimpfungen-duesseldorf.de
  18. ↑ Dr. med. Frühwein.Retrieved August 8, 2017.
  19. ↑ List of all countries with WHO vaccination recommendations (PDF; 436 kB) Archived from the original on April 21, 2009. Retrieved on October 11, 2009.
  20. ^ Gould EA, de Lamballerie X, Zanotto PM, Holmes EC: Origins, evolution, and vector / host coadaptations within the genus Flavivirus . In: Advances in Virus Research . 59, 2003, pp. 277-314. PMID 14696332 .
  21. ↑ Yellow Fever Attacks Philadelphia, 1793 . In: EyeWitness to History . Retrieved August 14, 2009.
  22. ↑ Josiah Clark Nott: Yellow fever contrasted with bilious fever: reasons for believing it a disease sui generis - its mode of propagation - remote cause - probable insect or animalcular origin . In: New Orleans medical and surgical journal . 4, 1848, pp. 563-601.
  23. ^ Duration CC, Carrera GM: Carlos Finlay's Contribution to the Epidemiology of Yellow Fever . In: Yale J Biol Med . 9, No. 6, July 1937, pp. 584.1-588. PMC 2601738 (free full text).
  24. ↑ Borio L, Inglesby T, Peters CJ, et al. : Hemorrhagic fever viruses as biological weapons: medical and public health management . In: JAMA . 287, No. 18, May 2002, pp. 2391-2405. PMID 11988060 .
  25. ↑ Furmanski M: Unlicensed vaccines and bioweapon defense in World War II . In: JAMA . 282, No. 9, September 1999, p. 822. PMID 10478686 .
  26. ↑ Powell K, Jayaraman KS: Mosquito researchers deny plotting secret biowarfare test . In: Nature . 419, No. 6910, October 2002, p. 867. doi : 10.1038 / 419867a . PMID 12410269 .
  27. ↑ Narender K. Sehgal: Doubts over US in India . In: Nature . 251, September 20, 1974, p. 177.
  28. ^ Potential Biological Weapons Threats . Retrieved October 14, 2009.
This article was added to the list of excellent articles on October 23, 2009 in this version .