available. mosquito repellents containing permethrin are not approved for application directly to the skin. the peak biting times for many mosquito species are dusk to dawn. however, a. aegypti, one of the mosquitoes that transmits yellow fever virus, feeds during the daytime. staying in accommodations with screened or air-conditioned rooms, particularly during peak biting times, also reduces the risk of mosquito bites. vaccination the cover of a certificate that confirms the holder has been vaccinated against yellow fever vaccination against yellow fever 10 days before entering this country/territory is required for travellers coming from... all countries risk countries (including airport transfers) risk countries (excluding airport transfers) no requirement (risk country) no requirement (non-risk country) main article: yellow fever vaccine vaccination is recommended for those traveling to affected areas, because non-native people tend to develop more severe illness when infected. protection begins by the 10th day after vaccine administration in 95% of people, and had been reported to last for at least 10 years. the world health organization (who) now states that a single dose of vaccine is sufficient to confer lifelong immunity against yellow fever disease. the attenuated live vaccine stem 17d was developed in 1937 by max theiler. the who recommends routine vaccination for people living in affected areas between the 9th and 12th month after birth. up to one in four people experience fever, aches, and local soreness and redness at the site of injection. in rare cases (less than one in 200,000 to 300,000), the vaccination can cause yellow fever vaccine-associated viscerotropic disease, which is fatal in 60% of cases. it is probably due to the genetic morphology of the immune system. another possible side effect is an infection of the nervous system, which occurs in one in 200,000 to 300,000 cases, causing yellow fever vaccine-associated neurotropic disease, which can lead to meningoencephalitis and is fatal in less than 5% of cases. the yellow fever initiative, launched by the who in 2006, vaccinated more than 105 million people in 14 countries in west africa. no outbreaks were reported during 2015. the campaign was supported by the gavi alliance and governmental organizations in europe and africa. according to the who, mass vaccination cannot eliminate yellow fever because of the vast number of infected mosquitoes in urban areas of the target countries, but it will significantly reduce the number of people infected. demand for yellow fever vaccine has continued to increase due to the growing number of countries implementing yellow fever vaccination as part of their routine immunization programmes. recent upsurges in yellow fever outbreaks in angola (2015), the democratic republic of congo (2016), uganda (2016), and more recently in nigeria and brazil in 2017 have further increased demand, while straining global vaccine supply. therefore, to vaccinate susceptible populations in preventive mass immunization campaigns during outbreaks, fractional dosing of the vaccine is being considered as a dose-sparing strategy to maximize limited vaccine supplies. fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose, which has been reconstituted as per manufacturer recommendations. the first practical use of fractional dose yellow fever vaccination was in response to a large yellow fever outbreak in the democratic republic of the congo in mid-2016. available evidence shows that fractional dose yellow fever vaccination induces a level of immune response similar to that of the standard full dose. in march 2017, the who launched a vaccination campaign in brazil with 3.5 million doses from an emergency stockpile. in march 2017 the who recommended vaccination for travellers to certain parts of brazil. in march 2018, brazil shifted its policy and announced it planned to vaccinate all 77.5 million currently unvaccinated citizens by april 2019. compulsory vaccination some countries in asia are considered to be potentially in danger of yellow fever epidemics, as both mosquitoes with the capability to transmit yellow fever as well as susceptible monkeys are present. the disease does not yet occur in asia. to prevent introduction of the virus, some countries demand previous vaccination of foreign visitors who have passed through yellow fever areas. vaccination has to be proved by a vaccination certificate, which is valid 10 days after the vaccination and lasts for 10 years. although the who on 17 may 2013 advised that subsequent booster vaccinations are unnecessary, an older (than 10 years) certificate may not be acceptable at all border posts in all affected countries. a list of the countries that require yellow fever vaccination is published by the who. if the vaccination cannot be given for some reason, dispensation may be possible. in this case, an exemption certificate issued by a who-approved vaccination center is required. although 32 of 44 countries where yellow fever occurs endemically do have vaccination programmes, in many of these countries, less than 50% of their population is vaccinated. vector control information campaign for prevention of dengue and yellow fever in paraguay control of the yellow fever mosquito a. aegypti is of major importance, especially because the same mosquito can also transmit dengue fever and chikungunya disease. a. aegypti breeds preferentially in water, for example, in installations by inhabitants of areas with precarious drinking water supplies, or in domestic refuse, especially tires, cans, and plastic bottles. these conditions are common in urban areas in developing countries. two main strategies are employed to reduce a. aegypti populations. one approach is to kill the developing larvae. measures are taken to reduce the water accumulations in which the larvae develop. larvicides are used, along with larvae-eating fish and copepods, which reduce the number of larvae. for many years, copepods of the genus mesocyclops have been used in vietnam for preventing dengue fever. this eradicated the mosquito vector in several areas. similar efforts may prove effective against yellow fever. pyriproxyfen is recommended as a chemical larvicide, mainly because it is safe for humans and effective in small doses. the second strategy is to reduce populations of the adult yellow fever mosquito. lethal ovitraps can reduce aedes populations, using lesser amounts of pesticide because it targets the pest directly. curtains and lids of water tanks can be sprayed with insecticides, but application inside houses is not recommended by the who. insecticide-treated mosquito nets are effective, just as they are against the anopheles mosquito that carries malaria. treatment as with other flavivirus infections, no cure is known for yellow fever. hospitalization is advisable and intensive care may be necessary because of rapid deterioration in some cases. certain acute treatment methods lack efficacy: passive immunization after the emergence of symptoms is probably without effect; ribavirin and other antiviral drugs, as well as treatment with interferons, are ineffective in yellow fever patients. symptomatic treatment includes rehydration and pain relief with drugs such as paracetamol (acetaminophen). however, aspirin and other non-steroidal anti-inflammatory drugs (nsaids) are often avoided because of an increased risk of gastrointestinal bleeding due to their anticoagulant effects. epidemiology yellow fever is common in tropical and subtropical areas of south america and africa. worldwide, about 600 million people live in endemic areas. the who estimates 200,000 cases of yellow fever worldwide each year. about 15% of people infected with yellow fever progress to a severe form of the illness, and up to half of those will die, as there is no cure for yellow fever. africa areas with risk of yellow fever in africa (2017) an estimated 90% of yellow fever infections occur on the african continent. in 2016, a large outbreak originated in angola and spread to neighboring countries before being contained by a massive vaccination campaign. in march and april 2016, 11 imported cases of the angola genotype in unvaccinated chinese nationals were reported in china, the first appearance of the disease in asia in recorded history. phylogenetic analysis has identified seven genotypes of yellow fever viruses, and they are assumed to be differently adapted to humans and to the vector a. aegypti. five genotypes (angola, central/east africa, east africa, west africa i, and west africa ii) occur only in africa. west africa genotype i is found in nigeria and the surrounding region. west africa genotype i appears to be especially infectious, as it is often associated with major outbreaks. the three genotypes found outside of nigeria and angola occur in areas where outbreaks are rare. two outbreaks, in kenya (1992–1993) and sudan (2003 and 2005), involved the east african genotype, which had remained undetected in the previous 40 years. south america areas with risk of yellow fever in south america (2018) in south america, two genotypes have been identified (south american genotypes i and ii). based on phylogenetic analysis these two genotypes appear to have originated in west africa and were first introduced into brazil. the date of introduction of the predecessor african genotype which gave rise to the south american genotypes appears to be 1822 (95% confidence interval 1701 to 1911). the historical record shows an outbreak of yellow fever occurred in recife, brazil, between 1685 and 1690. the disease seems to have disappeared, with the next outbreak occurring in 1849. it was likely introduced with the trafficking of slaves through the slave trade from africa. genotype i has been divided into five subclades, a through e. in late 2016, a large outbreak began in minas gerais state of brazil that was characterized as a sylvan or jungle epizootic. it began as an outbreak in brown howler monkeys, which serve as a sentinel species for yellow fever, that then spread to men working in the jungle. no cases had been transmitted between humans by the a. aegypti mosquito, which can sustain urban outbreaks that can spread rapidly. in april 2017, the sylvan outbreak continued moving toward the brazilian coast, where most people were unvaccinated. by the end of may the outbreak appeared to be declining after more than 3,000 suspected cases, 758 confirmed and 264 deaths confirmed to be yellow fever. the health ministry launched a vaccination campaign and was concerned about spread during the carnival season in february and march. the cdc issued a level 2 alert (practice enhanced precautions.) a bayesian analysis of genotypes i and ii has shown that genotype i accounts for virtually all the current infections in brazil, colombia, venezuela, and trinidad and tobago, while genotype ii accounted for all cases in peru. genotype i originated in the northern brazilian region around 1908 (95% highest posterior density interval : 1870–1936). genotype ii originated in peru in 1920 (95% hpd: 1867–1958). the estimated rate of mutation for both genotypes was about 5 × 10−4 substitutions/site/year, similar to that of other rna viruses. asia the main vector (a. aegypti) also occurs in tropical and subtropical regions of asia, the pacific, and australia, but yellow fever has never occurred there, until jet travel introduced 11 cases from the 2016 angola and dr congo yellow fever outbreak in africa. proposed explanations include: that the strains of the mosquito in the east are less able to transmit yellow fever virus. that immunity is present in the populations because of other diseases caused by related viruses (for example, dengue). that the disease was never introduced because the shipping trade was insufficient. but none is considered satisfactory. another proposal is the absence of a slave trade to asia on the scale of that to the americas. the trans-atlantic slave trade probably introduced yellow fever into the western hemisphere from africa. history early history the evolutionary origins of yellow fever most likely lie in africa, with transmission of the disease from nonhuman primates to humans. the virus is thought to have originated in east or central africa and spread from there to west africa. as it was endemic in africa, local populations had developed some immunity to it. when an outbreak of yellow fever would occur in an african community where colonists resided, most europeans died, while the indigenous africans usually developed nonlethal symptoms resembling influenza. this phenomenon, in which certain populations develop immunity to yellow fever due to prolonged exposure in their childhood, is known as acquired immunity. the virus, as well as the vector a. aegypti, were probably transferred to north and south america with the trafficking of slaves from africa, part of the columbian exchange following european exploration and colonization. however, some researchers have argued that yellow fever might have existed in the americas during the pre-columbian period as mosquitoes of