Technical Guidelines for Yellow Fever Prevention and Control

Yellow fever (yellow fever) is an acute infectious disease caused by yellow fever virus, transmitted by mosquitoes, belonging to one of the international quarantine infectious diseases. Clinical manifestations are mainly fever, yellow stain, hemorrhage, etc. In some outbreaks, the death rate can be as high as 20%-40%. The disease is prevalent mainly in the tropical areas of Central and South America and Africa, and the natural infection cycle occurs periodically between mosquitoes and non-human primates. I. Disease Overview (a) Pathogenesis. Yellow fever virus (yellow fever virus) belongs to the yellow virus family (Flaviviridae) of the genus Flavivirus (Flavivirus), the virus particles are spherical, 37-50 nm in diameter, outside the lipid envelope, the surface of the spines. The viral genome is a single-stranded positive-stranded RNA without segmentation, consisting of about 11,000 nucleotides, with a molecular weight of about 3.8×106. There is only one serotype of yellow fever virus. The virus can cross-serologically react with other members of the Flaviviridae family such as dengue virus, West Nile virus, and St. Louis encephalitis virus. Yellow fever viruses are endophilic (humans and primates) and neurophilic (mice). An attenuated strain capable of being used as a vaccine is obtained by multiple passages of chicken embryos. 1936, a live attenuated yellow fever 17D vaccine was produced by successive passages of chicken embryos, and is used to this day to routinely immunize infants up to 9 months of age in many yellow fever-endemic countries. Each year in the United States, 250,000 travelers and military personnel going to tropical areas are vaccinated against yellow fever to prevent the disease. In recent years, however, it has been found that the yellow fever vaccine may cause infections and lesions in certain vital organs, especially in vaccinees over the age of 60 years, at a rate of up to 1/50,000, and is therefore recommended only for people traveling to endemic countries who are at real risk of exposure. The virus is weak and susceptible to rapid inactivation by heat, ether, sodium deoxycholate, and commonly used disinfectants, and survives for several months in 50% glycerol solution and remains viable for many years when lyophilized. (ii) Epidemiology. 1, the source of infection The main source of infection of the urban type is the patient and the hidden infected, especially the patients within 4 days of the onset of the disease. The main sources of the jungle type are monkeys and other primates, and the virus can be isolated in the blood of infected animals. Yellow fever hidden infection and light cases are far more than severe patients, these cases play an extremely important role in the spread of the disease. 2, the transmission pathway The disease is transmitted through mosquito bites. Urban type to Aedes aegypti mosquitoes as the only vector, to people – Aedes aegypti mosquitoes – the way the epidemic. Jungle-type vector mosquito species are more complex, including Aedes aegypti, Simpson aegypti, blood mosquitoes (Hemagogus), brake mosquitoes (Sabethes), etc., to monkeys – Aedes aegypti or blood mosquitoes, etc. – monkeys in the way of the cycle. People are infected by going into the jungle to work. Mosquitoes sucking the blood of patients or sick monkeys after 9-12 days is infectious, can carry the virus for life and can be transmitted through the egg. People are generally susceptible to yellow fever virus. In the city type because most of the adults due to infection and immunity, so the patient to children. In the jungle type, most patients are adult males. After infection can obtain lasting immunity, not found to have re-infection. 4, geography and seasonal distribution of yellow fever is mainly prevalent in South America, Central America and Africa and other tropical regions, tropical countries in Asia also have distribution. China’s geography, climate, and mosquitoes, monkeys and other vectors and animal conditions are similar to the above areas, but so far there is no epidemic or confirmed cases of the disease reported. Yellow fever can be categorized into urban and jungle types. The disease can occur throughout the year, more cases in March-April. Second, the clinical manifestations of the incubation period is generally 3-6 days. The clinical manifestations of the disease vary greatly, and the condition can range from mildly self-limiting to lethal infection. The typical clinical course can be divided into the following 4 periods. (i) Viremia stage. Acute onset with chills and fever up to 39-40°C with relatively slow pulse. Severe headache, backache, generalized muscle pain, nausea and vomiting. Conjunctival and facial congestion, epistaxis. Proteinuria may be present. Symptoms last for 3-5 days. (ii) Period of remission. A 12-24 hour remission period occurs 3-5 days after the onset of the infectious phase and is characterized by a drop in temperature, disappearance of headache, and improvement in the general basic condition of the body. The virus is cleared from the body in this period and non-infectious immune complexes can be detected in the blood. Mild patients can be cured in this period. (iii) Liver and kidney damage period. This period lasts for 3-8 days, and about 15-25% of patients enter this period after remission. Body temperature rises again, systemic symptoms reappear, frequent vomiting, epigastric pain, etc. Jaundice appears and gradually deepens. Jaundice appears and gradually deepens, bleeding manifestations such as petechiae, ecchymosis, epistaxis, extensive bleeding from mucous membranes, and even cavernous hemorrhage. Renal function is abnormal with decreased urine output and proteinuria. Cardiac damage electrocardiogram shows ST-T segment abnormalities, and acute myocardial dilatation may occur in a few cases. Cerebral edema may occur, cerebrospinal fluid protein is elevated but not white blood cells. Hypertension, tachycardia, shock, and intractable eructation suggest a poor prognosis. About 20-50% of patients in this phase die 7-10 days after the onset of the disease. (iv) Recovery phase. This phase is characterized by extreme fatigue and weakness and may last for 2-4 weeks. Patients have also been reported to die during the recovery phase, partly due to cardiac arrhythmias. Elevated aminotransferases may persist for months after recovery. There are usually no sequelae. III.DIAGNOSIS, REPORTING AND TREATMENT There is no specific treatment for this disease, and symptomatic or supportive therapy is generally the mainstay. Medical institutions should do a good job of diagnosis and treatment in accordance with the Diagnosis and Treatment Program of Yellow Fever. When medical and health institutions at all levels find suspected or confirmed cases in line with the definition of cases, they should refer to the reporting requirements of Class A infectious diseases and report directly through the National Disease Surveillance Information Reporting Management System, and select “other infectious diseases” as the reporting disease category. If it meets the requirements of the “National Public Health Emergency Information Reporting Management Standards (Trial)”, it will be reported according to the corresponding regulations. Laboratory tests: The patient’s serum specific IgM antibody is positive, the recovery serum specific IgG antibody titer is more than 4 times higher than that of the acute stage, the patient’s specimen is positive for viral antigen, yellow fever virus RNA is positive, and yellow fever virus is isolated, all of which can confirm the diagnosis. (i) Serologic testing. Because of the antigenic crossover between flaviviruses, appropriate controls should be set up when performing serologic tests, and the results should be interpreted with caution. 1.Serum specific IgM antibody: ELISA, immunofluorescence and other methods are used to detect, and the results of capture method for IgM antibody are more reliable. Generally, IgM antibodies appear on the 5th-7th day after the onset of disease. 2.Serum specific IgG antibody: ELISA, immunofluorescence antibody determination, immunochromatography and other methods are used for detection. Serum IgG antibody titer in the recovery period of the patient is more than 4 times higher than that in the acute period, and the diagnosis can be confirmed. (ii) Pathologic examination. 1, antigen detection: due to the high titer of virus in the blood of yellow fever patients in the early stage, the diagnosis can be made by detecting viral antigen. Antigen detection methods are less sensitive than virus isolation, but require less time. The use of yellow fever virus-specific monoclonal antibodies to detect viral antigen can avoid cross-reactivity with other flaviviruses. 2. Nucleic acid detection: Apply RT-PCR, Real-Time PCR and other nucleic acid amplification techniques to detect yellow fever virus RNA, which are highly specific and sensitive, and can be used for early diagnosis. 3.Virus isolation: virus can be isolated from serum, whole blood or liver tissue of dead cases within 4 days of onset. The virus can be isolated by intracerebral inoculation of neonatal suckling rats or sensitive cell culture such as Vero cells and C6/36 cells. For patients before jaundice, blood specimens should be taken early for virus isolation and antigen and nucleic acid detection, and virus-specific antibodies should be mainly detected in the later stage. V. Preventive and control measures 1, to travel to the infected area of the personnel to carry out immunoprophylaxis and travel health knowledge mission Yellow fever can be prevented by vaccine. Vaccination with vaccine prepared by attenuated yellow fever virus strain 17D can effectively prevent yellow fever virus infection. Antibodies appear 7-10 days after vaccination and persist for at least 30-35 years. Active immunization is recommended for all persons 9 months of age and older at real risk of exposure who reside or travel to infected areas. Educate travelers to yellow fever infected areas to raise their awareness of precautionary measures and take anti-mosquito measures such as mosquito repellent and long-sleeved clothing to prevent infection and importation of yellow fever outside of the country, and to take the initiative to seek medical attention and inform their doctors of their travel history in the event of suspicious symptoms. 2, strengthen the border health quarantine, strictly prevent the importation of the disease The entry of people from endemic areas to strengthen the health quarantine, from the infected area must be presented with a valid certificate of vaccination. Once the quarantine department at the port finds a suspected case, it should inform the health department in time to do a good job of investigating and dealing with the epidemic. 3, do a good job of reporting and management of cases of medical institutions at all levels found suspected cases of yellow fever should be reported in a timely manner, so that the health administration and disease control departments as soon as possible to grasp the situation and take the necessary preventive and control measures, and suspected and confirmed cases of isolation and treatment, avoid contact with the patient’s blood and body fluids. Insecticide spraying and the use of mosquito nets are used in wards to prevent mosquito bites. Disease control departments should carry out epidemiological investigations on the source of infection of cases in a timely manner to search for cases and assess the risk of spread of the epidemic. 4, carry out emergency control of mosquito vectors The same as other mosquito-borne infectious diseases, reduce the density of mosquitoes is a key measure to control the epidemic. Once a case report is found, measures such as eliminating mosquito breeding sites and killing adult mosquitoes should be taken immediately to control the density of the vector and prevent the spread of the disease from occurring. 5, improve yellow fever detection and response capacity It is recommended to have the conditions of the provincial CDC and port city of the CDC to establish laboratory testing techniques and methods, and do a good job of technology and reagent reserves. Local health departments should organize and issue the relevant technical guidelines of the country to improve the detection and recognition ability of medical personnel on yellow fever, and improve the epidemiological investigation and outbreak handling ability of CDC personnel.