Zika virus disease treatment protocol (version 1, 2016)

Zika virus disease is a self-limiting acute infectious disease caused by Zika virus and is transmitted mainly by the bite of Aedes aegypti mosquito. Clinical features are mainly fever, rash, arthralgia or conjunctivitis, and rarely cause death. The World Health Organization (WHO) believes that microcephaly and Guillain-Barré syndrome (GBS) in newborns may be associated with Zika virus infection.
  Zika virus disease is predominantly endemic in tropical and subtropical regions of the world. 1952, the virus was isolated from humans in Uganda and Tanzania. Since then, disseminated cases have been reported in several countries, and the first outbreak of Zika virus occurred in 2007 on the island of Yap in the Western Pacific country of Micronesia. As of January 2016, there is evidence of Zika virus transmission in at least 45 countries in Africa, Asia, and the Americas, with the most severe outbreak in Brazil.
  I. Pathogenesis
  Zika virus is a mosquito-borne virus that was first identified in rhesus monkeys in Uganda in 1947. It belongs to the genus Flavivirus of the family Flaviviridae, and is a single-stranded positive-stranded RNA virus with a diameter of 40-70 nm and an envelope, containing 10,794 nucleotides and encoding 3419 amino acids. According to the genotype, it is divided into African type and Asian type, and the epidemic in America is the Asian type.
  The resistance of Zika virus is unknown, but the virus of the genus Flavivirus is generally not acid-resistant, heat-resistant. 60 ℃ 30 minutes can be inactivated, 70% ethanol, 1% sodium hypochlorite, lipid solvents, peroxyacetic acid and other disinfectants and ultraviolet radiation can be inactivated.
  II. Epidemiological characteristics
  (A) Source of infection
  Patients, latently infected persons and non-human primates infected with Zika virus are the possible sources of infection of the disease.
  (B) transmission route
  The bite of the virus-bearing Aedes aegypti mosquito is the main mode of transmission of the disease. The vector is mainly Aedes aegypti, Aedes albopictus, Aedes africanus and Aedes aegypti may also transmit the virus. It can also be transmitted from mother to child, including intrauterine infection and infection during delivery. Zika virus nucleic acid can be detected in breast milk, but there have been no reports of infection of newborns through breastfeeding. Blood-borne transmission and sexual transmission are rare.
  According to monitoring, Aedes aegypti and Aedes albopictus are the main species of mosquitoes associated with the transmission of Zika virus in China, with Aedes aegypti mainly distributed in Hainan Province, Leizhou Peninsula in Guangdong Province and Xishuangbanna Prefecture, Dehong Prefecture, Lincang City and other areas in Yunnan Province; Aedes albopictus is widely distributed in Hebei, Shanxi and Shaanxi south of China.
  (C) crowd susceptibility
  The population is generally susceptible. People who have been infected with Zika virus may have immunity to re-infection.
  III. Clinical manifestations
  The incubation period of Zika virus disease is still unknown, and the available information shows that it is 3-12 days. Only 20% of people infected with Zika virus develop symptoms, and the symptoms are mild, mainly manifested by fever (mostly low to moderate fever), rash (mostly maculopapular rash), and may be accompanied by non-purulent conjunctivitis, muscle and joint pain, general malaise, and headache, and a few patients may develop abdominal pain, nausea, diarrhea, mucosal ulcers, and pruritus of the skin. The symptoms last for 2-7 days and have a good prognosis; severe illness and death are rare.
  Pediatric cases of infection may also present with neurological, ocular, and hearing changes. Zika virus infection in pregnant women may lead to microcephaly and even fetal death in newborns.
  Cases of Guillain-Barre syndrome (GBS) associated with Zika virus infection have been reported, but the causal relationship between the two is not clear.
  IV. Laboratory tests
  (A) General examination
  Routine blood tests: some cases may have leukocytopenia and thrombocytopenia.
  (B) Serological tests
  1, Zika virus IgM detection: using enzyme-linked immunosorbent assay (ELISA), immunofluorescence method for detection.
  2, Zika virus neutralizing antibody detection: the use of empty spot reduction neutralization test (PRNT) to detect blood neutralizing antibody. Should try to collect the acute phase and recovery period double serum to carry out testing.
  Zika virus antibodies have strong cross-reactivity with dengue virus, yellow fever virus and West Nile virus antibodies of the same genus of flavivirus, which are easy to produce false positives and should be distinguished in the diagnosis.
  (C) Pathogenetic examination
  1, virus nucleic acid detection: the use of fluorescent quantitative RT-PCR detection of Zika virus.
  2, virus antigen detection: the use of immunohistochemical method to detect Zika virus antigen.
  3, virus isolation culture: specimens can be inoculated in mosquito-derived cells (C6/36) or mammalian cells (Vero) and other methods for isolation and culture, and can also be used for virus isolation by inoculation in the brain of mammary rats.
  V. Diagnosis and differential diagnosis
  (A) Diagnosis basis
  Based on epidemiological history, clinical manifestations and relevant laboratory tests.
  (B) Case definition
  1.Suspected cases: consistent with the epidemiological history and have corresponding clinical manifestations.
  (1) epidemiological history: travel or residence in areas where Zika virus infection cases are reported or endemic within 14 days before the onset of the disease.
  (2) clinical manifestations: fever, rash, arthralgia or conjunctivitis that are difficult to explain by other causes.
  2, clinical diagnosis of cases: suspected cases and positive Zika virus IgM antibody test.
  3.Confirmed cases: suspected cases or clinically diagnosed cases with laboratory tests that meet one of the following conditions.
  (1) Zika virus nucleic acid test positive.
  (2) isolation of Zika virus.
  (3) recovery period serum Zika virus neutralizing antibody positive or titer than the acute period is more than four times higher, while excluding dengue, B brain and other common flavivirus infection.
  (C) Differential diagnosis
  Differential diagnosis is required with the following diseases.
  1, mainly with dengue fever and chikungunya fever for differential diagnosis.
  2. Other: Differentiate from microviruses, rubella, measles, enterovirus, rickettsial disease, etc.
  VI. Treatment
  Zika virus disease usually has mild symptoms and does not require special treatment, mainly symptomatic treatment with antipyretic and analgesic drugs as appropriate. Avoid treatment with non-steroidal anti-inflammatory drugs such as aspirin until dengue fever is ruled out.
  Patients with unrelenting high fever may be treated with antipyretic and analgesic drugs such as paracetamol, 250-500mg/dose 3-4 times daily for adults and 10-15mg/kg/dose for children, at intervals of 4-6 hours, no more than 4 times in 24 hours. Patients with arthralgia may use ibuprofen at 200-400mg/dose 4-6 hours for adults and 5-10mg/kg/dose 3 times a day for children. In the presence of conjunctivitis, recombinant human interferon alfa eye drops may be used 1-2 drops/dose 4 times daily.
  Effective anti-mosquito isolation measures should be implemented within the first week of patient onset. For pregnant women infected with Zika virus, monitoring of fetal growth and development every 3-4 weeks is recommended.
  VII. Prevention
  There is no vaccine available for prevention, and the best form of prevention is to prevent mosquito bites. Women preparing for pregnancy and during pregnancy are advised to travel with caution to areas where Zika virus is endemic.