1. What is measles?
Measles is one of the most common acute respiratory infections in children. It is highly contagious and is prone to epidemics in densely populated areas without universal vaccination. Clinically, it is characterized by fever, inflammation of the upper respiratory tract, conjunctivitis, etc., while red papules on the skin and mucous membrane spots on the cheek mucosa and pigmentation with bran-like desquamation remain after the rash recedes. Since 1965, China began the generalization of live attenuated measles vaccine has controlled the pandemic.
2, antigenicity
Measles virus (measles virus) is the causative agent of measles, classified as belonging to the paramyxovirus family measles virus genus. Measles is an acute infectious disease common in children, which is highly contagious and characterized by papular rash, fever and respiratory symptoms. If there are no complications, the healing process is good. Since the application of live attenuated vaccine in China in the early 1960s, the incidence in children has decreased significantly. However, it is still a major cause of death in children in developing countries. After the extinction of smallpox, WHO has listed measles as one of the infectious diseases planned for eradication. In addition, subacute sclerosing panencephalitis (SSPE) was found to be associated with measles virus. The measles virus is only 100-250 nm in diameter (1 nm = 0.000001 mm). It is not considered very resistant in the external environment and is not resistant to dryness, sunlight, heat and general disinfectants. In the sun or air circulation environment in half an hour to lose vitality; at room temperature only survived 2 hours, 56 ℃ when 30 minutes will be destroyed. Can withstand cold and not afraid of freezing, 4 ℃ can survive for 5 months, -15 ℃ can survive for 5 years. So it always comes out in winter and spring. Measles virus antigenicity is more stable, with only one serotype, but recent studies have proven that there are also small variations in measles virus antigens. Depending on the nucleotide sequence, epidemic strains around the world can be divided into 8 different genomes and 15 genotypes.
3.Resistance
Virus resistance is weak, heating 56 ℃ for 30 minutes and general disinfectants can make it inactivate, sensitive to sunlight and ultraviolet light.
4.Pathogenicity
The only natural reservoir host of measles virus is human. Patients in the acute phase are the source of infection, and patients are infectious from 6 days before to 3 days after the rash. It is spread by droplets, but can also be spread by utensils, toys or close contact. Measles is highly contagious and almost all susceptible persons develop the disease after contact. The incubation period for the onset of the disease is 9 to 12 days. Since CD46 is the receptor for measles virus, most tissue cells with CD46 can be the target cells for measles virus infection. The virus entering via the respiratory tract first binds to and proliferates in the respiratory epithelial cell receptors, then invades the lymph nodes to proliferate, and then enters the bloodstream (where it proliferates well in the leukocytes) to form the first viraemia. The virus reaches the lymphoid tissues throughout the body and proliferates again into the blood, forming the second viremia. At this point, fever begins, followed by upper respiratory tract cicatrization due to virus proliferation in the conjunctiva, nasopharyngeal mucosa, and respiratory tract mucosa. The virus also proliferates in the dermis, and Koplik’s spots with a gray center and red periphery appear on the inner mucosa of the oral cavity. Generally, 24 hours after the rash appears, the body temperature begins to drop, the respiratory symptoms subside in about a week, and the rash becomes dark and pigmented. Some young and frail children are prone to bacterial infections, such as secondary bronchitis, otitis media, and especially to bacterial pneumonia, which is the main cause of death in children with measles. Encephalomyelitis occurs in about 0.1% of patients, and is a delayed hypersensitivity disease that often occurs after 1 week of recovery, showing typical demyelinating pathological changes and marked lymphocytic infiltration, often with permanent sequelae and a 15% mortality rate. Immunodeficient children infected with measles virus often have no rash, but can develop severe fatal measles giant cell pneumonia. Subacute sclerosing panencephalitis (SSPE) is a late complication of acute infection that manifests as progressive brain decline and death within 1 to 2 years. It has been found that although highly effective IgG or IgM anti-measles virus antibodies are present in the serum and cerebrospinal fluid of patients, it is difficult to isolate measles virus with these antibodies. It is now believed that the virus in the brain tissue is a measles-deficient virus that lacks the ability to synthesize measles virus M protein due to mutations in the viral M gene within the brain cells, thereby affecting the assembly, outgrowth, and release of the virus. Therefore, co-culture of SSPE autopsy brain tissue cells with cells sensitive to measles virus (e.g. HeLa, Vero, etc.) can isolate measles virus.
5. Microbiological examination method
Typical measles cases do not require laboratory tests and can be diagnosed based on clinical symptoms. For mild cases and atypical cases, microbiological examination is required to confirm the diagnosis. Because of the complex and time-consuming method of virus isolation and identification, which takes at least 2 to 3 weeks, serological diagnosis is mostly used.
(1) Virus isolation
Blood, pharyngeal washings or pharyngeal swabs from the early stage of the disease are taken from patients and treated with antibiotics, then inoculated in human embryonic kidney, monkey kidney or human amniotic cells for culture. The virus proliferates slowly and after 7-10 d typical CPE can appear, i.e., multinucleated giant cells, intracellular and intra-nuclear eosinophilic inclusion bodies, and then confirm the measles virus antigen in the inoculated culture by immunofluorescence technique.
(2) Serological diagnosis
Duplex sera are taken from patients in the acute and recovery phases, and HI tests are often performed to detect specific antibodies, or CF tests or neutralization tests may be used. When the antibody titer is increased more than 4 times, it can assist in clinical diagnosis. In addition, IgM antibody can also be detected by indirect fluorescent antibody method or ELISA.
(3) Rapid diagnosis
The mucosal cells in the pharyngeal gargle of the patient’s khat phase are examined for the presence of measles virus antigens using fluorescent labeled antibodies. The nucleic acid molecular hybridization technique can also be used to detect intracellular viral nucleic acids.
6. Transmission characteristics
Anyone who has not had measles and has not been vaccinated against measles (susceptible population) will be infected if they meet with a patient who is suffering from measles. The measles virus is spread by droplets in the secretions of a measles patient’s eyes, nose, mouth, throat, and trachea, through sneezing, coughing, and talking. It is extremely contagious, and more than 90% of susceptible people are sick after contact, so the measles virus is nicknamed “meet and greet”. In the past, an epidemic outbreak every 2 to 3 years was almost inevitable.
7, measles staging
(1) the incubation period is generally 10 to 14 days, but also as short as about 1 week. That is the rapid multiplication of measles virus in the local mucous membrane of the nasopharynx, while a small amount of virus invades the blood; there may be a mild increase in body temperature during the incubation period.
(2) The prodromal period, also known as the pre-rash period, is actually the stage when a large amount of measles virus enters the bloodstream, usually for 3 to 4 days. Patients show symptoms similar to those of upper respiratory tract infection: fever above moderate, cough, runny nose, lacrimation, other symptoms such as pharyngeal congestion, and special symptoms of the eyes: conjunctival inflammation, eyelid edema, teary eyes, shyness and photophobia, and an obvious congested horizontal line at the edge of the lower eyelid, plus small grayish-white dots on the buccal mucosa of the oral cavity about 1.0 mm in diameter, with a red halo of Koch’s (Koplik) spots outside, for early The identification of measles virus is very beneficial, but unfortunately often overlooked by physicians; it is most contagious at this time. Chen Jiquan, Department of Respiratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
(3) Rash stage
Mostly in 3-4 days after the onset of fever, the body temperature may suddenly rise to 40℃～40.5℃ and a rash appears, with red papules starting behind the ears and neck, developing downward within 24 hours, spreading over the face, trunk and upper limbs, with the rash involving the lower limbs and feet on the third day. This is the stage of immune warfare between measles virus and human body. High fever can lead to delirium, agitation and drowsiness in children, mostly transient, which disappears after the fever subsides.
(4) Recovery period
Three to four days after the rash appears, the rash begins to recede in the same order as when the rash appeared; in the absence of comorbidities, other symptoms such as appetite and mental health also improve. After the rash recedes, the skin is left with bran-like flaking and brown pigmentation, which heals in 7 to 10 days.
8, immune
Measles disease after the body can obtain lifelong immunity, including mainly humoral immunity and cellular immunity, cellular immunity plays a major role. Both anti-HA and HL antibodies produced after infection have a neutralizing effect on the virus, and HL antibodies can also prevent the spread of the virus between cells, with IgM predominating at the beginning of infection and IgG1 and IgG4 predominating later. Cellular immunity has a strong protective effect, such as immunoglobulin-deficient people with measles can heal and resist reinfection; while cellular immunity deficient people infected with measles is extremely serious, which indicates that cellular immunity plays a leading role in the recovery of the body. At the beginning of the rash, specific killer T cells can be detected in the peripheral blood. 6 months of age, infants are less susceptible to infection because of IgG antibodies obtained from the mother, but as they grow older, antibodies gradually disappear, autoimmunity is not yet complete, and susceptibility increases. Therefore, measles is most often seen in infants and children between the ages of 6 months and 5 years.
Generally speaking, the measles virus cannot defeat the body’s immune system and most of them end up in defeat, and the immunity gained by the body is enough to keep the measles virus at bay for life.
The measles virus kills sick children with the help of secondary pneumonia, laryngitis, and myocarditis, which are accomplices. Every time the measles virus plays a leading role, desperately fighting, although defeated, the human immune army is also greatly damaged, when the measles virus accomplices swarmed, sick children are often pneumonia and laryngitis after measles to take their lives.
9, the principles of prevention and control.
The main measures to prevent measles is to isolate patients; artificial active immunization of children to improve the immunity of the body.
(1) The current widespread implementation of live attenuated measles vaccination at home and abroad, so that the incidence of measles has dropped significantly. Measles vaccine, the full name is called live attenuated measles vaccine. China since 1965, the start of universal live attenuated measles vaccine, has controlled the pandemic. However, over the years, it has been observed that the measles vaccine is not perfect and the immunity it produces does not last a lifetime, while the use of the vaccine by humans is very irregular and many people are unaware of the need for booster immunization. Planned immunization requires that the measles vaccine be given at the beginning of the 8th month, repeated at the age of 1.5 years, and again at the age of 6 to 7 years. But many people just forget about the second and third booster. That means the measles virus still has a chance to take advantage of it. Those children who missed the vaccination are still the target of measles virus attacks.
Just because immunity is different after the natural occurrence of measles and after vaccination, young and middle-aged people who are currently 30 to 40 years old are those who received immunity from vaccination that year and have not had measles. Their immunity has been depleted year by year and does not play a protective role, which then becomes the target of the measles virus. Certain large cities in recent years, adults have accounted for 50% or even 60% of the measles patients; and the seriousness of adult measles, high mortality. China’s regulations, the initial immunization for 8 months of age, one year later and then a booster immunization before school age. This vaccine is injected subcutaneously, the positive conversion rate can reach more than 90%, with small side effects, and immunity can last about 10 years.
(2) For susceptible children who have not been vaccinated and are in contact with children with measles, intramuscular injection of whole blood of healthy adults, human serum or gammaglobulin in recovery from measles within 5 days after contact can have a certain preventive effect.
10. Weaknesses of the virus.
Humans are the only natural host of measles virus, which is the weakness of the measles virus. So far no measles virus can be found parasitic livestock animal hosts, can only be passed from person to person to preserve. The resistance of the measles virus to the environment is too weak, and once humans have a way to eliminate the measles virus in humans one day, the measles virus is in danger of genocide.
The world’s measles is a type, but also the weakness of the measles virus. There is only one serotype of the measles virus, only one type. This way you have had measles anywhere in the world, with immunity, and then anywhere in the world, where the measles virus can not help you. The only virus type is most easily killed by the vaccine weapon, live attenuated measles vaccine does not have lasting immunity, if there is a better measles vaccine, or humans can standardize the existing vaccine, regular booster vaccination on time, the measles virus will not be able to exploit.
11, measles prevention.
(1) strengthen physical exercise to improve the ability to resist disease.
(2) Isolation of patients. Measles is highly contagious, during the epidemic, the medical epidemic prevention department should organize regular family visits to patients, so that “patients do not go out, medicine sent to the door” until 5 days after the rash. Childcare centers and kindergartens should set up temporary isolation rooms to isolate patients. Contacts should be observed in isolation for 2 to 3 weeks; if there are no symptoms, they can return to their classes. Rooms where measles patients have stayed should be ventilated with windows and doors open for 20 to 30 minutes. Health care workers should remove their outer clothing and wash their hands after contact with patients, or spend 20 minutes outdoors before approaching susceptible persons.
(3) Take children to public places (especially hospitals) as little as possible during measles epidemics, and visit fewer doors to reduce the chance of infection and transmission.
(4) Pay attention to personal and environmental hygiene, do not be picky about food, and drink plenty of boiled water.
(5) Automatic immunization: Anyone over 8 months of age who has not had measles should receive live attenuated measles vaccine. Immunity can be produced about 12 days after vaccination, and even if you get sick, the disease will be mild.
(6) Passive immunity: During measles epidemics, young and weak susceptible people who have not been vaccinated should be given intramuscular injections of gammaglobulin or placental globulin within 5 days of contact with the patient, which may prevent them from getting sick or reduce their illness.