To prevent viral diseases, which of the five levels should you choose?

The “relationship spectrum” between humans and viruses

【From the perspective of infection status】

Exposure to a virus does not necessarily lead to infection, and infection with a virus does not necessarily lead to illness.

No infection occurred: Not all viruses can infect humans, and viruses that can infect humans do not always successfully infect humans. The successful spread of a virus requires the correct transmission route, sufficient viral particles, and a suitable host state.

Unsuccessful infection: When a host is infected with a pathogen, the host may spontaneously clear the pathogen without showing symptoms, which is called latent infection or subclinical infection . This situation may be caused by opportunistic infection (emphasizing the occasional infection of viruses that do not normally infect humans), abortive infection (emphasizing the failure of pathogens to establish infection and complete the replication cycle) or asymptomatic infection (emphasizing the lack of symptoms after pathogen infection). For example, after adults are infected with hepatitis B virus, there is a self-healing rate of more than 90%. A large number of asymptomatic COVID-19 infections also belong to this situation.

Incubation period : The incubation period refers to the period from the time the pathogen invades the body to the first clinical symptoms. People with a history of travel to high-risk areas or those who have been released from infection need to be isolated for a period of time. This isolation and observation period is set according to the length of the incubation period of the infectious disease, which is generally the average incubation period plus 1 to 2 days.

Clinical symptom period : refers to the period when patients with infectious diseases develop disease-specific symptoms and signs. This type of infection is called dominant infection or clinical infection . During this period, the number of pathogens in the patient's body is large, and the symptoms of the disease (vomiting, diarrhea, coughing, etc.) are conducive to the excretion and spread of pathogens, and the infectiousness is the strongest.

Recovery period : refers to the period when the patient's clinical symptoms have disappeared and the damage suffered by the body is gradually recovering. During the recovery period, the patient's immunity begins to emerge, and the pathogens in the body are gradually eliminated. Generally, they will no longer infect others. For example, chickenpox and measles will not be transmitted to others during the recovery period. However, for some infectious diseases, such as dysentery, typhoid fever, hepatitis B, etc., patients can still excrete pathogens during the recovery period and infect other people.

After the virus infects the human body, it replicates rapidly and causes disease, causing the patient to go through the above three stages in a shorter period of time, which is called acute infection .

Persistent infection : A host cannot recover from a pathogen infection in a short period of time and carries the pathogen for a long time. The state in which the pathogen is inactive and generally does not excrete toxins or cause further deterioration of the disease is called latent infection . Latent infection can be reactivated and cause disease under conditions such as low immunity and drug stimulation. For example, herpes simplex virus type 1 and human papillomavirus infection show the characteristics of persistent infection.

Chronic infection refers to an infection in which the pathogen is actively replicating, continuously releasing pathogens and causing the disease to slowly worsen. For example, infection with hepatitis B virus, hepatitis C virus and HIV, if left unchecked, will have serious consequences.

We should pay attention to the distinction: acute infection does not necessarily mean it is serious, and chronic infection does not mean "easy". "Acute/slow" is just the speed of the disease progression. Causing acute infection and spreading rapidly among the population, or persisting in the body of the infected person and waiting for the opportunity to infect other individuals are two strategies for the virus to survive.

Immune protection status : People who recover from the disease are generally immune to the pathogen. People whose bodies spontaneously clear the pathogen after infection also have this type of immunity. However, whether or not you will be infected with the pathogen again depends on the type of pathogen. Viruses such as hepatitis A and smallpox are generally only infected once in a lifetime, while hepatitis C and other viruses are prone to reinfection because the acquired immunity after infection is not high enough to prevent new infections.

Figure 1: The consequences of viral infections are not the same. Most infections do not cause disease. Some acute or chronic infections can lead to serious diseases. | Author provided

Understanding the possible states after virus infection is also conducive to formulating reasonable epidemic prevention measures. For example, the new coronavirus infection is an acute infection, and there is no persistent infection. Therefore, after the new coronavirus infected person recovers, it is impossible to turn positive without contacting a new source of infection. There is no scientific basis for treating recovered new coronavirus patients differently.

Even for virus carriers or those who test positive for nucleic acid, specific discussions are needed based on the characteristics of different viruses.

For example, it is almost impossible to completely eliminate the human immunodeficiency virus (HIV), but as more and more people have access to effective AIDS prevention, diagnosis, treatment and care measures, HIV infection has become a manageable chronic health disease, and people with HIV may live a long and healthy life. If they can receive antiretroviral therapy, take antiviral drugs as prescribed every day, and achieve and maintain a viral load so low that it cannot be detected, then these HIV carriers will not be at risk of transmitting the virus to their sexual partners. In other words, after treatment, HIV-infected people cannot detect the virus and are not contagious (Undetectable = Untransmittable, U=U). (For details, see "Where is HIV hiding? To enjoy a happy sex life, you must avoid these high-risk actions | AIDS Day Special)

Usually, people will only do relevant pathogen tests under the advice of doctors when they have symptoms, which leads to the fact that asymptomatic infections are rarely found under normal circumstances. In fact, for many viruses, many people do not become ill after infection. The discovery of a large number of asymptomatic infections is one of the characteristics of new coronavirus infection and also a feature of the current era. What is the clinical significance of these asymptomatic infections , what role do they play in the spread of the epidemic, and how much resources are needed to control them? To answer these questions, it comes down to answering one question: What is the probability that asymptomatic infections will spread to other people and cause severe illness?

For some viruses, even if signs of the virus can be detected in the human body, it does not mean that the person can serve as a source of infection and spread the virus to others. In June 2020, the Wuhan Municipal Health Commission announced that the Wuhan Institute of Virology of the Chinese Academy of Sciences conducted virus culture tests on samples of 300 asymptomatic infected persons found in the centralized nucleic acid testing and screening in Wuhan from May 14 to June 1, 2020, and found that no "live virus" was present. In addition, the toothbrushes, masks, towels and other personal items of these asymptomatic infected persons were also tested, and no live viruses were detected. Experts believe that the reasons why no live viruses were detected in the samples of asymptomatic infected persons may be: 1) the virus content in the samples is extremely low, and 2) there is no "live virus" with pathogenicity. Epidemiological surveys show that the nucleic acid test results of 1,174 close contacts of these 300 asymptomatic infected persons were all negative. The above research results show that the asymptomatic infected persons found in Wuhan at that time were not contagious. [1]

Scientifically defining the source of infection or high-risk groups based on the characteristics of the virus during infection or disease progression can help us better implement intensive epidemic prevention.

【From the perspective of pathogenicity】

We can look at the harmfulness of the virus from two dimensions: first, the transmission rate; second, virulence or mortality (the two concepts are related but not completely equivalent). The former represents the breadth of the virus's harm; the latter represents the depth of the harm. For individuals, there is no doubt that virulence has a greater impact; and for all human beings, the health damage caused by the virus is the "product" of the two: viruses with strong transmission ability but low harm, or viruses with extremely strong virulence but poor transmission ability, will relatively not cause huge disasters to human society (but it must be noted that social panic and medical resource runs caused by the mixed epidemic information will also have a negative impact on society in ways other than causing disease).

Virulence is a relatively general concept, referring to the ability of microorganisms to infect and damage hosts. It is a complex characteristic determined by pathogens, hosts and environmental factors . The harmfulness of different genotypes or strains of the same virus may vary greatly. For example, there are more than 170 genotypes of human papillomavirus (HPV), of which more than a dozen genotypes may develop into cancer after years of persistent infection. According to the probability of carcinogenesis, or the frequency of detection in cancer tissues, the carcinogenic risk of these HPVs can be divided into three levels: high risk, dangerous, and risky. HPV16 and HPV18 are the most dangerous types of HPV, and 65%-85% of cervical cancers worldwide are caused by these two HPVs. Therefore, we can greatly reduce the incidence of cervical cancer by focusing on a few highly pathogenic HPV genotypes for key prevention and control. (For details, see "Is it safe after the HPV vaccine? Do boys have to get it too? At what age is it most useful? One article explains everything about HPV | Virus Super Topic")

The direction of viral evolution is not to pursue high virulence, but to pursue high adaptability . Adaptation can theoretically be measured by fitness, which refers to the relative ability of individuals of a certain genotype in a group to survive and pass on their genes to the next generation (comparative advantage compared with other genotypes). The greater the fitness, the higher the chance of survival and reproduction. For example, for the same new coronavirus, the Omicron variant has stronger adaptability than the original strain (manifested by increased infectivity, gradually replacing other strains). For a certain virus, whether natural selection increases or decreases virulence depends on the specific combination of host, virus and environment . Therefore, the evolution of the virus does not necessarily lead to an increase in viral virulence, but often exchanges "low virulence + high transmissibility" for stronger adaptability. Therefore, we can observe that emerging viral diseases often have very severe symptoms because the new virus has a shorter contact time with humans, while viruses that have co-evolved with humans for a long time are less likely to cause severe acute diseases. For example, AIDS has extremely low pathogenicity in its original non-human primate hosts, but after encountering a new host (humans), the symptoms it causes are very severe; and the herpes virus has coexisted with humans for a very long time, so they have "adapted" to each other's existence.

Figure 2: The trade-off between virulence and transmission rate: A virus with too high virulence will prevent the infected person from contacting new potential hosts, limiting its ability to spread; while a virus with moderate virulence will produce fewer viruses, but because its host activity is not restricted, it can infect more new hosts, thus gaining higher adaptability. [2]

The pathogenicity of the virus is related to the host to a certain extent, and the host is also involved in the pathogenic process of the virus. For example, the symptoms of the common cold are actually mainly caused by the virus stimulating the body's natural immune system and producing cytokines. Cytokines are a group of low-molecular-weight extracellular signaling proteins that are mostly secreted by various immune cells. Tumor necrosis factor and interferon can cause headaches in humans; interleukin 1, interleukin 6 and tumor necrosis factor can all cause an increase in body temperature, that is, fever.

Fever itself is a normal anti-infection response of the body, and high or persistent body temperature is also harmful to the human body. Uncontrolled cytokine release can also lead to catastrophic consequences - cytokine storm syndrome . Cytokine storm is a common systemic inflammatory response caused by viral infection, characterized by the production and release of large amounts of pro-inflammatory cytokines by many cells. Uncontrolled inflammatory response causes septic shock, multi-organ damage, and even organ failure - these are one of the reasons why patients with new coronary pneumonia become seriously ill.

The consequences of viral infection are also closely related to the host's condition. The same virus can cause different degrees of disease when infecting people of different genders, ages, nutritional status, and immune status. For example, when studying cases of severe COVID-19, people found that being male, smoking, old age, and having underlying diseases are important predictors of severe illness. For fetuses, infants, the elderly, and people with compromised immune systems with low immunity, any pathogen infection can be dangerous.

Figure 3: The occurrence and progression of viral diseases are related to the virus, the host, and environmental factors, which together determine the harm of viral diseases.

Differences in strains or host factors must be taken into account in epidemic prevention, with a focus on preventing highly virulent strains and protecting susceptible populations.

【From the perspective of epidemic prevention measures】

Epidemic prevention measures are not limited to pathogen screening, isolation and blockade. The intervention strategy of preventive medicine includes five levels:

1. Primary prevention: Avoiding health risk factors before birth or early in life. Examples include environmental, economic and social factors and eugenics measures. Primary prevention is a general preventive measure for almost all health threats.

2. Primary prevention: Eliminate pathogens or increase resistance to disease to prevent it from happening . Get immunized against infectious diseases, follow a diet and exercise regimen to stay healthy, and avoid smoking, etc.

For infectious diseases, primary prevention emphasizes "preventing infection" to avoid causing disease. Because different pathogens have different epidemiological characteristics, the primary prevention measures for different pathogens will also be different. For example, the new coronavirus is mainly transmitted through droplets, so the primary prevention measures for the new coronavirus are mainly to block droplet transmission and contact transmission. In addition, the cheapest and most effective infectious disease prevention measure is vaccination, and the development and use of vaccines are the key to defeating infectious diseases.

3. Secondary prevention: Detecting and addressing existing disease before symptoms develop. Examples include pathogen testing, treatment of hypertension (to prevent it from causing cardiovascular disease), and cancer screening.

For infectious diseases, secondary prevention emphasizes "detecting infection" to prevent it from developing into a disease. Detecting and isolating the source of infection is an important measure in epidemic prevention. In addition, some pathogens have a long incubation period from infection to onset. Early detection of pathogens and intervention treatment can prevent the development of more serious diseases. Testing and treating all those who need to be tested are important measures to improve the detection and treatment rates of infectious diseases.

4. Tertiary prevention: Treatment to reduce the harm of existing diseases. For example, treatments that prevent the spread or progression of a disease.

For infectious diseases, the third-level prevention emphasizes "treating infection" to prevent the disease from worsening. Patients with confirmed infectious diseases are an important source of infection and are also the main group of people who need medical treatment. Managing and treating confirmed cases is an important measure to slow down the deterioration of their condition and prevent them from further infecting others.

5. Level 4 prevention: Reduce or avoid unnecessary and excessive intervention in the health system, and protect the rights of medical staff and patients. In terms of infectious disease prevention and control, medical staff are the frontline workers fighting against the epidemic, and their protective measures and working conditions must be guaranteed. In addition, discrimination and even infringement on patients or cured people are also extremely wrong and need to be avoided.

Therefore, preventive medicine measures in a broad sense are all-encompassing, covering all stages before, during and after the disease occurs, involving various aspects such as the environment, society and individuals.

For some highly contagious and pathogenic viruses, we mainly try to eliminate them through primary prevention and control, relying on virus elimination and vaccination. For example, the state legally mandates free vaccination to prevent viral diseases.

China's Law on the Prevention and Control of Infectious Diseases divides infectious diseases into three categories: Class A, Class B, and Class C. Different categories of infectious diseases have different prevention measures. In addition to Class A infectious diseases such as plague and cholera, Class B infectious diseases such as SARS, pulmonary anthrax, and highly pathogenic avian influenza are also subject to Class A prevention and control measures. For other Class B infectious diseases and sudden infectious diseases of unknown causes that require the adoption of Class A prevention and control measures, the health administrative department of the State Council shall promptly report to the State Council for approval before announcing and implementing them. At present, China still manages the new coronavirus as a Class A infectious disease. Professor Li Lanjuan, an academician of the Chinese Academy of Engineering, said in an interview on a program that "as prevention and control measures are gradually put in place, the impact of the new coronavirus on people's lives will definitely become smaller and smaller." Academician Li Lanjuan believes that after "comprehensive evaluation by experts, combined with comprehensive analysis of the harm of the virus to human health, the future development trend of the virus, and the impact of the virus on human economic life," the new coronavirus will eventually return to the management of Class B infectious diseases at the appropriate time. [3]

For some viruses with limited infectivity but high mortality, we should prepare vaccines or immune serum for high-risk groups or emergency exposure situations. For example, rabies virus belongs to this category of viruses. Vaccines for this type of virus are not widely used.

For some viral diseases that are easy to spread and have no obvious symptoms in the early stage of infection, but long-term infection can cause serious consequences, we should strengthen secondary prevention on the basis of primary prevention, improve the detection rate of pathogens, detect and treat them early, and try to avoid more serious diseases. HIV, HBV, HCV, HPV and other viral infections belong to this category.

For some infectious diseases that are highly contagious but have mild symptoms, the third level of prevention should be the main focus. This type of viral disease is mainly diagnosed when the individual is sick and seeks medical treatment. Strengthen treatment and care to prevent the disease from getting worse and prevent the infected person from spreading the virus to others.

In addition, during the epidemic prevention process, the safety of medical staff must be guaranteed, and attention must be paid to protecting the rights and interests of patients or those who have recovered.

Figure 4: Take the tertiary prevention of cervical cancer as an example. The peak of HPV infection occurs during the sexually active period. Most infections are cleared spontaneously. Some infections cause lesions three to five years later. Continuous deterioration of lesions may lead to cervical cancer. Vaccination (primary prevention) and pathological screening (secondary prevention) are important means of preventing cervical cancer. Precancerous lesions or early cervical cancer should be detected and treated in time (tertiary prevention). Primary and quaternary prevention are not listed, but should be carried out throughout. Author referenced WHO data to make the map

Similarly, different infectious diseases require different and reasonably available preventive measures.

Can humans completely eradicate a virus? Yes. For extremely harmful viral diseases, long-term and feasible eradication plans can be developed, and the virus can be eventually eradicated through international collaboration. Currently, the world has eradicated smallpox, a serious infectious disease. On October 24, 2019, on the occasion of World Polio Day (October 24), the World Health Organization (WHO) officially announced through the Global Commission for the Certification of Poliomyelitis Eradication (GCC) that type 3 wild poliovirus has been eradicated worldwide! This is another historic achievement in the history of human public health, following the global eradication of smallpox and type 2 wild poliovirus[4].

Conclusion

Figure 5: Viruses are complex and diverse, and it is important to prevent and control infectious diseases. The public also needs to understand viral diseases. As for the viral diseases that the public needs to participate in preventing and controlling, and the prevention and control measures that need to be taken, they must be carefully selected. Just as the law has a low presence for law-abiding people, and we don't deal with the police and judges every day, excellent epidemic prevention should also have a low presence for healthy people.

Viruses are "others" and are very different from us; but viruses are closely related to us. They exist silently on our bodies or in the environment around us, endangering and harassing us all the time. There are many examples of people and viruses coexisting, and there are also examples of humans completely eliminating viruses. If "the man has his own reasons and the woman has her own reasons", it can only be said that the two factions have grasped part of the facts. The experience of any individual case cannot be copied in its entirety. When it comes to the prevention of a certain virus, we should seek truth from facts, analyze specific issues specifically, and constantly adjust prevention measures according to the development of the epidemic.

References

[1] https://mp.weixin.qq.com/s/k1A1jlVhfU_bVqIVVfx01A

[2] http://evolution.berkeley.edu/

[3] https://zj.zjol.com.cn/news.html?id=1912949

[4] http://www.chinacdc.cn/jkzt/crb/zl/jshzy/yqdt/201910/t20191025_206468.html