Event Analysis //
The girl's sore throat is only 10 minutes from the time of consultation to death, or the vaccine that can "save her life" is only in a special position in China
A 26-year-old girl rushed to a hot pot restaurant to celebrate her friend's birthday after working overtime at night. After returning home from dinner, the girl felt a little sore throat, thinking that the hot pot was too spicy, and did not pay attention. Early the next morning, the girl's throat pain worsened, and even breathing was a little difficult, she took some anti-inflammatory drugs at home to go to work, but I didn't expect the situation to be more serious, and there was a breath holding and chills. She hurriedly took leave to go to the hospital. When she arrived at the hospital, the girl suddenly exhaled heavily, fell to the ground, suffered cardiac arrest, and stopped breathing. From medical treatment to rescue, in just 10 minutes, a young life fell.
- Urban Express
The deceased in the news reported by the media suffered from a disease called "epiglottitis" that affects both adults and children, and this disease that can kill people in a short period of time is not only caused by pathogen infection, but even prevented by vaccines.
However, vaccines that can protect against related pathogens have a different status at home and around the world.
Asphyxiating diseases
When it comes to "epiglottitis", we have to understand what "epiglottitis" is.
会厌，图源：Anatomy, Head and Neck: Larynx Cartilage[1]
It may be difficult to understand that the epiglottis is a leaf-like elastic cartilage connected to the ligaments of the epiglottis. But to put it another way: the epiglottis opens to let air into the trachea when breathing, and closes when eating to let food enter the esophagus instead of the trachea, and everyone understands its role.
When inflammation of the epiglottis develops, the epiglottis, which is supposed to help block food, swells that not only prevent food from entering, but also air from entering the airways, causing suffocation and respiratory arrest [2], which is why many people die quickly after acute epiglottitis because of lack of oxygen.
Left: Swollen epiglottis, Source: References [3]
Right: Laryngoscopic image of epiglottitis, Source: References [3]
It should be known that brain cells will be damaged after a few minutes of hypoxia, and once disposed of in time, permanent brain damage or even death will occur [4].
Epiglottitis is so dangerous, but it is caused by a very common bacterial infection.
In the era when there was no vaccine, almost all of the bacteria that caused epiglottitis were "Haemophilus influenzae type b (abbreviated as Hib)", and a few cases were found to be associated with pathogens including Staphylococcus aureus, Streptococcus pneumoniae, and hemolytic streptococcus after the vaccine became popular [2,5].
And Hib's disease burden, perhaps many medical personnel in the public health field are unclear until now.
Invisible killer
Although the name "Haemophilus influenzae" carries the word "influenza", it is not influenza.
In 1892, German bacteriologist Richard Pfeiffer isolated what he believed to be the pathogen of influenza [6]. Because the influenza virus originated from the 1889 influenza pandemic (also known as the Russian influenza pandemic, the likely epidemic strain was H3N8 or H2N2], the scientist mistakenly identified Haemophilus influenzae as the pathogen that caused the flu, and it was not until many years later that the influenza virus was confirmed.
Although not the causative agent of influenza, which kills hundreds of thousands of respiratory-related diseases each year [8], the disease burden of Haemophilus influenzae should not be underestimated, and Haemophilus influenzae type b is the main cause of invasive disease.
Haemophilus influenzae, source: Buy at your own expense
You know, although Haemophilus influenzae type b does not cause influenza, it is the main cause of pneumonia and meningitis.
In 2000, experts at the University of Helsinki conservatively estimated that there were more than 2.2 million cases of Hib infection and 520,000 deaths from Hib-related infections worldwide each year (compared with about 290,000 to 650,000 deaths from respiratory diseases caused by influenza each year), but the true number may be much larger [9].
According to the World Health Organization, the total number of children who died from Hib worldwide in 2008 was estimated at 199,000, mainly from meningitis and pneumonia. In addition, complications following Hib infection include blindness, deafness, mental retardation, learning disabilities, and death, with 10% to 15% of survivors experiencing severe neurological sequelae and 15% to 20% of survivors experiencing deafness. [10]。
Even 45 years after the introduction of the Hib vaccine [9] in 1975, the University of Edinburgh estimated that Hib was responsible for approximately 7645 cases of meningitis and 857 deaths of Hib-related meningitis in 2020 [11].
Proportion of Haemophilus influenzae in each province, source: Reference [9]
What's more troublesome is that Haemophilus influenzae is still a bacterium that colonizes the human body after infection, with a Hib carrier rate of about 20% in 1-year-old children and more than 50% by 5 years old [2]. The results of the meta-analysis of Haemophilus influenzae in mainland China showed that the carrier rate of minors was 17%, and that of adults was 14%[12]; In a cross-sectional study of cities at high altitudes on mainland China, Haemophilus influenzae carriers in children under 15 years of age were as high as 44.7 percent [13].
In addition, Hib infection can also cause many other diseases, including the epiglottitis just mentioned, and is the main cause of epiglottitis; Other non-invasive diseases include otitis media and cellulitis.
Since Haemophilus influenzae b infection is not included in the list of notifiable infectious diseases in mainland China, the specific disease burden caused by Hib in China is unknown.
Embarrassing vaccines
As just mentioned: the Hib vaccine has been invented for 45 years, and even the conjugate vaccine that is currently used around the world has been approved for more than 30 years.
After the introduction of Hib vaccines in various countries, the incidence of various diseases related to Hib has dropped significantly [14], especially in the United States, which reduced the incidence of Hib infection by more than 99% through immunization as early as the early 90s of the 20th century [15].
Effect of Hib vaccine on incidence of children under 5 years of age in the United States, 1980–2012, Source: References [14]
Given the severe burden of disease caused by Hib and the effectiveness of vaccines, in order to achieve the goal of defeating meningitis by 2030, the World Health Organization mentioned in its 2020 Global Roadmap to Defeat Meningitis by 2030[16]:
Haemophilus influenzae type b conjugate vaccine (by 2022) and Streptococcus pneumoniae conjugate vaccine (by 2025) are included in routine infant immunization programmes in all countries.
Global roadmap to defeat meningitis by 2030, image source: References [16]
So, what is going on with measures that can help defeat meningitis and reduce the risk of various diseases caused by Hib?
In two words: embarrassing!
So far, according to publicly available information, China is the only member state of the World Health Organization that has not included the Hib vaccine in its national immunization program (NIP) [17,18].
Global Hib vaccine inclusion in NIP, source: World Health Organization website
However, it should be noted that the inclusion of a vaccine in the NIP is not only a consideration of whether the relevant disease is included in the notifiable infectious disease, but also a comprehensive consideration of cost-effectiveness.
In a mathematical model analysis [17] conducted by the Chinese Center for Disease Control and Prevention and Peking University, it was found that the inclusion of Hib in immunization programmes in different provinces in mainland China was not always cost-effective.
Cost-effectiveness of introducing Hib vaccine in national immunization programmes in provinces, Source: References [17]
Therefore, it is not known whether the Hib vaccine will be included in the immunization programme and free vaccination for children, but this does not mean that we cannot reduce the risk of Hib-related diseases, including epiglottitis, for children through Hib vaccination.
Vaccine against Hib
Because of the low risk of Hib infection in people older than five years of age, there is no vaccine available for children over six years of age and older or adults, and the United States allows Hib vaccine to be given to adults who are asplenic or who are scheduled for elective splenectomy [19].
Mainland China has approved a number of Hib or Hib-containing vaccines for people under 6 years of age, including:
(1) Hib single-component vaccine (prevention of Hib)
(2) AC-Hib triple vaccine (prevention of meningococcal group A and group C and Hib)
(3) DTaP-Hib quadruple vaccine (prevention of pertussis, diphtheria, tetanus, Hib)
(4) DTaP-Hib-IPV vaccine (prevention of pertussis, diphtheria, tetanus, Hib, poliomyelitis)
The immunization schedule for these vaccines is shown below:
Immunization programs for different Hib or Hib-containing vaccines, source: homemade
Although the above vaccines are not included in the mainland NIP, they are all non-immunization program vaccines and can be vaccinated at their own expense.
Children or adults who are not vaccinated or unable to receive the Hib vaccine also do not need to be anxious, and seeing a doctor as soon as possible after symptoms of the disease develops can also reduce the risk of illness.
All in all, in the face of epiglottitis mentioned at the beginning of the article, in fact, ordinary people can only do what they can do, namely: vaccination and timely medical attention.
bibliography
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[7] Valleron, Alain-Jacques et al. “Transmissibility and geographic spread of the 1889 influenza pandemic.” Proceedings of the National Academy of Sciences of the United States of America vol. 107,19 (2010): 8778-81. doi:10.1073/pnas.1000886107
[8] World Health Organization. Up to 650 000 people die of respiratory diseases linked to seasonal flu each year. Available: http://www.who.int/mediacentre/news/releases/2017/seasonal-flu/en/. Accessed: 30 May 2021.
[9] Peltola, H. “Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates.” Clinical microbiology reviews vol. 13,2 (2000): 302-17. doi:10.1128/CMR.13.2.302
[10] “Disease Burden.” World Health Organization, www.emro.who.int/health-topics/haemophilus-influenzae-type-b/disease-burden.html. Accessed 27 May 2023.
[11] Park, Jay J et al. “Estimating the global and regional burden of meningitis in children caused by Haemophilus influenzae type b: A systematic review and meta-analysis.” Journal of global health vol. 12 04014. 5 Mar. 2022, doi:10.7189/jogh.12.04014
[12] Yang, Peng et al. “The pharyngeal carriage of Haemophilus influenzae among healthy population in China: a systematic review and meta-analysis.” BMC infectious diseases vol. 19,1 547. 21 Jun. 2019, doi:10.1186/s12879-019-4195-9
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[14] Gilsdorf, Janet R. “Hib Vaccines: Their Impact on Haemophilus influenzae Type b Disease.” The Journal of infectious diseases vol. 224,12 Suppl 2 (2021): S321-S330. doi:10.1093/infdis/jiaa537
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[17] Zhang, Haijun, et al. "National and provincial impact and cost-effectiveness of Haemophilus influenzae type b conjugate vaccine in China: a modeling analysis." BMC medicine 19.1 (2021): 1-14.
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May the world be free of epidemics
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