What do the ten diseases have in common?
The Italian pediatric schedule requires 10 vaccinations, and Law 119 of 2017 made all ten mandatory for children and adolescents up to 16 years of age. The ten are the ones the law requires, and they are easiest to understand when grouped by the type of vaccine that prevents each. The reason is that the vaccine platform is the reason the disease behaves the way it does.
Three groups appear. Toxigenic disease is prevented by a toxoid. An encapsulated bacterium needs a conjugate. Viral diseases are prevented by live-attenuated or inactivated vaccines, depending on the virus.
Six of the diseases (diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B and Haemophilus influenzae type b) are delivered together in the hexavalent vaccine. It combines diphtheria and tetanus toxoids, acellular pertussis antigens, inactivated poliovirus, hepatitis B surface antigen and the Hib conjugate. It is given as a single injection at 2, 4 and 10 months. It mixes several platforms in one product, and none of its components can replicate. The other four (measles, mumps, rubella and varicella) are delivered as the quadrivalent MMRV vaccine or as MMR plus a monovalent varicella vaccine.
Schedules for children with underlying conditions, and the immunisation of immunocompromised children, follow national guidance and specialist advice.
Why are diphtheria and tetanus diseases of a toxin?
In both diseases the harm is done by a toxin. A toxoid is the toxin chemically inactivated, so that it raises antibody without causing disease. The toxoid is the vaccine for the two toxin-mediated diseases, diphtheria and tetanus.
Diphtheria
Corynebacterium diphtheriae colonises the pharynx and produces an exotoxin. After an incubation of 2 to 5 days come malaise, sore throat, difficulty swallowing, loss of appetite, hoarseness and mild fever.
Within two or three days an adherent grey membrane appears on the oral mucosa. An extensive membrane causes life-threatening airway obstruction. The toxin produces systemic disease, above all myocarditis and neuritis. The death rate is 5% to 10% even with treatment.
The membrane bleeds when it is peeled. Bleeding distinguishes it from the non-bleeding pseudo-membrane of Epstein–Barr virus.
Treatment starts on suspicion, before bacteriology returns. It is antitoxin plus antibiotics for 14 days plus airway support. Antitoxin neutralises only circulating toxin that has not yet bound to tissue. The antibiotics are penicillin, or erythromycin 40–50 mg/kg/day in divided doses, maximum 2 g/day.
The vaccine is a toxoid. Immunity lasts at least ten years after the primary series and a booster, and vaccine efficacy is about 90%. In the minority who are fully vaccinated and still become ill, the disease is milder. Diphtheria has re-emerged where coverage has fallen, and imported cases appear in countries whose immunisation programmes have been disrupted. The note on Pediatric Vaccination Coverage and Herd Immunity follows what falling coverage does.
Tetanus
Clostridium tetani is a spore-forming anaerobe. Its spores are environmental. Disease therefore follows a wound, and tetanus is not transmitted between people.
Its toxin, tetanospasmin, blocks inhibitory neurotransmission. Tetanus produces trismus (spasm of the jaw muscles), risus sardonicus (a fixed grimace from facial spasm) and opisthotonus (arching of the back from spasm of the trunk muscles). Tetanus produces autonomic instability.
Neonatal tetanus is the commonest form in low-income settings. The incubation is about 3 to 14 days after birth. It begins with sudden failure to suck and irritability, then convulsions that become increasingly frequent. Mortality is 25% to 90%, depending on intensive care.
Treatment is human tetanus immunoglobulin, a single dose of 500 IU intramuscularly (3,000 to 6,000 IU is also cited as effective), plus wound cleaning and debridement, spasm control, antibiotics and supportive care. When immunoglobulin is unavailable, equine antitoxin is the alternative, and it carries a risk of serum reactions. As with diphtheria, the immunoglobulin binds only toxin that is still free.
The vaccine is a formaldehyde-inactivated toxoid adsorbed onto aluminium salts, which increases its antigenicity. Toxoid content is measured in Lf (flocculation units): 10 to 20 Lf per dose in DTP vaccines and about 5 Lf per dose in the Td preparations used from around 6 to 7 years of age.
Why does pertussis need boosters, and why are infants the group at risk?
Bordetella pertussis causes a paroxysmal cough that lasts weeks. Whooping occurs in older children.
In young infants the picture is apnoea. Infants are also the group at risk of death and the group most likely to need hospitalisation for supportive care, sometimes in intensive care. Antitoxin is not available for pertussis.
The treatment is a macrolide for 14 days, erythromycin 40–50 mg/kg/day in divided doses; shorter courses of azithromycin or clarithromycin have similar efficacy. Early treatment may modify the course. Treatment at any stage limits spread, so it is given even to a child whose cough has already lasted two weeks.
The pertussis vaccine is acellular (DTaP). Immunity wanes after both disease and vaccination, so boosters are needed in the preschool and adolescent years. Vaccinating the mother in the third trimester of pregnancy protects a newborn too young to be vaccinated.
How does a poliovirus infection become paralysis?
Poliovirus enters by mouth and replicates in the pharynx and gastrointestinal tract. It may then spread haematogenously to the lymphatics and the central nervous system, where it destroys motor neurons. Most infections are silent: about 70% of polio infections in children are asymptomatic, about 24% produce a minor, non-specific illness, and fewer than 1% produce paralysis.
The vaccine used in Italy is inactivated polio vaccine, introduced in 1955 and now used as enhanced-potency IPV. After two doses it produces protective antibody to all three poliovirus types in 90% or more of recipients, and after three doses in at least 99%. Immunity is probably life-long, and only rare local reactions occur.
The oral live vaccine is no longer used in Italy. It can cause vaccine-associated paralytic poliomyelitis and can generate circulating vaccine-derived poliovirus. The two polio vaccines must be distinguished because of this.
Why must a newborn be protected from hepatitis B in the first hours?
Hepatitis B virus has infected more than 2 billion people alive today. About 254 million were living with chronic hepatitis B infection in 2022; earlier estimates were around 350 million. Roughly 1.1 million deaths a year are attributed to hepatitis B, chiefly through cirrhosis and hepatocellular carcinoma. Hepatocellular carcinoma is one of the leading causes of cancer death in Africa, Asia and the Pacific region.
Perinatal transmission is the mechanism that makes infant vaccination urgent. Two maternal blood viral markers predict the risk, HBsAg and HBeAg. HBsAg-positive and HBeAg-positive mothers infect 70% to 90% of newborns, and about 90% of infected infants become chronic carriers. HBsAg-positive, HBeAg-negative mothers infect about 20% of newborns, and of these roughly 90% also become chronic carriers.
There is no specific therapy for acute hepatitis B infection. Interferon alfa achieves long-term remission in a minority, and nucleos(t)ide analogues such as entecavir or tenofovir are used for chronic infection.
Hepatitis B vaccines have been available since 1982. The first was derived from the plasma of HBsAg-positive carriers. The recombinant vaccine was the first genetically engineered vaccine and is now standard. Infants born to HBsAg-positive mothers receive the first dose within 12 to 24 hours of birth, together with hepatitis B immunoglobulin.
What does the conjugate vaccine do for Hib?
The last member of the hexavalent vaccine is an encapsulated bacterium. Hib causes meningitis, epiglottitis, pneumonia and sepsis, and before conjugate vaccination it was a leading cause of childhood bacterial meningitis.
Its vaccine is the textbook illustration of the conjugate principle, taught in Pediatric Vaccines: Types and the Italian Schedule. The original pure polysaccharide product was not consistently immunogenic under 2 years and produced no booster response. The conjugated vaccine is immunogenic in infants and is boosted by repeat doses. Invasive Hib disease has become rare wherever conjugate vaccine is used.
Why are measles, mumps, rubella and varicella given as live vaccines?
These four are all prevented by live-attenuated vaccines. Such a vaccine copies the infection, so it works by replicating. They are given as quadrivalent MMRV or as MMR plus monovalent varicella, at 12 months and again at 5 years. The first dose waits until 12 months because maternal antibody would neutralise the vaccine in early infancy.
Measles
Measles is the most transmissible of the vaccine-preventable diseases. Its basic reproduction number is 12 to 18. The basic reproduction number is the average number of people one case infects in a fully susceptible population.
Infectious droplets remain airborne for up to 2 hours. That is long enough for transmission in a waiting room, an airport queue or a crowded indoor space after the index case has left. The child is also contagious for days before the rash appears, so the diagnosis comes too late to prevent exposure. Measles follows the clinical course in detail.
Measles begins with conjunctivitis, coryza and cough. A cranio-caudal maculopapular rash then follows and spreads as the fever continues.
The complications are common, and they are the reason the disease is taken seriously:
- Otitis media occurs in about 1 in 10 cases, often as a bacterial superinfection.
- Pneumonia occurs in as many as 1 in 20 cases and is the commonest cause of death from measles. It may be viral, bacterial or mixed. Viral pneumonia during the rash does not respond to antibiotics; bacterial pneumonia after the rash does respond.
- Acute encephalitis occurs in 1 per 1,000 cases and often results in permanent brain damage.
- Death occurs in 1 to 3 per 1,000 cases, from respiratory and neurological complications.
Subacute sclerosing panencephalitis (SSPE) is rare, and it is more frequent the younger the child was at infection: around 1 in 1,367 when measles occurred before age 5. It develops 7 to 10 years after the acute illness and is always fatal. Its features are behavioural and cognitive decline, myoclonus, seizures and progressive neurological loss.
Treatment is supportive. WHO recommends vitamin A for children with measles, two doses on consecutive days. Antibiotics are given only for bacterial complications.
Prevention requires two doses and a measles vaccination coverage of 93% to 95%. In 2019 an estimated 207,500 people died of measles worldwide, in a resurgence that followed a period of falling coverage and vaccine hesitancy. Why a coverage that high is needed is explained in Pediatric Vaccination Coverage and Herd Immunity.
What does mumps do beyond the parotid gland?
Mumps has an incubation of 12 to 25 days. A non-specific prodrome of myalgia, malaise, headache and low-grade fever precedes the parotid swelling, which is not present in every case. The complications include:
- Orchitis occurs in 12% to 66% of postpubertal males; the higher figures come from the pre-vaccine era.
- Aseptic meningitis occurs in up to 10% of unvaccinated patients.
- Pancreatitis occurs in up to 4%.
- Encephalitis occurs in 0.02% to 0.3%.
- Sensorineural hearing loss occurs, usually unilateral.
In the post-vaccine era, meningitis, encephalitis, pancreatitis and hearing loss are each reported in 1% or less of infected people.
The vaccine is a live-attenuated component of MMR. Mumps outbreaks still occur among vaccinated adolescents and young adults because immunity wanes, and public health authorities may recommend an additional dose during an outbreak.
Why does rubella matter in pregnancy?
Rubella is usually a mild illness. The incubation is about 14 days, and a prodrome is rare in children. The rash is a 2- to 3-day pink maculopapular rash starting on the face and neck. Lymphadenopathy begins before the rash and lasts weeks. Arthralgia or arthritis occurs in up to 70% of adult women and is rare in children.
The importance of rubella is entirely obstetric. Rubella infection in the first trimester affects up to 85% of infants. It causes deafness, eye defects, cardiac defects, microcephaly, intellectual disability, bone lesions and liver or spleen damage, and it can cause fetal death or premature delivery.
The live-attenuated rubella vaccine is therefore given to children chiefly to protect future pregnancies through herd immunity. Susceptible women are vaccinated postpartum rather than during pregnancy. Childhood Exanthems sets rubella alongside the other febrile rashes of childhood.
What makes varicella dangerous at the extremes of age?
Varicella-zoster virus spreads by droplets, direct contact and airborne aerosol. The incubation is 14 to 16 days (range 10 to 21), and the infectious period begins 1 to 2 days before the rash. Successive crops of lesions appear over several days, so lesions at different stages of evolution are present at the same time. They start on the scalp, face and trunk.
Bacterial infection of the skin lesions is the commonest complication. Pneumonia may be viral or bacterial. Cerebellar ataxia occurs in about 1 in 4,000 cases, and encephalitis, aseptic meningitis and facial nerve palsy are recognised CNS complications. Reye syndrome is associated with aspirin use during the acute illness. In children, hospitalisation occurs in 2 to 3 per 1,000 cases and death in about 1 per 60,000 cases.
The extremes of age are the fetus and the newborn. Congenital varicella syndrome follows maternal infection before 20 weeks. It causes limb hypoplasia, dermatomal skin scarring, eye abnormalities and neurological damage, and it carries high mortality in affected infants. The risk after primary maternal infection appears to be low, below 2%.
Neonatal varicella occurs when the mother’s rash appears from 5 days before to 2 days after delivery. The newborn is exposed to a high viral load without having received protective maternal antibody. Roughly 20% to 50% of exposed newborns become infected, and case fatality was historically as high as 30% when the rash began at 5 to 12 days of life.
The vaccine is live-attenuated and given in two doses. It is mandatory in Italy for children born from 2017. Given within 3 to 5 days of exposure to a susceptible contact, it may prevent or attenuate the illness. Immunocompromised children, pregnant women and neonates who cannot receive the vaccine are offered varicella-zoster immunoglobulin or prophylactic aciclovir. Post-exposure prophylaxis protocols, for varicella as for the other diseases here, follow national guidance and specialist advice. Varicella covers treatment thresholds and risk groups in more detail.
What is offered beyond the ten?
Italy also offers other vaccines actively and free of charge without making them mandatory. They are against pneumococcal and meningococcal disease, rotavirus, HPV, influenza and hepatitis A. Pediatric Vaccines Outside the Mandatory Schedule. Why does Italy offer these vaccines but not require them?