Haemophilus Influenzae Type B Disease (HiB Vaccine)

Haemophilus   influenzae type B disease

Haemophilus influenzae type B disease has been largely decreased in developed countries since effective HiB vaccine was launched in national immunization schedule. The morbidity and mortality due to Haemophilus influenza disease is still a major health concern in the countries from developing world. This situation in developing world is due to incomplete coverage or non compliance with the immunization program.

About Haemophilus influenza

Haemophilus influenzae is a bacterium. It is single cellular organism. It is surrounded by the polysaccharide capsule. It is gram negative pleomorphic cocobacilli. For its growth it needs 2 important factors, they are hematin and phosphopyridine. Hematine is called as factor V and phopshopyridine is called as factor X. According to antigens present on the polysaccharide capsule and biochemical characteristics it is identified as different types. These types are called as a, b, c, d, e, and f.

Epidemiology of Haemophilus influenzae disease:

It was the major health concern in developed world before the Haemophilus influenzae type b vaccine was introduced in national immunization programs. Now because of effectiveness of the vaccine this disease occurs only sporadically in developed world. Still it continues to be a major health concern in developing countries like India.

Striking characteristics of this infectious disease is it mainly affects young children those who are less than 5 years old. 90 percent of these cases are those who are less than 2 years of age. The invasive disease caused by Haemophilus inflenzae is still an important cause of death in children less than 5 years old particularly in poor regions of the world. 

Majority of Haemophilus invasive disease are caused by Haemophilus influenzae type B. Non B type Haemophilus influenzae too can cause invasive disease but it is not so common, only sporadically it dose. Non typeable Haemophilus too can cause the invasive deadly disease but only in neonates or those who are severely immumocompromized. 

Only natural host for Haemophilus influenzae is Human. No other animal can harbor this microorganism. Pre vaccination era 60-90 percent population used to be carrier of Haemophilus influenzae. 2-5 percent of healthy preschool and school children used to have Haemophilus influenzae type B in there respiratory tract. After introduction of vaccine the invasive disease cases are decreasing and so the proportion of asymptomatic population in whom Haemophilus is present in respiratory tracts.

Children with chronic medical conditions like those with asplenia and sickle cell disease, immunodeficiency and malignancy show increased susceptibility and risk of mortality from the invasive H. influenzae type b disease. Children who previously had developed invasive Haemophilus influenzae disease do not develop immunity against it and they do need HiB vaccination. 

Childcare outside home, school going sibling, short duration of breast feeding and parental smoking are associated with increased risk of infection. Generally otitis media precedes the invasive disease.

How does Haemophilus influenzae disease spread?

It is infectious disease it spreads from one person who is infected to other person who is susceptible to infection. This spread occurs by direct contact. It is spread by respiratory droplet infection. When these contaminated respiratory droplets are inhaled by the susceptible person he/she gets infected. Incubation period for invasive disease to occur is still unknown. 

Pathogenesis of Haemophilus influenzae disease:

When the susceptible contact inhales the contaminated respiratory droplets the H. influenzae gains access to the respiratory tract. H. influenzae settles on the epithelium in the respiratory tract. Many different factors help it to get attached to the respiratory tract. They are philus and non philus factors. After multiplying in respiratory tracts H. influenzae enters the blood vessels. It gains entry into the blood velles with help of various cytotoxins. Once inside the blood vessles it is carried by the blood stream in entire body. Once in the blood stream various protective factors from the host attack the bacterium. H. influenzae resists this attack with the help of its polysaccharide capsule. Longer it stays in blood stream more are the chances that it will cause invasive form of disease such as meningeal infection or joint disease.

Sinusitis, otitis media and bronchitis are non invasive form of disease caused by Haemophilus influenzae. These non invasive forms pf disease are mainly caused by non typeable H. influenzae. The microorganism enters these sites through blood as well as direct extension from the already colonized nasopharynx. Eustachian tube dysfunction and viral infection predispose the child to the increased risk of such infection. Bottle fed babies have more chance of getting such invasive and non invasive disease. Vaccinated and exclusively breast fed infants are relatively protected from the infection. 

Haemophilus influenzae becomes antibiotic resistant by various mechanisms. It may produce beta lactamase enzyme by which it becomes resistant to ampicillin and amoxicillin. It may undergo the change in cell wall structure thus can be beta lactamase negative antibiotic resistance. Amoxicillin-clavulinate can kill beta lactamase producing bacteria but cannot kill the beta lactamase negative resistant H. influenzae. For this purpose azithromycin and third generation cephalosporins and quinolons appear to be very effective.

Upon infection the hosts produce immunity against Haemophilus influenzae. The PRP (Polyribosyl ribisitol phosphate) is the target antigen for the host immunity. Antibodies directed against PRP are called as anti PRP antibodies. These antibodies are important in opsonization effect in killing the bacterium with the help of complementary system. So, role of complementary system is important in clearing organisms from the system. Antibody response is thought to be age related. So, younger the child more is the susceptible to the infection due to immaturity of the immune system. Conjugated HiB vaccine produces the maturity of the thymus inducing the production of effective antibodies and production. Memory response occur rapidly when exposed to the conjugated vaccine. 

What are clinical manifestation? 

Meningitis: This is infection intra cranial. Meninges are membranes covering of the brains which protect the brain. The clinical manifestations are those of high grade fever, not accepting feed, excess irritability, lethargy, convulsion, neck rigidity, loss of consciousness, paralysis, loss of hearing and vision, may lead to death. There can be permanent residual paralysis and hearing loss even after treatment of infection. In younger children index of suspicion of meningitis should be high as all the symptoms and classic findings may not be there. This condition needs treatment with antibiotics and hospitalization. Third generation cephalosporins are generally choice antibiotics for the treatment. Along with treatment of antibiotics supportive care to sustain the vitals and nutrition is very much needed.

Cellulitis: Cellulitis is the infection under the skin tissues. This occurs due to the seeding of the Haemophilus influenzae by the blood after bacteremia. Generally upper respiratory tract infection by H. influenzae precedes the cellulitis. Eyelids, head, neck, preseptal cellulitis are the forms usually seen. Cellulitis usually have tender swelling without distinct borders. Aspiration from the margin of the cellulitis region and blood culture may show the causative organisms. Cellulitis needs treatment with antibiotics. It may need surgical debridement with antibiotics. Parenteral antibiotics are to be used till child becomes afebrile then can be shifted to oral antibiotics.

Preseptal cellulitis: Preseptal cellulitis is infection of the tissues outside the septum of the eye orbit. Fever, edema, tenderness and warmth around the eyes with occasional purple discoloration skin are the manifestations of the preseptal cellulitis. This condition needs antibiotic therapy with amoxicillin and clavulinate combination. Parenteral therapy is preferable. In unvaccinated child and if the S. pneumonia is suspected cause beta lactamase resistance may be present.

Orbital cellulitis: This is inflammation of the tissues in the orbit. It is characterized by swelling of the lid with impaired vision and pain while moving the globe. There is limitation for movement of the extraoccular muscles. Making distinction between orbital cellulitis and preseptal cellulitis can be clinical difficult and may need CT scan for the diagnosis. This condition is treated with parenteral antibiotics. Close observation of the patient is needed as it may lead to permanent loss of vision and complication of meningitis. This condition may need surgical intervention by ophthalmologist.

Acute epiglotitis: This is potentially lethal manifestation of the Haemophilus influenzae type b disease. There is swelling of the epiglottis and it can block the laryngeal inlet. It can induce obstruction and spasm of the laryngeal inlet to cause the airway obstruction leading to death. This condition though common in unimmunized children can occur at any age. These cases are handled with care and it is generally admitted in ICU where facility of intubation and ventilation is available. Any time case can worsen and may need tracheostomy immediately. Injectable intibiotics with third generation cephalosporins are needed but started only after intubation in the ICU.

Pneumonia; This is infection of the lungs and lower respiratory tract it is invasive complication of the Haemophilus influenzae type b disease. This condition needs antibiotics. Treatment with amoxicillin and clavulinate combination or third generation cephalosporins is needed. Depending on severity of disease patient may need oxygenation and ventilation with life support.

Suppurative arthritis: This is a manifestation of the invasive Haemophilus influenzae type b disease. The focus of the infection can be elsewhere from where the infection is disseminated to the joint. Large joints such as knee, hip, elbow, ankle joints may be typically involved. Teeatment is started after culture is taken. Initially injectable antibiotics with third generation cephalosporin and after fever and swelling is decreased patient is shifted to oral antibiotics. Long course of antibiotics till 3 weeks are needed to be given. These cases may need surgical intervention.

Pericarditis: H. influenzae is rare cause of pericarditis. The initial focus of infection is respiratory tract. The bacterium can be obtained from blood culture and pericardial fluid too. Respiratory distress and tachycardia are the consistent findings. This condition needs injectable antibiotics and close monitoring of the patient. These patients may need cardoiologic intervention for pericardiocentesis.

Bacteremia: Haemophilus influenzae bacterium circulating in the blood is the common manifestation of the H. influenzae disease. This can lead to high grade fever without the focus and then bacterial seeding occurs to various organs. It needs theyapy with antibiotics preferably third generaion cephalosporins.

Invasive disease of the neonates: In cases of neonates H. influenzae infection occurs to neonate from mother from chorioamnionitis or prolonged rupture of membranes. It can manifest as meningitis or pneumonia or sepsis. These cases are needed to be treated aggressively with injectable antibiotics.

Otitis media: Otitis media is middle ear infection. It is very common infection in children. Along with H. influenzae, Streptococcus pneumoniae and Moraxella catarrhalis are the most common culprits causing otitis media. These bacteria gain access to middle ear cavity by eustachian tube. Viral infection generally precedes the middle ear infection. Depending on severity of infection oral therapy with antibiotics amoxicillin-clavulinate is needed. 

Conjunctivitis: Bacterial conjunctivitis in older children is commonly caused by H. influenzae. It can present with ipsilateral otitis media and may systemic antibiotics. Local antibiotic eye drop may be needed.

Sinusitis: Sinusitis is frequently caused by the H. influenzae. Most common cause of sinusitis is S. pneumonia after that second most common cause is H. influenzae. It needs treatment with antibiotics oral. If severe may need hospitalization for injectable antibiotics and surgical intervention.

How to prevent Haemophilus influenzae type B disease?

HiB vaccine is incorporated in routine immunization schedules for all children by many nations across the world. The vaccine contains PRP antigen of Haemophilus influenzae type b and it is conjugated to the Tetanus toxoid

This vaccine when injected is recognized by the immunity of the host and immunity is produced against Haemophilus influenzae type b. This produces long term life long immunity against the invasive disease.

This vaccine is generally given at age 6-10 and 14 weeks with a booster at 15-18 months age. It is generally given as comnbination vaccine with DPT as quadrivalent or pentavalent or hexavalent vaccine.  These vaccine also contains diphtheria, tetatnus toxoid and pertussis components.

Local pain and swelling and fever are the most common side effects after the vaccine is given. It is injectable vaccine.

This HiB vaccine is very effective vaccine and has drastically reduced the invasive disease incidence and mortality and morbidity due to disease in countries where it was included in national immunization programs and where vaccine coverage was good in the population.

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