What Is Haemophilus Influenzae?

Haemophilus influenzae is a small gram negative coccobacillus that is a commensal part of the human microbiome, including human upper respiratory tract. There are many strains of H. influenzae, and they are considered as part of natural flora.

H. influenzae is an opportunistic bacterium, meaning that they live with their host without causing disease, and may be associated with disease when host conditions are compromised, such as malnutrition, viral infection, reduced immune function or chronically inflamed tissues, chronic lung disease, and major imbalances in the microbiome allow them to.

Approximately 20% of infants are colonized in the first year of life and this rises progressively over time.

Hib carrier state increased from 4% to 47.5% in children attending day care for longer than 6 months.

By the age of 5–6 years more than 50%-75% of children will be colonized with this bacterium and most healthy adults (at least 75 %) will be.

There are encapsulated and nontypable unencapsulated bacteria. There are six encapsulated serotypes: a, b, c, d, e, and f. The Hib vaccine targets one strain: strain b.

If host conditions are challenged, H. influenzae (all types) can cause respiratory tract infections and invasive disease, including:

• pneumonia
• otitis media
• epiglottitis (swelling in the throat)
• eye infections 
• bloodstream infection
• meningitis
• cellulitis (skin infection)
• infectious arthritis (inflammation of the joint)

First described in 1892 by Richard Pfeiffer, H. influenzae was thought to be the cause of influenza well into the 1930s.

Before the introduction of vaccination, Hib incidence was 30/100,000 among caucasians, and 600/100,000 among indigenous people in Alaska.

In the United States, the incidence of invasive HI meningitis quadrupled between 1940 and 1970, with the most dramatic increase from 1955 to 1970.(1) The polio vaccine came out in 1955.

The same sudden rise after 1939 was recorded in Helsinski, Finland. Notice how few cases are recorded until 1948/1949. The DPT vaccine came out in 1948.

The same trend occurred in Scotland and Sweden. In Orebro County, Sweden, a 2.5-fold increase in the incidence of Haemophilus influenzae (HI) meningitis was found between 1970 and 1980.

The incidence of invasive Hib disease increased as fewer and fewer infants were being breastfed, and as more and more infants and young children were being vaccinated. Breastfeeding is extremely protective against HI meningitis.

Routine vaccination against diphtheria, tetanus and pertussis began in 1948, the polio vaccine began testing in 1954, approved in 1955–could vaccinations have increased the rate at which this commensal bacteria became invasive, by “provoking” invasive disease?

This is similar to what happened with poliomyelitis.

Breastfeeding

Breastfeeding naturally prevents invasive Hib meningitis. Breastfeeding was discovered to have a protective effect from Hib meningitis, a protection that lasts 5-10 years. A short breastfeeding period (less than 13 weeks) increases the risk of invasive Hib by 3.8 times. Children with a history of frequent infections have an increased risk of  4.5 times more often. For each additional week a child is breastfed, their risk for invasive hib disease decreases 5%.

Breast milk has an inhibitory effect on the attachment of bacteria to the mucous membrane of the nasopharynx.

The graph show below shows that a decrease in the number of breastfed babies is followed by an increase in the Hib incidence, and when the number of breastfed babied increased again – Hib incidence decreased.

This graph also demonstrates a correlation between vaccine coverage rates. As more and more infants were vaccinated, the incidence of invasive hib increased. After introduction of the Hib vaccine, cases of meningitis due to hib b decreased, however, other serotypes have taken their place.

Vaccination

The first Hib vaccine was introduced in the United States in 1985. The Hib vaccine targets only strain b.

While cases of invasive Hib caused by the b strain decreased initially, other strains have taken their place and invasive Hib disease is on the rise:

“Compared with 2002–2008, the estimated incidence of invasive H. influenzae disease increased by 16%, driven by increases in disease caused by serotype a and nontypeable strains.”

Nontypeable H. influenzae now causes the majority of invasive H. influenzae disease in all age groups.

Instances of invasive disease have occurred in recently vaccinated infants. For example, a 10-week old baby girl and a 5-month-old baby boy both presented with bacterial meningitis caused by Haemophilus influenzae type b a few days after vaccination. 

A healthy, 15-month-old girl, previously vaccinated, developed HI meningitis strain b.

A 17-month-old vaccinated Kuwaiti boy presenting with meningitis, also Hib type b.

A study found an unbalanced distribution of reports of meningitis in the first 6 weeks after vaccination, suggesting of the possibility that some cases are triggered by vaccination. Forty-three percent of the meningitis cases occurred after hemophilus influenzae b vaccination.

Vaccine Types

The first conjugate vaccine against Hib was introduced in December 1987.

Currently, there are three FDA approved vaccines against invasive Hib disease. They are polysaccharide conjugate vaccines, which is a type of inactivated bacterial vaccine. All three vaccines target Hib type b.

Each vaccine is a 4 dose series given at: 2m, 4m, 6m and 15-18m. ActHIB & HIBERIX contain 25 mcg of tetanus toxoid in lieu of an aluminum adjuvant. PedvaxHIB contains an aluminum adjuvant in the form of amorphous aluminum hydroxyphosphate sulfate.

Click vaccine to read vaccine insert:

ActHIB  >>>

PedvaxHIB >>>

HIBERIX >>>

Postmarketing Adverse Reactions for HIB Vaccines

• Syncope
• Apnea
• Anaphylaxis
• Urticaria
• Angioedema
• Convulsions
• Febrile seizures
• Lymphadenopathy
• Hypotonia
• Cyanosis
• Somnolence
• Extensive limb swelling
• Peripheral edema
• Pruritis
• Rash

Invasive Hib disease by serotype, Minnesota 2017 (n=119)

While the vaccine only targets serotype b, over 98% of invasive hib is caused by other serotypes. See the graph here.

1. Protective effect of breastfeeding: an ecologic study of Haemophilus influenzae meningitis and breastfeeding in a Swedish population

“There seems to be an association between high breastfeeding rate in the population and a reduced incidence of HI meningitis 5 to 10 years later.”

2. Protective effect of breastfeeding on invasive Haemophilus influenzae infection: a case-control study in Swedish preschool children

“Multivariate analysis showed a significant association between invasive HI infection and two independent factors, i.e. short duration (< 13 weeks) of exclusive breastfeeding, odds ratio (OR) 3.79 (95% confidence interval [CI] 1.6-8.8) and history of frequent infections, OR 4.49 (95% CI : 1.0-21.0). For the age at onset 12 months or older, the associations were stronger, OR 7.79 (95% CI : 2.4-26.6) and 5.86 (95% CI : 1.1-30.6), respectively.”

3. Breastfeeding protects against infectious diseases during infancy in industrialized countries. A systematic review

“Four out of five studies observed decreased effects on overall infections in breastfed infants. With regard to gastrointestinal infections, six out of eight studies suggested that breastfeeding had a protective effect. Thirteen out of 16 studies concluded that breastfeeding protects infants against respiratory tract infections. Five studies combined duration and exclusiveness of breastfeeding. All studies observed a protective dose/duration-response effect on gastrointestinal or respiratory tract infections. These studies strongly suggest that breastfeeding protects infants against overall infections, gastrointestinal and respiratory tract infections in industrialized countries.”

4. Haemophilus influenzae Type b Meningitis in the Short Period after Vaccination: A Reminder of the Phenomenon of Apparent Vaccine Failure

We present two cases of bacterial meningitis caused by Haemophilus influenzae type b (Hib) which developed a few days after conjugate Hib vaccination. This phenomenon of postimmunization provocative time period is reviewed and discussed. These cases serve as a reminder to clinicians of the risk, albeit rare, of invasive Hib disease in the short period after successful immunization.

Case 1: A 10-week-old girl presented to another hospital with fever, refusal to eat, grunting respirations, and hypertonicity of 48-hour duration. All symptoms began one day after she had received the first dose of the combination Infanrix-IPV+Hib vaccine (a combined vaccine against diphtheria, tetanus, pertussis, polio, and Hib infections). Her parents reported that she had been perfectly healthy the day before vaccination.

Case 2: A 5-month-old boy presented to our hospital with fever, apathy, vomiting, and diarrhea of 24-hour duration. All symptoms began 6 days after he received the second dose of the Infanrix-IPV+Hib vaccine. His parents reported that he had been perfectly healthy on the day before vaccination.

5. Haemophilus influenzae and the lung (Haemophilus and the lung)

“H. influenzae is a component of the normal upper respiratory tract flora and is well recognized to be an important cause of systemic infection. It is also a major cause of a variety of respiratory conditions and has had a relatively low profile in this respect in comparison to some other pathogens; such as Mycobacterium tuberculosisand Streptococcuspneumoniae.”

“Recently there has been increasing recognition that this bacterium has a role in chronic lower respiratory tract inflammation. However the interaction between H. influenzae and the lung is still not well defined. A combination of bacterial pathogenic features and deficiency of host defense may permit this bacterium to establish infection in the lower respiratory tract resulting in inflammation and clinical disease. This review will discuss the role of H. influenzae in the lower respiratory tract in particular its role in bronchitis.”

6. Incidence of Haemophilus influenzae type b and other invasive diseases in South Korean children

“From September 1999 to December 2001, 2176 children were evaluated for possible meningitis, 1541 had no cerebrospinal fluid (CSF) findings of meningitis, 605 had CSF abnormalities (suspected bacterial meningitis) but no pathogen identified; six patients had probable Hib meningitis and eight had confirmed Hib meningitis. Hib vaccine coverage was negligible initially but increased to 16% (complete Hib immunization) and 27% (partial immunization) in final months of study. Suspected bacterial meningitis incidence was high but proven invasive Hib meningitis incidence was low. Hib was identified in only 4% of abnormal CSF.”

7. Haemophilus influenzae type b meningitis in a vaccinated and immunocompetent child

“We report a case of a fifteen-months-old girl, previously healthy and vaccinated, admitted in the emergency room with fever and vomiting. She was irritable and the Brudzinski’s sign was positive.  Despite vaccination compliance and absence of risk factors, invasive Hib disease can occur due to vaccine failure.”

8. Haemophilus influenzae type f meningitis in a previously healthy boy

“We report a case of acute bacterial meningitis in a 14-year-old boy, who was previously healthy and had been immunised againstH influenzaeserotype b (Hib). The causative pathogen was identified asH influenzaeserotype f (Hif), and was successfully treated with ceftriaxone.”

9. Invasive Haemophilus influenzae Serotype f Case Reports in Mazovia Province, Poland

“Both patients were previously healthy, were not asplenic, they received all 4 doses of anti-Hib vaccination, and to our best knowledge, had no contact with anybody contagiously ill.”