Haemophilus influenzae is a Gram-negative bacterium that can cause several types of infections in humans, most notably meningitis in young children. There are six serotypes of H. influenzae defined by their capsular polysaccharides. Type b is the most virulent and was a major cause of childhood meningitis, pneumonia, and epiglottitis prior to the development of effective vaccines in the 1990s. Diagnosis involves culture and identification of the bacteria, while treatment requires prompt antibiotic therapy. Vaccination against H. influenzae type b has dramatically reduced the incidence of invasive disease in children under 5 years old.

1. 1

2. University of Azad Jammu &
Kashmir
Faculty Of Health Sciences

3. Presentation Topic:
Haemophilus Influenza

4. Contents
• Introduction
• Epidemiology
• Types
• Identification Methods
• Pathogenecity
• Virulence Factors
• Diagnosis
• Vaccination

5. Introduction
 Taxonomic Confusion in Family Pasteurellaceae
 Three Genera:
• Haemophilus: Most Common in Human Disease
• Actinobacillus
• Pasteurella
 Haemophilus
 Common Characteristics of Family
• Small (0.2 x 0.3-2.0 mm) Gram-negative Nonmotile bacilli
• Aerobic or facultatively anaerobic
• Fastidious growth requirements

6. Scientific Classification
Domain
• Kingdom
• Phylum
• Class
• Order
• Family
• Genus
• Species
Bacteria
• Eubacteria
• Proteobacteria
• Gammaproteobacteria
• Pasteurelales
• Pasteurellaceae
• Haemophilus
• H.influenzae

7. Characteristics of
Haemophilus influenzae
• Formerly called Pfeiffer's bacillus or Bacillus
influenzae.
• Aerobic gram-negative bacteria
• Polysaccharide capsule Pathogenic bacterium
• Six different serotypes (a-f) of polysaccharide
capsule
• 95% of invasive disease caused
by type b
• H. influenzae was first described in 1892 by Richard
Pfeiffer during an influenza pandemic.

8. Characteristics Cont.
• Most strains of H. influenzae are opportunistic
pathogens; that is, they usually live in their
host without causing disease, but cause
problems only when other factors (such as a
viral infection, reduced immune function or
chronically inflamed tissues, e.g. from
allergies) create an opportunity. They infect
the host by sticking to the host cell using
trimeric autotransporter adhesins.

9. Epidemiology
• Occurrence:
Hib disease occurs worldwide.
• Reservoir:
Humans (asymptomatic carriers) are the only known
reservoir. Hib does not survive in the environment on
inanimate surfaces
• Transmission:
The primary mode of Hib transmission is presumably by
respiratory droplet spread, although firm evidence for this
mechanism is lacking. Neonates can acquire infection by
aspiration of amniotic fluid or contact with genital tract
secretions during delivery.

10. Epidemiology Cont.
• Temporal Pattern:
Several studies in the prevaccine era described a
bimodal seasonal pattern in the United States, with one
peak during September through December and a
second peak during March through May. The reason
for this bimodal pattern is not known.
• Communicability:
The contagious potential of invasive Hib disease is
considered to be limited. However, certain
circumstances, particularly close contact with a case-
patient (e.g., household, child care, or institutional
setting) can lead to outbreaks or direct secondary
transmission of the disease

11. Gram Staining
• Gram-stained and microscopic
observation of a specimen of
H. influenzae will show Gram-
negative, rod shapes with no
specific arrangement.
• The cultured organism can be
further characterized using
catalase and oxidase tests,
both of which should be
positive.
• Further serological testing is
necessary to distinguish the
capsular polysaccharide and
differentiate between H.
influenzae b and
nonencapsulated species

12. Serotypes
In 1930, two major categories of H.
influenzae were defined: the
unencapsulated strains and the
encapsulated strains. Encapsulated
strains were classified on the basis of
their distinct capsular antigens. There
are six generally recognized types of
encapsulated H. influenzae: a, b, c, d, e,
and f.

13. Haemophilus influenzae types
• Haemophilus influenzae was first described by Pfeiffer in 1892.
Forty years later Pittman identified six capsular polysaccharides
(types) of H. influenzae (a, b, c, d, e, and f) whose structures
were later elucidated.
• Systemic infections in otherwise healthy children caused by this
bacterial species occur throughout the world and are due mostly
to H. influenzae type b (Hi b). Pittman also showed that a small
fraction of H. influenzae infections was caused by type a (Hi a)
and by type b & type f.
• In a longitudinal study of 104 children with H.
influenzae infections from June 1964 through October 1965, Sell
et al. found Hi a among carrier and disease isolates. The peak Hi
a carriage was in children up to 1 year of age.

14. Culture
• Bacterial culture of H.
influenzae is performed on
agar plates, the preferable
one being chocolate agar,
with added X (hemin) and V
(nicotinamide adenine
dinucleotide) factors at
37 °C in a CO2-enriched
incubator. Blood agar
growth is only achieved as
a satellite phenomenon
around other bacteria.
Colonies of H. influenzae
appear as convex, smooth,
pale, grey or transparent
colonies
Chocolate Agar

15. • Hemin (trade
name Panhematin) is
an iron-
containing porphyrin. Mo
re specifically, it
is protoporphyrin
IX containing
a ferric iron ion (heme B)
with a chloride ligand.
• Hematin is considered
the "X factor" required
for the growth
of Haemophilus
influenzae
Solid Hemin
Hemin

16. Clinical Features
• Invasive disease caused by H.
influenzae can affect many organ
systems. The most common types
of invasive disease are meningitis,
epiglottitis, pneumonia, septic
arthritis, and cellulitis.

17. • Pneumonia (lung infection)
• Bacteremia (blood
infection)
• Meningitis (infection of the
covering of the brain and
spinal cord)
• Epiglottis (swelling of the
windpipe that can cause
breathing trouble)
• Cellulites (skin infection)
• Infectious arthritis
(inflammation of the joint)
Diseases

18. Meningitis
• Meningitis is infection of the
membranes covering the brain and
spinal cord and is the most common
clinical manifestation of invasive Hib
disease, accounting for 50%-65% of
cases in the prevaccine era.
• Hallmarks of Hib meningitis are
fever, decreased mental status, and
stiff neck (these symptoms also
occur with meningitis caused by
other bacteria).
• Hearing impairment or other
neurologic sequelae occur in 15%-
30% of survivors.
• The case-fatality rate is 3%-6%,
despite appropriate antimicrobial
therapy

19. Symptoms of Meningitis
• Possible symptoms of Haemophilus meningitis
include:
• Nausea or vomiting
• Fever
• Headache
• Sensitivity to light
• Seizures
• Anorexia
• Change in mental status, such as irritability
• Stiff neck

20. Long-term effects of H. Meningitis
• Survivors of
Haemophilus meningitis
may experience
permanent damage
caused by inflammation
around the brain, mostly
involving neurological
disorders.
• Long-term complications
include brain damage,
hearing loss, and mental
retardation.

21. Epiglottitis
• Epiglottitis is an
infection and
swelling of the
epiglottis, the tissue
in the throat that
covers and protects
the larynx during
swallowing.
Epiglottitis may
cause life-
threatening airway

22. Cellulitis
• Cellulitis is a bacterial
infection involving the inner layers of
the skin. It specifically affects
the dermis and subcutaneous fat.
• Signs and symptoms include an area
of redness which increases in size
over a few days. The borders of the
area of redness are generally not
sharp and the skin may be swollen.
While the redness often turns white
when pressure is applied, this is not
always the case. The area of
infection is usually painful.
• Lymphatic vessels may occasionally
be involved, and the person may
have a fever and feel tired.

23. Sites of Infection of
Cellulitis
• The legs and face are the most
common sites involved, though cellulitis
can occur on any part of the body. The
leg is typically affected following a break
in the skin. Other risk factors
include obesity, leg swelling, and old
age. For facial infections, a break in the
skin beforehand is not usually the case.

24. Pneumonia
• Pneumonia occurs when
the lungs become infected,
causing inflammation
(swelling).
• H. influenzae pneumonia
is considered non-invasive
if there’s not bacteremia or
pleural fluid (fluid
surrounding the lungs)
infection occurring at the
same time.
• When there is pneumonia
with either bacteremia or
pleural fluid infection
occurring at the same time,
it is considered invasive.

25. . Symptoms of pneumonia
Symptoms of pneumonia usually include:
• Fever and chills
• Cough
• Shortness of breath
• Sweating
• Chest pain
• Headache
• Muscle pain or aches
• Excessive tiredness

26. Bacteremia
• Bacteremia is an infection of the blood. It can cause symptoms such
as:
• Fever and chills
• Excessive tiredness
• Pain in the belly
• Nausea with or without vomiting
• Diarrhea
• Anxiety
• Shortness of breath or difficulty breathing
• Altered mental status (confusion)
Bacteremia from H. influenzae can occur with or without pneumonia

27. Bacteremia

28. Septic arthritis
• Septic arthritis (joint infection), cellulitis
(rapidly progressing skin infection which
usually involves face, head, or neck), and
pneumonia (which can be mild focal or severe
empyema) are common manifestations of
invasive disease. Osteomyelitis (bone
infection) and pericarditis (infection of the sac
covering the heart) are less common forms of
invasive disease.

29. Septic Arthritis

30. Otitis media and acute bronchitis
• Otitis media and
acute bronchitis due
to H. influenzae are
generally caused by
nontypeable strains.
Hib strains account
for only 5%-10%
of H.influenzae cau
sing otitis media.

31. Other Infections
• Non-type b encapsulated strains can cause
invasive disease similar to type b infections.
Nontypeable (unencapsulated) strains may
cause invasive disease but are generally less
virulent than encapsulated strains.
Nontypeable strains are rare causes of
serious infection among children but are a
common cause of ear infections in children
and bronchitis in adults

32. Haemophilus influenzae type b
• Organism colonizes nasopharynx
• In some persons organism invades
bloodstream and cause infection at
distant site
• Antecedent upper respiratory tract
infection may be a contributing factor

33. Type b Infections
• Naturally acquired Diseases:
H. influenzae seems to occur in
humans only. In infants and young children, H.
influenzae type b (Hib) causes bacteremia,
pneumonia, epiglottitis and acute bacterial
meningitis. On occasion, it causes cellulitis,
osteomyelitis, and infectious arthritis.
• Serious complications:
The serious complications of HiB are brain
damage, hearing loss, and even death.

34. Medical Management
• Hospitalization is generally required for invasive Hib
disease. Antimicrobial therapy with an effective third-
generation cephalosporin (cefotaxime or ceftriaxone),
or chloramphenicol in combination with ampicillin
should be begun immediately. The treatment course
is usually 10 days. Ampicillin-resistant strains of Hib
are now common throughout the United States.
Children with life-threatening illness in which Hib may
be the etiologic agent should not receive ampicillin
alone as initial empiric therapy.

35. Diagnosis
• H. influenzae, in a Gram stain of a sputum sample,
appear as Gram-negative coccobacilli.
• Haemophilus influenzae requires X and V factors for
growth. In this culture haemophilus has only grown
around the paper disc that has been impregnated with X
and V factors. There is no bacterial growth around the
discs that only contain either X or V factor.
• Clinical features may include initial symptoms of an
upper respiratory tract infection mimicking a viral
infection, usually associated with fevers, often low-grade.
This may progress to the lower respiratory tract in a few
days, with features often resembling those of a wheezy
bronchitis.

36. Risk Factors
• While the Haemophilus influenzae bacteria is unable to
survive in any environment outside of the human body,
humans can carry the bacteria within their bodies without
developing any symptoms of the disease.
• It spreads through the air when an individual carrying
the bacteria coughs or sneezes. The risk of developing
Haemophilus meningitis is most directly related to an
individual's vaccination history, as well as the
vaccination history of the general public.

37. Prevention & Vaccination
• Act HIB (Hib-vaccine)
• Effective vaccines for Haemophilus influenzae Type B have been available
since the early 1990s, and is recommended for children under age 5 and
asplenic patients. The World Health Organization recommends a
pentavalent vaccine, combining vaccines against diphtheria, tetanus,
pertussis, hepatitis B and Hib. There is not yet sufficient evidence on how
effective this pentavalent vaccine is in relation to the individual vaccines.
• Hib vaccines cost about seven times the total cost of vaccines against
measles, polio, tuberculosis, diphtheria, tetanus, and pertussis.
Consequently, whereas 92% of the populations of developed countries was
vaccinated against Hib as of 2003, vaccination coverage was 42% for
developing countries, and only 8% for least-developed countries.
• The Hib vaccines do not provide cross-protection to any other Haemophilus
influenzae serotypes like Hia, Hic, Hid, Hie or Hif.

38. Side Effects of Vaccination
• Due to routine use of the Hib conjugate vaccine in the
U.S. since 1990, the incidence of invasive Hib
disease has decreased to 1.3/100,000 in children.
However, Hib remains a major cause of lower
respiratory tract infections in infants and children in
developing countries where the vaccine is not widely
used. Unencapsulated H. influenzae strains are
unaffected by the Hib vaccine and cause ear
infections (otitis media), eye infections
(conjunctivitis), and sinusitis in children, and are
associated with pneumonia.

39. Haemophilus influenzae Incidence
NOTE: Dramatic decrease in
children <5 years; remains
constant in older children
(per100,000)