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Haemophilus influenzae infection

Category: Illness or disabilities

Type

Involuntary

Introduction and description

Haemophilus influenzae (formerly called Pfeiffer's bacillus or Bacillus influenzae) is a bacteria, not a virus despite its name.  It was first described in 1892 by Richard Pfeiffer during an influenza pandemic and was mistakenly considered to be the cause of influenza until 1933, when the viral etiology of influenza became apparent.
It is a Gram-negative, coccobacillary, facultatively anaerobic pathogenic bacterium belonging to the Pasteurellaceae family and the Genus: Haemophilus.

Haemophilus genus of bacteria

The Haemophilus genus of bacteria inhabit the mucous membranes of the upper respiratory tract, mouth, vagina, and intestinal tract. This genus has also been found to be part of the salivary microbiome.  The genus not only includes organisms showing commensalism with humans, but includes some significant pathogenic species such as H. ducreyi, the causative agent of chancroid. All members are either aerobic or facultatively anaerobic.   

From 1976 to 1985, 27 adult invasive Haemophilus infections were observed at the University Medical Center in Lausanne. Only 5 cases (19%) were caused by Haemophilus influenzae type b, while 12 cases (44%) were due to Haemophilus species other than H. influenzae.    PMID:  3492762

H. influenza strains

H. influenzae may be either encapsulated (typeable) or unencapsulated (nontypeable).

  • Encapsulated strains are classified on the basis of their distinct capsular antigens. Six antigenically distinct capsular types of H. influenzae  -known as types a, b, c, d, e, and f -  have been identified.   These are often referred to as strains eg Haemophilus influenzae type b strain (Hib)
  • The unencapsulated strains -  Genetic diversity among unencapsulated strains is greater than within the encapsulated group. Unencapsulated strains are termed nontypable (NTHi) because they lack capsular serotypes.

Vaccines and antibiotics

Vaccines - A vaccine for Haemophilus influenzae Type B has been available since the early 1990s, and is usually given to children under age 5 in developed countries and asplenic patients [absence of normal spleen function].  Vaccination with Hib conjugate vaccine is intended to prevent Hib infection, but does not prevent infection with NTHi strains.  Unencapsulated H. influenzae strains are unaffected by the Hib vaccine, as are all other encapsulated strains.

Antibiotics - Haemophilus influenzae produces beta-lactamases, and it is also able to modify its penicillin-binding proteins, so it has gained resistance to the penicillin family of antibiotics. Many cases are diagnosed after presenting chest infections do not respond to penicillins or first-generation cephalosporins.  Fluoroquinolone-resistant Haemophilus influenzae has been observed.  Resistance to Macrolide antibiotics (e.g., clarithromycin) has also been observed.  Resistance to trimethoprim-sulfamethoxazole (SXT) has been found.

Many nontypeable strains are resistant, this is just one study in Korea

Of the 53 NTHi isolates, 69.8% were ampicillin nonsusceptible. The nonsusceptibility rates for cefaclor were 81.1%, cefpodoxime 69.8%, and amoxicillin/clavulanate 32.1%. About 60.3% and 32.1% of the isolates were genetically β-lactamase-nonproducing ampicillin-resistant (gBLNAR) and genetically β-lactamase-producing amoxicillin/clavulanate-resistant (gBLPACR) strains, respectively. Group III amino acid substitutions comprised 65.6% of the gBLNAR strains and 70.6% of the gBLPACR strains. PMID:  30484742

Strains were also resistant to cefuroxime, cefpodoxime, and cefixime;  

Symptoms and diagnosis

Initial symptoms are usually those of an upper respiratory tract infection mimicking a viral infection, usually associated with a temperature, often low-grade. This may progress to the lower respiratory tract in a few days, with features often resembling those of a wheezy bronchitis. Sputum may be difficult to expectorate and is often grey or creamy in colour. 

Most strains of H. influenzae are under normal circumstances not pathogenic; that is, they usually live in their host without causing disease, but cause problems only when other factors - such as

  • reduced immune function
  • chronically inflamed tissues, e.g. from allergies

create an opportunity.  

In both cases one can see that the immune system and its state is key, as chronically inflamed tissues usually indicate an attack by toxins or pathogens and a severely strained immune system would also be the consequence of other pathogenic attack from for example viruses.  In general therefore these bacteria only become pathogenic when the immune system has been suppressed, compromised or is under significant pressure.

For this reason, clinical diagnosis of apparent H. influenza infection is only considered confirmed when the organism is isolated from a sterile body site. In this respect, H. influenzae cultured from the nasopharyngeal cavity or sputum would not indicate H. influenzae disease, because these sites are colonized in disease-free individuals. However, H. influenzae isolated from cerebrospinal fluid or blood would indicate H. influenzae infection.

Furthermore, use of antibiotics prior to sample collection greatly reduces the ability to diagnose which strain of the bacteria or even the bacteria itself is causing the infection, as it may kill the bacteria in the sample selected before identification is possible. This has relevance, as the bacteria may still be present in other sites.  Beyond this, H. influenzae is a finicky bacterium to culture, and any modification of culture procedures can greatly reduce isolation rates.

In the following it is important to note which strain is causing the infection as the vaccine available is strain specific.  Remember that a vaccine is only available for Haemophilus influenzae Type B, and all the strains are very quickly becoming antibiotic resistant.

Sinusitis, COPD,: acute otitis media

Nontypeable Haemophilus influenzae (NTHi) is a commensal microbe often isolated from the upper and lower respiratory tract. This bacterial species can cause sinusitis, acute otitis media in preschool children, chronic obstructive pulmonary disease, as well as conjunctivitis and bacteremia. … the burden of H. influenzae-related infections has been increasingly dominated by NTHi. Understanding the ability of NTHi to cause infection is currently an expanding area of study. PMID:  27508518

Bronchitis

Colonization of the adult respiratory tract with nontypable Haemophilus influenzae is a dynamic process with new strains being acquired and replacing old strains periodically. The organism is a common cause of exacerbations of chronic bronchitis based on 3 lines of evidence: quantitative culture of the lower airways obtained by protected specimen brush, antibiotic trials, and serological studies. Nontypable H. influenzae expresses multiple adhesin molecules that mediate adherence to the respiratory tract mucosa. Recent studies have established that the bacterium penetrates the mucosal surface and survives intracellularly and in the interstitium of the submucosa. The organism shows a remarkable degree of antigenic diversity on its surface, including phase variation of lipooligosaccharide, antigenic heterogeneity of surface proteins, point mutations in genes encoding surface proteins and horizontal transfer of genes. These strategies facilitate evasion of the human immune response. Substantial progress has been made in identifying vaccine antigens to prevent infections caused by nontypable H. influenzae.  PMID:  10749549

Bacteremia or sepsis

Haemophilus influenzae is an important cause of invasive disease. The infant rat is the accepted model of invasive H. influenzae disease. Here, we report the genome sequences of six nontypeable H. influenzae strains that establish bacteremia in the infant rat.  PMID:  26404588

Septic arthritis

Haemophilus influenzae …. can cause endocarditis, meningitis, septicemia, pneumonia, & septic arthritis. …... Non-typeable H.influenzae are emerging pathogens especially in the elderly population. We report a case of a 73 year old woman with bacteremia, endocarditis and septic arthritis due to H.influenzae serotype f. PMID:  28725560

Pericarditis

This example shows that not only H. infleunzae can cause pericarditis, but other members of the Haemophilus genus can

Purulent pericarditis is most often caused by Staphylococcus aureus, Streptococcus pneumoniae, or Haemophilus influenzae. The number of H. parainfluenzae infections has been increasing; in rare cases, it has caused endocarditis. We report a case of purulent pericarditis caused by H. parainfluenzae in a 62-year-old woman who reported a recent upper respiratory tract infection. PMID: 24391338

Cellulitis

Orbital cellulitis is inflammation of eye tissues behind the orbital septum. It is most commonly caused by an acute spread of infection into the eye socket from either the adjacent sinuses or through the blood.  The implications here are that the vaccine introduced the bacteria into the blood and caused the cellulitis:

To evaluate the microbiology of paediatric orbital cellulitis in blood cultures and abscess drainage cultures following the introduction of the Haemophilus influenzae serotype b (Hib) vaccine.  Although there were no cases of H. influenzae bacteremia or meningitis in our cases of orbital cellulitis, abscess drainage fluid microbiology indicated that H. influenzae remains a cause of orbital cellulitis. H. influenzae abscess volume was significantly larger than other bacterial abscesses and was associated with abscesses of mixed bacterial growth in older children.  PMID:  25900771

Pneumonia

Bacteria are the most common cause of community acquired pneumonia with Streptococcus pneumoniae isolated in nearly 50% of cases.  Other commonly isolated bacteria include: Haemophilus influenzae in 20%, Chlamydophila pneumoniae in 13%, , and Mycoplasma pneumoniae in 3%.

Stroke

The Haemophilus influenzae bacteria is implicated in causing strokes.....

Children, who presented with stroke, were evaluated at the Division of Pediatric Neurology or admitted to King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia during the periods July 1992 to February 2001  …Of the 104 Saudi children with stroke, seen during the study periods ….. infectious and inflammatory disorders of the circulatory system were the identified risk factor in 18 (17.3%). …. The causative organism was identified in 3 of them and consisted of Haemophilus influenzae (in a 5-month-old girl), ….. PMID:16532131

Osteomyelitis

Osteomyelitis or OM -  is infection and inflammation of the bone or bone marrow. It can be usefully subclassified on the basis of the causative organism - pyogenic bacteria or mycobacteria -  and the route, duration and anatomic location of the infection.  For example, osteomyelitis of the jaws is different in several respects from osteomyelitis present in a long bone. Vertebral osteomyelitis is another possible presentation

Endometritis

A 48-year-old female presented to the emergency department with a 3-day history of lower abdominal pain and fever. On physical examination she was tachycardic, hypotensive and had fundic tenderness to palpation. Imaging showed uterine leiomyomas and no IUD. Blood cultures grew a non-typable H. influenzae. Endometrial biopsy demonstrated acute endometritis. Tissue Gram stains and cervico-vaginal cultures were negative; however, polymerase chain reaction (PCR) determined presence of H. influenzae on the formalin-fixed, paraffin-embedded tissue biopsy. Evidence of H. influenzae in the endometrium demonstrates that the uterus can be the nidus for sepsis when invasive H. influenzae is found with no distinct usual primary focus. This case underscores the importance pathologic diagnosis and molecular testing.  PMID: 23537790

Premature birth, Miscarriages and stillbirths

There are a great number of bacteria that can attack both the mother and fetus in the womb.  For example

Unencapsulated Haemophilus influenzae frequently causes noninvasive upper respiratory tract infections in children ... A number of studies have reported an increased incidence in neonates [in the study]…. The incidence rate of invasive unencapsulated H. influenzae disease was 17.2 times greater among pregnant women compared with nonpregnant women. ...infection during the first 24 weeks of pregnancy was associated with fetal loss and extremely premature birth.  ..... infection during the second half of pregnancy was associated with premature birth in 8 of 28 cases and stillbirth in 2 of 28 cases .    PMID:  24643602

Meningitis

Several types of bacteria can cause meningitis.   In premature babies and newborns up to three months old, common causes are  group B streptococci, Escherichia coli and  Listeria monocytogenes. Older children are more commonly affected by Neisseria meningitidis (meningococcus), and Streptococcus pneumoniae .  And those under five by Haemophilus influenzae type B.  

Conjunctivitis

Common bacteria responsible for non-acute bacterial conjunctivitis are Staphylococci and Streptococci.  Bacteria such as Chlamydia trachomatis or Moraxella can also cause persistent conjunctivitis without much redness. Other cases of bacterial conjunctivitis are associated with Neisseria gonorrhoeae, β-hemolytic streptococci, Corynebacterium diphtheria, Haemophilus influenzae.  Hyperacute cases are usually caused by Neisseria gonorrhoeae or N. meningitidis.

Urinary tract infection

Haemophilus influenzae commonly causes upper respiratory tract infections and has only rarely been reported etiology of urinary tract infections. Since the introduction of the Haemophilus influenzae b (Hib) vaccine, non-typable haemophilus species now cause the majority of invasive disease in Europe.  We report a case of an adult man with non-typable Haemophilus influenzae septicemia, urinary tract infection and bilateral renal stone disease. The patient presented with right sided flank pain and a CT scan showed bilateral renal stones and a right sided ureteral stone causing obstruction. Haemophilus influenzae was identified in blood and urine.  PMID:  30197697

Urogenital infection

Haemophilus influenzae rarely causes pyogenic infections in the female genital tract, and even less commonly does this lead to systemic infections. Novel monoclonal antibody therapies targeting interleukin-17 may impair mucosal immunity, … Here, we describe a case of H. influenzae bacteremia associated with pyosalpinx and hypothesize that immunomodulatory treatment for psoriasis predisposed our patient to this infection.  PMID:  30581886

Causes

We saw that the immune system and its state is key, as to the whether these bacteria become pathogenic.  In general these bacteria only become pathogenic when the immune system has been suppressed, compromised or is under significant pressure.

Significant co-morbidity

Haemophilus influenzae is an important cause of invasive infection but contemporary data in non-selected populations is limited.  A Population-based surveillance for Haemophilus influenzae bacteremia was conducted in seven regions in Australia, Canada, and Denmark during 2000-2008.

Very young and old patients were at highest risk. The serotypes causing disease varied according to age with nearly all cases in the elderly due to NTHi. The presence of comorbid medical illness was common …. Factors independently associated with death at 30-days in logistic regression analysis included male gender, hospital-onset disease, and older age …. PMID: 21094183

Vaccines - overload

The DTaP-IPV-Hib vaccination contains Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b.  It has already been “associated with an increased risk of febrile seizures on the day of the first 2 vaccinations given at 3 and 5 months."  This vaccine also contains aluminium – see list below.   Aluminium is known to destroy the blood brain barrier.  In this case we have a vaccine that would put the immune system under significant pressure.

vaccine Excipient and adjuvant
DTaP/Hib (TriHIBit) Aluminum potassium sulfate, ammonium sulfate, bovine extract, formaldehyde or formalin, gelatin, polysorbate 80, sucrose, thimerosal
DTaP-IPV (KINRIX) Aluminum hydroxide, calf serum, formaldehyde, glutaraldehyde, lactalbumin hydrolysate, neomycin sulfate, polymyxin B, polysorbate 80
DTaP-HepB-IPV (Pediarix) Aluminum hydroxide, aluminum phosphate, calf serum, lactalbumin hydrolysate, formaldehyde, glutaraldhyde, neomycin sulfate, polymyxin B, polysorbate 80, yeast protein
DtaP-IPV/Hib (Pentacel) Aluminum phosphate, bovine serum albumin, formaldehyde, glutaraldehyde, MRC-5 cellular protein, neomycin, polymyxin B sulfate, polysorbate 80, 2-phenoxyethanol


Vaccines and Epiglottitis

Historically epiglottitis has been considered a childhood disease. However, the introduction of the Haemophilus influenzae type B vaccine has decreased the incidence of epiglottitis in children. It is important to recognize modern epiglottitis as a disease of adults. This report describes a case of acute bacterial epiglottitis in an adult patient secondary to infection caused by Streptococcus pyogenes, a group A streptococcal infection. …. The progression of this disease can lead to abrupt airway obstruction necessitating emergent airway management.  PMID:  30443621

An exceptionally important rider needs to be added to this paragraph.  Both H. influenzae and S. pneumoniae can be found in the upper respiratory system of humans. When both bacteria are placed together into a nasal cavity, within 2 weeks, only H. influenzae survives. When either is placed separately into a nasal cavity, each one survives. Upon examining the upper respiratory tissue from mice exposed to both bacteria species, an extraordinarily large number of neutrophils (immune cells) was found. In mice exposed to only one bacterium, the cells were not present.

Lab tests showed neutrophils exposed to dead H. influenzae were more aggressive in attacking S. pneumoniae than unexposed neutrophils.  It is the combination of the two species that triggers an immune system response that is not set off by either species individually.

By vaccinating anyone against H. influenza, we have thus ensured that our immune system no longer works – it has been compromised.

Immunosuppressants

The standard form of treatment for diseases classified as ‘auto-immune’ is to provide various forms of immunosuppressants.  Immunosuppressants suppress the immune system.   By doing so the actual pathogen causing the disease spreads and it can go all over the body.  Haemophilus Influenzae bacteria are just one type of bacteria amongst many that become pathogenic when immunosuppressants are used to suppress symptoms.

Medicine is almost entirely based currently on symptom suppression, not in addressing the cause.  By classifying any disease as auto-immune, - the immune system apparently attacking the body, -the medical profession have ignored any suggestion that a pathogen or toxin may be responsible.

Hydroxychloroquine is used as an immunosuppressant  to “reduce inflammation in the treatment of rheumatoid arthritis and lupus”.  Bisphosphonates are immunosuppressants used to treat osteoporosis.

Eye involvement represents a common finding in patients with systemic autoimmune diseases, particularly  rheumatoid arthritis, Sjogren syndrome, seronegative spondyloarthropathy, and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. …. The eye injury may be .... infectious, as well as iatrogenic, as in the case of hydroxychloroquine, chloroquine, corticosteroids, and bisphosphonates. PMID:  2649448

Iatrogenic illness is disease caused by the diagnosis, manner, or treatment of a physician.  It may result from medical errors, such as mistakes made in surgery, or the prescription or dispensing of the wrong therapy, such as a drug.

Hospital equipment

Please note that there are other examples of hospitals themselves being the source of infection

Haemophilus influenzae rarely causes acute endometritis and the few published cases have always been associated with intrauterine devices (IUD). PMID: 23537790

Surgery

Bacterial meningitis is a rare complication of adenotonsillectomy. We present a case of meningitis due to nontypeable Haemophilus influenzae … after adenotonsillectomy.  Pulsed-field gel electrophoresis patterns indicated that the oral cavity was the source of H. influenzae …..  As bacteremia is thought to be one of the etiologies of meningitis, we prospectively investigated the rate of bacteremia as a complication of adenotonsillectomy. Of the 46 patients included in the study, mean age of five years old, 11 (24%) had positive blood cultures during the operation. H. influenzae was the commonest organism grown  PMID:  24396981

Treatment

Address the cause

References and further reading

  • Semin Respir Infect. 2000 Mar;15(1):41-51.  Haemophilus influenzae in chronic bronchitis.  Murphy TF1.  1 Department of Medicine, State University of New York at Buffalo, NY, USA.
  • Open Microbiol J. 2018 Jul 31;12:243-247. doi: 10.2174/1874285801812010243. eCollection 2018. Nontypable Haemophilus influenzae Septicemia and Urinary Tract Infection Associated with Renal Stone Disease. Stærk M1, Tolouee SA2, Christensen JJ1,3.
  • Open Forum Infect Dis. 2018 Jun 26;5(7):ofy146. doi: 10.1093/ofid/ofy146. eCollection 2018 Jul.  Breech at the Border: An Atypical Case of Invasive Haemophilus influenzae in a Patient on a Novel Immunotherapeutic.  Howard-Anderson J1, Satola SW1,2, Collins MH1.
  • Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b JAMA 2012, Yuelian Sun, Jakob Christensen, Anders Hviid, Jiong Li
  • Diagn Microbiol Infect Dis. 2013 Jun;76(2):235-6. doi: 10.1016/j.diagmicrobio.2013.02.010. Epub 2013 Mar 26.  Haemophilus influenzae acute endometritis with bacteremia: case report and literature review.  Martin D1, Dbouk RH, Deleon-Carnes M, del Rio C, Guarner J.
  • Pelvic abscess associated with Haemophilus influenzae bacteremia.  Guerrier G, Morisse L, Perrin D.  Int J Gynaecol Obstet. 2009 Nov;107(2):152-3. doi: 10.1016/j.ijgo.2009.06.004. Epub 2009 Jul 7. No abstract available.   PMID:  19586626
  • Haemophilus influenzae type e meningitis and bacteremia in a healthy adult. -Al-Tawfiq JA. Intern Med. 2007;46(4):195-8. Epub 2007 Feb 15. Review. PMID: 17301516
  • Transient Haemophilus influenzae type b bacteremia in a healthy child.  Matsuda K, Sakata Y, Tani H, Kimura K, Matsuishi T.  Kurume Med J. 2005;52(1-2):53-6.  PMID: 16119613
  • Biliary infection and bacteremia caused by beta-lactamase-positive, ampicillin-resistant Haemophilus influenzae in a diabetic patient.  Oksuz S, Ozturk E, Sahin I, Ertor O, Kaya D.  Jpn J Infect Dis. 2005 Feb;58(1):34-5.  PMID:  15728989
  • Clin Pract Cases Emerg Med. 2018 Oct 16;2(4):338-340. doi: 10.5811/cpcem.2018.9.39280. eCollection 2018 Nov.  Acute Epiglottitis with Concurrent Pneumonia and Septic Shock in an Alcoholic Adult Patient.  Chitty A1, Taylor K1.
  • IDCases. 2017 Jun 27;9:79-81. doi: 10.1016/j.idcr.2017.06.008. eCollection 2017.  Haemophilus influenzae serotype f endocarditis and septic arthritis.  Oikonomou K1, Alhaddad B1, Kelly K1, Rajmane R1, Apergis G1.

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