Haemophilus influenzae meningitis …

Pooja Raibagkar MD

Infectious Disorders

Updated 04.02.2024
Released 02.28.2005
Expires For CME 04.02.2027

Haemophilus influenzae meningitis

Author: Pooja Raibagkar MD

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Editor: Christina M Marra MD

Haemophilus influenzae meningitis

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Introduction

Overview

Haemophilus influenzae is a significant public health concern in many parts of the world, inducing up to 3 million cases of severe disease every year. H. influenzae type b (Hib) is a leading cause of meningitis and epiglottitis in children and pneumonia in adults in vaccine-deprived areas of the globe. In this article, the author reviews key features of epidemiology, pathophysiology, and clinical manifestations, with a focus on making timely diagnoses and preventing mortality and morbidity. Newer methods for identification and typing of the organism are discussed. With the increase in antibiotic resistance to Hib, vaccination is a powerful public health measure to rapidly reduce incidence globally. The most current vaccination guidelines and treatment recommendations are discussed in detail.

Historical note and terminology

Haemophilus influenzae was first isolated by Pfeiffer during the 1889 influenza pandemic (73), and it was believed to be the causative agent of influenza. It was called the “influenza bacillus.” Eventually, the error of this diagnostic association was recognized. The organism was given the genus name Haemophilus, meaning “blood-loving,” and the species name influenzae in recognition of the historical association.

Clinical manifestations

Presentation and course

Meningitis is the most serious form of Haemophilus influenzae type b (Hib) disease. A history of an upper respiratory tract infection preceding the onset of meningitis frequently can be obtained. Meningitis symptoms typically include fever, headache, nausea, vomiting, irritability, and lethargy, proceeding to further clouding of consciousness and, ultimately, death. Neonates with meningitis often show nonspecific signs and symptoms, such as poor feeding, irritability, hypertonia or hypotonia, and respiratory distress. (98; 99). Clinical signs include evidence of meningeal irritation, though this can be lacking in neonates, the elderly, and the deeply comatose. Focal signs may also appear, probably reflecting a complicating vasculitis. The course is frequently fulminant, with rapid neurologic deterioration leading to respiratory arrest and death (44). Therefore, initiation of appropriate antibiotic treatment must not be delayed. From an initial respiratory infection, the bacteria typically spread to the meninges hematogenously; therefore, it is no surprise that vasogenic shock frequently occurs (63). For similar reasons, Hib meningitis is frequently associated with other blood disorders, including coagulopathy, purpura, and anemia (83).

Non-type b H influenzae can also cause meningitis and manifests similarly to Hib meningitis. Widespread vaccination programs in the early 1990s shifted the paradigm with decreased incidence of Hib and increases in non-type H. influenzae. One study in Brazil found 98% of H. influenzae meningitis cases were type b from 1990 to 1999 versus 59% from 2000 to 2008, whereas non-b serotypes increased from 1% to 19% and non-typeable H. influenzae increased from 2% to 22% (34; 64; 17; 112). The mortality of these strains can be quite significant; for example, type f showed a mortality of 20% in children and 30% in adults in the United States (96), and type a showed mortality of 17% in children in Brazil (77).

Unencapsulated, nontypeable strains of H. influenzae can also cause meningitis. However, these strains usually spread by direct extension from a focus of infection rather than hematogenously (79). Thus, most patients who develop nontypeable H. influenzae (NTHi) meningitis have a preceding NTHi sinusitis or otitis media. Patients can also develop NTHi meningitis after head trauma, after a neurosurgical procedure, or if they have another cause of a cerebrospinal fluid leak. In fact, because of the association with the presence of a CSF leak, NTHi is a relatively common cause of recurrent bacterial meningitis (102; 82). Though the CSF leak can be difficult to diagnose and repair, the possibility should be carefully evaluated in any case of NTHi meningitis because repair can prevent recurrence (08; 82).

Due to its life-threatening nature, meningitis is usually the predominant clinical concern when it develops in patients with H. influenzae infection. However, the presence of meningitis does not exclude the presence of the other complications of this infection as well. As a respiratory pathogen, the most typical coexisting complications will be seen to affect the upper or lower airways. Epiglottitis is seen most often in children, involves edema of the upper airway, and can be life-threatening because acute airway obstruction can occur. It usually occurs before the development of meningitis and may be the manifestation that brings the patient to the hospital. Symptoms are often sudden in onset and include high fever, pharyngitis, stridor, cough, and dyspnea. As the throat closes, the child cannot swallow, secretions pool, and drooling occurs. Some warning symptoms may be lacking, and throat closure can be rapid. Rapid recognition of epiglottitis is important because death can occur within hours unless an airway is established (79).

Concomitant pneumonia is frequent in patients with Hib meningitis. Hib pneumonia typically has an insidious onset compared to many other bacterial pneumonias and may become clinically important before or after the onset of meningitis. On chest x-ray, the infiltrate usually appears lobar, and an associated pleural effusion often occurs. The presence of a lung focus was an independent poor prognostic factor in a Danish study (72). Unfortunately, the infection can spread directly to the pericardium, causing a purulent pericarditis (35). This complication may initially manifest as severely worsening dyspnea and tachycardia and can eventually lead to cardiac failure. However, with proper monitoring and treatment, the outcome in patients with Hib pneumonia can be good (79).

Other complications of H. influenzae infection include pyogenic arthritis and osteomyelitis, especially in children under 2 years old and usually in a single large joint (33). Sometimes arthritis can develop after a week or more of treatment for H. influenzae meningitis. These latter cases are frequently culture negative, generally considered a reactive inflammation, and attributed to immune complex deposition in the joint (76).

There is no typical rash associated with H. influenzae infection that can help in making the diagnosis, as there is for other bacterial meningitides. However, in young children who become bacteremic with H. influenzae, warm, tender cellulitis can develop, usually affecting the face. The facial location and violaceous color of this cellulitis can suggest the diagnosis (79). Because this cellulitis develops in the setting of bacteremia, patients with cellulitis are at increased risk for the bacteria to seed in yet another location, such as the meninges. Meningitis develops in up to 10% of children with H. influenzae cellulitis (36; 07; 22).

Other manifestations of H. influenzae infection include otitis media, conjunctivitis, sinusitis, urinary tract infection, and peritonitis. There have been cases of venous sinus thrombosis as a complication of meningitis (38) as well as sphenoid sinusitis related to H. influenzae (70). A strain of NTHi has been linked to a case of Fisher syndrome via molecular mimicry (42).

Prognosis and complications

Complications during acute illness are similar to those seen with meningitides of any etiology and include subdural effusion, empyema, ischemic or hemorrhagic stroke, cerebritis, ventriculitis, abscess, and hydrocephalus (79).

Biological basis

Etiology and pathogenesis

Haemophilus influenzae is a small (0.3 to 1.0 µm), gram-negative coccobacillus, sometimes appearing in short chains. It can grow under both aerobic and anaerobic conditions, is nonmotile, and often is difficult to visualize in clinical specimens.

Six distinct serotypes of H. influenzae have been identified based on the structure and antigenicity of their polysaccharide capsules. These are designated types a through f. A two-step, real-time, PCR-based assay that can differentiate all six capsulation loci in clinical specimens with high sensitivity and specificity has been developed (55). Moreover, a newer triplex direct real-time PCR detecting all six serotypes of H. influenzae in two reactions with high sensitivity and specificity has been described (57). Additionally, nonencapsulated serotypes are identified based on failure to react with antisera against capsules; these are termed “nontypeable” H. influenzae. Nontypeable strains are classified into biotypes (109). A PCR-based assay for identifying nontypeable H. influenzae has also been developed (10).

Typical, community-acquired H. influenzae meningitis is usually caused by type b, with an incidence of 4% in adults, whereas meningitis developing as a result of risk factors such as sinusitis or head trauma or remote neurosurgery is usually caused by NTHi (14; 23). Before vaccination availability, about 20,000 young children developed meningitis from Hib; now, fewer than 50 cases of Hib disease occur, most commonly in those who did not get any or all recommended doses of Hib vaccine (18; 19).

Encapsulated H. influenzae is transmitted by the respiratory route. Many individuals, particularly school-aged children, are asymptomatically colonized (86; 66). The development of symptomatic infection has largely been attributed to host factors. These include smoking or alcohol abuse, coinfection with a viral respiratory pathogen, and probable genetic susceptibilities related to local respiratory immune function and anatomy (78; 98; 99).

Various bacterial factors have also been identified that assist in pathogenicity. The bacterium has factors that promote adherence to respiratory mucous and epithelial cells (107; 80; 74; 51). Interestingly, a study suggested that viral coinfection can increase the expression of receptors for bacteria on respiratory epithelial cells, including non-typeable H. influenzae, thus promoting bacterial adhesion, colonization, and possibly subsequent disease (06). Encapsulated H. influenzae uses proteins such as protein H and Haemophilus surface fibrils (Hsf) (48). H. influenzae also has several mechanisms to evade the respiratory tract’s immune response, including the production of IgA protease, antigenic variation, and microcolony formation (49; 31; 30; 41; 62). Several components of the bacteria’s capsule interfere with mucociliary clearance from the lung. These include the lipo-oligosaccharide lipid A, peptidoglycan, and a glycerophosphodiesterase called protein D (46; 47; 45).

Transient bacteremia is common in nearly all invasive Hib and NTHi infections and is related to the bacteria’s ability to adhere to and enter the epithelial cells and penetrate the epithelial tight junctions of the nasopharynx and respiratory tract (81; 108; 87; 103; 104; 105; 16). Hib (and probably other encapsulated types) is more likely than NTHi to persist in the blood and seed distant sites such as the meninges. Survival in the bloodstream is facilitated by an anti-phagocytic polysaccharide capsule that acts as an inert shield, inhibiting surface deposition of opsonins such as complement factors and promoting evasion of immune recognition (79; 98; 99). In in vitro and animal models, strains of Haemophilus associated with invasiveness and meningitis interact with toll-like receptors, particularly -2 and -4, to trigger an inflammatory response (60) and a shift from Th1 to Th2 cytokines (24). Interestingly, two pediatric cases of severe central nervous system infection with H. influenzae type a occurred in the same week by capsule switching by horizontal gene transfer, suggesting another mechanism of vaccine evasion (92).

Epidemiology

	• Vaccination with Hib conjugate vaccine leads to decreases in oropharyngeal colonization among both vaccinated and unvaccinated children.
	• Most of the Hib disease in the United States occurs among unimmunized and underimmunized infants and children.

Hib conjugate vaccines have reduced the incidence of invasive Hib disease in children younger than 5 years by 99% in the United States. Although invasive Hib disease occurs primarily in unimmunized children and among infants too young to have completed the primary immunization series in the United States, Hib remains an important pathogen in many resource-limited regions where Hib vaccine coverage is less optimal (50).

Before development of the Hib vaccine, Hib was found colonizing the nasopharynx of 3% to 5% of children and a smaller percentage of adults (52). Hib was the leading cause of bacterial meningitis in children under 5 years of age and accounted for 20,000 cases per year in the United States (18; 19). Both colonization and meningitis due to this organism have now been nearly eradicated in infants and children who are routinely vaccinated (11; 75). Nontypeable strains, on the other hand, continue to colonize 10% to 60% of both children and adults (20; 40), frequently causing otitis media and rarely causing severe disease.

Before the vaccine, Hib was the most common cause of bacterial meningitis in young children, and approximately 1 in 200 children in the United States developed bacteremia with this organism, along with its associated complications, including meningitis, by the age of 5 years. Peak incidence was 6 to 18 months of age (79; 50). Again, these complications have largely been eradicated in vaccinated populations (43). With the vaccination of children, the epidemiology of H. influenzae has shifted toward an adult age distribution and also toward women, perhaps as unvaccinated primary caregivers for children (32). The higher incidence of invasive Hib infection in adults in the United States and Canada is particularly evident in those 65 years and older. Vaccination guidelines may require reconsideration to include age groups of 65 years and older (02; 28).

Ethnic groups at increased risk include non-Hispanic Black, American Indian or Alaska Native (AI/AN), and Hispanic adults (12). Even with good vaccine coverage, Native Alaskans have higher rates of H. influenzae disease than non-Native Alaskans and other U.S. children, probably due to other environmental and household factors contributing to transmission (85). Additionally, serotype replacement with non-type b strains has resulted in a re-emergence of invasive disease in these children (15). Other risk factors include childcare center attendance and overcrowded living conditions (68; 39). Of course, the greatest risk factor is inadequate vaccination.

Although vaccine coverage in the United States in 2019 was estimated to be 92% per the World Health Organization, global coverage is estimated to be 72%; six nations failed to achieve greater than 60% coverage: Venezuela, Ukraine, Nigeria, Papua New Guinea, South Sudan, and Samoa. It is also still important to consider the possibility of Hib-associated meningitis in patients from low- and middle-income countries. In fact, worldwide cases of severe Hib disease in children younger than 5 years of age have been estimated to have declined from more than 8 million to 340,000, with estimated Hib-related deaths in the same age group also noted to decline from 371,000 to less than 30,000 (106).

Another important population at risk includes those with medical conditions that produce immunocompromise, especially compromise of the ability to clear encapsulated organisms. Such conditions would include asplenia (anatomic or functional), sickle cell disease, HIV infection or IgG2 subclass deficiency, chemotherapy, and bone marrow transplantation (79). Unfortunately, the Hib vaccination may not be as effective in some of these conditions, such as in persons living with HIV (56). Vaccination of bone marrow donors prior to transplant may improve antibody concentrations in recipients after transplant (69).

There is a rise in the prevalence of multidrug-resistant H. influenzae in Asian countries (24.6%) compared to Western regions (15.7%), especially cases of meningitis (01).

Prevention

• Hib still accounts for 3 million cases of serious disease every year globally.

The increasing resistance of Hib to antibiotic agents has been reported from many parts of the world, and vaccination is the only public health tool that can rapidly reduce the incidence of Hib disease globally (World Health Organization 2023).

There are at least five (three single antigen or monovalent, and two combination) highly effective vaccines to prevent infection with Haemophilus influenzae type b. These vaccines conjugate the capsular antigen of type b, polyribosylribitol phosphate, to an immunogenic adjuvant. The available vaccines essentially differ in the choice of adjuvant and type of linkage between adjuvant and capsular antigen. As a result, they have slightly differing immunogenicities, and it is important to read the prescribing information for each vaccine to ensure it is administered appropriately. For example, some vaccines require a series of four injections, and some require three. All of the vaccines are well tolerated, highly effective, and can be administered simultaneously as other vaccines (50).

The Hib vaccine is one of the greatest success stories in the field of neurology and, indeed, all of medicine. Since it was first introduced in 1987, 192 countries worldwide now routinely use Hib conjugate vaccines in childhood vaccination programs. Some developing countries with high meningitis rates (for example, Chile, Uruguay, and the Gambia) have shown promising results with trials introducing Hib vaccination. This has had a significant beneficial effect on the global disease burden of bacterial meningitis (99).

There are no available vaccines that offer protection against NTHi. Although an investigational NTHi vaccine was tested in a phase 2, observer-blind, controlled trial in adults with chronic obstructive pulmonary disease with acceptable safety, reactogenicity profile, and good immunogenicity (110), a multicentre, randomized, placebo-controlled phase 2b trial did not show efficacy in reducing the yearly rate of moderate to severe exacerbation of chronic obstructive pulmonary disease (04).

A bacterial polysaccharide immunoglobulin (BPIg) preparation was tested for passive immunization. It was prepared from the plasma of adult donors immunized with Hib, meningococcal, and pneumococcal polysaccharide vaccines. Due to the need for frequent, large-volume injections and the subsequent availability of effective conjugate vaccines for infants, BPIg was not licensed for use in the United States (21).

When a case of Hib is discovered in a household with one or more children under 12 months of age, with children under 4 years who have not been adequately vaccinated, or with immunocompromised children, everyone in the household should receive prophylaxis with rifampin (20 mg/kg orally, maximum dose 600 mg) once daily for four days in individuals older than 1 month). This effectively prevents the spread of disease and decreases the incidence of severe disease, including meningitis. Similar guidelines are suggested for all children and personnel at a childcare center that has experienced two cases within a 60-day period. Prophylaxis after a single case at a childcare center is controversial (50).

Differential diagnosis

The history and examination data obtained from any given case of acute bacterial meningitis can be variable. This is especially true for young children, the most common patient population to get H. influenzae meningitis. Invariably, some of the typical findings are present, whereas others are absent. Additionally, the signs and symptoms frequently seen with acute bacterial meningitis, including fever, behavioral or personality changes, and mental status changes, can be nonspecific and suggest other diagnoses, including systemic infection or sepsis, viral encephalitis or meningitis, fungal or tuberculous meningitis, trauma or closed head injury or child abuse, multiple metabolic abnormalities (hypoglycemia, ketoacidosis, electrolyte imbalance, uremia, toxic exposure), seizure, and brain tumor. Even meningismus, which is often not present in children, does not exclude alternative diagnoses such as subarachnoid hemorrhage, intracranial hemorrhage, and epidural abscess. To prevent morbidity and mortality from missed diagnoses, it is important to keep a high index of suspicion for acute bacterial meningitis and err on the side of starting treatment early.

Before widespread use of the Hib vaccine, H. influenzae type b was the leading cause of acute bacterial meningitis in children under the age of 5 years (25). It is still prevalent in developing countries but is largely eradicated in the United States (11; 75). Streptococcus pneumoniae and Neisseria meningitidis are now the most common etiological agents in children after the neonatal period. In children under 1 year of age, group B streptococci and gram-negative enteric bacilli, particularly Escherichia coli, are the leading etiologic agents, presumably because of exposure to these agents during birth. Due to the passive transfer of maternal antibodies, these neonates did not typically develop H. influenzae, streptococcal meningitis, or meningococcal meningitis, even prior to the use of the vaccine (88).

In the setting of a preceding sinusitis, otitis media, head trauma, neurosurgical procedure, or cerebrospinal fluid leak, S. pneumoniae and NTHi are both common etiologic agents of recurrent meningitis (102; 82), as both are a common part of “normal” skin and nasopharyngeal colonization. There is good evidence that surgical repair of CSF leaks of various origins effectively prevents recurrent bacterial meningitis (08; 82).

In patients over 65 years of age, the most common causes of bacterial meningitis include Streptococcus pneumoniae, Neisseria Meningitidis, and Listeria monocytogenes (100; 101; 98; 99). S. aureus is common in neurosurgical patients (94).

Diagnostic workup

	• PCR identification of bacterial DNA in CSF and blood is becoming a quick and highly specific method for early pathogen identification.
	• CSF culture is the gold standard for diagnosing bacterial meningitis due to any organism, including Hib.

Bacterial meningitis, including that caused by H. influenzae, should be considered and promptly treated in any patient with a compatible presentation–keeping in mind that the presentation may be atypical in some patients, especially young children. CSF examination showing a predominantly neutrophilic pleocytosis is strongly suggestive of bacterial meningitis and should prompt broad coverage treatment; though, in the proper clinical setting, treatment should not be delayed even to obtain CSF. Brain imaging (CT scan) should also be considered before CSF examination because many of these organisms, including H. influenzae, can cause enough brain edema to make a lumbar puncture hazardous. Other contraindications to immediate lumbar puncture include coagulation disorders, septic shock, and respiratory failure. No tests are available to confirm H. influenzae as the causative organism are rapid enough to base initial treatment on. Therefore, the primary value of these tests is to confirm the correct initial clinical diagnosis (99).

With H. influenzae meningitis, both blood and CSF cultures will usually be positive. However, treatment should be initiated without delay, even prior to obtaining culture samples. Gram stain of the CSF will be positive for gram-negative coccobacilli in approximately 70% of cases (79). Antigen testing, such as latex agglutination, has become less favorable due to false-positive results, low sensitivity, and lower likelihood of helping with decision-making for treatment (93).

The US Food and Drug Administration approved the multiplex nucleic acid amplification test (NAAT) (meningitis/encephalitis [ME] panel from BioFire Diagnostics), which detects most common causes of community-acquired bacterial meningitis, such as N. meningitidis, H. influenzae, and S. pneumoniae, with a sensitivity of 65% to 75% for H. influenzae meningitis (95; 54). It has the advantage of being useful in patients who have already received antibiotic treatment. However, its limitations include false-negative and false-positive results. Therefore, cultures, as well as H. influenzae-specific quantitative PCR(qPCR), are highly recommended whenever multiplex NAATs are used (111). A two-step, real-time PCR-based assay that can differentiate all six capsulation loci in clinical specimens with high sensitivity and specificity has been developed (55), as has a PCR-based assay for identifying nontypeable Haemophilus influenzae (10); however, these assays are not commercially available, so culture is required to determine serotype and antimicrobial susceptibility.

Metagenomic next-generation sequencing (mNGS) is a rapidly evolving molecular technology that can provide accurate analysis of H. influenzae genomes and their genotype/serotypes rapidly without reliance on targeted molecular tests or traditional culture (61; 29). mNGS results should be confirmed by another method. No molecular method is able to provide antibiotic sensitivity profiles, which can only be provided by bacterial culture.

Management

	• Bacterial meningitis is a medical emergency, start the treatment without waiting for speciation.
	• Dexamethasone should be strongly considered in any patient with suspected community-acquired bacterial meningitis, especially in children at risk for H. influenzae meningitis.

When bacterial meningitis is suspected, emergent antibiotic treatment must be initiated, without waiting for speciation to be made. Due to the widespread use of the H. influenzae vaccine, H. influenzae is no longer considered a common etiology for community-acquired meningitis, even in children (25; 11; 75). Treatment is, therefore, directed primarily against S. pneumoniae and N. Meningitidis. Recommendations for treatment of community-acquired meningitis for ages 1 months to 18 years is vancomycin 60 mg/kg/day intravenously (maximum dose 4 g/day) in four divided doses plus ceftriaxone 100 mg/kg/day intravenously (maximum dose 4 g/day) in two divided doses, or cefotaxime 300 mg/kg/day intravenously (maximum dose 12 g/day) in three to four divided doses (50). Recommendations for adults include ceftriaxone 2 g intravenously every 12 hours or cefotaxime 2 g intravenously every 4 to 6 hours plus vancomycin 15 to 20 mg/kg intravenously every 8 to 12 hours (not to exceed 2 g per dose; achieve vancomycin serum trough concentration 15 to 20 mcg/mL) (99). The recommended treatment for patients with a penicillin or cephalosporin allergy includes carbapenems and fluroquinolones (50). In adults older than 50 years, add ampicillin 2 g intravenously every 4 hours in addition to the above regimen (99).

After speciation of H. influenzae, the cephalosporin, either cefotaxime or ceftriaxone, is continued. Both have potent activity against H. influenzae, and both penetrate the CSF well (37; 05; 67). The total duration of treatment is 7 to 10 days (88). Alternative antibiotics for beta-lactamase-positive pathogens include cefepime or meropenem (88). Ampicillin is used only if the infecting pathogen is beta-lactamase negative (67).

Dexamethasone 0.15 mg/kg every 6 hours given at the same with antibiotics or up to 4 hours after starting treatment with antibiotics for the first 4 days of therapy may also be beneficial for the initial treatment of community-acquired bacterial meningitis. Studies show a decrease in the risk of mortality, severe hearing loss, and neurologic sequelae in adults and children with community-acquired bacterial meningitis treated with dexamethasone (53; 65; 89; 97).

It is imperative that appropriate supportive care be instituted in addition to medication therapies. Advancements in intensive care techniques offer significant benefits for patients with bacterial meningitis, including H. influenzae meningitis.

Outcomes

The prognosis of H. influenzae meningitis, as with most bacterial meningitis, relates directly to early diagnosis and initiation of appropriate antibiotic therapy. With appropriate therapy instituted early, mortality is 5% or less. Unfavorable outcomes (Glasgow Outcome Scale score lower than 5 at discharge) are reduced over the years to less than 20% (23). Acute neurologic complications are also associated with later behavioral and developmental difficulties (91; 90), hearing loss, and seizures (58; 27). H. influenzae meningitis was once the leading cause of acquired intellectual disability in the United States, with about a third of patients going on to have intellectual disability (13). Intellectual disability due to Hib has now been almost completely eliminated due to the vaccination. Hearing loss remains the most common sequelae in adults (10% to 25%) and children (16%) (14; 72).

Special considerations

Pregnancy

Haemophilus influenzae is no longer considered a common maternal pathogen after introduction of the Hib vaccination program in many regions of the world. However, pregnancy is associated with 6- to 25-fold increased risk of invasive H. influenzae diseases (71; 09). A retrospective observational study in Israel found NTHi was the predominant cause in pregnant women suffering from H. influenzae infection (113). Maternal infections were associated with maternal and neonatal adverse outcomes, such as invasive neonatal H. influenzae disease within 24 hours of birth, longer length of hospitalization, lower birth weight, and a higher rate of early neonatal sepsis (26; 113; 48). Little is known about the neurologic complications of H. influenzae infection in pregnancy, but they are presumably similar to the complications seen in nonpregnant individuals. Treatment is also similar; the cephalosporins are felt to be safe in pregnancy.

Vaccination of pregnant women against the polyribophosphate capsular antigen of Haemophilus influenzae type b at 34 to 36 weeks gestation leads to a large boost in their antibody levels against this antigen. This boost is transferred to their newborn infants, such that newborn serum antipolyribophosphate capsular antigen level at birth is 100-fold greater than that of control newborn infants. Furthermore, this antibody persists at a protective level for 12 months, whereas control newborn infants lose significant antibodies by 3 months (03).

Postpartum infections, such as endometritis, tubo-ovarian abscess, chronic salpingitis, and sepsis, have been linked to NTHi (48).

Anesthesia

H. influenzae accounted for 19% of cases of postoperative pneumonia in a case series of 837 patients (59). Pneumonia in trauma patients in intensive care was significantly more likely due to H. influenzae (54%) (84).

References

01: Abavisani M, Keikha M, Karbalaei M. First global report about the prevalence of multi-drug resistant Haemophilus influenzae: a systematic review and meta-analysis. BMC Infect Dis 2024;24(1):90. PMID 38225571
02: Adam HJ, Richardson SE, Jamieson FB, Rawte P, Low DE, Fisman DN. Changing epidemiology of invasive Haemophilus influenzae in Ontario, Canada: evidence for herd effects and strain replacement due to Hib vaccination. Vaccine 2010;28(24):4073-8. PMID 20398617
03: Amstey MS, Insel R, Munoz J, Pichichero M. Fetal-neonatal passive immunization against Hemophilus influenzae, type b. Am J Obstet Gynecol 1985;153:607-11. PMID 3877464
04: Andreas S, Testa M, Boyer L, et al. Non-typeable Haemophilus influenzae-Moraxella catarrhalis vaccine for the prevention of exacerbations in chronic obstructive pulmonary disease: a multicentre, randomised, placebo-controlled, observer-blinded, proof-of-concept, phase 2b trial. Lancet Respir Med 2022;10(5):435-446. PMID 35026180
05: Auwaerter P. Bacterial meningitis, acute, community-acquired. In: Johns Hopkins Antibiotic Guide. Baltimore: Johns Hopkins University Press, 2009.
06: Avadhanula V, Rodriguez CA, Devincenzo JP, et al. Respiratory viruses augment the adhesion of bacterial pathogens to respiratory epithelium in a viral species and cell type dependent manner. J Virol 2006;80:1629-36. PMID 16439519
07: Baker RC, Bausher JC. Meningitis complicating acute bacteremic facial cellulitis. Pediatr Infect Dis 1986;5:421-3. PMID 3523459
08: Bernal-Sprekelsen M, Alobid I, Mullol J, Trobat F, Tomás-Barberán M. Closure of cerebrospinal fluid leaks prevents ascending bacterial meningitis. Rhinology 2005;43(4):277-81. PMID 16405272
09: Berndsen MR, Erlendsdóttir H, Gottfredsson M. Evolving epidemiology of invasive Haemophilus infections in the post-vaccination era: results from a long-term population-based study. Clin Microbiol Infect 2012;18(9):918-23. PMID 22070637
10: Billal DS, Hotomi M, Suzumoto M, et al. Rapid identification of nontypeable and serotype b Haemophilus influenzae from nasopharyngeal secretions by the multiplex PCR. Int J Pediatr Otorhinolaryngol 2007;71:269-74. PMID 17118463
11: Bisgard KM, Kao A, Leake J, Strebel PM, Perkins BA, Wharton M. Haemophilus influenzae invasive disease in the United States, 1994-1995: near disappearance of a vaccine-preventable childhood disease. Emerg Infect Dis 1998;4:229-37. PMID 9621193
12: Black CL, O'Halloran A, Hung MC, et al. Vital signs: influenza hospitalizations and vaccination coverage by race and ethnicity-United States, 2009-10 through 2021-22 influenza seasons. MMWR Morb Mortal Wkly Rep 2022;71(43):1366-73. PMID 36302226
13: Brosco JP, Mattingly M, Sanders LM. Impact of specific medical interventions on reducing the prevalence of mental retardation. Arch Pediatr Adolesc Med 2006;160:302-9. PMID 16520451
14: Brouwer MC, van de Beek D, Heckenberg SG, Spanjaard L, de Gans J. Community-acquired Haemophilus influenzae meningitis in adults. Clin Microbiol Infect 2007;13(4):439-42. PMID 17359331
15: Bruce MG, Deeks SL, Zulz T, et al. Epidemiology of Haemophilus influenzae serotype a, North American Arctic, 2000-2005. Emerg Infect Dis 2008;14(1):48-55. PMID 18258076
16: Butler DF, Myers AL. Changing epidemiology of haemophilus influenzae in children. Infect Dis Clin North Am 2018;32(1):119-28. PMID 29233576
17: Centers for Disease Control and Prevention. Haemophilus influenzae invasive disease among children aged less than 5 years--California, 1990-1996. MMWR Morb Mortal Wkly Rep 1998;47:737-40.
18: Centers for Disease Control and Prevention. Meningococcal Disease. Best practices for use of polymerase chain reaction (PCR) for diagnosing Haemophilus influenzae and Neisseria meningitidis disease and public health importance of identifying serotype/serogroup. Accessed March 16, 2024. www.cdc.gov/meningococcal/laboratory/pcr-guidance-mening-hflu.html. CDC 2021a.
19: Centers for Disease Control and Prevention. Vaccines and preventable diseases: What everyone should know. Accessed March 18, 2024. https://www.cdc.gov/vaccines/vpd/hib/public. CDC 2021b.
20: Cerquetti M, Giufre M. Why we need a vaccine for non-typeable Haemophilus influenzae. Hum Vaccin Immunother 2016;12(9):2357-61. PMID 27171854
21: Chandran A, Watt JP, Santosham M. 13 – Haemophilus influenzae vaccines, Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. Sixth edition. W.B. Saunders, 2013:167-82.
22: Chartrand SA, Harrison CJ. Buccal cellulitis reevaluated. Am J Dis Child 1986;140:891-3. PMID 3488675
23: Chekrouni N, Koelman DL, Brouwer MC, van der Ende A, van de Beek D. Community-acquired Haemophilus influenzae meningitis in adults. J Infect 2021;82(5):145-50. PMID 33774020
24: Chen SJ, Chu ML, Wang CJ, et al. Kinetic Th1/Th2 responses of transgenic mice with bacterial meningitis induced by Haemophilus influenzae. Clin Sci (Lond) 2006;111:253-63. PMID 16623660
25: Cochi SL, Broome CV. Vaccine prevention of Haemophilus influenzae type b disease: past, present, and future. Pediatr Infect Dis 1986;5:12-9. PMID 3511454
26: Collins S, Ramsay M, Slack MP, et al. Risk of invasive Haemophilus influenzae infection during pregnancy and association with adverse fetal outcomes. JAMA 2014;311(11):1125-32. PMID 24643602
27: D’Angio CT, Froehlke RG, Plank GA, et al. Long-term outcome of Haemophilus influenzae meningitis in Navajo Indian children. Arch Pediatr Adolesc Med 1995;149:1001-8. PMID 7655584
28: Danuz W. Epidemiology of invasive Haemophilus influenzae type b disease and the susceptibility of aggregate hosts. J Am Assoc Nurse Pract 2015;27(2):114-9. PMID 24958314
29: Ding M, Yang C, Li Y. Clinical application of metagenomic next-generation sequencing in purulent meningitis: a case seri. Turk J Pediatr 2023;65(4):679-86. PMID 37661684
30: Duim B, Bowler LD, Eijk PP, Jansen HM, Dankert J, van Alphen L. Molecular variation in the major outer membrane protein P5 gene of nonencapsulated Haemophilus influenzae during chronic infections. Infect Immun 1997;65:1351-6. PMID 9119473
31: Duim B, Vogel L, Puijk W, et al. Fine mapping of outer membrane protein P2 antigenic sites which vary during persistent infection by Haemophilus influenzae. Infect Immun 1996;64:4673-9. PMID 8890224
32: Farhoudi D, Lofdahl M, Giesecke J. Invasive Haemophilus influenzae type b disease in Sweden 1997-2003: epidemiological trends and patterns in the post-vaccine era. Scand J Infect Dis 2005;37:717-22. PMID 16191888
33: Fink CW, Nelson JD. Septic arthritis and osteomyelitis in children. Clin Rheum Dis 1986;12:423-35. PMID 3492327
34: Fountain LA, Hendley JO, Cody EJ, Perriello VA, Donowitz LG. The emergence of Haemophilus influenzae types e and f as significant pathogens. Clin Infect Dis 1995;21:1322-4. PMID 8589168
35: Garg P, Gupta R, Szalados JE. Bacterial pericarditis and tamponade due to nonencapsulated Haemophilus influenzae complicating a case of adult community-acquired pneumonia. MedGenMed 20067;8(4):48. PMID 17415329
36: Ginsburg CM. Hemophilus influenzae type b buccal cellulitis. J Am Acad Dermatol 1981;4:661-4. PMID 6972388
37: Goldwater PN. Cefotaxime and ceftriaxone cerebrospinal fluid levels during treatment of bacterial meningitis in children. Int J Antimicrob Agents 2005;26:408-11. PMID 16216469
38: Gonullu E, Ozkan N, Soysal A, et al. Nontypeable Haemophilus influenzae otitis media: mastoiditis and meningitis complicated with central venous thrombosis in an immunocompetent child. Case Rep Infect Dis 2021;2021:8845200. PMID 34007496
39: Granoff DM, Basden M. Haemophilus influenzae infections in Fresno County, California: a prospective study of the effects of age, race, and contact with a case on incidence of disease. J Infect Dis 1980;141:40-6. PMID 6965975
40: Haro K, Ogawa M, Saito M, Kusuhara K, Fukuda K. Bacterial composition of nasal discharge in children based on highly accurate 16S rRNA gene sequencing analysis. Sci Rep 2020;10(1):20193. PMID 33214657
41: Hendrixson DR, Saint Geme JW. The Haemophilus influenzae Hap serine protease promotes adherence and microcolony formation, potentiated by a soluble host protein. Mol Cell 1998;2:841-50. PMID 9885571
42: Houliston RS, Koga M, Li J, et al. A Haemophilus influenzae strain associated with Fisher Syndrome expresses a novel disialylated ganglioside mimic. Biochemistry 2007;46:8164-71. PMID 17567050
43: Hufnagel M, Burger A, Bartelt S, Henneke P, Berner R. Secular trends in pediatric bloodstream infections over a 20-year period at a tertiary care hospital in Germany. Eur J Pediatr 2008;167(10):1149-59. PMID 18231812
44: Jacobs RF, Hsi S, Wilson CB, Benjamin D, Smith AL, Morrow R. Apparent meningococcemia: clinical features of disease due to Haemophilus influenzae and Neisseria meningitides. Pediatrics 1983;72:469-72. PMID 6412207
45: Janson H, Carl NB, Cervin A, et al. Effects on the ciliated epithelium of protein D producing and nonproducing nontypeable Haemophilus influenzae in nasopharyngeal tissue cultures. J Infect Dis 1999;180:737-46. PMID 10438362
46: Johnson AP, Inzana TJ. Loss of ciliary activity in organ cultures of rat trachea treated with lipo-oligosaccharide from Haemophilus influenzae. J Med Microbiol 1986;22:265-8. PMID 3490578
47: Kanthakumar K, Taylor GW, Cundell DR, et al. The effect of bacterial toxins on levels of intracellular adenosine nucleotides and human ciliary beat frequency. Pulm Pharmacol 1996;9:223-30. PMID 9160410
48: Khattak ZE, Anjum F. Haemophilus influenzae infection. 2023 Apr 27. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2024. PMID 32965847
49: Kilian M, Poulsen K. Enzymatic, serologic, and genetic polymorphism of Haemophilus influenzae IgA1 proteases. J Infect Dis 1992;165:S192-3. PMID 1588161
50: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, editors. Haemophilus influenzae infections. In: Red Book: 2021-2024 Report of the Committee on Infectious Diseases. 32nd Ed. American Academy of Pediatrics: Itasca IL, 2021:345, 519, 639.
51: Kubiet M, Ramphal R, Weber A, Smith A. Pilus-mediated adherence of Haemophilus influenzae to human respiratory mucins. Infect Immun 2000;68:3362-7. PMID 10816486
52: Kuklinska D, Kilian M. Relative proportions of Haemophilus species in the throat of healthy children and adults. Eur J Clin Microbiol 1984;3:249-52. PMID 6332018
53: Lebel MH, Freij BJ, Syrogiannopoulos GA, et al. Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo-controlled trials. N Engl J Med 1988;319:964-71. PMID 3047581
54: Liesman RM, Strasburg AP, Heitman AK, Theel ES, Patel R, Binnicker MJ. Evaluation of a commercial multiplex molecular panel for diagnosis of infectious meningitis and encephalitis. J Clin Microbiol 2018;56(4):e01927-17. PMID 29436421
55: Maaroufi Y, De Bruyne JM, Heymans C, Crokaert F. Real time PCR for determining capsular serotypes of Haemophilus influenzae. J Clin Microbiol 2007;45(7):2305-8. PMID 17507524
56: Madhi SA, Kuwanda L, Saarinen L, et al. Immunogenicity and effectiveness of Haemophilus influenzae type b conjugate vaccine in HIV infected and uninfected African children. Vaccine 2005;23:5517-25. PMID 16107294
57: Marasini D, Whaley MJ, Jenkins LT, et al. Direct real-time PCR for the detection and serotyping of haemophilus influenzae without DNA extraction. J Clin Microbiol 2022;60(4):e0211121. PMID 35306833
58: McIntyre P, Jepson R, Leeder S, Irwig L. The outcome of childhood Haemophilus influenzae meningitis: a population based study. Med J Aust 1993;159:766-72. PMID 8264465
59: Montravers P, Veber B, Auboyer C, et al. Diagnostic and therapeutic management of nosocomial pneumonia in surgical patients: results of the Eole study. Crit Care Med 2002;30(2):368-75. PMID 11889312
60: Mogensen TH, Paludan SR, Kilian M, Ostergaard L. Live Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis activate the inflammatory response through Toll-like receptors 2, 4, and 9 in species-specific patterns. J Leukoc Biol 2006;80(2):267-77. PMID 16731773
61: Morsli M, Kerharo Q, Delerce J, Roche PH, Troude L, Drancourt M. Haemophilus influenzae meningitis direct diagnosis by metagenomic next-generation sequencing: a case report. Pathogens 2021;10(4):461. PMID 33921275
62: Murphy TF, Kirkham C, Jones MM, Sethi S, Kong Y, Pettigrew MM. Expression of IgA proteases by Haemophilus influenzae in the respiratory tract of adults with chronic obstructive pulmonary disease. J Infect Dis 2015;212(11):1798-805. PMID 25995193
63: Naqvi SH, Chundu KR, Friedman AD. Shock in children with gram-negative bacillary sepsis and Haemophilus influenzae type b sepsis. Pediatr Infect Dis 1986;5(5):512-5. PMID 3489928
64: Nitta DM, Jackson MA, Burry VF, Olson LC. Invasive Haemophilus influenzae type f disease. Pediatr Infect Dis J 1995;14:157-60. PMID 7746705
65: Odio CM, Faingezicht I, Paris M, et al. The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. N Engl J Med 1991;324:1525-31. PMID 2027357
66: Oh SY, Griffiths D, John T, et al. School-aged children: a reservoir for continued circulation of Haemophilus influenza type b in the United Kingdom. J Infect Dis 2008;197(9):1275-81. PMID 18422439
67: Oliver SE, Rubis AB, Soeters HM, et al. Secondary cases of invasive disease caused by encapsulated and nontypeable Haemophilus influenzae - 10 U.S. jurisdictions, 2011-2018. MMWR Morb Mortal Wkly Rep 2023;72(15):386-90. PMID 37053119
68: Parke JC, Schneerson R, Robbins JB. The attack rate, age incidence, racial distribution, and case fatality rate of Hemophilus influenzae type b meningitis in Mecklenburg County, North Carolina. J Pediatr 1972;81:765-9. PMID 5074353
69: Parkkali T, Kayhty H, Hovi T, et al. A randomized study on donor immunization with tetanus-diphtheria, Haemophilus influenzae type B, and inactivated poliovirus vaccines to improve recipient responses to the same vaccines after allogeneic bone marrow transplantation. Bone Marrow Transplant 2007;39:179-88. PMID 17211432
70: Pavlovich P, Looi A, Rootman J. Septic thrombosis of the cavernous sinus: two different mechanisms. Orbit 2006;25:39-43. PMID 16527775
71: Perdue DG, Bulkow LR, Gellin BG, et al. Invasive Haemophilus influenzae disease in Alaskan residents aged 10 years and older before and after infant vaccination programs. JAMA 2000;283(23):3089-94. PMID 10865303
72: Pedersen TI, Howitz M, Ostergaard C. Clinical characteristics of Haemophilus influenzae meningitis in Denmark in the post-vaccination era. Clin Microbiol Infect 2010;16(5):439-46. PMID 19548927
73: Pfeiffer R. Die Aetiologie der Influenzae. Z Hyg Infect 1893;13:357.
74: Rao VK, Krasan GP, Hendrixson DR, Dawid S, Saint Geme JW 3rd. Molecular determinants of pathogenesis of disease due to non-typable Haemophilus influenzae. FEMS Microbiol Rev 1999;23:99-129. PMID 10234841
75: Rosenstein NE, Perkins BA. Update on Haemophilus influenzae serotype b and meningococcal vaccines. Pediatr Clin North Am 2000;47:337-52. PMID 10761507
76: Rush PJ, Shore A, Inman R, Gold R, Jadavji T, Laski B. Arthritis associated with Haemophilus influenzae meningitis: septic or reactive. J Pediatr 1986;109:412-5. PMID 3489088
77: Russo DO, Torres BR, Romanelli RM, Rocha FS, Viegas EC, Diniz LM. Haemophilus influenzae serotype a as a cause of meningitis in children in Brazil. Pediatr Infect Dis J 2022;41(2):108-11. PMID 35017451
78: St Geme JW. Nontypeable Haemophilus influenzae disease: epidemiology, pathogenesis, and prospects for prevention. Infect Agents Dis 1993;2(1):1-16. PMID 8162349
79: St Geme JW. Haemophilus influenzae. In: Long SS, Pickering LK, Prober CG, editors. Principles and practice of pediatric infectious diseases. New York: Churchill Livingstone, 2003:921-5.
80: St Geme JW, Cutter D. Evidence that surface fibrils expressed by Haemophilus influenzae type b promote attachment to human epithelial cells. Mol Microbiol 1995;15(1):77-85. PMID 7752898
81: St Geme JW, Falkow S. Haemophilus influenzae adheres to and enters cultured human epithelial cells. Infect Immun 1990;58(12):4036-44. PMID 2254028
82: Shin H, Kim G, Han SB, Jeong DC, Kang JH. Recurrent meningitis caused by β-lactamase-positive amoxicillin/clavulanate-resistant non-typeable Haemophilus influenzae in a child with an inner ear malformation: a case report. Infect Chemother 2021;53(4):808-13. PMID 33124213
83: Shurin SB, Anderson P, Zollinger J, Rathbun RK. Pathophysiology of hemolysis in infections with Hemophilus influenzae type b. J Clin Invest 1986;77:1340-8. PMID 3485660
84: Singh N, Falestiny MN, Rogers P, et al. Pulmonary infiltrates in the surgical ICU: prospective assessment of predictors of etiology and mortality. Chest 1998;114(4):1129-36. PMID 9792588
85: Singleton R, Hammitt L, Hennessy T, et al. The Alaska Haemophilus influenzae type B experience: lessons in controlling a vaccine-preventable disease. Pediatrics 2006;118:421-9. PMID 16882783
86: Spinola SM, Peacock J, Denny FW, Smith DL, Cannon JG. Epidemiology of colonization of nontypeable Haemophilus influenzae in children: a longitudinal study. J Infect Dis 1986;154:100-9. PMID 3486923
87: Stephens DS, Farley MM. Pathogenic events during infection of the human nasopharynx with Neisseria meningitidis and Haemophilus influenzae. Rev Infect Dis 1991;13(1):22-33. PMID 1901998
88: Swanson D. Meningitis. Pediatr Rev 2015;36(12):514-24. PMID 26628732
89: Syrogiannopoulos GA, Lourida AN, Theodoridou MC, et al. Dexamethasone therapy for bacterial meningitis in children: 2- versus 4-day regimen. J Infect Dis 1994;169:853-8. PMID 8133101
90: Taylor HG, Schatschneider C, Minich NM. Longitudinal outcomes of Haemophilus influenzae meningitis in school age children. Neuropsychology 2000;14:509-18. PMID 11055253
91: Taylor HG, Schatschneider C, Watters GV, et al. Acute phase neurologic complications of Haemophilus influenzae type b meningitis: association with developmental problems at school age. J Child Neurol 1998;13:113-9. PMID 9535236
92: Terrat Y, Farnaes L, Bradley J, Tromas N, Shapiro BJ. Two cases of type-a Haemophilus influenzae meningitis within the same week in the same hospital are phylogenetically unrelated but recently exchanged capsule genes. Microb Genom 2020;6(4):e000348. PMID 32213257
93: Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004;39(9):1267-84. PMID 15494903
94: Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases Society of America's Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis. Clin Infect Dis 2017;64(6):e34-65. PMID 28203777
95: US Food and Drug Administration. Evaluation of Automatic Class III Designation for FilmArray Meningitis/Encephalitis (ME) Panel. Publication date: October 8, 2015. Available at: https://www.accessdata.fda.gov/cdrh_docs/reviews/DEN150013. US FDA, 2015.
96: Urwin G, Krohn JA, Deaver-Robinson K, Wenger JD, Farley MM. Invasive disease due to Haemophilus influenzae serotype f: clinical and epidemiologic characteristics in the H. influenzae serotype b vaccine era. Clin Infect Dis 1996;22:1069-76. PMID 8783712
97: van de Beek D, Brouwer MC, Koedel U, Wall EC. Community-acquired bacterial meningitis. Lancet 2021;398(10306):1171-83. PMID 34303412
98: van de Beek D, Brouwer M, Hasbun R, Koedel U, Whitney CG, Wijdicks E. Community-acquired bacterial meningitis. Nat Rev Dis Primers 2016a;2:16074.** PMID 27808261
99: van de Beek D, Cabellos C, Dzupova O, et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clin Microbiol Infect 2016b;22 Suppl 3:S37-62. PMID 27062097
100: van de Beek D, de Gans J, McIntyre P, Prasad K. Steroids in adults with acute bacterial meningitis: a systematic review. Lancet Infect Dis 2004a;4:139-43. PMID 14998499
101: van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 2004b;351(18):1849-59. PMID 15509818
102: van Driel JJ, Bekker V, Spanjaard L, van der Ende A, Kuijpers TW. Epidemiologic and microbiologic characteristics of recurrent bacterial and fungal meningitis in the Netherlands, 1998-2005. Clin Infect Dis 2008;47(5):e42-51. PMID 18643757
103: van Schilfgaarde M, van Alphen L, Eijk P, Everts V, Dankert J. Paracytosis of Haemophilus influenzae through cell layers of NCI-H292 lung epithelial cells. Infect Immun 1995;63:4729-37. PMID 7591129
104: van Schilfgaarde M, van Ulsen P, Eijk P, et al. Characterization of adherence of nontypeable Haemophilus influenzae to human epithelial cells. Infect Immun 2000a;68:4658-65. PMID 10899870
105: van Schilfgaarde M, van Ulsen P, van Der Steeg W, et al. Cloning of genes of nontypeable Haemophilus influenzae involved in penetration between human lung epithelial cells. Infect Immun 2000b;68:4616-23. PMID 10899864
106: Wahl B, O'Brien KL, Greenbaum A, et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15. Lancet Glob Health 2018;6(7):e744-57. PMID 29903376
107: Weber A, Harris K, Lohrke S, Forney L, Smith AL. Inability to express fimbriae results in impaired ability of Haemophilus influenzae b to colonize the nasopharynx. Infect Immun 1991;59:4724-8. PMID 1682268
108: Weiser JN, Williams A, Moxon ER. Phase-variable lipopolysaccharide structures enhance the invasive capacity of Haemophilus influenzae. Infect Immun 1990;58:3455-7. PMID 2401571
109: Whittaker R, Economopoulou A, Dias JG, et al. Epidemiology of invasive Haemophilus influenzae disease, Europe, 2007-2014. Emerg Infect Dis 2017;23(3):396-404. PMID 28220749
110: Wilkinson TM, Schembri S, Brightling C, et al. Non-typeable Haemophilus influenzae protein vaccine in adults with COPD: a phase 2 clinical trial. Vaccine 2019;37(41):6102-11. PMID 31447126
111: Zanella MC, Cherkaoui A, Hinic V, et al. Unexpectedly High false-positive rates for Haemophilus influenzae using a meningoencephalitis syndromic PCR panel in two tertiary centers. Front Cell Infect Microbiol 2021;11:639658. PMID 33763388
112: Zanella RC, Bokermann S, Andrade AL, Flannery B, Brandileone MC. Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H. influenzae type b in Brazil. Vaccine 2011;29(48):8937-42. PMID 21945960
113: Zilberman-Itskovich S, Oren C, Zaidenstein R, et al. Haemophilus influenzae infections in pregnancy: a retrospective, nested case-control study. J Obstet Gynaecol 2022;42(2):346-8. PMID 34404313

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Patient Profile

Age range of presentation: 1 month to 65+ years
Sex preponderance: male>female, >1:1
Heredity: none
Population groups selectively affected: Eskimo

Native American Indian

African American
Occupation groups selectively affected: child care center personnel

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Haemophilus influenzae meningitis

Associated Disorders

Cellulitis
Epiglottitis
Pneumonia

Differential Diagnosis

encephalitis
systemic infection
sepsis
viral encephalitis
viral meningitis
- fungal meningitis
- tuberculous meningitis
- trauma
- closed head injury
- child abuse
- hypoglycemia
- ketoacidosis
- electrolyte imbalance
- uremia
- toxic exposure
- seizure
- brain tumor
- subarachnoid hemorrhage
- intracranial hemorrhage
- epidural abscess
- Streptococcus pneumoniae
- Neisseria meningitidis
- Group B streptococci
- gram-negative enteric bacilli
- Escherichia coli
- Enterobacter
- Pseudomonas
- Listeria monocytogenes
- S. aureus

Also Relevant

Bacterial meningitis
Gram-negative bacillary meningitis
Molecular diagnosis of CNS infections
Neurologic complications of vaccination
Recurrent meningitis

Haemophilus influenzae meningitis …

Haemophilus influenzae meningitis

Introduction

Overview

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

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Haemophilus influenzae meningitis

Introduction

Overview

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Neuropathies associated with cytomegalovirus infection

Genital herpes: neurologic complications

Zika virus: neurologic complications

Gram-negative bacillary meningitis

Pneumococcal meningitis

HTLV-1 associated myelopathy

Infective endocarditis

Japanese encephalitis

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