Meningitis and bacteremia caused by Haemophilus influenzae Type e in an immunocompetent child

Haemophilus influenzae infection is a well-known cause of severe invasive disease in adults and children. But the incidence of the common serotypes is type b, f, and a. There is very little information on the invasive disease of Haemophilus influenzae type e (Hie) in China, especially in children. We report a case of an immunocompetent child with a clinical diagnosis of bacterial meningitis and bacteremia caused by Hie. The literature on infection, especially meningitis caused by Hie, is reviewed.


Introduction
Some recent reports of invasive Haemophilus influenzae disease in children and the elderly have shown that Haemophilus influenzae can cause pneumonia, meningitis, septicemia, septic arthritis, genitourinary infections, and endocarditis. [1]. Based on the research of polysaccharide capsule antigens, H. influenzae strains can be classified as encapsulated (denoted serotypes a-f) and unencapsulated (NTHi). Serotype b (Hib) is the most common strain of H. influenzae, causing 95% of severe invasive diseases, especially in children [2]. With the introduction of Hib conjugate vaccines, the threat of invasive Hib infection among children has dramatically decreased in many countries, regardless of development level or economic status [3]. Unfortunately, the incidence of invasive disease caused by non-Hib serotypes, which are not cross-protected by the Hib vaccine, has increased in recent decades [4,5]. Hif and Hia are the most common non-b strains in some countries [6].
Little knowledge is available concerning the epidemiological, microbiological, and clinical significance of Hie. Limited Hie infection has been obtained from reports of sporadic clinical cases of meningitis, pneumonia, peritoneal infection, and bacteremia [7]. To our knowledge, reports regarding the invasive disease of Hie are negligible in China, especially in children. We report a case of an immunocompetent child who was clinically diagnosed with bacterial meningitis with bacteremia caused by H. influenza. The serotype of H. influenza was identified, and the importance of monitoring non-vaccinepreventable H. influenza strains for effective surveillance of invasive H. influenzae disease was discussed.

Case Report
The patient was an 11-year-old boy with hearing loss that presented to a local hospital with fever and headache. He was subsequently admitted to Children Hospital, Shanxi, China, on November 11, 2018, with a four -day history of fever, headache, frequent vomiting, and refusal of food. He had no history of rash, allergy, trauma, blood transfusion, or contact with animals.
Initially, on examination, he was febrile (temperature of 41 °C) with tachypnea, weakness, and photophobia. Physical examination revealed a heart rate with 92 beats/min sinus rhythm and a respiratory rate of 24 breaths/min. Brudzinski's sign was positive. The remainder of the physical examination findings, including the fundus, was unremarkable. The patient was empirically started on intravenous cefotaxime and vancomycin. Blood routine test (BRT) and routine examinations of cerebrospinal fluid were conducted in our hospital (Table 1).
BRT and routine examination of CSF were conducted in our hospital ( Table 1). The examination of CSF revealed 6.0351×10 10 leukocytes/L (85% neutrophils), 2.7 g/L of protein, 0.29 mmol/L of glucose and 12.97 mmol/L of lactate. The results of CSF routine examination also support the conjecture of bacterial meningitis. The renal and liver function tests were normal; levels of serum calcium, troponin T, immunoglobulins, and total complement were within normal limits; and the computed tomography of the head was normal. On the day of admission, a CT scan of the head revealed unremarkable.
The day after hospital admission, the presence of H. influenzae was confirmed in blood and CSF cultures. H. influenzae isolate was serotyped as type e using the slide agglutination method with polyclonal serotypespecific antisera (BD, New Jersey USA). Real-time polymerase chain reaction (RT-PCR) was performed for confirmation. Using the nitrocefin disc method, H. influenzae isolate was found to be β-lactamase producing, ampicillin-resistant. Vancomycin was stopped after culture results arrived. Anti-infection therapy (cefotaxime, 4g/day) was continued following the sensitivity results (β-lactamase producing, ampicillin-resistant, but susceptible to other tested antimicrobial drug (cefotaxime, ceftriaxone, meropenem, levofloxacin, azithromycin, etc.), and dexamethasone (20 mg/day for three days) was simultaneously administered intravenously.
A favorable clinical outcome without sequelae was achieved, and laboratory results returned to normal after 21 days of antibiotic therapy. The patient was discharged home without sequelae. No neurodevelopmental disabilities were detected in the six-month follow-up.

Discussion
Recently, there has been an increase in reports of invasive disease caused by non-type b H. influenzae in both adults and children [8]. The most common serotypes have been serotype f and NTHi. Interestingly, the distribution of non-b invasive demonstrates geographic variations [9]. Hia meningitis has been reported mainly in Canada, the United States, and Australia. Hif has been mainly distributed in Brazil and England, while Hie has been distributed primarily on England, Italy, and Spain [7,10,11]. To the best of our knowledge, infection with non-type b H. influenzae has been very limited in China in recent years, although non-type b H. influenzae is a significant cause of invasive infection in other parts of the world [10]. In contrast to disorders in childhood, invasive Hie infections in adults usually occur in individuals with an underlying disease [11]. We encountered a case of bacterial meningitis with bacteremia due to Hie in an immunocompetent child.
The clinical symptoms of the patient showed relatively stable when he was admitted to our hospital. This observation is less like a study showing that Hie appears to cause more severe clinical disease and poor infection-attributable outcomes by evaluating invasive infection with Hie and Hif among children in England [11]. Thus, even in the post-Hib conjugated vaccine era,  Table 1, inflammatory parameters slightly decreased in the first 12 hours after admission. These results may be related to the use of antibiotics. In this case, although the patient's symptoms were moderately severe, the infection was quickly brought under control, and he gradually recovered fully after hospitalization. This outcome was due to the correct prediction of pathogens and the use of effective antibiotics. Thus, effective empiric therapy is essential for the treatment and prognosis of patients. The antibiotic resistance of non-b types of H. influenzae is a matter of concern and is vital in guiding empirical therapy.
Previous studies [12,13] have shown that Non-type b H. influenzae infection is associated with significant morbidity in the pediatric population. The knowledge of non-type b H. influenzae as an important pathogen in the pediatric population is constantly improving. The contribution of non-type b H. influenzae to invasive disease in children is not well understood. In this paper, we report our case of invasive H. influenzae type e infection whose clinical and drug resistance features may provide some valuable information for Hie invasive disease. We want to emphasize that extensive monitoring of the circulating non-vaccine-preventable strains is crucial for an effective surveillance of invasive H. influenzae disease.