1. Case Study Pathogenic Bacteriology 2009 Case #41 Angela Augustus

2. Case Summary 13 month old – HIV negative – Up to date on immunizations Initial symptoms: runny nose, low grade fever – Treated with Tylenol Later in the day: – Seizures – Lethargic, limp, unresponsive, post ictal – Temperature 39 o C – Supple neck Blood and urine cultures were taken Intravenous ceftriaxone

3. Case Summary (cont) Next Day: – No improved mental status – CSF with: WBC count of 4650 cells/μl (95% neutrophils) Low glucose level Elevated protein level – Peripheral WBC count increased from 6,600 to 14,600 cells/ μl

4. Case Summary (cont) Transferred to University Hospital: – Irritable, stiff neck – Blood culture: positive – CSF culture: negative Bacterial antigen test is consistent with blood culture – Normal: Antibodies for Hib and pneumococci Complement Immunoglobulin class and subclass levels Lymphocyte function

5. Case Study (cont) Gram Stain Choc CBA

6. Key Information Pointing to Diagnosis DISEASE: – Fever – Decreased mental status – Stiff neck – Positive blood culture and bacterial antigen test ORGANISM: – Gram Stain Eliminated S. aureus and S. agalactiae (Micrococcaceae and Streptococcaceae) – Lack of growth on CBA, growth on Choc Eliminated E. coli – Normal complement and lack of petechial rash Eliminated N. meningitidis

7. Diagnosis Meningitis caused by Haemophilus influenzae – Serotype b (vaccine failure) “32% of children aged 6-59 months with confirmed type b disease had received 3 or more doses of the Hib vaccine” (Atkinson, 2008) – Serotype a “No cross protection is afforded to type a by immunization with Hib conjugate vaccines” (Jin, et al, 2007) As “the incidence of Hib meningitis decreased by 69% during the first year following initiation of Hib conjugate immunization…the incidence of Hia meningitis increased eightfold” (Jin, et al, 2007)

8. H. influenzae Classification: Pasteurellaceae Gram Stain: Gram negative coccobacilli Requires both X and V – Grows on Choc – Grows poorly on CBA Ferments xylose – H. aegyptius is - "The Normal Flora of Humans." The Microbial World. 11 Jan 2009. Kenneth Todar University of Wisconsin-Madison Department of Bacteriology. 2 Mar 2009.

9. Pathogenesis and Disease H. influenzae: – Colonizes the nasopharynx – Invades local tissues and bloodstream to spread – Human carrier, possibly transmitted by respiratory droplets – Causes: Meningitis  2mo – 3 years – Fever, decreased mental status, stiff neck Epiglottitis  2-4 year old boys Pneumonia Septic arthritis Cellulitis Pericarditis

10. Change in Epidemiology (Atkinson, 2008) An increase in vaccine use has led to a 99% decrease in Hib disease CDC hopes to eliminate Hib disease by 2010

11. Diagnosis of H. influenzae Diagnosis requires: – Isolation and culturing of MO from sterile body sites: Blood, CSF, joint, pericardial, or pleural fluid – Detection of Hib specific antigen in sterile site especially after intravenous antibiotic treatment Latex agglutination Counterimmunoelectrophoresis Serotyping should also be done to identify specific type causing the disease

12. Therapy, Prevention, and Prognosis Treatment: Hospitalization and 10 days of: – Effective 3 rd generation cephalosporin Cefotaxime Ceftriaxone – Chloramphenicol with ampicillin Ampicillin resistant strains have now emerged Prognosis: 2-5% mortality rate even with appropriate antimicrobial therapy

13. Treatment, Prevention, and Prognosis Prevention: Hib vaccine – 2, 4, and 6 mo old with booster at 12-15 months – Safe for HIV patients (but immunogenicity varies) and premature infants – Conjugate vaccines: poorly antigenic polysaccharide binds to effective protein carrier PRP-T (ActHib) PRP-OMP (Pedvax HIB) – Combination vaccines: combine two vaccines DTaP-Hib (TriHIBit) Hepatitis B-Hib (COMVAX)

14. Childhood Immunizations http://www.cdc.gov/vaccines/recs/schedules/child-schedule.htm#printable

15. Primary Research Article Ellen Hyun-Ju Lee, et al, 2008, Haemophilus influenzae type b conjugate vaccine is highly effective in the Ugandan routine immunization program: a case-control study, Tropical Medicine and International Health, 13:495-502. Test Hib vaccine effectiveness in Uganda – Case patients – 12 weeks to 59 mo w/ confirmed Hib disease – Control groups – 3/case patient, age matched from: Neighborhood Hospital Data regarding immunizations and environment were collected using: – Structured questionnaires – Written documentation and logbooks

16. Primary Research Article TABLE 2 FROM ARTICLE Vaccine effectiveness increases with # of doses (as high as 98.7%)

17. Take Home Message Meningitis involves symptoms of fever, decreased mental status and stiff neck Though it is caused by a variety of agents, H. influenzae is a common cause in young children (~2 mo to 3 years) Potentially transmitted through aerosols, the organism colonizes the nasopharynx and infects the bloodstream Diagnosis involves culturing/ isolating the organism from sterile body sites or a positive bacterial antigen test Therapy includes a 10 day cycle of a 3rd generation cephalosporin or a combination of chloramphenicol and ampicillin. Preventative measures with the Hib vaccine have led to a decreased threat. In the future, this threat may be nonexistant.

18. References Atkinson, William, Jennifer Hamborsky, Lynne McIntyre, and Charles Wolfe.Epidemiology and Prevention of Vaccine-Preventable Diseases. 10 th ed. Washington DC: Public Health Foundation, 2008. Jin, Zhigang, Sandra Romero-Steiner, George M. Carlone, John B. Robbins, and Rachel Schneerson. "Haemophilus influenzae Type a Infection and Its Prevention." Infection and Immunity. 75(2007): 2650-2654. Lee, Ellen Hyun-Ju, Rosamund F. Lewis, Issa Makumbi, Adeodata Kekitiinwa, Tom D. Ediamu, monic Bazibu, Fiona Braka, Brendan Flanery, Patrick L. Zuber, and Daniel R. Feikin. "Haemophilus influenzae type b conjugate vaccine is highly effective in Ugandan routine immunization program: a case-control study." Tropical Medicine and International Health 13(2008): 495-502. "Recommended Immunization Schedule for Persons Aged 0 Through 6 Years." Centers for Disease Control and Prevention. 26 Feb 2009. Centers for Disease Control and Prevention. 2 Mar 2009. Roush, Sandra W., Lynne McIntyre, and Linda M. Baldy. Manual for the Surveillance of Vaccine-Preventable Diseases. 4th ed. Atlanta, GA: Centers for Disease Control and Prevention, 2008. Seehusen, M.D., Dean, Mark M. Reeves, M.D., and Demitria A. Fomin, M.D.. "Cerebrospinal Fluid Analysis." American Family Physician 68(2003): 1103-1108.