Case Study Pathogenic Bacteriology 2009

1. Case StudyPathogenic 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 39oC • 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 <http://bioinfo.bact.wisc.edu/themicrobialworld/NormalFlora.html>.

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 3rd 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. 10th 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 <http://www.cdc.gov/vaccines/recs/schedules/downloads/child/2009/09_0-6yrs_schedule_pr.pdf>. 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.