Georgia epidemiology report, Vol. 24, no. 8 (Aug. 2008)

August 2008

volume 24 number 08

Haemophilus influenzae Disease in Georgia

Introduction Haemophilus influenzae is a small, pleomorphic gram-negative bacterium that is highly adapted to its human host and does not survive for long in the environment. Most strains of H. influenzae are opportunistic pathogens, i.e. they live in the human respiratory tract without causing invasive disease unless other factors such as viral infections, chronic lung disease, or a compromised immune system create the opportunity. H. influenzae type B (Hib), although now rare because it is vaccinepreventable, is one type of the pathogen that is highly virulent and noted for causing devastating disease in healthy young children. The effect of the Hib vaccine has been a major public health success story. This report describes the history of ongoing surveillance, and for emerging issues in H. influenzae disease in Georgia.
Serotypes of H. influenzae Serotyping of H. influenzae is based on the presence of a polysaccharide (polyribosyl-ribitol phosphate) capsule surrounding the organism--6 types (a, b, c, d, e, and f ) have been identified. Although the capsule is considered to be a primary virulence factor, most invasive H. influenzae disease is now caused by non-encapsulated (non-typeable) H. influenzae organisms. Non-typeable H. influenzae commonly colonize the upper airway, where they often cause ear infections in children, and the lower respiratory tract of adults with chronic obstructive pulmonary disease, where they can cause bronchitis and pneumonia, and may invade the bloodstream.
Manifestations of Hib Disease Hib is a uniquely virulent serotype of H. influenzae. Invasive Hib disease may manifest as meningitis, pneumonia, bacteremia, mastoiditis, arthritis, epiglottitis or periorbital cellulitis. Other less common manifestations include endocarditis and osteomyelitis. A characteristic feature of Hib disease is agedependent susceptibility; before the availability of the Hib conjugate vaccine, Hib disease was most common in children under age 5 years (2). In the post-vaccine era (i.e. since the late 1980s), unvaccinated young children are at risk for developing Hib disease as they are not fully immune. Approximately, 3% to 6% of invasive Hib cases are fatal. Of surviving patients, up to

20% have permanent hearing loss or other long-term sequelae (3).
H. influenzae infections can be diagnosed by isolating the bacteria from a normally sterile body site (blood, cerebrospinal fluid, pleural fluid, etc.) using chocolate agar media.
Impact of Hib Vaccines Until the introduction and routine use of Hib vaccines, Hib was the leading cause of bacterial meningitis in infants and children in the U.S., with annual incidence of 40 to100 cases per 100,000 children, resulting in death or permanently disability for approximately 6,000 children per year.
The Hib polysaccharide vaccine became available for toddlers in 1985 for children aged 18 months and older in the U.S., pioneering a gradual decline in Hib disease (3). Routine use of Hib conjugate vaccines began in 1991 for infants aged 2 months, and the impact was immediate and profound (1). By 1993, the Centers for Disease Control and Prevention (CDC) reported a 95% reduction in Hib disease in the U.S., and the incidence has now decreased by 99% to a national rate less than 1 case per 100,000 children. Hib vaccines have saved thousands of lives and prevented more than 100,000 cases of deafness and severe mental retardation. In addition, the vaccine decreases the rate of Hib carriage among vaccinated children, thereby decreasing the chance that unvaccinated children will be exposed to Hib. While Hib disease has virtually disappeared in the U.S. and the developed world, the cost of the conjugate vaccine has limited its use in developing countries where the disease remains a major cause of morbidity and mortality (4).
Surveillance of H. influenzae Disease in the U.S. & Georgia Invasive H. influenzae disease became nationally reportable in 1991, just after Hib conjugate vaccines became licensed and routinely recommended. While H. influenzae infections have been reportable since 1991 in Georgia, methods of surveillance have improved and expanded over time. From 1991 to 1996, active and audited surveillance was performed in the 8-county Atlanta metropolitan statistical area (MSA). Active surveillance

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expanded to the 20-county Atlanta MSA for 1997 through 1999 and statewide since 2000.
Figure 1 depicts the rate of H. influenzae disease reported in Georgia since 1991 and the projected national rate since 1997, which is based on active surveillance performed under the Active Bacterial Core Surveillance (ABCs) of the Emerging Infections Program.1
Hib Disease in the U.S. & Georgia The estimated national incidence of Hib disease from 1997 to 2007 remained below or equal to 1.0 per 100,000 population in the ten states monitored by the ABCs (5, 6, 7, 8, 9, 10, 11, 12, 13, 14). Eighteen Hib cases were recognized in Georgia between 1998 and 2007. One case patient was younger than age 2 months, 13 case patients were older than age 5 years, and four case patients were age-eligible for vaccination. Of the four Hib case patients that were eligible for vaccination, 3 had not been vaccinated and the vaccination status of the remaining case patient was unknown.
Hib disease is now rare, but continued surveillance for Hib disease is important to monitor effectiveness of current vaccines. However, monitoring H. influenzae serotypes in the current era requires sustained efforts to send isolates to the Georgia Public Health Laboratory for serotyping and serotype verification. Figure 2 illustrates how challenging complete serotype ascertainment has been. Between 2004 and 2007, roughly half of H. influenzae isolates in Georgia were not serotyped by the Georgia Public Health Laboratory. The highest rates of serotyping have been achieved under active statewide ABCs surveillance, a system that requires substantial public health resources. Efforts to encourage isolate submission are being redoubled at this time, in view of emerging events that further underscore the importance of serotyping.
Emerging Issues Two emerging issues make serotyping of all H. influenzae isolates increasingly important: measuring the potential impact of Hib vaccine shortages, and monitoring the effectiveness of newer Hib vaccine formulations.
First, in late 2007, Merck & Co. voluntarily recalled over 1 million Hib vaccine doses because of concerns over potential

Figure 1:
FIingcuidreenc1e :ofIInncvaidsiveenHc.einoflfueInnzvaea(sAivlleTHype.s)i,nGfleuoregniaz, 1a9e91(-A20l0l7Types), Source: SENGDSeSorgia, 1991-2007
2.5

A

B

C

2.0

Cases per 100,000

1.5

1.0

U.S. (Projected*)

.5

Georgia

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Year
A 1991 to 1996, active surveillance in the 8-county Atlanta metropolitan statistical area (passive in the remainder of the state) B 1997 to 1999, active surveillance in the 20-county Atlanta metropolitan statistical area (passive in the remainder of the state) C 2000 to 2007, statewide active surveillance. *U.S. Rate projected by ABCs (EIP) Active Surveillance (References 5-14).

Figure 2: Percent of H. influenzae Isolates Serotyped, Georgia, 1991-2007

Percent of Isolates

100

90

80

70

60

50

40

30

Missing Information

Missing Information

20

Not Serotyped

10

Not Serotyped Serotyped

0

Serotyped

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Year

1The Active Bacterial Core surveillance (ABCs), which is a core component of the CDC-sponsored Emerging Infections Program (EIP) and collaboration between 10 state health departments and universities across the country established in 1995, collects comprehensive data on H. influenzae and other emerging pathogens. This program aims to establish risk factors for disease, track disease trends, monitor efficacy of vaccines, and assess the effectiveness of prevention policies; based on data collected from nationally representative surveillance areas with over 35,500,000 persons.

Division of Public Health http://health.state.ga.us
S. Elizabeth Ford, M.D., M.B.A., F.A.A.P. Acting Director, State Health Officer
Martha N. Okafor, Ph.D. Deputy Director, HIPSA

John M. Horan, M.D., M.P.H. State Epidemiologist
Director, Epidemiology Section http://health.state.ga.us/epi
Cherie Drenzek, D.V.M., M.S. Director, Acute Disease Epi Section

Georgia Epidemiology Report Editorial Board
Carol A. Hoban, M.S., M.P.H. Editor Kathryn E. Arnold, M.D.
Cherie Drenzek, D.V.M., M.S. John M. Horan, M.D., M.P.H. S. Elizabeth Ford, M.D., M.B.A., F.A.A.P. Angela Alexander - Mailing List Jimmy Clanton, Jr. - Graphic Designer

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Two Peachtree St., N.W. Atlanta, GA 30303-3186 Phone: (404) 657-2588
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product contamination, resulting in a vaccine shortage. The recall involved two of Merck's Hib-containing vaccine products: a monovalent Hib conjugate vaccine (PedvaxHIB), and a combination Hib/hepatitis B vaccine (COMVAX). Merck suspended production of the two vaccines at that time and projected that distribution of these products would not resume until the fourth quarter of 2008.
As a result, the Advisory Committee on Immunization Practices (ACIP) recommended that health care providers temporarily defer administration of the Hib vaccine booster dose normally given at age 12-15 months, except for children in specific groups at higher risk. These groups include children with sickle cell disease, leukemia and malignant neoplasms, HIV and certain other immuno-compromising conditions, asplenia, as well as American Indian and Alaska Native children (15). Providers are receiving limited allocations of vaccine, and conceivably, some children might also be missing doses in the primary series, normally given at ages 2, 4, and 6 months of age.
It is important to know whether additional cases of Hib might result from the disrupted vaccine supply.
Second, on June 23, 2008, the U.S. Food and Drug Administration (FDA) licensed a new 5-component Hibcontaining vaccine for the first time. The vaccine, called Pentacel, contains Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccines, and is made by Sanofi Pasteur. The Pentacel vaccine is approved for use in infants and children 6 weeks through 4 years of age (prior to fifth birthday) as a four-dose series at 2, 4, 6 and 15 to 18 months of age. Uptake of the new vaccine could be considerable, because of current shortages of other vaccine formulations and as a means to reduce the number of required injections during early childhood. As a newer vaccine formulation, it is important to monitor for vaccine effectiveness and post-licensure safety.
Request for H. influenzae Isolates
To accurately document the number of Hib cases occurring in Georgia and to monitor effects of Hib vaccine shortages and newer formulations, it is important to determine serotypes in all cases of invasive H. influenzae disease. Public Health strongly encourages hospitals and laboratories across the state to submit all isolates of invasive H. influenzae to the Georgia Public Health Laboratory for serotype information.

This article was written by Snehal R. Patel, M.P.H., and Kate E. Arnold, M.D.
References 1. Centers for Disease control & Prevention. Epidemiology
and Prevention of Vaccine-Preventable Diseases. Atkinson W, Hamborsky J, McIntyre L, Wolfe S, eds 10th ed. Washington DC: Public Health Foundation, 2007. 2. http://www.cdc.gov/ncidod/dbmd/diseaseinfo/ haeminfluserob_t.htm accessed 4.15.2008 3. http://www.who.int/mediacentre/factsheets/fs294/en/ accessed 4.15.2008 4. Centers for Disease Control and Prevention. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Haemophilus influenzae, 1997. 5. Centers for Disease Control and Prevention. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Haemophilus influenzae, 1998. 6. Centers for Disease Control and Prevention. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Haemophilus influenzae, 1999. 7. Centers for Disease Control and Prevention. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Haemophilus influenzae, 2000. 8. Centers for Disease Control and Prevention. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Haemophilus influenzae, 2001. 9. Centers for Disease Control and Prevention. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Haemophilus influenzae, 2002. 10. Centers for Disease Control and Prevention. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Haemophilus influenzae, 2003. 11. Centers for Disease Control and Prevention. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Haemophilus influenzae, 2004. 12. Centers for Disease Control and Prevention. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Haemophilus influenzae, 2005. 13. Centers for Disease Control and Prevention. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Haemophilus influenzae, 2006 provisional. 14. http://www.cdc.gov/vaccines/recs/recalls/hib-recall-faqs12-12-07.htm#12 accessed 5.29.2008

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The Georgia Epidemiology Report Epidemiology Branch Two Peachtree St., NW Atlanta, GA 30303-3186

PRESORTED STANDARD U.S. POSTAGE
PAID ATLANTA, GA PERMIT NO. 4528

August 2008

Volume24Number08

Reported Cases of Selected Notifiable Diseases in Georgia, Profile* for May 2008

Selected Notifiable Diseases
Campylobacteriosis Chlamydia trachomatis Cryptosporidiosis E. coli O157:H7 Giardiasis Gonorrhea Haemophilus influenzae (invasive) Hepatitis A (acute) Hepatitis B (acute) Legionellosis Lyme Disease Meningococcal Disease (invasive) Mumps Pertussis Rubella Salmonellosis Shigellosis Syphilis - Primary Syphilis - Secondary Syphilis - Early Latent Syphilis - Other** Syphilis - Congenital Tuberculosis

Total Reported for May 2008
2008 67 32 16 2 49 13 6 5 17 2 4 1 1 0 0 176 176 7 31 18 68 1 57

Previous 3 Months Total Ending in May

2006

2007

2008

145

161

153

10214

11047

2934

36

37

69

9

2

5

139

139

127

4864

4489

1042

34

40

30

15

21

13

57

31

31

6

12

8

0

2

6

8

3

6

1

0

2

3

3

3

0

0

0

262

296

377

221

489

402

38

26

22

88

130

124

98

115

76

270

310

253

3

3

2

136

134

138

Previous 12 Months Total Ending in May

2006

2007

2008

623

588

695

36728

41758

33927

183

272

269

36

37

46

699

683

673

17825

19706

13961

114

124

134

105

68

56

180

177

151

35

49

37

6

9

15

19

18

25

2

3

2

38

28

15

0

0

0

1944

1940

2046

830

1701

1577

139

108

98

487

530

605

401

420

388

1004

1071

1141

7

9

10

516

516

475

* The cumulative numbers in the above table reflect the date the disease was first diagnosed rather than the date the report was received at the state office, and therefore are subject to change over time due to late reporting. The 3 month delay in the disease profile for a given month is designed to minimize any changes that may occur. This method of summarizing data is expected to provide a better overall measure of disease trends and patterns in Georgia.
** Other syphilis includes latent (unknown duration), late latent, late with symptomatic manifestations, and neurosyphilis.
AIDS Profile Update

Report Period
Latest 12 Months

Disease

Total Cases Reported*

Classification <13yrs

>=13yrs Total

HIV, non-AIDS 24

2,780

2,804

Percent Female MSM

28

25

Risk Group Distribution %

IDU

MSM&IDU HS

Unknown Perinatal White

2

1

5

66

1

17

Race Distribution %

Black

Hispanic Other

76

4

3

7/07-6/08

AIDS

8

1,933

1,941

28

28

3

1

8

59

<1

18

76

5

<1

Five Years Ago:**

HIV, non-AIDS -

-

-

-

-

-

-

-

-

-

-

-

-

-

7/03-6/04

AIDS

8

1,843

1,851

28

35

7

2

16

38

<1

20

74

5

<1

Cumulative: HIV, non-AIDS 220

11,886

12,106

32

27

6

2

10

52

2

21

73

4

2

07/81-6/08 AIDS

241

32,761

33,002

20

43

14

5

14

23

1

30

66

3

1

Yrs - Age at diagnosis in years

MSM - Men having sex with men

IDU - Injection drug users

HS - Heterosexual

* Case totals are accumulated by date of report to the Epidemiology Section ** Due to a change in the surveillance system, case counts may be artificially low during this time period

***HIV, non-AIDS was not collected until 12/31/2003

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