Module 10 Bacterial Vaccines Part 2

1
Module 10 Bacterial Vaccines Part 2 PHB
4998 Vaccines
Joseph B. McCormick MD, MS 2004
2
(No Transcript)
3
PNEUMOCOCCAL DISEASE A MAJOR HEALTH THREAT

• Pneumococcal disease caused by Streptococcus
  pneumoniae
• Pneumococcal disease a major threat to health
• Non-invasive diseases (e.g. otitis media,
  pneumonia)
• Invasive diseases (e.g. bacteraemia, meningitis)
• Invasive pneumococcal disease is serious and has
  a high risk of mortality
• Groups at high risk include elderly persons,
  persons with chronic diseases, asplenic
  patients, immunocompromised patients

1.2
4
DISEASES CAUSED BY STREPTOCOCCUS PNEUMONIAE
PNEUMOCOCCAL INFECTION

• Non-invasive disease
• Sinusitis (sinuses)
• Otitis media (middle ear)
• Pneumonia (lungs)

• Invasive disease
• Bacteraemia (blood)
• Meningitis (CNS)
• Endocarditis (heart)
• Peritonitis (body cavity)
• Septic arthritis (bones and joints)
• Others (appendicitis, salpingitis, soft-tissue
  infections)

Musher, in Principles and Practice of
Infectious Diseases, 1995
5
PNEUMOCOCCUS TRANSMISSION AND COLONISATION
Fedson, Musher, in Vaccines, 1994 Musher, in
Principles and Practice of Infectious Diseases,
1995
6
PNEUMOCOCCUS PATHOGENESIS
Salyers, Whitt, in Bacterial Pathogenesis, 1994
2.6
7
Pneumococcal Pneumonia and Pneumococcal Invasive
Disease
Fedson DS. Drugs Aging 1999.
8
Pneumococcal Disease At-Risk Groups

• Infants and Elderly
• Laboratory reports of bacteraemic pneumococcal
  infection per 100 000 population, by age group,
  in England and Wales

1986
1982
1992
Bacteraemia
35
30
25
Reports per 100 000 population
20
15
10
5
19
1019
2044
4564
6569
7074
75
Age (yrs)
lt1
Aszkenasy et al., CDR Review, 1995
CDSC Communicable Disease Surveillance Centre
9
PNEUMOCOCCAL DISEASE PNEUMONIA

• Complications
• Bacteraemia in 15-30 of patients with
  pneumonia1,2
• high mortality despite appropriate antibiotic
  therapy
• overall case fatality rate 15-20 for
  pneumococcal bacteraemia
• higher case fatality rates (30-40) for elderly
  persons and other vulnerable groups
• Spread of pneumococci in the blood to other
  normally sterile sites can cause other invasive
  pneumococcal diseases (e.g. meningitis)
• Empyema (pus in the pleural cavity) in about 2
  of cases3

1 Salyers, Whitt, in Bacterial Pathogenesis,
1994 2 Fedson, Musher, in Vaccines, 1994 3
Musher, Clin Infect Dis, 1992
10
EPIDEMIOLOGY INVASIVE PNEUMOCOCCAL DISEASE

• PNEUMOCOCCAL MENINGITIS1,2
• Annual incidence 1-2/100 000 persons
• Higher among young children and elderly persons
• at least 10 times the incidence among an elderly
  (³60 years) population than among younger adults
  (20-29 years of age)2
• Case-fatality rates are high
• about 30 in adults and 6 in children3

1 CDC, MMWR, 1997 2 Wenger et al., J Infect Dis,
1990 3 Fedson, Musher, in Vaccines, 1994
11
PNEUMOCOCCAL DISEASE MENINGITIS (1)

• Meningitis
• Inflammation of the meninges (membranes
  surrounding the brain)
• Can be caused by a range of microorganisms, as
  well as be a manifestation of some non-infectious
  diseases
• Pneumococcal meningitis
• Invasive pneumococcal disease
• Generally, pneumococci invade the CNS from the
  blood stream
• Signs and symptoms1
• Early stages fever, irritability, neck
  stiffness, drowsiness
• Later stages headache, seizures, coma
• The signs and symptoms are not specific to
  pneumococcal disease

1 Salyers, Whitt, in Bacterial Pathogenesis, 1994
12
PNEUMOCOCCAL DISEASE MENINGITIS (2)

• Pneumococcal meningitis¾a high risk of mortality
• Case-fatality rate about 30 in adults1
• Higher (about 55) in older patients and other
  vulnerable groups2
• Disability among survivors1
• Learning disability
• Hearing loss
• Blindness
• Paralysis

1 Fedson, Musher, in Vaccines, 1994 2 CDC, MMWR,
1989
13
Pneumococcal Disease in the Elderly
Pathogenic agents in bacterial meningitis in
persons aged ³ 60 years in the USA
Group B streptococcus 3
Haemophilus influenzae 4
Others 26
Streptococcus pneumoniae 49
Neisseria meningitidis 4
Listeria monocytogenes 14
Wenger et al., J Infect Dis, 1990
14
PNEUMOCOCCAL DISEASE MEDICAL MANAGEMENT (1)

• Hospitalisation
• Often required in high-risk groups and/or in
  severe forms of pneumococcal disease
• Sometimes admission to an intensive care unit is
  necessary
• Empiric treatment using broad-spectrum
  antimicrobial agents
• To cover all possible bacterial aetiological
  agents
• To overcome increasing antimicrobial resistance
  to antibiotics
• High-cost management

15
PNEUMOCOCCAL DISEASESUMMARY

• S. pneumoniae
• A bacterium surrounded by a polysaccharide
  capsule that protects it from phagocytosis
• Many different serotypes
• Pneumococcal disease
• Invasive pneumococcal disease is serious and has
  a high risk of mortality
• Risk factors include old age, chronic illness,
  asplenia and immunodeficiency
• Mortality remains high despite appropriate
  antibiotic therapy
• S. pneumoniae resistance to antimicrobials is
  increasing (with concomitant increasing cost of
  management)
• Prevention of pneumococcal disease among
  high-risk groups is a priority

16
PNEUMOCOCCUS DIVERSITY OF SEROTYPES

• There are at least 90 different serotypes of
• S. pneumoniae1,2
• Each has a capsule of a different chemical
  composition
• Each stimulates the production of a different
  antibody
• Only a minority of serotypes cause most cases of
  human disease
• 8-10 cause two-thirds of serious pneumococcal
  infections in adults3

1 Fedson, Musher, in Vaccines, 1994 2 Henrichsen,
J Clin Microbiol, 1995 3 UK DoH, Immunisation
Against Infectious Disease, 1996
17
(No Transcript)
18
PNEUMOCOCCAL VACCINES ANTIGEN COMPOSITION

• 23-valent pneumococcal vaccine contains purified
  capsular polysaccharides derived from 23 S.
  pneumoniae serotypes1
• 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A,11A, 12F,
  14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F
• Serotype coverage2,3
• 85-90 of serotypes responsible for all cases of
  invasive pneumococcal disease
• Vaccine includes major serotypes that have
  developed antimicrobial resistance
• Cross protection within some serotypes1
• For example, antibody response to serotype 6B
  protects against serotype 6A, which is not in the
  vaccine

1 CDC, MMWR, 1989 2 Fedson, Musher, in Vaccines,
1994 3 Geslin et al., Méd Mal Infect, 1992
19
PNEUMOCOCCAL VACCINES iMMUNE RESPONSE

• Vaccine stimulates 23 type-specific anti-capsular
  antibodies1
• Antibodies aid the destruction of pneumococci by
  white blood cells
• The immune response in most elderly patients ³ 65
  years of age
• is as good as that of healthy younger adults1
• is variable according to serotypes2
• The response is decreased in
• immunosuppressed individuals (e.g. patients with
  leukaemia, lymphoma, multiple myeloma, or AIDS)3
• Antibody levels generally last 5 years or more4
• Note it is inappropriate to use 23-valent
  vaccine in children under 2 years of age, because
  the immune response in this age group is poor 3

1 Fedson, Musher, in Vaccines, 19942 Rubins et
al., Infect Immun, 19993 CDC, MMWR ,19974
Butler et al., JAMA ,1993
20
Need information on other vaccine, particularly
conjugate vaccine
21
Local reactions Pain ( with reaction)
FinOM Vaccine Trial
1st to 3rd DTP/Hib, 4th IPV
22
SAEs assessed to be possibly related to the study
vaccine
FinOM Vaccine Trial
23
Response following primary immunization with
PncCRM
Rennels ea 1998
24
Antibody concentrations after PncPS at two years
of age
Obaro ea 1997
25
Salivary antibodies after PncTPncPS
ve
Korkeila, unpublished
26
Pneumococcal conjugate vaccines

• Serotypes
• - 4, 6B, 9V, 14, 18C, 19F, 23F
• - 1, 5
• - 3, 7F
• Protein carriers
• tetanus or diphtheria toxoid
• CRM197 protein
• meningococcal outer membrane complex
• Haemophilus influenzae protein

27
Carriage of vaccine-related serotypes
Dagan 1997
28
Conclusion 1 Pneumococcal conjugate vaccines

• Are safe and well tolerated
• Are immunogenic in infancy and early childhood
• Induce immunologic priming
• Induce functionally active antibodies
• Induce an immune response on mucosal membranes
• Reduce mucosal carriage of vaccine-type strains

29
Study design
Kaiser Permanante Trial

• 37,000 children recruited in Northern California
• All children were randomized to receive PncCRM or
  control (MenCRM) vaccine at 2, 4, 6, and 12-15 mo
• Primary end point invasive pneumococcal
  infection
• Protection against clinical pneumonia and
  clinical otitis (irrespective of etiology) could
  also be evaluated from the computerised data base
  of the HMO

30
Analysis of vaccine efficacy
Kaiser PermanenteTrial

• Invasive infections 97.4 (PP analysis CI95
  82.7-99.9 )
• Pneumonia
• any pneumonia 11.4 (1.3-20.5 )
• X-ray positive pneumonia 33.0 (7.3-51.5 )
• consolidation in X-ray 73.1 (38.0-88.3 )

Black ea 2000
31
Analysis of vaccine efficacy
Kaiser PermanenteTrial
per child-year per 100 child-years
Black ea 1999
32
Study design
FinOM Vaccine Trial

• 2497 children recruited in Tampere, Nokia and
  Kangasala
• All children were randomized to receive
  PncCRM/PncOMPC, or control (HBV) vaccine at 2, 4,
  6, and 12 mo
• Follow-up from 2 to 24 mo
• All respiratory infections requiring medical
  attention were evaluated and treated at the study
  clinic

33
(No Transcript)
34
AOM episodes due to vaccine serotypes
FinOM Vaccine Trial
Primary analysis
Vaccine efficacy 57 (95 CI 44 to 67)
35
Summary of PncCRM efficacy results
FinOM Vaccine Trial
36
Efficacy of PncCRM by serotype
FinOM Vaccine Trial
Acute Otitis Media

• Excellent for 6B (84 )
• Good for 14 (69 ) and 23F (59 )
• Good cross-protection for 6A (57 )
• Possibly present for 19F (25 )
• Episodes due to other than vaccine or
  cross-reactive serotypes increased by 34 (95
  CI 0-81 )
• Overall reduction in Pnc AOM 34 (21-45 )

37
Conclusion 2Pneumococcal conjugate vaccines

• Are highly efficacious against invasive
  pneumococcal infections
• Reduce the number of visits due to pneumonia and
  otitis (irrespective of etiology)
• Efficacy of PncCRM against AOM varies from 6
  (all episodes) to 34 (pneumococcal) to 57
  (vaccine serotypes)
• If efficacy same in all age groups, wide use of
  the vaccine would prevent 1.2 million
  episodes/year in US

38
PNEUMOCOCCAL VACCINES OVERVIEW OF EFFECTIVENESS

• Case-control and indirect cohort studies on the
  effectiveness of the pneumococcal vaccine in
  preventing invasive pneumococcal disease

Type of infection Location Vaccine
Source (no of cases) efficacy (95 CI) All
serotypes Connecticut (1054) 47 (30-59) Shapiro
et al. 1991 Philadelphia (122) 70 (37-86) Sims
et al. 1988 Charlottesville (85) 81 (34-94) Farr
et al. 1995 Alaska (159) 64 (32-81) Davidson
et al.1994 Vaccine type Connecticut (983) 56
(42-67) Shapiro et al. 1991 VT-related Denver
(89) -21 (-221-55) Forrester et al. 1987 Alaska
(87) 79 (49-92) Davidson et al. 1994 CDC
57 (45-66) Butler et al. 1993
only patients with pneumococcal isolates from
normally sterile body sites were included. VT
indicates vaccine-type pneumococcal infection.
unpublished observations. indirect cohort
study 515 vaccinated and 2322 unvaccinated
subjects.
Fedson, in The Clinical Impact of Pneumococcal
disease and Strategies for its Prevention, 1995
5.14
39
PNEUMOCOCCAL VACCINES CLINICAL EFFECTIVENESS

• Estimation of effectiveness of pneumococcal
  vaccination in preventing invasive pneumococcal
  disease caused by vaccine serotypes
• US Centers for Disease Control study in 2837
  patients (³ 5 years old) by underlying illness,
  1978-1992

Overall effectiveness of 57
95 CI
75
Immunocompetent, gt65 years (70,373)
57-85
84
50-95
Diabetes mellitus (9,122)
23-90
73
Coronary vascular disease (15,73)
65
26-83
Chronic pulmonary disease (50,186)
14-95
77
Anatomic asplenia (89,23)
69
17-88
Congestive heart failure (20,96)
Underlying disease/condition (no of isolates from
vaccinated, unvaccinated subjects)
Note data are for patients who received
14-valent or 23-valent vaccine. Overall
effectiveness for patients receiving 23-valent
vaccine was 60.
Butler et al., JAMA ,1993
40
PNEUMOCOCCAL DISEASE PREVENTION VACCINATION
RECOMMENDATIONS

• WHO view (Technical Advisory Group convened by
  WHO Regional Office for Europe, 1988)1
• Pneumococcal vaccination should be recommended
  for all elderly persons (aged ³60-65 years) and
  for persons of any age at high risk of acquiring
  pneumococcal infection
• National recommendations
• Many countries recommend vaccination for specific
  at-risk groups or conditions
• Some countries recommend vaccination for elderly
  persons aged
• ³60 years Belgium, Germany, Iceland
• ³65 years Denmark, Finland, Norway, Sweden,
  USA, Canada, New Zealand

1 Fedson et al., Infection 1989
41
PNEUMOCOCCAL DISEASE PREVENTION VACCINATION
RECOMMENDATIONS
Pneumococcal vaccination recommendations in the
USA Europe (1997 data)

• Immunocompromised Cardiopulmonary Nurs
  ing Age gt
• Country Asplenia Haematological HIV diabetes,
  renal Other home 65 years
• Austria l - - l l - -
• Belgium l l l l l l l
• Denmark l l l l - - l
• Finland l l l l l - l
• France l l - l l - -
• Germany l l - l - - -
• Iceland l l - l l l l
• Ireland l l l l l - -
• Italy l - l - - - -
• Luxembourg l l l l l l l
• Netherlands l - -
• Norway l l l l l - l
• Sweden l l l l l - l
• Switzerland l l l l l - -
• UK l l l l l - -
• USA l l l l l l l

recommended for any person at increased risk
because of chronic illness. Austria not
diabetes mellitus or renal disease France not
heart disease. Belgium, Iceland ³60 years
Luxembourg ³55 years. - not recommended. There
are no national recommendations for Greece,
Portugal or Spain. For Switzerland,
recommendations are from an advisory note only in
the national vaccination recommendations
4.4
D Fedson, personal communication, 1997
42
PNEUMOCOCCAL DISEASE PREVENTION OPPORTUNITIES
FOR VACCINATION
Who When Age ³65 years and/or persons at
risk Regular return visits to general
practitioners or hospitals Concomitantly with
influenza vaccine (at a different injection
site) Discharge from hospital Residency in
nursing home or other chronic care
facility Persons undergoing splenectomy, 2
weeks before elective surgery, organ
chemotherapy transplantation, cancer
chemotherapy, immunosuppressive
treatment Persons with HIV infection On
diagnosis of HIV positivity
CDC, MMWR, 1997
43
PNEUMOCOCCAL DISEASE PREVENTION OVERALL
VACCINATION RATES

• Pneumococcal vaccination rates in the USA, Canada
  and western Europe in 1996

USA
OthersSpain (5)Portugal (0)Netherlands
(3)Italy (2)Ireland (5)Greece(2)Germany (5)
Canada
Belgium
UK
Sweden
Norway
Finland
Iceland
Austria
France
Switzerland
Denmark

Others
0
40
80
120
160
200
240
280
Fedson, Clin Infect Dis, in press
Doses of pneumococcal vaccine distributed per 10
000 population
4.6
44
PNEUMOCOCCAL DISEASE PREVENTION
PHARMACOECONOMICS

• The cost-effectiveness of vaccination to prevent
  pneumococcal bacteraemia in persons aged ³65
  years was recently evaluated in the USA

Net medical expenditure per QALY gained for
single pneumococcal vaccination was compared with
treatment of the disease if it occurred
Vaccination was COST-SAVING in each age group
analysed (65-74, 75-84, ³85 years)
'Based on preventing bacteraemia alone, these
results lend strong support to US policies for
universal pneumococcal vaccination for elderly
people'
Sisk et al., JAMA, 1997
45
PNEUMOCOCCAL DISEASE CONCLUSIONS

• Pneumococcal disease
• Major cause of morbidity and mortality worldwide
• Diagnosis not always made and difficult to
  establish
• Treatment may be complicated by antibiotic
  resistance
• Management can be costly
• Prevention by vaccination is a priority in
  populations who are at risk
• The elderly
• Patients with chronic cardiovascular, pulmonary,
  renal, hepatic and metabolic disorders
• Patients who are immunocompromised
• Patients with asplenia

46
(No Transcript)
47
Pneumococcal Conjugate Vaccine

• Vaccination of all children beginning age 2
  months through 59 months

• Priority given to children at increased risk

48
Future of pneumococcal vaccines

• Will be used in infants and children for
  prevention of
• invasive infections and severe pneumonia
• acute otitis media
• spread of antibiotic resistant strains of Pnc
• Efficacy/effectiveness in pregnant women and in
  the elderly population needs to be evaluated
• May be included in wide spectrum combination
  vaccines with other (Hib/Men) conjugates
• PsPA is a possible pan pneumococcal protein
  vaccine

49
Sao Paulo Brazil
50
(No Transcript)
51
(No Transcript)
52

• MENINGITISMeningitis inflammation of the
  lining surrounding brain spinal cord. Can be
  caused by different organisms such as bacteria
  and viruses. Viruses viral meningitis is the
  most common and usually occurs in the Summer
  early Fall - viral meningitis is benign and
  resolves within some days, without permanent
  damage.Bacteria bacterial meningitis is an
  uncommon disease, but can be very serious,
  causing death or permanent neurologic damage, it
  can occur sporadically throughout the year.

53

• BACTERIAL MENINGITIS Neisseria
  meningitidis Epidemic meningitis, 2500-3000
  cases per year in US
• Streptococcus pneumoniae annual incidence in
  the USA 500,000 pneumonia, 50,000 bacteremia
  3,000 meningitis.
• Haemophilus influenzae meningitis, nearly
  eradicated now by vaccine.

54
MENING CONJUGATE

• NEISSERIA MENINGITIDIS
• Neisseria Meningitidis is a bacterium
• 13 serotypes based on the structure of the
  capsular Polysaccharide
• (A, B, C, D, X, Y, Z, W135, 29E, H, I, K, L)
• But only 3 (A, B, C) are responsible for 90 of
  the cases.

55
MENING CONJUGATE

• PATHOLOGY
• Neisseria meningitidis is responsible for
• Meningococcal Meningitis
• Fever, headache, photophobia, vomiting,
  increased intracrainial pressure in children
  under 1 year.
• Meningococcal septicaemia (blood poisoning)
• Fever, rash, skin bleeding (petechia, purpura),
  low blood pressure,altered mental states,
  seizures, coma.

56

• SEROGROUPS of Neisseria meningitidisSerogroup
  A main cause of large epidemics dominates in
  Africa. It is unknown why it has virtually
  disappeared from the USA since 50
  years.Serogroup B generally associated with
  sporadic disease - but may cause outbreaks in
  Europe America - is the most common in Latin
  America Europe, causing over 50 of
  cases.Serogroup C has been responsible of
  large outbreaks in Latin America, Asia Africa -
  is increasing in America Europe - is the most
  common in Canada USA, where a virulent clone,
  ET-15, seems to be increasing.Serogroup Y
  currently increasing in North America.

57

• BACTERIAL MENINGITISIncidence 1-1.2 million
  yearly world-wide with 135-200,000 deaths2/3 in
  children lt 5 years 2.5-10 per 100,000 in
  industrialized countries 50 per 100,000 in
  developing countries.Major causal triad
  N.meningitidis, S.pneumoniae, H. influenzae b,
  
• H. influenzae regression following vaccination
  in the mid-80s, itsincidence decreased by gt 80
  in children lt 5 years, in USA
  Europe.Resistance to antibiotics a second
  epidemiological trend is a world-wide increase of
  infections with antibiotic-resistant strains of
  S. pneumoniae.

58
BACTERIAL MENINGITIS causal agents according
to age

• New-borns Infants lt 3 months Streptococcus
  agalactiae (group B), Escherichia coli , Listeria
  monocytogenes, Pseudomonas aeruginosa, Klebsiella
  pneumoniae.
• Children lt 5-6 years Haemophilus influenzae
  (dramatic fall due to the vaccination),
  Streptococcus pneumoniae, Neisseria meningitis.
• Older children Adults Streptococcus
  pneumoniae, Neisseria meningitis, Listeria
  monocytogenes, Haemophilus influenzae more
  particularly in elderly patients.

59

• TRANSMISSIONReservoir asymptomatic
  nasopharyngeal carriers (5-10 of adult
  population (30 in 15-20 yrs 80 after 5 weeks
  of military service- carriage lasts for some
  months.Mode of spread person to person
  transmission by aerosolisation air borne
  disease - MD is transmitted by asymptomatic
  carriers more than by MD patients. Natural
  immunity - it is unknown why one individual on
  acquiring the organism develops invasive disease
  whereas hundreds of others do not.
• -Immunity develops after carriage.

60
MENING CONJUGATE

• TRANSMISSION
• Neisseria Meningitidis is a human pathogen,
  transmission by direct contact or droplets from
  asymptomatic carriers.
• EPIDEMIOLOGY
• Endemic sporadic cases in temperate countries
• 1 to 5 per 100.000 in industrialized countries
• 10 to 25 per 100.000 in developing countries
• Epidemic Sub-Saharan meningitis belt
• gt 1.000 per 100.000

61

• RISK FACTORSAge risk is higher in children
  decreases with age. Immune deficiencies HIV
  (?).Contact with respiratory secretions
  kissing or sharing a glass -households.Overcrowd
  ing conditions military barracks - school
  university - hadji pilgrimage - sport team -
  small communities.Climatic conditions dry
  season or prolonged drought dust storms in
  sub-Saharan areas, winter-spring in temperate
  areas.Factors increasing carriage active
  passive smoking - concurrent viral (Flu)
  mycoplasma infections - recent acquisition of
  carriage. Others alcoholism.

62

• LETHALITY according to disease causal
  agentDefinition Case-fatality rate (CFR)
  proportion of infected ill patients who die from
  the disease during the 1-year period.
• Mortality rate proportion of the whole
  population who die from the disease during the
  1-year period.Septicaemia CFR is higher in
  blood infection than in meningitis N. meningitis
  CFR 18-53 (septicemia), lt10 (meningitis)
  7-19 (meningococcal disease).
• Meningitis CFR (from a 45-study metanalysis)
• H. influenzae about 4, 2-5 from other
  sources
• N. Meningitidisabout 8, 10 from other
  sources
• S. pneumoniaeabout 15, 19-21 in USA from
  other sources

63

• LETHALITY according to age groupAge groups
  higher CFRs in extreme agesAll organisms in
  UK, CFR 19.9 in neonates versus 5.4 in
  post-neonate infants (gt 1 month).
• N. meningitidis in USA, CFR gt 25 in lt1 year
  children gt35-year adults versus lt 8.4 in 9-34
  year patients.
• S. pneumoniae in USA, global CFR 19 versus
  31 in people aged gt 60 years.
• H. influenzae in USA, global CFR 14 versus
  10 in lt1 year children - 6 in 1-29 year people
  - 13 in 30-39 year adults - and 24 in gt 59
  years adults.

64

• SEQUELAE according to causal
  agentsDefinition mainly CNS sequelae, firstly
  hearing loss (HL), mental retardation (MR),
  spasticity (SP), convulsions (CV), etc...
• Frequency among BM survivors
  (a) Globally15-20 of sustained neurological
  sequelae H. influenzae 6.1 MR, 5.1 HL,
  6.1 SP, 10.2 CV. N. meningitidis 2.1 MR,
  2.1 HL,1.4 SP, 6.4 CV. S.
  pneumoniae17.0 MR,11.5 HL,14.3 SP, 27.7
  CV.Prevention of sequelae Antibiotics early

65
MENINGITIS in The World
BC
BC
BC
A
Y
BC
AB
ACB
BC
A
A
A
AC
BC
AC
A
A
A
AC
A
A
A
BC
BC
BC
BC
66
AFRICAN MENINGITIS BELT

Mauritania
Mali
Senegal Gambia Guinea-Bissau Guinea Sierra-Leone L
iberia
Niger
Chad
Burkina Faso
Sudan
Ethiopia
Djibouti Somalia Uganda Kenya
Centafrican Rep
Ivory Coast, Ghana, Togo, Benin, Nigeria, Cameroun
67
(No Transcript)
68
Situation regarding N. meningitis
epidemics Africa as of April 7, 2002
Benin From 1 January to 7 April, 502 cases, 50
deaths Cote d'Ivoire From 1 January to 7
April, 244 cases, 43 deaths Gambia From 1
January to 7 April, 50 cases, 3 deaths. Guinea
From 1 January to 31 March, 123 cases, 23 deaths
(CFR 19) Neisseria meningitidis serogroups A
and C Mali From 1 January to 7 April, 382 cases
including 33 deaths ( 9) Senegal From 1
January to 7 April, 121 cases including 7 deaths
(6) Togo From 1 January to 7 April, 589 cases
including 95 deaths (16) . Neisseria
meningitidis serogroup A
69
MENING CONJUGATE

• POLYSACCHARIDE VACCINES
• PS acts as a T-cell independent antigen (like H
  flu and P. Pneumoniae)
• Poor antibody response in children less than 18
  months
• No immunological memory
• Rapid decrease of antibodies after vaccination.

70
MENING CONJUGATE

• CONJUGATE VACCINES
• Good antibody response in infants
• Immune memory
• Long duration of antibodies after vaccination
• Decrease in the carriage ---gt herd immunity

71
MENING CONJUGATE

• Available mening vaccines
• Bivalent A/C polysaccharide vaccine
• A is effective in children over 3 months old
• C is effective in children over15 months old
• Quadrivalent A, C, W135, Y polysaccharide
  vaccine
• effective in ³ 2 years old.

72
MENING CONJUGATE

• Initial objective to have a vaccine for infants
• Research is looking for an improved formulation
  of tetravalent conjugate vaccine effective in
  infants
• Adjuvanted formulation
• PsPa as a carrier protein

73
Typhoid Conjugate Vaccine
74
Typhoid Conjugate Vaccine
75
Typhoid Conjugate Vaccine
76
Typhoid Conjugate Vaccine
77
Typhoid Conjugate Vaccine
78


TUBERCULOSIS
TUBERCULOSIS


CDC
79
Tuberculosis
Transmission and Pathogenesis
cdc
80
(No Transcript)
81
Pathogenesis

• 10 of infected persons with normal immune
• systems develop TB at some point in life
• HIV strongest risk factor for development of TB
  if infected
• Risk of developing TB disease 7 to 10 each
  year
• Certain medical conditions increase risk that
  TB infection will progress to TB disease

cdc
82
Transmission of M. tuberculosis

• Spread by droplet nuclei
• Expelled when person with infectious
• TB coughs, sneezes, speaks, or sings
• Close contacts at highest risk of becoming
• infected
• Transmission occurs from person with
  infectious TB disease (not latent TB infection)

83
Probability TB Will Be Transmitted

• Infectiousness of person with TB
• Environment in which exposure occurred
• Duration of exposure
• Virulence of the organism

cdc
84
Reported TB Cases United States, 1953 - 1998
100,000
70,000

50,000
Cases (Log Scale)

30,000
20,000
10,000
53
60
70
80
90
98
Year
Change in case definition
85
Reported Cases of TB by Country of Birth -
United States, 1986-1998
40
35
30
25
Foreign-born
Recent Cases per 100,000 population
20
15
10
All Cases
5
U.S.-born
0
86
98
87
88
89
90
91
92
93
94
95
96
97
Year
cdc
86
MDR TB Cases, 1993 - 1998
None
gt 1 case
87
Tuberculosis

• TB is the leading cause of death from infectious
  disease in developing countries, and kills 3
  million people a year worldwide.
• In Western Europe and other industrialized
  countries where TB has become a rare disease, the
  declining incidence has been halted or reversed.
• Between 1985 1991, an 18 increase in TB
  incidence was reported in the USA, and a doubled
  incidence of TB in New York city. Contributing
  factors are
• influx of immigrants from countries with endemic
  TB,
• b. increased number of social outcasts living in
  crowded places,
• c. AIDS-epidemic,
• d. emergence of MDR-TB (19 of new TB cases in
  New York in 1991), and e. dismantling of TB
  control programs.

88
Tuberculosis

• The incidence of TB in sub-Saharan Africa is
  rapidly increasing due to the HIV epidemic. It is
  estimated that 4 of the 7,5 M (million) new TB
  cases worldwide was attributable to HIV in 1990,
  and that in 2000, 14 of the 10,2 M new cases
  will be attributable to HIV.
• For the period 1990-1999, the WHO (World Health
  Organization) estimated 30 M deaths from TB 2,9
  M (9,7) due to TB in association with HIV. The
  majority of these deaths expected in sub-Saharan
  Africa and South East Asia.
• In Western Europe and industrialized countries a
  similar problem may arise if
• Contact tracing and surveillance of high risk
  groups are relaxed,
• AIDS epidemic in allochtones and natives expands
  further,
• immigrants with high endemic TB prevalence escape
  radiological check-up and follow-up.

89
BCG Vaccine
 Reported data from clinical trials included in
the meta-analysis providing estimated efficacy of
bacillus Calmette-Guérin (BCG) vaccine against
tuberculosis (TB) and TB-related death.
Brewer, TF Preventing Tuberculosis with Bacillus
Calmette-Guérin Vaccine A Meta-Analysis of the
Literature Clinical Infectious Diseases 200031S6
4-S67

90
Vaccine Strategies