Childhood Immunization Practice

Dr Réghana Taliep

Acknowledgements Prof Brian Eley

Millennium Development Goals

• By 2015: reduce, from 1990 levels

MDG 4 Reduce mortality in under-5 by 2/3

MDG 5 Reduce maternal mortality ratio by 3/4

MDG 6 Combat HIV/malaria/other diseases

Global causes of under-5 mortality, 2008

Total estimated number of deaths: 8.795 million Total estimated number of pneumonia deaths: 1.575 million

Black RE, et al. Lancet 2010;375:1969-1987

Under-5 mortality in SA, 2008 (Countdown to 2015 Decade Report (2000-2010)

Neonatal

29%

Diarrhoea

9%

Injuries, 2%

Pneumonia, 6%

Other, 9%

Preterm, 41%

Asphyxia, 23%

Infection, 18%

Other, 9%

Congenital, 8%

Tetanus, 1% Diarrhoea, 1%

Expanded Programme for Immunisation (EPI)

• Launched by WHO in 1974

• Expand access to vaccination

• 1974: 80% of the world’s 130 million children vaccinated before their first birthday

• Prevented: >3 000 000 deaths/ year

>750 000 disabilities/year

Immunisation Schedule: April 2009

Age Vaccines

Birth BCG, OPV(0)

6 weeks OPV(1), RV(1), DTaP-IPV/Hib(1), Hep B(1),

PCV13 (1)

10 weeks DTaP-IPV/Hib(2), Hep B(2)

14 weeks RV(2), DTaP-IPV/Hib(3), Hep B(3), PCV13 (2)

9 months Measles(1), PCV13 (3)

18 months DTaP-IPV/Hib(4), Measles(2)

6 years Td

12 years Td

Coverage rates: Western Cape

Age

BCG

OPV

DPT

Measles

Birth

99 [99-99.5]

99.2 [98-100]

6 weeks

94.4 [93-96]

97 [96-98]

10 weeks

88 [86-90]

90.8 [89-92]

14 weeks

81.3 [79-84]

85.2 [83-87]

9 months

92.7 [91-94]

18 months

54.4 [51-58]

58.7 [55-65]

60 [56-64]

J Corrigall; SAMJ 2008;98:41-45

BCG immunisation (1)

• HIV uninfected: - Protective efficacy against -TB meningitis: 73% -miliary TB: 77% -pulmonary TB: variable1 - Safe • HIV infected: - no evidence of protective effect1 • Adverse events in HIV infection

– BCG adenitis: up to 6% (local cohort)2 – Disseminated BCG infection: est incidence:992 per 100 000 (95% CI: 567-1495)1

– IRIS events (n=352): 6% (95% CI: 3.7 – 8.0%)2

– Early ART: reduced incidence from 15.7% (8.6-25.3%) to 5.2 (2.8-25.3%)3

1 Hesseling A, et al, WHO Bull 2009; 87:505-511 2 Nuttall J, et al, Int J Infect Dis 2008;12:e99 3 Rabie, et al. 2009, 15th CROI meeting, Abstract 600

BCG immunisation (2)

• WHO position (2007)1

Children known to be HIV-infected should no longer be

immunised with BCG Local factors should be considered National decision

• ? Selectively delayed vaccination eg. 14 weeks

• Impact of policy change2

reduce risk of BCG vaccination in small proportion of HIV infected infants

potential risk of HIV-uninfected infants not receiving BCG

1 WHO, Wkly Epidemiol Rec 2007;82:193 2 Hesseling A, et al, SAMJ 2009;99:88-91

BCG immunisation (3)

• Conditions for selectively delayed vaccination2

- Early virological diagnosis of HIV infection in exposed infants

- Rapid turnaround time of results

- High retention of HIV positive infants in care

- Early initiation of ART in HIV-infected infants

- Co-ordination of PMTCT, vaccination and TB programmes

• Immunisation policy in South Africa2

– South Africa has continued neonatal BCG irrespective of HIV status because of concerns about switching to a stratified immunisation policy without carefully considering the practical implications

2 Hesseling A, et al, SAMJ 2009;99:88-91

Poliomyelitis

Poliomyelitis eradication

• 1988: Resolution calling for eradication by year 2000 adopted

• 4-pronged strategy to prevent infection:

– high routine vaccine cover with OPV

– supplementary immunisation (mass campaigns) • National immunization days (NIDs) > 100 countries

– effective surveillance • Non-polio AFP rate: ≥ 2 per 100,000 population aged ≤ 15 yrs

• Stool collection for ≥ 80% of AFP cases

– “mopping up”

OPV / IPV • OPV: live attenuated vaccine

– oral

– Systemic and local, mucosal immune response

– Disadvantage: 1 case of vaccine-associated polio every 2.5 million doses

– Outbreaks of circulating vaccine-derived polioviruses (cVDPV): 464 cases in 15 countries since 2000

• IPV (Salk): inactivated vaccine

- intramuscular injection - triggers excellent immune response

- no risk of VAPP

• New SA approach involves both OPV and IPV • Recommendations for OPV identical for HIV-negative and HIV-

infected children

WHO, CDC, UNICEF:http://www.polioeradication.org

WHO. Wkly Epidemiol Rec 2010;85:213-228

http://www.polioeradication.org/

Rotaviruses

• Occur widely among humans and many animal species throughout the world

• By 3 years 90% of children will have been infected

• Incidence of rotavirus disease similar in rich and poor countries, but mortality is higher in poor countries

• Public measures (clean water, hygiene & sanitation) prevent diarrhoea caused by bacteria but not rotavirus

Cuncliffe NA, et al. Bull World Health Organ 1998;76:525-537

Diarrhoea deaths per 100,000 children < 5 years

Santosham M, et al. Lancet 2010;376:63-67

39% Global diarrhoea deaths due to rotavirus

Rotavirus vaccine & HIV

• HIV infection does not appear to alter the clinical course of rotavirus infection1

• Efficacy established in Southern African RCT2

• Immunogenicity and safety evaluated in South Africa3

• Incorporated in the SA national immunisation schedule

1Cuncliffe NA, et al. Lancet 2001;358:550-555 2Madhi SA, et al. N Engl J Med 2010;362:289-298 3Steele AD, et al. P Infect Dis J 2011;30:125-130

Pneumococal conjugate vaccine

• Streptococcus pneumoniae is a leading vaccine-preventable cause of childhood death: est 716 000 deaths annually1

• SA: 70% Invasive Pneumococcal Disease (IPD) occurring in HIV infected children

• Indirect protection

• 90 immunologically distinct capsular polysaccharides within

45 serogroups have been characterised • Routine clinical practice: 7-valent vaccine (serotypes: 4, 6B,

9V, 14, 18C, 19F, 23F) plus cross protection against 6A • Recently: 13-valent vaccine introduced

1. Madhi, SA. South Afr J Epidemiol Infect 2008; 23(4):05-09

Efficacy of pneumococcal conjugate vaccine against IPD

Study Vaccine serotypes All serotypes

South Africa1

HIV-infected 65% (CI: 24-86) 53% (CI: 21-73)

HIV-uninfected 83% (CI: 39-97) 42% (CI: -28-75)

South Africa2

HIV-infected 39% (CI: -8-65) 46% (CI: 19-64)

HIV-uninfected 78% (CI: 34-93) 35% (CI: -61-68)

Gambia3 92% (CI: 44-99) 45% (CI: 19-63)

Follow up until age 2.5 years

Follow-up until age 6 years

1. Klugman K, et al. N Engl J Med 2003;349:1341

2. Madhi SA, et al. Vaccine 2007;25:2451

3. Cutts FT, et al. Lancet 2005;365:1139

IPD causing serotypes in 7-valent vaccine (2007: 1077 isolates typed)

Eastern Cape 72%

Free State 76%

Gauteng 69%

KwaZulu-Natal 75%

Limpopo 86%

Mpumalanga 76%

Northern Cape 64%

North West 74%

Western Cape 68%

South Africa 71.2%

Von Gottberg A. Com Dis Surveillance Bull 2008;6(1):16

PCVs: Potential Serotype coverage

Shouval DS, et al. Pediatr Infect Dis J 2009;28:277-282

Measles

Measles: annual global cases & vaccine coverage, 1980-2008

WHO. http://whqlibdoc.who.int/hq/2009/WHO_IVB_2009_eng.pdf

http://whqlibdoc.who.int/hq/2009/WHO_IVB_2009_eng.pdf

HIV & Measles immunisation

• Measles in countries with high attack rates: – Early immunisation: usually 9 months for HIV-negative

children; booster at 15-18 months

– HIV-infected children: immunised at 6 months and repeated at 9 months; booster at 15-18 months

– Loss of acquired maternal neutralising antibodies by 6 months • 91.1% of HIV-infected infants • 83.3% of HIV-exposed but uninfected children • 57.7%of HIV-negative infants

R Scott, et al. Clin Infect Dis 2007;45:1417-1424

HIV & Reimmunisation

• Several reimmunisation studies published recently

• Reimmunisation based on antibody titre screening

• Reimmunisation protocols: many studies administered single boosters; few repeated primary immunisation schedule

• Predictors of favourable response: CD4 > 15%, VL< 1000 copies/mL at the time of vaccination

• Re-immunisation generally safe, although some vaccines e.g. DPT not evaluated

the end.