Pertussis preventable diseases vaccination an update Ute - PowerPoint PPT Presentation

One of the most prevalent vaccine- Pertussis preventable diseases vaccination – an update Ute Hallbauer Department Paediatrics and Child Health University of the Free State

Pertussis • Diagnosis • The increasing incidence and the morbidity • Why is there an increase? • How should the pertussis problem be tackled?

Difficulty in estimating number of cases and true incidence • Variable clinical presentation • Few people seek help • Clinicians don’t always suspect pertussis • Heterogenous diagnostic approaches • Few places have resources for laboratory confirmation • Clinical and laboratory diagnostic cases often go unreported • Diverse laboratory tests available • Different surveillance systems

Case Definition • Clinical case definition (WHO) # : • ≥ 2 weeks of cough plus one of: • Paroxysms, inspiratory whoop, post-tussive vomiting • Laboratory confirmed. Any cough duration plus: • Culture positive or • PCR positive • Positive paired serology NB. Laboratory confirmation is not required for notification in South Africa # http://www.who.int/immunization_monitoring/diseases/pertussis_surveillance/en/

Improved Diagnostics • Improved diagnosis and subsequent reporting • Volume of PCR based testing (correct technique with experience, contamination may be problem with high volume) • IS481 • Used in many assays • Higher sensitivity, decreases with increasing cough duration • [Also found in B. holmesii, which does not occur in Africa] • Less specific • Still limited testing in low income countries

1940’s whole cell pertussis vaccine 195 7 1990’s change to acellular pertussis vaccine 1994

Pertussis is a disease of adolescents and adults…….. Wymann MN et al. Prospective pertussis surveillance in Druzian AF et al. Pertussis in the central-west region of Switzerland, 1991 – 2006. Vaccine 2011;29:2058-2065 Brazil: one decade study. Braz J Inf Dis 2014;18(2): 177-180

Country 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 Algeria 104 1 0 1 28 0 23 18 7 22 57 Angola 1259 1554 2539 1127 1148 921 1328 0 1675 2654 0 Benin 0 0 53 0 0 0 99 49 Botswana 0 0 0 0 0 0 0 0 0 Burkina Faso 0 6 13 68 171 44 54 170 420 171 212 Burundi 0 0 0 0 0 0 0 0 154 Cameroon Cape Verde 0 1 0 6 0 0 0 7 0 Central African Republic (the) 124 100 1 63 2 65 87 561 80 10 Chad Comoros (the) 0 0 0 0 0 0 0 0 Congo (the) 12 0 0 0 0 55 108 0 38 Côte d'Ivoire 0 0 DR Congo 3407 2452 2157 830 3190 3799 3558 4564 7104 2534 Equatorial Guinea 0 0 0 Eritrea 208 91 11 0 30 65 46 6 53 149

200 Country 2012 2011 2010 2009 2008 7 2006 2005 2004 2003 2002 Namibia 2 16 0 0 15 0 8 7 22 10 Niger (the) 0 983 30 1354 1199 3204 1985 1206 2159 2109 2613 Nigeria 11628 0 11281 13240 12573 10997 15609 10976 11894 Rwanda 0 0 0 0 0 0 0 Sao Tome and Principe 0 0 0 0 0 0 0 0 0 0 0 Senegal 0 45 50 7 21 0 Seychelles 0 5 2 0 0 0 0 0 0 0 0 Sierra Leone 23 0 0 South Africa 181 4 8 5 South Sudan Swaziland 0 0 6 0 0 0 1 0 0 0 0 Togo 32 34 53 72 156 27 88 71 177 Uganda 0 United Republic of Tanzania 0 0 0 0 0 0 0 0 0 33 1 Zambia 0 0 0 681 162 34 120 185 180 391 595 Zimbabwe 0 0 0 0 0 0 0 0 9 0 0

South African surveillance data Year 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 S. African 1 181 4 8 5 Notification RXH 2 10 2 7 2 2 3 3 1 6 7 3 NICD 311 cases

Cherry JD et al. Clinical definitions of pertussis: Summary of a Global Pertussive Initiative roundtable meeting, February 2011. CID 2012;54(12):1756-1764

Pertussis is a disease of Morbidity adolescents and adults……… ………..but infants are worst affected • Hospitalization 5.4% • Of all hospitalized - 78% were infants < 1 yr (only 12.5% of whole group) - 61% < 3 months • Infants < 1year: 25 - 33.5% • With increasing age, decrease % hospitalization • Those who required ventilation: 95% < 3month • > 90% fatalities in < 3 months old Stein-Zamir C, Shoob H, Abramson N, Zentner G. The impact of additional pertussis vaccine doses on disease Wymann MN et al. Prospective pertussis surveillance in incidence in children and infants. Vaccine 2011; 29:207-211 Switzerland, 1991 – 2006. Vaccine 2011;29:2058-2065

WHY? WHY? Reasons for Resurgence • Vaccine-driven evolution of Bordetella pertussis problem • less natural immunity • shorter vaccine induced immunity, waning of immunity after immunization • acellular pertussis vaccine has somewhat limited ability to induce immunological memory compared to whole-cell vaccine • cessation of natural immune boosting • less exposure to pertussis • adults as source of infection

WHY? WHY? Reasons for Resurgence • Switch from whole cell to acellular vaccines in 1990’s , imperfect vaccine • wP promotes Th1 response, aP a Th2 and Th17 response • Incomplete protection from vaccination • Changing strains: mutations in pertussis toxin and pertactin • Do we know the serological correlate of immunity? • Improved surveillance, increased awareness (literature and press) • Changes in diagnostic tests

Mills KHG et al. Do we need a new vaccine to control pertussis? Trends in Microbiology 2014;22(2):49

WHY? WHY? Reasons for Resurgence Waning of immunity • Following both vaccination and infection • Duration of protection o after natural infection: 7-20 years o whole cell: 4 – 14 years o acellular: 5-6 years • Reduced opportunities for boosting immunity • Decreased circulation of Bordetella pertussis organism Cherry J et al. Pediatrics 2003; 115: 1422–1427 Wendelboe A et al Pediatr Infect Dis J 2005; 24: S58–S61

Resurgence was …..We conclude that the alarming resurgence of predicted using pertussis among adults and mathematical model adolescents in Britain and elsewhere may simply be a Assumptions legacy of historically inadequate coverage • Lifelong immunity after employing imperfect vaccines. natural infection (70yrs) Indeed, we argue that the • Gain of susceptible absence of resurgence at this members: after vaccination, late date would be more newborn, elderly surprising…… Riolo MA, King AA, Rohai P. • Age 75 years Can vaccine legacy explain the British pertussis resurgence? • Vaccine 85% efficacy Vaccine 2013;31:5903-8

Declining vaccination coverage • Important to maintain the primary vaccination series • Unvaccinated patients have higher risk of developing complications • With increasing vaccination doses risk of complications and disease severity decreases

Older children and adults as source of infection – a prominent role • Reservoirs – pre-school children, adolescents and adults with waning immunity • Transmission of pertussis unvaccinated/partially vaccinated infants • Household contact(s) in up to 83% • School outbreaks affecting adolescent disease Elliot E et al. Pediatr Infect Dis J 2004; 23: 246–252 Wendelboe AM et al. Pediatr Infect Dis J , 2005, 24(Suppl. 5):S58-S61 Edwards K. Pediatr Infect Dis J 2005; 24: S104–S108 Van der Maas NAT et al. Pertussis in the Netherlands, is the current vaccination strategy sufficient to reduce disease burden in young infants? Vaccine 2013;31:4541-4547

Pertussis antigens in vaccine • Pertussis toxin ( ptxP, ptxA ) • Pertactin ( prn ) • Fimbrial antigens ( fim 2 and fim 3 ) • Filamentous haemaglutinin (FHA)

Strain changes: Antigenic divergence • Suggestion that pertussis toxin (PT ) and pertactin (PRN) strains have now changed such that they are distinct from the vaccine strain G odfroid F, et al. Expert Rev Vaccines 2005; 4: 757–778 • • Strains produce more PT. PT inhibits innate and adaptive immunity • Mooi FR. Bordetella pertussis and vaccination: the persistence of a genetically monomorphic pathogen. Infection, Genetics and Evolution 2010;10(1):36-49 • Van Gent M et al. SNP-based typing: a useful tool to study Bordetella pertussis populations. PLoS ONE 2011;65(5):e20340. Epub 2011/06/08 • Mooi FR et al. Bordetella pertussis strains with increased toxin production associated with pertussis resurgence. Emerging Infectious Diseases 2009;15(8):1206-13 Epub 2009/09/16

Temporal trends in strain frequencies and notifications in The Netherlands in the period 1949–2010 Van Gent et al. Small mutations in Bordetella pertussis are associated with selective sweeps. PloS ONE 2012

Vaccination strategies To decrease pertussis in the population • wP vs aP – do we keep what we have? • Combination of wP and aP • Boosting strategy To protect the young infants • Cocooning • Vaccinate neonate (birth, 1 month) – not recommended by WHO • Vaccinate mother in 3 rd trimester pregnancy • Vaccinate health care workers – cost effective if high coverage • Vaccinate adults and older people

Adult & adolescent (booster) vaccination • Reduction in the adult/adolescent reservoir • Repeat vaccination every 10 years • Booster dose of Tdap • Universal vaccination for adolescents • Cocoon strategy • Vaccination of household members, including parents and siblings of newborn infants – not very practical, poor coverage