ESP17-1077 A TIME-TREND ANALYSIS ON MORBIDITY AND MORTALITY OF PERTUSSIS

DISEASE IN CHILDREN <12 MONTHS OF AGE AFTER Tdap MATERNAL

VACCINATION INTRODUCTION IN BOGOTA, COLOMBIA
G. Carrasquilla1, 2, A. Porras1,3, S. Martinez1, R. DeAntonio4, R. Devadiga5, D. Caceres6, P. Juliao4
1
ASIESALUD, Bogotá, Colombia; 2 Fundación Santa Fe de Bogotá, Division of Public Health, Bogotá, Colombia; 3 Universidad El Bosque, Grupo de Medicina Comunitaria, Bogotá, Colombia;
4
Epidemiology and Health Outcomes, GSK, Panama City, Panama; 5 Biometrics, GSK, Bangalore, India; 6 GSK, Bogotá, Colombia

• A total of 2,299 pertussis cases were reported in Bogotá from • A total of 55 pertussis deaths were reported in Bogotá from
BACKGROUND RESULTS 2005–2015 in children <12 months of age. 2005–2015 in children <12 months of age.
• A 67.9% (95% CI: 62.4-72.7) reduction in mean pertussis in- • A 100% reduction in mean pertussis mortality (95% CI: 100-.)
• Pertussis, also known as “whooping cough” is a highly contagious • Yearly maternal vaccination coverage with Tdap vaccine of cidence was observed in the post- vs pre-vaccination period was observed in the post- vs pre-vaccination period with a
pediatric disease caused by Bordetella pertussis. In 2008, it was esti- 90% was reported for Bogotá for 2013-2015 (Figure 1). when comparing the mean incidence rate of 209 cases per mean mortality rate of 6 deaths per 100,000 in 2005–2012 com-
mated there were 16 million cases including 195,000 deaths world- • Yearly pediatric DTPw vaccination coverage of greater than 100,000 in 2005–2012 to the 67 per 100,000 in 2014-2015. pared to 0 per 100,000 in 2014-2015.
wide [WHO, 2011]. 90% was reported for 2005-2012. A drop to 87.6% was report- • A significant level change reduction in monthly pertussis in- • An increasing trend in monthly pertussis mortality rates was
• Infants≤12 months (m) are very vulnerable, especially those <6m ed in 2012, the same year as the pertussis outbreak within the cidence of 80.6% was observed (p<0.001) in the post-vacci- observed pre-vaccination. A drop to 0 death was observed
who did not complete their primary pertussis vaccination. Infants
city. Year 2013 reported a temporary increase of 95.8%, but nation period compared to the pre-vaccination period, when in 2012 and was maintained in the post-vaccination period.
with pertussis infection in this age group are often hospitalized.
Possible complications include pneumonia, encephalopathy, and
dropped below 85% in the following two years (Figure 1). controlling for secular trends (Figure 2, Table 1). A NBR model could not be fitted to determine trends and im-
seizures, which might lead to death [CDC, 2010]. pact of maternal vaccination due to 0 case reported post-vac-
• Data from several studies showed that maternal vaccination could Figure 1. Vaccination coverage of pediatric DTPw and maternal Figure 2. Trend over time for monthly predicted and observed cination (Figure 3).
offer protection against pertussis infection by transplacental trans- Tdap in Bogotá incidence rate of pertussis in children aged <12 months in Bogotá,
fer of maternal antibodies to the foetus [Zinkernagel, 2001; Van SIVIGILA data Figure 3. Pertussis mortality rate over time in children aged <12
Rie, 2005; Healy, 2006] As such this can serve as an effective immu- months in Bogotá
nization strategy to prevent pertussis infection in this vulnerable
population [Gall, 2011].
• Following a local outbreak of pertussis reported in 2012, the Nation-
al Committee on Immunisation Practices recommended and started
to implement in 2013 vaccinating all pregnant women with a dose
of Tetanus Diphtheria Acellular Pertussis (Tdap) vaccine in Bogotá
(Colombia’s capital).
• This study (NCT02569879) aims to describe pertussis-related morbid-
ity and mortality trends in children, before and after introduction
of Tdap vaccination program in pregnant women in Bogotá.

DTPw, Diphteria Tetanus whole-cell Pertussis; Tdap, Tetanus Diphteria acellular Pertussis.

METHODS Table 1. Summary of negative binomial regression (NBR) model for the monthly incidence of pertussis in Bogotá in children aged
• Databases from the Colombian Ministry of Health National Immu- *Aged <3 months - all acute respiratory infections accompanied <12 months
nization Program (PAI), the National Public Health Surveillance Sys- at least one of the following symptoms: coughing episodes, stri- Outcome type Independent variables eβ 95% CI of eβ p-value Rate of change 95% CI of rate of change
tem (SIVIGILA) and the National Administrative Department of Sta- dor, apnea, cyanosis or vomiting after coughing; Aged ≥3 months
tistics (DANE) were examined retrospectively from 2005 to 2015 for -≤12 months - all respiratory infections with cough for more than LL UL LL UL
Bogotá, Colombia. one week duration accompanied by one or more of the follow- Month & Year 1.01 59.6 1.01 0.0167 0.8 0.14 1.4
• Vaccination coverage data for maternal vaccination of Tdap and pe- ing symptoms: paroxysmal cough, stridor or vomiting after cough Pertussis
diatric Diphtheria Tetanus whole-cell Pertussis (DTPw) vaccine (PAI) without other apparent cause; or severe paroxysmal cough accom- Post-vs. Pre-vaccination 0.19 0.11 0.36 <.0001 -80.6 -89.48 -64.35
as well as population estimates (DANE) were collected. panied by stridor at the time of disease onset.
eβ:Exponential regression coefficients [i.e. exp(B)); p-value: Probability value at alpha – 0.05 level; NBR model: log(No. of pertussis cases) = log (population at risk) + intercept
• The number of confirmed pertussis associated cases and deaths + +(coeff × month_year)+((coeff 1×transition period) + (coeff 2×post vaccination period)); Rate of change is calculated by (eβ-1) x100%; 95%CI of eβ: Lower and upper limit
were collected using case definitions from SIVIGILA and defined as • Monthly pertussis incidence and mortality rates were plotted for the two sided 95% Wald confidence interval of eβ | Data source: SIVIGILA for numerator and DANE for population projections. LL, lower limit; UL, upper limit
follows [SIVIGILA, 2014]: during the study period and were compared between pre-vac-
o Laboratory confirmed case: Clinically defined case* of per- cination (2005-2012) and post-vaccination period (2014-2015).
tussis that is laboratory confirmed by culture or Polymerase The percent reductions in incidence and mortality rates post vs. CONCLUSIONS
Chain Reaction (PCR) or with direct Immunofluorescence pre-vaccine introduction were computed using the exact Poisson
(IFD) positive, confidence limit. • A significant trend for reduction in pertussis-related cases in infants <12 months of age was observed following Tdap vaccination implemen-
o Clinically confirmed case: Clinically defined case* without • A negative binomial regression (NBR) model was used to fit tation in pregnant women within Bogotá, with a 68% reduction observed descriptively post vaccination and an increase to 80% reduction
when controlling for secular trends.
laboratory confirmation and for which an epidemiological monthly rates to determine overall secular trends for the study • A substantial trend for reduction in pertussis-related deaths in infants <12 months of age was also observed following Tdap vaccination
link with a confirmed case could not be demonstrate, period and to assess vaccination impact by comparing observed implementation in pregnant women within Bogotá with a 100% reduction in mortality observed throughout the post-vaccination period.
o Epidemiological link confirmed case: Clinically de- rates post vaccination with expected rates derived from the • Since this is an ecological analysis, other health interventions and improvements in socio-economic conditions could have contributed to the
fined case* without laboratory confirmation but is NBR model. observed results. Trend analysis stratified by age in month within the <1-year-old population is needed to further characterize the impact
epidemiologically linked directly to a laboratory of maternal immunization on pertussis.
confirmed case.

REFERENCES: Centres for Disease Control and Prevention (CDC). NCHS Data on Pertussis Hospitalisations in Young Children. Updated in January 2010. http://www.cdc.gov/nchs/data/hestat/pertussis/pertussis.htm. Accessed on: 31 March 2015 | Cherry. The Present and Future Control of Pertussis. Clin Infect Dis.,
2010. 51: 663-667 | Healy et al. Prospects for prevention of childhood infections by maternal immunisation. Curr Opin Infect Dis., 2006. 19: 271–276 | Gall et al. Maternal immunization with tetanus-diphtheria-pertussis vaccine: effect on maternal and neonatal serum antibody levels. Am J Obstet Gynecol.
2011; 204: 334.e1-5. | Van Rie et al. Role of Maternal Pertussis Antibodies in Infants. Pediatr Infect Dis J, 2005. 24: S62-S65. | Vigilancia y Analysis del Riesgo en Salud Publica de Colombia [SIVIGILA] (National Public Health Surveillance System of Colombia). Protocolo de Vigilancia en Salud Publica Tos
Ferina PRO-R02.013( Pertussis Surveillance Protocol). Version 3, Apr 14, 2014. http://www.ins.gov.co/lineas-de-accion/Subdireccion-Vigilancia/sivigila/Paginas/protocolos.aspx. | World Health Organisation (WHO). Immunisation, Vaccines and Biologicals. Updated in June 2011. http://www.who.int/
immunisation/topics/pertussis/en/. Accessed on: 05 May 2017 | Zinkernagel. Maternal antibodies, childhood infections, and autoimmune diseases.N Engl J Med, 2001. 345: 1331–1335. ACKNOWLEDGEMENTS: GlaxoSmithKline Biologicals S.A. funded this study (NCT02569879) and all costs related
to the development of all related publications. Authors would like to thank Business & Decision Life Sciences platform for editorial assistance and manuscript coordination, on behalf of GSK. Vincent Laporte coordinated abstract development and editorial support. The authors also
Presenting author: thank Pierre-Paul Prevot (Business & Decision Life Sciences, on behalf of GSK) for providing medical writing support. CONFLICT OF INTERESTS: The institution of G. Carrasquilla, A. Porras, and S. Martinez (ASIESALUD) received a grant from the GSK group of companies for the
Gabriel Carrasquilla conduct of this study. R. DeAntonio, R. Devadiga, D. Caceres and P. Juliao are employed by the GSK group of companies; R. DeAntonio, and P. Juliao also hold shares in the GSK group of companies.

gcarrasquillag@gmail.com
35th Annual Meeting of the European Society for Paediatric Infectious Diseases – May 23-27, 2017 – Madrid, Spain