Assessing the impact of pneumococcal conjugate vaccines on invasive pneumococcal disease using polymerase chain reaction-based surveillance: an experience from South Africa.
BACKGROUND
The use of molecular diagnostic techniques for the evaluation of the impact of pneumococcal conjugate vaccines (PCVs) has not been documented. We aimed to evaluate the impact of PCVs on invasive pneumococcal disease (IPD) using polymerase chain reaction (PCR)-based techniques and compare with results obtained from culture-based methods.


METHODS
We implemented two independent surveillance programs for IPD among individuals hospitalized at one large surveillance site in Soweto, South Africa during 2009-2012: (i) PCR-based (targeting the lytA gene) syndromic pneumonia surveillance; and (ii) culture-based laboratory surveillance. Positive samples were serotyped. The molecular serotyping assay included targets for 42 serotypes including all serotypes/serogroups included in the 7-valent (PCV-7) and 13-valent (PCV-13) PCV. The Quellung reaction was used for serotyping of culture-positive cases. We calculated the change in rates of IPD (lytA- or culture-positive) among HIV-uninfected children aged <2 years from the year of PCV-7 introduction (2009) to the post-vaccine years (2011 or 2012).


RESULTS
During the study period there were 607 lytA-positive and 1,197 culture-positive cases that were serotyped. Samples with lytA cycle threshold (Ct)-values ≥35 (30.2 %; 123/407) were significantly less likely to have a serotype/serogroup detected for serotypes included in the molecular serotyping assay than those with Ct-values <35 (78.0 %; 156/200) (p < 0.001). From 2009 to 2012 rates of PCV-7 serotypes/serogroups decreased -63.8 % (95 % CI: -79.3 % to -39.1 %) among lytA-positive cases and -91.7 % (95 % CI: -98.8 % to -73.6 %) among culture-positive cases. Rates of lytA-positive non-vaccine serotypes/serogroups also significantly decreased (-71.7 %; 95 % CI: -81.1 % to -58.5 %) over the same period. Such decline was not observed among the culture-positive non-vaccine serotypes (1.2 %; 95 % CI: -96.7 % to 58.4 %).


CONCLUSIONS
Significant downward trends in IPD PCV-7 serotype-associated rates were observed among patients tested by PCR or culture methods; however trends of non-vaccine serotypes/serogroups differed between the two groups. Misclassifications of serotypes/serogroups, affecting the use of non-vaccine serotypes as a control group, may have occurred due to the low performance of the serotyping assay among lytA-positive cases with high Ct-values. Until PCR methods improve further, culture methods should continue to be used to monitor the effects of PCV vaccination programs on IPD incidence.
Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. stefanot@nicd.ac.za.|Influenza Program, Centers for Disease Control and Prevention, Pretoria, South Africa. stefanot@nicd.ac.za.|Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. stefanot@nicd.ac.za.
Stefano
S
Tempia
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. nicolew@nicd.ac.za.|School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. nicolew@nicd.ac.za.
Nicole
N
Wolter
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. cherylc@nicd.ac.za.|School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. cherylc@nicd.ac.za.
Cheryl
C
Cohen
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. sibongilew@nicd.ac.za.|School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. sibongilew@nicd.ac.za.
Sibongile
S
Walaza
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. clairevm@nicd.ac.za.|School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. clairevm@nicd.ac.za.
Claire
C
von Mollendorf
Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. dvj1@cdc.gov.|Influenza Program, Centers for Disease Control and Prevention, Pretoria, South Africa. dvj1@cdc.gov.
Adam L
AL
Cohen
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. jocelynm@nicd.ac.za.|School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. jocelynm@nicd.ac.za.
Jocelyn
J
Moyes
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. lindag@nicd.ac.za.
Linda
L
de Gouveia
School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. nzenzes@rmpru.co.za.|Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa. nzenzes@rmpru.co.za.
Susan
S
Nzenze
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. florettet@nicd.ac.za.
Florette
F
Treurnicht
Division of Global Health Protection, Centers for Disease Control and Prevention, Pretoria, South Africa. yds8@cdc.gov.
Marietjie
M
Venter
Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa. groomem@rmpru.co.za.|Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa. groomem@rmpru.co.za.
Michelle J
MJ
Groome
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. shabirm@nicd.ac.za.|Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa. shabirm@nicd.ac.za.|Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa. shabirm@nicd.ac.za.
Shabir A
SA
Madhi
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. annev@nicd.ac.za.|School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. annev@nicd.ac.za.
Anne
A
von Gottberg
D000293:Adolescent; D000328:Adult; D000368:Aged; D001431:Bacteriological Techniques / Q000379:methods; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000453:epidemiology / Q000382:microbiology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology / Q000494:pharmacology*; D016133:Polymerase Chain Reaction / Q000379:methods*; D012703:Serotyping / Q000379:methods; D013019:South Africa / Q000453:epidemiology; D013296:Streptococcus pneumoniae / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology / Q000494:pharmacology*; D055815:Young Adult
C538862:13-valent pneumococcal vaccine; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate