A Study of Streptococcus Pneumonia Colonisation and Invasive Disease in Cambodian Children

Streptococcus pneumoniae (the pneumococcus) remains a leading cause of childhood mortality and morbidity. Between 2007 and 2012, Angkor Hospital for Children (AHC), Siem Reap, Cambodia documented that S. pneumoniae was responsible for around 10% of bloodstream infections in hospitalised children, with a case fatality rate of 15.6%.

The use of pneumococcal conjugate vaccines (PCV), covering between 7 and 13 of the \>90 pneumococcal serotypes, has resulted in significant declines in invasive pneumococcal disease (IPD) incidence in countries where they are included in routine childhood immunisation schedules. Paediatric radiologic pneumonia incidence is also reduced by PCV, but the impact on clinical pneumonia is minimal. The vaccines have had an effect on reducing the burden of drug resistant IPD, although this may not be sustained. Given the large number of serotypes not included in the current PCV formulations, it is not surprising that initial declines in overall IPD incidence have been eroded by, for the time being, small increases in IPD due to non-vaccine serotypes. To date most data on this serotype replacement disease has come from high-income countries. It less clear how much serotype replacement will occur in low and middle income countries, where pre-PCV disease incidence is generally higher and other factors, such as unregulated antimicrobial consumption, may play a role in encouraging non-vaccine serotype infections.

Nasopharyngeal colonisation by S. pneumoniae is common in childhood and is an essential prerequisite for invasive disease. Surveillance of pneumococcal colonisation can provide important data regarding serotype replacement and disease-associated serotypes, and may also allow prediction of likely IPD incidence changes post-vaccine introduction. A recent study of pneumococcal colonisation in children attending the AHC out-patients has documented an overall colonisation prevalence of approximately 65%.

In January 2015, Cambodia will introduce the 13-valent PCV (PCV13; serotypes covered 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F, 19A, 23F). The vaccine will be rolled out nationally with a 3+0 dosing schedule (6, 10 and 14 weeks) and no catch up campaign. There is no robust national surveillance system in place to monitor the effects of PCV13 introduction.


Eligibility Criteria:
Group1: PCV-D

Inclusion:

* Age: 0 - 59 months on the day of assessment / culture AND
* S.pneumoniae identified from a normally sterile site culture. OR
* WHO Coordinated Invasive Bacterial Vaccine Preventable Diseases (IB-VPD) Surveillance Network Case Definition for probable bacterial meningitis. Clinically suspected meningitis and a CSF examination with at least one of:

  * Turbid appearance.
  * Leucocytosis (WBC count of \>100 cells/mm3).
  * Leucocytosis (10-100 cells/mm3) AND either an elevated protein (\>100 mg/dL) or decreased glucose (\<2.2 mmol/L).

Exclusion:

* Previous enrolment within the last 14 days.
* Parent / guardian or caretaker refused consent.

Group2: PCV-P

Inclusion:

* Age: 0 - 59 months on the day of admission AND
* Admission to the IPD, ER/ICU, or NICU/SCBU. AND
* Meets the WHO Coordinated Invasive Bacterial Vaccine Preventable Diseases (IB-VBD) Surveillance Network pneumonia / severe pneumonia case definition:

  * Cough and/or difficulty breathing. AND
  * Tachypnoea OR
  * Inability to breast feed or drink.
  * Vomiting everything.
  * Convulsions.
  * Prostration/lethargy.
  * Chest indrawing.
  * Stridor when calm.

Exclusion:

* Previous enrolment within the last 14 days.
* Parent / guardian or caretaker refused consent.

Group3: PCV-C

Inclusion:

• Age: 0 - 59 months on the day of recruitment

Exclusion:

* Parent / guardian or caretaker reports symptoms of potential acute lower respiratory tract illness.
* Triage nurse selects child for doctor review / hospital admission.
* Previous enrolment in the current annual survey.
* Parent / guardian or caretaker refused consent.