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

NCT ID: NCT03331952

Last Updated: 2020-10-09

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 4111 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-08-03
• Study Completion Date: 2018-10-19

Brief Summary

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.

Conditions

Streptococcal Pneumonia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Invasive pneumococcal disease study (PCV-D)

Prospective study of children with invasive pneumococcal disease / probable bacterial meningitis (PCV-D)

Clinical procedures

At study enrolment:

• Admission clinical findings / laboratory results will be recorded.
• A questionnaire will be administered to the parent / guardian or caretaker to assess the child's immunisation status, household structure, environmental exposures, and recent antimicrobial use.

Radiology procedures As part of routine clinical management at AHC, a digital chest radiograph (CXR) may be performed as part of a child's diagnostic work up. CXRs will be read and interpreted primarily by the AHC radiologists. All CXR will subsequently be re-read by two study clinicians and interpreted according to the WHO paediatric radiologic pneumonia criteria.

Laboratory procedures

• Residual routine clinical specimens further analysed as part of the study protocol:

• Blood and cerebrospinal fluid culture specimens.
• EDTA / serum specimens.
• Urine.

Prospective study

Intervention Type: OTHER

To identify and characterise patients with culture proven invasive pneumococcal disease or probable bacterial meningitis over the first three years after PCV13 introduction in Cambodia in January 2015.

Pneumonia study (PCV-P)

Prospective study of children hospitalised with clinical and/or radiologic pneumonia (PCV-P)

Clinical procedures As described for PCV-D.

Radiology procedures As part of routine clinical management at AHC, a digital chest radiograph (CXR) is performed on all children with an admission diagnosis of pneumonia. CXRs will be handled as described for PCV-D.

Laboratory procedures

• Study specific specimens:

o Nasopharyngeal swab at enrolment.

• Residual routine clinical specimens further analysed as part of the study protocol:

• As described for PCV-D.

Prospective study

Intervention Type: OTHER

To identify and characterise patients hospitalised with clinical and/or radiologic pneumonia over the first three years after PCV13 introduction in Cambodia in January 2015

Pneumococcal colonisation study (PCV-C)

Cross-sectional pneumococcal colonisation surveys in children attending the AHC out-patient department (PCV-C)

Three annual surveys, enrolling 450 children each year, will be done to identify and characterise pneumococcal nasopharyngeal colonisation in AHC out-patient department (OPD) attendees.

Clinical procedures

• Subjects will be recruited from the OPD waiting area after nurse triage. A questionnaire will be administered to the parent / guardian or caretaker to assess the child's immunisation status (by review of the handheld immunisation card where possible), household structure, environmental exposures, and recent antimicrobial use.

Laboratory procedures • Study specific specimens:

o Nasopharyngeal swab at enrolment. A nasopharyngeal swab will be collected from each participant and these will be processed as described for PCV-P.

Cross-sectional surveys

Intervention Type: OTHER

Three annual surveys, enrolling 450 children each year, will be done to identify and characterise pneumococcal nasopharyngeal colonisation in AHC out-patient department (OPD) attendees

Interventions

Prospective study

To identify and characterise patients with culture proven invasive pneumococcal disease or probable bacterial meningitis over the first three years after PCV13 introduction in Cambodia in January 2015.

Intervention Type: OTHER

Prospective study

To identify and characterise patients hospitalised with clinical and/or radiologic pneumonia over the first three years after PCV13 introduction in Cambodia in January 2015

Intervention Type: OTHER

Cross-sectional surveys

Three annual surveys, enrolling 450 children each year, will be done to identify and characterise pneumococcal nasopharyngeal colonisation in AHC out-patient department (OPD) attendees

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

• Minimum Eligible Age: 0 Months
• Maximum Eligible Age: 59 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Angkor Hospital for Children

Siem Reap, , Cambodia

Countries

Cambodia

Other Identifiers

COMRU1501

Identifier Type: -

Identifier Source: org_study_id