Opportunistic Pneumococcal Immunisation Trial in MALnutrition

Immunogenicity of Opportunistic Pneumococcal Conjugate Vaccination (Pneumosil®) Versus Control (Typhoid Conjugate Vaccine, Typbar TCV®) in Children Aged 6-59 Months Hospitalised With Severe Acute Malnutrition: a Single-centre, Double-blind, Randomised Controlled Trial in Timor-Leste

The goal of the OPTIMAL clinical trial is to learn if a dose of a pneumococcal conjugate vaccine (PCV) generates a good immune response in young children who are in hospital with severe acute malnutrition.

Researchers will compare an intervention group who get a dose of a PCV (Pneumosil) to a control group who get a dose of a Typhoid conjugate vaccine (Typbar TCV). To ensure all participants receive timely potential benefits, at 3 months participants in the intervention group with receive a dose of Typbar TCV, and those in the conrol group will receive a dose of Pneumosil.

Participants will be visited 4 times at their homes over six months after vaccination, with a phone review at 12 months after vaccination.

This is a prospective, single-centre, double-blind, randomised controlled trial in 264 children aged 6-59 months hospitalised with severe acute malnutrition.

Participants will be randomised (1:1) to receive either a dose of a pneumococcal conjugate vaccine (Pneumosil, the intervention group) or a dose of a Typhoid conjugate vaccine (Typbar TCV, the control group). Stratification for randomisation will be done on (a) prior immunisation with a PCV (confirmed or unknown/unvaccinated); and (b) severity of malnurition (weight-for-height/length z-score <-4 or >=-4). Participants will be enrolled as soon as practical after admission to hospital, while randomisation and vaccine administration will occur once the participant is medically stable in the 'transition phase' of SAM care.

The primary objective is to demonstrate that immune responses to the 10 pneumococcal serotypes in Pneumosil are better in participants who receive Pneumosil, compared to those who receive Typbar TCV, when measured 28 days after vaccination.

Inclusion Criteria:

1. Aged 6-59 months at the time of hospitalisation

2. Hospitalised with severe acute malnutrition (SAM, defined as any one of a, b, or c):

   1. weight-for-length/height z-score <-3; or
   2. middle upper arm circumference <11.5cm; or
   3. bilateral pitting pedal oedema unexplained by other causes

3. Parent/carer is willing for their child to participate in the study and has provided written informed consent

4. Parent/carer is willing to comply with all study procedures outlined in the protocol, including specimen collection, for the duration of the study

Exclusion Criteria:

1. Known history of allergy or hypersensitivity to any component of either study vaccine, including diphtheria toxoid, or a history of anaphylactic shock.
2. Treatment with another investigational drug or other intervention in the 30 days prior to randomisation, or ongoing participation in another clinical trial.
3. Suspected primary or secondary immunodeficiency or prolonged administration (>14 days) of an immune modifying drug (including oral glucocorticoids) in the past 3 months.
4. Known terminal illness expected to result in death within 6 months.
5. Participants who, in the opinion of the site Principal Investigator, are unable to comply with the study protocol, including scheduled visits, assessments, and any other protocol-required procedures.
6. Previously enrolled in this trial.