William Pomat, Papua New Guinea

Papua New Guinea Institute of Medical Research Infection and Immunity

Author Of 9 Presentations

DISCOVERY OF A GENETIC VARIANT IN COQ6 PREDISPOSING TO SEVERE CHILDHOOD PNEUMONIA (ID 1080)

Abstract

Background

Severe pneumonia is the major cause of childhood mortality worldwide. Streptococcus pneumoniae remains a leading pathogen in severe acute lower respiratory illness (ALRI) in children globally. Increased incidence of severe ALRI in defined genetic groups suggests heritable components to ALRI susceptibility. We aimed to identify novel susceptibility alleles to severe childhood ALRI.

Methods

In a case-control study, we consented and collected saliva samples from children presenting with ALRI (Cases) and their healthy biological parents or siblings (Controls). Whole exome analysis was performed on 6 children and their controls from Papua New Guinea.

Results

A rare aspartate to tyrosine variant allele of COQ6, COQ6D→Y, was found in a homozygous state in 3 of 6 ALRI cases. The variant was either present in a heterozygous state or absent in controls and enriched above background levels. COQ6 is a required enzyme in ubiquinone biosynthesis. Current work on additional samples seek to validate a genetic association of COQ6D→Y with ALRI.

Conclusions

A novel single nucleotide variant in a ubiquinone biosynthesis enzyme is highly enriched in pediatric populations very susceptible to severe ALRI. Validating COQ6D→Y variant as causative to severe ALRI will inform novel interventional trials using nutritional supplements to treat high risk children, thereby improving ALRI outcomes.

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HIGH RATES OF MULTIPLE NASOPHARYNGEAL PNEUMOCOCCAL CARRIAGE IN CHILDREN WITH PNEUMONIA IN PAPUA NEW GUINEA FOLLOWING PNEUMOCOCCAL CONJUGATE VACCINE INTRODUCTION (ID 731)

Abstract

Background

Pneumococcal carriage rates in Papua New Guinean (PNG) children are among the highest globally. One aim of the multi-site PneuCAPTIVE study is to determine the impact of PCV13 (introduced in 2014) on nasopharyngeal carriage in PNG.

Methods

Nasopharyngeal (NP) swabs and blood were collected from children aged <5 years with moderate or severe pneumonia, and/or suspected meningitis at Eastern Highlands Provincial Hospital or outpatient clinics in Goroka (2016-2018). Pneumococci were identified and quantified by lytA qPCR, and serotyped by microarray. IPD was identified by standard blood culture.

Results

PCV13 coverage was 62%. 1043 were enrolled: 90% had pneumococcal carriage, with median density of 6.59 log10 genome equivalents (GE)/ml (IQR 6.00-7.11). Serotype data were available on 914 cases: 37% were PCV13-types; and 55% had multiple pneumococcal-type carriage. 74 different serotypes and genetic lineages of acapsular pneumococci were identified, the most common being acapsular lineage NT2>19A>15B/C>16F>14. PCV13-type carriage was 28% in vaccinated children vs 46% in unvaccinated children. IPD was confirmed in 7 cases (vaccinated – serotype 1; unvaccinated – serotypes 2, 6B, 15F, 19A, 23A, 29): 4/7 carried the homologous serotype.

Conclusions

There is some evidence of PCV13 being effective against PCV13-types but the high diversity of serotypes in PNG warrants extended valency vaccines.

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PNEUMOCOCCAL CONJUGATE VACCINE IS EFFECTIVENESS AGAINST HYPOXIC PNEUMONIA IN LAOS, MONGOLIA AND PAPUA NEW GUINEA: A NOVEL CASE-CONTROL VARIANT STUDY (ID 852)

Abstract

Background

We describe a novel approach to determine PCV13 effectiveness (VE) against hypoxic pneumonia in children admitted with pneumonia in Lao PDR (Laos), Mongolia and Papua New Guinea (PNG).

Methods

A 3-5 year prospective hospital-based observational study of children <59 months admitted with pneumonia was undertaken. Pneumonia was defined using the 2013 WHO definition. Hypoxia was defined as an oxygen saturation <90% in room air or requiring oxygen supplementation during hospitalisation. PCV13 status was determined by written record. VE was calculated using logistic regression comparing the odds of hypoxia between vaccinated and undervaccinated pneumonia cases. To handle potential confounders a propensity score (PS) analysis using inverse probability of treatment weighting (IPW) was used. In Laos, multiple imputation (MI) analysis was undertaken for missing data.

Results

The VE against hypoxic pneumonia were: in Laos, unadjusted 23% (95% CI: -9, 46%; p=0·14), PS adjusted IPW 37% (6, 57%; p=0·02), MI adjusted 35% (7, 55%; p=0·02); in Mongolia, unadjusted 33% (26, 40%; p<0.001), PS adjusted IPW 33% (16, 47%; p<0.001); and in PNG, unadjusted 6% (-15, 24%; p=0.532), PS adjusted IPW 36% (17, 51%; p=0.001).

Conclusions

Our novel approach shows that PCV13 is effective against hypoxic pneumonia. PCV13 will contribute to reducing child mortality.

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