Landmark findings on antibiotic resistance based on SMRU Maela Acute Respiratory Infections (ARI) study

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A young infant receiving treatment for pneumonia in the SMRU clinic in-patient department at Maela

Using a dataset of over 3,000 samples of Streptococcus pneumoniae data collected at Maela Refugee Camp, researchers at Wellcome Trust Sanger Institute have developed a powerful new tool to identify genetic changes in the disease-causing bacteria responsible for antibiotic resistance.

The data were collected as part of an Acute Respiratory Infections (ARI) study run by Drs Claudia and Paul Turner at MORU’s Shoklo Malaria Research Unit (SMRU) in-patient department at Maela to determine the epidemiology of pneumonia and bacterial colonisation of the nasopharynx in refugee infants born in Maela camp on the Thailand-Myanmar border. A particular aim of this longitudinal birth cohort study was to describe in detail the characteristics of colonisation by S. pneumoniae, an important and partially vaccine preventable cause of pneumonia and meningitis in young children. The pneumococcal colonisation work was funded by a Wellcome Trust Clinical Research Training Fellowship to Paul Turner.

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Siriporn Pongpanapacharoen, a Karen laboratory technician at SMRU, serotyping pneumococcal isolates collected during the ARI study

Over a one year period 999 pregnant women were recruited from SMRU’s antenatal clinic in Maela. Following delivery all infants were seen at monthly intervals until their second birthday and nasopharyngeal swabs were collected. A quarter of the mother-infant pairs were randomised to have additional specimens taken at each monthly visit: A blood specimen was collected from the infant and the mothers were also swabbed. The infants were also reviewed when unwell and, if a diagnosis of pneumonia was suspected, then additional swabs and blood specimens were collected.

Key findings of the ARI study included: a high incidence of WHO-defined clinical pneumonia (0.73 episodes per child-year); respiratory syncytial virus (RSV) was a key pneumonia pathogen in this population; colonisation by S.pneumoniae occurred early and was persistent at least until two years of age. A very broad range of serotypes were carried by the cohort infants and their mothers; and experimental work demonstrated that traditional methods to identify colonisation by multiple pneumococcal serotypes lack sensitivity and two alternate methods, latex sweep serotyping and molecular typing by microarray, both perform significantly better.

In addition to the work done at the SMRU laboratories, a large scale whole genome sequencing project was established with Prof Stephen Bentley at the Wellcome Trust Sanger Institute to better understand the genetic characteristics of colonising strains of Streptococcus pneumoniae. To date this work has improved our understanding of how these organisms share DNA to become antibiotic resistant and potentially evade currently available vaccines.

Most recently, researchers from Wellcome Trust Sanger Institute say that new tools to identify the genetic changes responsible in disease-causing bacteria for antibiotic resistance could be used in clinics within a decade to decide on the most effective treatments for diseases such as pneumonia and meningitis.

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Drs. Claudia and Paul Turner are now based at COMRU in Siem Reap, Cambodia

“The results of this research are very interesting,” says Claire Chewapreecha, first author of the paper, Comprehensive Identification of Single Nucleotide Polymorphisms Associated with Beta-Iactam Resistance within Pneumococcal Mosaic Genes, published last week in PLOS Genetics. “For the first time, we are able to see, at large scale, causative variants that allow bacteria such as Streptococcus pneumoniae to resist our efforts to treat and control it.”

“We can begin to see how this might help us to develop more effective treatment strategies in the near future.”

8th August (Bangkok)