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Yale Unexplained Pneumonia Project


The Yale Unexplained Pneumonia Project’s (YUPP) purpose is to describe the etiologic spectrum of severe pneumonia in previously healthy persons and to identify clinical characteristics and risk factors for unexplained pneumonias.

Goals & Objectives

  • Describe the etiologic spectrum of previously unexplained pneumonias
  • Identify clinical characteristics and risk factors for unexplained pneumonias
  • Develop a standardized approach to data collection, specimen retrieval and laboratory testing
  • Improve public health capacity to evaluate cases and clusters of pneumonias


YUPP is a multi-site Emerging Infections Program (EIP) project. A common protocol was established and is being followed between EIP sites. Active and passive surveillance has been established in intensive care units (ICU) in New Haven County to identify previously healthy patients admitted to the ICU for “pneumonia” between 6 months – 49 years of age. Infectious diseases physicians/staff and intensive care physicians were requested to report potential cases of severe pneumonia from patients hospitalized in the intensive care units. In addition to hospital staff reporting, daily reports of pneumonia admissions are received by querying hospital databases. After agreement from the patient’s attending physician, eligible patients (or their parents/guardians or proxies) are approached and invited to participate. Enrolled patients are assigned a study identification number, and a detailed case report form is completed on all enrolled cases. Enrolled patients are asked to provide acute-phase and convalescent-phase specimens. Residual specimens collected during clinical care are also collected.

Enrolled cases have serologic assays performed at the Connecticut Department of Public Health Laboratory and real-time polymerase chain reaction assays performed at Yale University’s Emerging Infections Program Laboratory. Assays will be performed for the following respiratory pathogens: Mycoplasma pneumoniae Chlamydia pneumoniae, influenza A/B, respiratory syncytial virus, parainfluenza 1-4, adenovirus, enterovirus, human metapneumovirus, coronaviruses OC43 and 229E, Picornavirus, Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila, and Bordetella pertussis. SARS-CoV testing is performed on enrolled cases that meet Connecticut’s Department of Public Health SARS-CoV testing criteria. Once testing for the above respiratory pathogens are complete, the remaining specimens are forwarded to the Centers for Disease Control in Atlanta, GA to be banked. This bank of well-characterized specimens is available for additional testing as new diagnostic assays become available. They are also available for use in pathogen discovery efforts by CDC or EIP partners.

The time frame for this kind of investigative work is long, the largest payoffs may well come in the future when new information sheds light on existing cases, and banked specimens may be used to identify new agents.