Nontypeable H. Influenzae in Healthy Adults

Haemophilus Influenzae (NTHI)

nontypeable Haemophilus influenzae, NTHi

The purpose of this study is to learn more about the safety of Haemophilus (H.) influenzae, its ability to produce adverse reactions and to live in the nose and throat. The nose and throat of healthy adults will be populated with a specific type of H. influenzae Nontypeable Haemophilus influenzae (NTHi) 2019 Streptomycin Resistant (StrR) number 1. Researchers will study whether the germ settles in the nose and throat, whether it causes symptoms after it has been placed in the nose, how long the germs last in the nose and throat, and whether the body tries to produce a permanent defense to the germ. Volunteers will receive a lower dose (3,200 germs) or a higher dose (32,000 germs). Active participation will last about 28 days, including a 3 night hospital stay, additional follow-up visits, followed by a 6 month follow-up phone call. Study procedures will include blood samples, saliva samples, several nose washes and throat swabs.

Haemophilus (H.) influenzae continues to be a major human pathogen causing upper and lower respiratory tract diseases ranging from otitis media and sinusitis to invasive pneumonia. The inoculation by nasal droplets proposed in this trial will introduce the organism into the nasal mucosa, the natural host tissue for H. influenzae colonization. It is hypothesized that this inoculum will elicit the typical nasal colonization seen in healthy individuals. To further develop this colonization model, healthy adults devoid of chronic medical conditions that might predispose the subject to invasive disease, will be enrolled. This study is linked to Division of Microbiology and Infectious Diseases (DMID) protocol 04-022. Final safety and reactogenicity data from DMID 04-022, have been collated. This nasal colonization model evaluated 15 volunteers and determined that the model was safe in these individuals and identified a human colonizing dose (HCD) 50 and HCD 90. However, the confidence intervals for these HCD doses were broad. The goals of this study are to further characterize the safety of this trial and to further refine the HCD 50 and 90 doses. This study is a single-site, randomized and blinded study designed to develop a colonization model for Nontypeable Haemophilus influenzae (NTHi). Ten healthy young adults ages 18-54 will be enrolled and inoculated with either 3,200 colony forming units (CFU) or 32,000 CFU of NTHi strain 2019 Streptomycin Resistant (StrR) number 1 and will be followed with nasal wash and throat swabs to determine whether colonization with NTHi 2019 StrR number 1 develops. Subjects that meet enrollment criteria will be admitted to the inpatient clinical research unit to a private room to stay from day 0 thru the morning of day 3 (visits 2-5) to evaluate for reactogenicity after nasal inoculation. During the hospital stay, subjects will remain in respiratory isolation. On day 0, five volunteers will be inoculated at the lower dose, 3,200 CFU, and five will be inoculated with higher dose, 32,000 CFU. After inoculation, primary volunteers will be followed daily for 6 days (visits 2-8, days 0-6) for clinical assessment and culture. Days 4-6, inoculated volunteers will return on a daily basis for a review of reactogenicity parameters, solicitation of adverse events (AEs), a targeted physical exam and pharyngeal swab and nasal wash specimens will be obtained. On day 6, visit 8, after pharyngeal swab and nasal wash samples have been collected and women of child bearing potential have had a urine pregnancy test performed, inoculated volunteers will receive 3 days of levofloxacin to eradicate any potential colonizing study organisms. Participants will return on days 14 and 28 to assess for any AEs, a targeted physical exam will be performed and pharyngeal swab, nasal wash, blood and saliva will be collected. A telephone visit will be performed 6 months after inoculation. A substudy will be performed to evaluate whether casual contact can serve as a mechanism for transmission of NTHi 2019 StrR number 1 from a colonized individual to a casual contact. Three and up to 10 subjects will be recruited to this substudy. They will spend 3-5 hours per day for 6 days with the subject in nonintimate contact and will be followed with nasal wash and throat swabs to determine whether colonization with NTHi 2019 StrR develops. The primary objective of the study is to evaluate the safety and reactogenicity of NTHi Strain 2019 StrR number 1 administered by nasal drop inoculation. The secondary objectives are to: evaluate the frequency and duration of colonization with NTHi strain 2019 StrR number 1 and to establish a human colonizing dose 5

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