Nontypeable H. Influenzae in Healthy Adults

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 50 and 90 (HCD50 or HCD90); and evaluate the transmissibility of
NTHi 2019 StrR number 1 to casual contacts.