SUMMARY
While U.S. CDC annual estimates of Chlamydia trachomatis (Ct) sexually transmitted infections (STIs) are
about 3 million, global World Health Organization (WHO) estimates are >131 million. Over 61 million people
are infected among the Pacific Island Countries and Territories (PICT) of the Western Pacific Ocean with a
prevalence rate of ~40% among teens and young adults. These percentages reflect the fact that STIs are a
major area of health disparity in the PICT as well as in other parts of the world. In the U.S., Hawaiian and other
Pacific Islanders have the 3rd highest prevalence of STIs, which is 3.7 times that of Whites. In these resource-
constrained regions, syndromic management of Ct is the norm. This is problematic because ~80% of females
and 50% of males are asymptomatic and do not seek medical care. Transmission from these asymptomatic yet
infected individuals to partners likely fuels the ongoing worldwide epidemic. Further, lack of treatment can
result in serious sequelae such as pelvic inflammatory disease, infertility, ectopic pregnancy, and hemorrhagic
proctitis. While the endocervix is considered the primary site of infection, female Ct rectal infections now
outnumber those in the urogenital tract. Without adequate detection, the rectum, which requires 7 to 21 days of
treatment with high rates of recurrence, is a potential reservoir of Ct for transmission within the host and to
partners. Our unifying hypothesis is that the natural history of Ct STIs is defined by the interaction of the
microbiomes, immune responses and pathogen populations of three key body sites: the vagina, endocervix
and rectum. We will employ metagenome shotgun sequencing (MSS) to understand healthy, dysbiotic and Ct-
associated microbiota in addition to host immune responses and Ct pathogen characteristics for a high-
incidence cohort of Fijian women. This work will naturally transition to improving future Ct diagnostics that
utilize metgenomic methods, and we will determine whether these data can predict protection from Ct and/or
incident Ct and infection severity. With prospective samples and clinical data collected prior to and at incident
Ct infection (or no Ct) from our cohort, we aim to: 1) identify taxonomic diversity, richness and abundance of
DNA-based organisms in the endocervix, vagina and rectum using MSS cross-referenced to 16S sequencing
at both time points; 2) quantitate immune responses in the context of the microbiota for each site, time point
and clinical outcome; 3) determine microbiota/immune response profiles that correlate with incident Ct genomic
strains and whether strain plays a role in clinical outcome at each site. Our research will aid in selecting
optimal sites for Ct screening and designing strategies such as vaginal and/or rectal therapy with beneficial
microbiota, especially for the latter site given the long and often ineffective treatment regimens. The steady
global increase in Ct cases necessitates research especially among those who suffer from health disparities
and are at increased risk for STIs. We have assembled a unique cohort of Fijian women with high rates of Ct
(up to 38%) without which it would not be possible to study the natural history of Ct urogenital and rectal STIs.