Rapid Establishment of a Biospecimen Resource To Study the Global Impact of COVID-19 Vaccines.

The emergence and explosive spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 highlighted the need to rapidly develop curated biobanks to inform the etiology, diagnosis, and treatment options for global outbreaks of communicable diseases. Recently, we undertook efforts to develop a repository of biospecimens from individuals aged 12 and older who were to be vaccinated against coronavirus disease 19 (COVID-19) with vaccines developed with support from the United States Government. We planned to establish 40 or more clinical study sites in at least six countries to collect biospecimens from 1,000 individuals, 75% of whom were to be SARS-CoV-2 naive at the time of enrollment. Specimens would be used to (i) ensure quality control of future diagnostic tests, (ii) understand immune responses to multiple COVID-19 vaccines, and (iii) provide reference reagents for the development of new drugs, biologics, and vaccines. Biospecimens included serum, plasma, whole blood, and nasal secretions. Large-volume collections of peripheral blood mononuclear cells (PBMCs) and defibrinated plasma were also planned for a subset of subjects. Participant sampling was planned at intervals prior to and following vaccination over a 1-year period. Here, we describe the selection of clinical sites for specimen collection and processing, standard operating procedure (SOP) development, design of a training program for tracking specimen quality, and specimen transport to a repository for interim storage. This approach allowed us to enroll our first participants within 21 weeks from the study's initiation. Lessons learned from this experience should benefit the development of biobanks in response to future global epidemics. IMPORTANCE The ability to rapidly create a biobank of high-quality specimens in response to emergent infectious diseases is critical to allow for the development of prevention and treatment, as well as to effectively monitor the spread of the disease. In this paper, we report on a novel approach to getting global clinical sites up and running within a short time frame and to monitor the quality of specimens collected to ensure their value in future research efforts. Our results have important implications for the monitoring of the quality of biospecimens collected and to design effective interventions to address shortcomings, where needed.

Preference among female Army recruits for use of self-administrated vaginal swabs or urine to screen for Chlamydia trachomatis genital infections.

BACKGROUND: Use of self-administered vaginal swabs (SAS) for the detection of Chlamydia trachomatis by nucleic acid amplification tests simplifies specimen collection and transport, especially for women in nonclinical settings. GOAL: We investigated the preference and comfort level of military women for the collection of SAS, compared with urine, for the diagnosis of genital chlamydial infections. STUDY DESIGN: During March through August 1999, female Army recruits in basic training at Fort Jackson, South Carolina, were invited to participate in the study. Participants were requested to complete a questionnaire after providing both first-void urine (FVU) and SAS specimens. Participant characteristics, preferences, and comfort levels were assessed using multivariate logistic regression. RESULTS: From 4496 eligible female recruits, 1403 (31%) completed questionnaires and 1382 provided both specimens; 11.8% (166 of 1403) of participants were infected with chlamydia. The relative sensitivity and specificity of the C. trachomatis Ligase Chain Reaction test on SAS in 1382 matched pairs was 81.1% and 98.6%, respectively, using the test result on urine specimens as the comparison standard. Most of the participants (90.8%) reported that they felt comfortable collecting the FVU specimen, and 69.6% indicated that they felt comfortable collecting SAS. Either specimen collection type received high acceptability at home and in the field, and more women reported that they would collect FVU than reported they would collect SAS in the future (in the field: FVU: 79.4%, SAS: 68.8%, P <0.001); at home: FVU: 90.9%, SAS: 82.9%, P <0.001). When questioned about ease of use, 60.4% of women reported that urine was the easier method. Preferences for SAS were associated with being white and having had sexual risk behaviors in the past 3 months. CONCLUSION: A study of preferences for urine versus self-administered vaginal swabs for the detection of C. trachomatis in military women showed that women generally found SAS acceptable. SAS should be a feasible alternative to urine collection in situations in which specimen storage or transport is an issue.

Geographic epidemiology of gonorrhoea and chlamydia on a large military installation: application of a GIS system.

OBJECTIVES: The geographic epidemiology of infectious diseases can help in identifying point source outbreaks, elucidating dispersion patterns, and giving direction to control strategies. We sought to establish a geographic information system (GIS) infectious disease surveillance system at a large US military post (Fort Bragg, North Carolina) using STDs as the initial outcome for the model. METHODS: Addresses of incident cases were plotted onto digitised base maps of Fort Bragg (for on-post addresses) and surrounding Cumberland County, NC (for off-post addresses) using MAPINFO Version 5. We defined 26 geographic sectors on the installation. Active duty soldiers attending the post preventive medicine clinic were enrolled between July 1998 and June 1999. RESULTS: Gonorrhoea (GC) was diagnosed in 210/2854 (7.4%) and chlamydia (CT) in 445/2860 (15.6%). African-American male soldiers were at higher risk for GC (OR = 4.6 (95% CL 3.0 to 7.2)) and chlamydia (OR = 2.0 (1.4 to 2.7)). For women, there were no ethnic differences in gonorrhoea prevalence, but chlamydia was higher in African-Americans (OR = 2.0 (1.4-2.7)). Rank and housing type were associated with gonorrhoea and chlamydia in men, but were not significant factors in women. For gonorrhoea, two geographic sectors had prevalences between 14.0%-16.5%, three between 10.3%-13.9%, three between 7.1%-10.2%, and five between 3.0%-7.1%. The geographic distribution demonstrated a core-like pattern where the highest sectors were contiguous and were sectors containing barracks housing lower enlisted grade personnel. In contrast, chlamydia prevalence was narrowly distributed. CONCLUSION: GIS based disease surveillance was easily and rapidly implemented in this setting and should be useful in developing preventive interventions.

Features of Chlamydia trachomatis and Neisseria gonorrhoeae infection in male Army recruits.

Non-health care-seeking male United States Army recruits were tested for Chlamydia trachomatis (n=2245) and Neisseria gonorrhoeae (n=884), using a urine ligase chain reaction test to determine prevalence and potential risk factors for infection. The prevalence of chlamydial infection was 5.3%. Black race, a new sex partner, a history of trichomonas, and the presence of symptoms were associated with chlamydial infection. The prevalence of N. gonorrhoeae infection was 0.6%. Only a reported history of or positive test for C. trachomatis was associated with gonorrheal infection. Of those testing positive for chlamydia, 14% reported symptoms versus 40% of those with gonorrhea. Younger age was not a predictor of either infection, as has been shown for women. A substantial number of male army recruits are infected with C. trachomatis, but few are infected with N. gonorrhoeae. Screening on the basis of symptoms alone would miss the majority of both infections.

Evaluation of use of a single intravaginal swab to detect multiple sexually transmitted infections in active-duty military women.

The accuracy and suitability of use of a single intravaginal swab (SIS) for polymerase chain reaction detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and human papillomavirus infection was assessed in a cross-sectional study of 841 active-duty military women. The SIS, compared with standard diagnostic tests, allowed detection of more gonorrhea, more chlamydial infection, and more trichomoniasis. Sensitivity and specificity of SIS detection compared with adjudicated true-positive diagnoses were 95.8% and 97.8%, respectively, for gonorrhea, 94.6% and 99.3% for chlamydial infection, and 92.2% and 98.2% for trichomonal infection. Results with SISs were comparable to those with cervical swabs tested for human papillomavirus. Assay of clinician-collected and self-collected SISs yielded prevalences similar to those of standard diagnostic tests for all sexually transmitted infections. Therefore, the use of SISs is acceptable for the simultaneous diagnosis of multiple sexually transmitted infections and has potential for use as a self-administered diagnostic tool with widespread applicability among women.

Diagnosis of human papillomavirus infection by dry vaginal swabs in military women.

OBJECTIVE: Human papillomavirus (HPV) assays are likely to be used with increasing frequency in clinical management of women with abnormal Papanicolaou smears and in cervical cancer screening. Our objective was to simplify the method of collection of female genital tract specimens. The utility of vaginal dry swabs for HPV diagnosis was evaluated. METHODS: Specimens for cytology and for HPV identification were collected by a clinician from 189 female soldiers attending a military clinic. Three methods of specimen collection for HPV identification were compared: a vaginal dry swab (v-DRY), and vaginal and cervical swabs placed into specimen transport medium (v-STM and c-STM). Swabs were shipped to a STD laboratory for processing. Specific HPV types were identified by a consensus primer based PCR based method. Results from 165 women were evaluable. RESULTS: HPV prevalence by the three methods was similar and ranged from 44.8% to 50.9%. 53 (32.1%) women were HPV positive and 60 (36.4%) women were HPV negative by all three collection methods. With respect to the risk categories of specific HPV types, there was greater agreement between the results from the two vaginal (v-DRY and v-STM) samples (kappa values of 0.69-0.81) than between the cervical (c-STM) and either of the vaginal samples (kappa values of 0.37-0.55). The HPV yield from c-STM was somewhat greater than that from the vaginal specimens but the correlation between cytological abnormalities and HPV was high for all three methods. CONCLUSION: A dry vaginal swab may be an acceptable method of specimen collection for HPV diagnosis.

Application of a geographic information system to the tracking and control of an outbreak of shigellosis.

A personal computer-based commercial geographic information system (GIS) was applied to an outbreak of Shigella sonnei infection at Fort Bragg, North Carolina. We used a database consisting of demographic, temporal, and home-address information for all recognized cases of S. sonnei that occurred among health care beneficiaries from 23 May 1997 through 14 August 1997. We imported this database into the GIS, which contained a digitized basemap of the local community. Through simultaneous examination of temporal and spatial distribution of the 59 identified cases of S. sonnei, a focus of infection in a single housing area was identified. Targeted education among residents of the neighborhood in which there was intense transmission was associated with prompt extinction of the epidemic. A GIS offers an efficient and practical way to directly visualize the dynamics of transmission of infectious diseases in the setting of a community outbreak.

Correlates of human immunodeficiency virus infection risk behavior in male attendees of a clinic for sexually transmitted disease.

Human immunodeficiency virus (HIV) infection risk behavior was evaluated in a cross-sectional survey of 400 male active-duty US Army personnel who presented at a sexually transmitted disease (STD) clinic with symptoms of acute urethritis. High-risk partners were common, and nearly one-quarter of the sample had previously had STDs. Logistic regression models examined correlates of HIV exposure risk, of inconsistent condom use, and of having partners with increased risk of HIV infection. Frequent partner turnover, sex "binging," negative attitudes toward condom use, and engaging in sex during military leaves were important correlates of risk. Individuals with HIV infection risk behavior generally were cognizant of their risk for HIV infection. Implications for intervention are discussed.

Reducing risk of sexually transmitted disease (STD) and human immunodeficiency virus infection in a military STD clinic: evaluation of a randomized preventive intervention trial.

Three single-session preventive interventions for reducing sexually transmitted disease (STD) and human immunodeficiency virus infection risk behaviors were evaluated with a sample of 400 men who attended a large military STD clinic. A quasi-experimental, pre-evaluation/postevaluation design was used, comparing standard clinic care alone versus standard care combined with 1 of 3 experimental interventions: health-risk appraisal, interactive video, and targeted situational behaviors. Questionnaire data were collected at baseline and during follow-up visits at 2 weeks and 2 months. Findings indicated that the health-risk appraisal and interactive video increased adherence with clinic recommendations to abstain from sex (chi(2)3199=19.67; P<.001) and increased readiness to change "risky" partner-selection behavior (chi(2)2194=6.42; P<.04). Follow-up data suggested that STD-related risk behavior was particularly resistant to change but that the single-session intervention had some impact, which could be viewed as a "priming" effect that enhances multisession interventions.

Features of urethritis in a cohort of male soldiers.

Of 400 cases of urethritis in male soldiers enrolled in a behavioral intervention project, the etiology of 69% was defined at study enrollment, as well as the etiology of 72% of 25 repeated episodes involving 21 men during the first 78 days of active follow-up (5% of the cohort). Chlamydia trachomatis (36%), Neisseria gonorrhoeae (34%), and Ureaplasma urealyticum (19%) were the most common causes of infection identified at enrollment and during subsequent visits (44%, 28%, and 12%, respectively). By univariate analysis, patients with repeated infection ("repeaters") were significantly more likely to report a history of sexually transmitted disease (STD; relative risk [RR], 3) and sex with sex workers (RR, 4) than were nonrepeaters. By multivariate analysis, only STD history was significant (RR, 2.8). Characteristics of repeaters in this cohort suggest that specific patterns may be used to establish screening "profiles" of potential repeaters, by which such individuals might be targeted for aggressive intervention at the time of the initial diagnosis.

Trends of gonorrhea and chlamydial infection during 1985-1996 among active-duty soldiers at a United States Army installation.

High rates of sexually transmitted diseases (STDs) have been reported in military populations. However, it remains uncertain whether the incidence of STDs is higher among military personnel than in the civilian population. The annual incidence of gonorrhea and chlamydia from 1985 through 1996 at Fort Bragg, North Carolina, was determined by use of a clinic database and demographic information for the entire installation. A direct standardization for age, sex, and race/ethnicity was performed, and the adjusted annual rates among active duty soldiers were compared with rates among men and women in North Carolina and the United States. Results showed that the adjusted incidence of gonorrhea and chlamydia among Fort Bragg soldiers remained higher overall than comparable state and national rates during the period of analyses. The 1996 adjusted chlamydia rates for male and female active duty soldiers were 3-fold to 6-fold higher than rates for males and females in North Carolina and in the United States as a whole. STDs continue to lead to significant morbidity in this representative military population.

Control of Chlamydia trachomatis infections in female army recruits: cost-effective screening and treatment in training cohorts to prevent pelvic inflammatory disease.

CONTEXT: Chlamydia trachomatis genitourinary infections in females can lead to serious and costly sequelae. Programs such as basic (initial entry) military training with controlled points of entry offer an opportunity to screen large cohorts of women at risk for infection. OBJECTIVE: To assess the cost-effectiveness of three interventions for C. trachomatis infections in women beginning Army training: 1) screening using urine ligase chain reaction (LCR) by age, 2) unrestricted testing using urine LCR, and 3) universal antibiotic treatment with azithromycin. DESIGN: Cost-effectiveness analysis from a military perspective. SETTING AND PATIENTS: A hypothetical cohort of 10,000 women who intended to complete at least 2 years of military service was studied. Analysis was based on data from 13,204 female trainees screened for chlamydial infection at Fort Jackson, SC. OUTCOMES: Program and training costs, cost of illness averted, and pelvic inflammatory disease (PID) prevented were determined for a 1-year follow-up period. Using sensitivity analysis, outcomes over 2 years were studied. RESULTS: At a 9.2% prevalence, no screening resulted in $220,900 in training and sequelae costs and 276 cases of PID. Screening by age produced the lowest cost $217,600, over a 1-year period and prevented 222 cases of PID for a cost-savings of $15 per case of PID prevented. Universal testing prevented an additional 11 cases of PID at a cost of $226,400, or costing $800 per additional case of PID prevented over age-targeted screening. Universal treatment prevented an additional 32 cases of PID and cost $221,100, saving $167 per additional cases of PID prevented over universal screening. Over a 2-year period, universal treatment provided the highest cost-savings and prevented the most disease. CONCLUSION: Screening by age provided a cost-savings to the Army over a 1-year period. Other organizations accessing large cohorts of young women could also benefit, even in the short term, from implementation of an age-based chlamydial screening program. Universal testing or universal treatment may be warranted in which long-term societal goals, such as maximum reduction of PID, are relevant.

Rubella outbreak, Fort Bragg, North Carolina, 1995: a clash of two preventive strategies.

An outbreak of rubella occurred among visiting German troops involved in a combined military exercise at Fort Bragg, North Carolina, in April 1995. Public health and military operational concerns centered on the significant contact the German soldiers had had with host battalion dependents and the impact of the outbreak on the exercise. Ten of the 120 German soldiers were found to be nonimmune; six of these soldiers developed clinical rubella. The four nonimmune soldiers who did not develop skin rashes had received serum immune globulin within 12 hours of identification of the index case. The impact of this outbreak on the Fort Bragg community and its military operations, and the methods used to control the outbreak and salvage the military mission, are described.

Clinical case definitions for Argentine hemorrhagic fever.

Argentine hemorrhagic fever (AHF) is a potentially lethal infection in Argentina. The case-fatality ratio is >15%, but treatment reduces the mortality rate to <1%. Diagnosis is based on clinical and laboratory criteria, but no case definition has been validated. A chart review was conducted for patients hospitalized with suspected AHF. Individuals with a fourfold rise in antibody titer were classified as cases. The combination of a platelet count of <100,000/mm3 and a white blood cell (WBC) count of <2,500/mm3 had a sensitivity and specificity of 87% and 88%, respectively, thus suggesting that the use of these criteria in a case definition would be helpful for epidemiological studies of AHF. The combination of a platelet count of <100,000/mm3 and a WBC count of <4,000/mm3 had a sensitivity of 100% and a specificity of 71%; the use of these criteria in a case definition should be helpful for screening patients for therapy with immune plasma in the region where AHF is endemic.

Disease and nonbattle injury among United States soldiers deployed in Bosnia-Herzegovina during 1997: summary primary care statistics for Operation Joint Guard.

Systematic surveillance of outpatient (primary care) encounters with the health care system has been performed for North Atlantic Treaty Organization coalition forces during peace-keeping operations in Bosnia-Herzegovina since 1995. The present study presents an analysis of disease and nonbattle injury (DNBI) surveillance findings for U.S. forces participating in Operation Joint Guard during 1997. The mean DNBI rate for this 1-year period was 8.1/100/week (range, 5.7-11.1/100/week). Most frequently cited causes for soldier visits to medical treatment facilities were injuries and orthopedic conditions (27%), respiratory disease (26%), miscellaneous "other" medical conditions (13%), dermatologic disorders (12%), and dental disease (10%). Gastroenteritis was infrequently seen (2% of visits). Our findings extend previous observations that indicate that the Bosnia peacekeeping mission is relatively safe and healthy for U.S. forces.

Human immunodeficiency virus (HIV) education and HIV risk behavior: a survey of rapid deployment troops.

A paper-and-pencil questionnaire was administered to 1,377 U.S. Army troops from rapid deployment units at Fort Bragg, North Carolina. This yielded 1,368 surveys available for analysis. The primary goal of the survey was to evaluate this group's experience with the Army human immunodeficiency virus (HIV) education program and to determine their level of HIV risk behaviors as related to participation in the Army's HIV education program. Seventy-seven percent of the respondents (1,052 of 1,368) reported receiving some HIV education from the Army. Of those, 55% (578 of 1,052) reported receiving 1 hour of education within the past year. Soldiers of Asian, Native American, and "other" race/ethnicity, and to a lesser extent, Hispanic background, were more likely to report receiving no HIV education compared with whites and African Americans. Self-reported receipt of HIV education did not strongly differentiate individuals in their partner selection or in key sexual risk behaviors in which they engaged.

Diagnosis of Trichomonas vaginalis infection by PCR using vaginal swab samples.

Trichomonas vaginalis infection is the most prevalent nonviral sexually transmitted disease (STD) in the world. A PCR test using vaginal swab samples for the detection of T. vaginalis was developed to add T. vaginalis infection to the growing list of STDs that can be detected by DNA amplification techniques. A primer set, BTUB 9/2, was designed to target a well-conserved region in the beta-tubulin genes of T. vaginalis. All strains (15 of 15) of T. vaginalis tested were successfully detected by PCR giving a single predicted product of 112 bp in gel electrophoresis. No such targeted product was amplified with DNA from Trichomonas tenax, Trichomonas gallinae, Chlamydia trachomatis, Neisseria gonorrhoeae, Giardia lamblia, Chilomastix sulcatus, Dientamoeba fragilis, and Entamoeba histolytica. An optimal analytical sensitivity of one T. vaginalis organism per PCR was achieved. Culture, performed with the Inpouch TV culture system, was examined daily with a light microscope to identify T. vaginalis. Twenty-three of 350 (6.6%) vaginal swab samples from women attending an army medical clinic were culture positive for T. vaginalis. Of these culture positive specimens, PCR detected 22 of 23 (96%) with primer set BTUB 9/2, and wet preparation detected only 12 of 23 (52%). Seventeen specimens were BTUB 9/2-PCR positive and culture negative. Ten of these discordant specimens were determined to be as true positive by PCR using primer sets TVA 5-1/6 and/or AP65 A/B, which target different regions in the T. vaginalis genome, and seven were determined to be false positive. The sensitivity of BTUB 9/2-PCR was 97% and the specificity was 98%. The sensitivities of culture and wet preparation were 70 and 36%, respectively. The diagnosis of T. vaginalis infection by PCR is a sensitive and specific method that could be incorporated into a joint strategy for the screening of multiple STDs by using molecular amplification methods.

Chlamydia trachomatis infections in female military recruits.

BACKGROUND: Asymptomatic genital Chlamydia trachomatis infections in women can lead to pelvic inflammatory disease, infertility, and ectopic pregnancy. To design a chlamydia-control program, we conducted a large survey of women in the U.S. military. METHODS: From January 1996 through December 1997, urine samples from 13,204 new female U.S. Army recruits from 50 states were screened by ligase chain reaction for C. trachomatis infection. Information on potential risk factors was obtained by questionnaire. With multivariate analysis, we identified criteria for a screening program. RESULTS: The overall prevalence of chlamydial infection was 9.2 percent, with a peak of 12.2 percent among the 17-year-old recruits. The prevalence was 15 percent or more among the recruits from five southern states. The following risk factors were independently associated with chlamydial infection: having ever had vaginal sex (odds ratio for infection, 5.9), being 25 years of age or less (odds ratio, 3.0), being black (odds ratio, 3.4), having had more than one sex partner in the previous 90 days (odds ratio, 1.4), having had a new partner in the previous 90 days (odds ratio, 1.3), having had a partner in the previous 90 days who did not always use condoms (odds ratio, 1.4), and having ever had a sexually transmitted disease (odds ratio, 1.2). A screening program for subjects 25 years of age or less (87.9 percent of our sample) would have identified 95.3 percent of the infected women. CONCLUSIONS: Among female military recruits, the prevalence of chlamydial infection is high. A control program that screens female recruits who are 25 years old or younger with urine DNA-amplification assays has the potential to reduce infection, transmission, and the sequelae of chlamydial infection.