Chlamydia trachomatis (Ct), an intracellular pathogen, is the most common bacterial sexually transmitted infection. In addition to acute cervicitis and urethritis, Ct can lead to serious sequelae of significant public health burden including pelvic inflammatory disease (PID) and infertility. Ct control efforts have not resulted in desired outcomes such as reduced incidence and reinfection, and this highlights the need for the development of an effective Ct vaccine. To this end, NIAID organized a workshop to consider the current status of Ct vaccine research and address critical questions in Ct vaccine design and clinical testing. Topics included the goal(s) of a vaccine and the feasibility of achieving these goals, animal models of infection including mouse and nonhuman primate (NHP) models, and correlates of protection to guide vaccine design. Decades of research have provided both whole cell-based and subunit vaccine candidates for development. At least one is currently in clinical development and efforts now need to be directed toward further development of the most attractive candidates. Overall, the discussions and presentations from the workshop highlighted optimism about the current status of Ct vaccine research and detailed the remaining gaps and questions needed to move vaccines forward.

Gonorrhea remains a major public health challenge, and current recommendations for gonorrhea treatment are threatened by evolving antimicrobial resistance and a diminished pipeline for new antibiotics. Evaluations of potential new treatments for gonorrhea currently make limited use of new understanding of the pharmacokinetic and pharmacodynamic contributors to effective therapy, the prevention of antimicrobial resistance, and newer designs for clinical trials. They are hampered by the requirement to utilize combination ceftriaxone/azithromycin therapy as the comparator regimen in noninferiority trials designed to seek an indication for gonorrhea therapy. Evolving gonococcal epidemiology and clinical trial design constraints hinder the enrollment of those populations at the greatest risk for gonorrhea (adolescents, women, and persons infected with antibiotic-resistant Neisseria gonorrhoeae). This article summarizes a recent meeting on the evaluation process for antimicrobials for urogenital gonorrhea treatment and encourages the consideration of new designs for the evaluation of gonorrhea therapy.

Background

Genital infection with herpes simplex virus type 2 (HSV-2) is common and increases risk of human immunodeficiency virus (HIV) transmission and acquisition. Pericoital use of tenofovir (TFV) gel provided protection from HSV-2 acquisition in the CAPRISA 004 study.

Methods

We measured estimate of effect of vaginal TFV 1% gel in preventing HSV-2 acquisition among women in VOICE, randomized, double-blinded, placebo-controlled trial assessing daily use of oral and vaginal TFV for HIV-1 preexposure prophylaxis. The TFV level in plasma at the first quarterly visit was used as a measure of gel use.

Results

Of 566 participants at risk for HSV-2 acquisition, 532 (94%) had first-quarter plasma TFV and end-of-study HSV-2 serologic data available. Over a follow-up period of 501 person-years, 92 incident cases of HSV-2 acquisition occurred: 77 were in women with no TFV detected in plasma, and 15 occurred in women with TFV detected in plasma (incidence, 20.6 cases/100 person-years [95% confidence interval [CI], 16.2-25.7] vs 11.9 cases/100 person-years [95% CI, 6.6-19.6], respectively). TFV detection in plasma was associated with a trend toward a reduced risk of HSV-2 seroconversion, with an unadjusted hazard ratio (HR) of 0.59 (95% CI, .34-1.02; P = .060) and a HR adjusted for site, age, having ≥2 male sex partners in the past 3 months, use of hormonal contraception, having anal sex in the past 3 months, and HIV status of 0.60 (95% CI, .33-1.08; P = .086).

Conclusions

Detection of TFV in plasma among TFV gel users was associated with a trend toward a reduced risk of HSV-2 acquisition, after controlling for sexual behavior and HIV-1 acquisition.

Chlamydia trachomatis and Neisseria gonorrhoeae infections in the rectum and pharynx are important extragenital reservoirs of infection. Few assays approved by the US Food and Drug Administration are commercially available to diagnose pharyngeal or rectal infections. The current study reports on the analytical performance of the Abbott RealTime CT/NG assay, including the limit of detection, inclusivity, and analytical specificity for C. trachomatis and N. gonorrhoeae in rectal and pharyngeal specimens. The limit of detection was performed using known concentrations of organisms, elementary bodies per milliliter (EB/mL) for C. trachomatis and colony-forming units per milliliter (CFU/mL) for N. gonorrhoeae, in clinical rectal and pharyngeal swab matrices. Inclusivity was performed against 12 serovars of C. trachomatis and seven strains of N. gonorrhoeae. The analytical specificity was performed using 28 different bacteria and viruses. The limit of detection for C. trachomatis was 2.56 EB/mL in pharyngeal specimens and 12.8 EB/mL in rectal specimens. The limit of detection for N. gonorrhoeae was 0.0256 CFU/mL for both pharyngeal and rectal specimens. The inclusivity and analytical specificity were 100% for both rectal and pharyngeal specimens. These analytical performance data demonstrate that the Abbott CT/NG RealTime assay is an accurate, sensitive, and specific assay in rectal and pharyngeal specimens, supporting the potential of the assay for detection of rectal and pharyngeal C. trachomatis and N. gonorrhoeae infections.

Background

In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025.

Methods

We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts.

Results

Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour.

Conclusion

These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed.