Background. We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)–vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. Methods. Sixty-five HIV-1–uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0...
Innovative approaches to the use of existing antibiotics is an important strategy in efforts to address the escalating antimicrobial resistance crisis. We report a new approach to the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections by demonstrating that oxacillin can be used to significantly attenuate the virulence of MRSA despite the pathogen being...
Background. Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings. Methods. We conducted a nested, case-control...
Background. Respiratory syncytial virus (RSV) is a leading cause of childhood bronchiolitis and pneumonia, particularly in early infancy. Immunization of pregnant women could boost preexisting immune responses, providing passive protection to newborns through placental transfer of anti-RSV antibody. Methods. In this first-in-humans clinical trial of a purified recombinant RSV...
Background. Vaccines and antivirals against respiratory syncytial virus (RSV) are being developed, but there are scarce data on the full impact of RSV infection on outpatient children. Methods. We analyzed the burden of RSV illness in a prospective cohort study of children aged ≤13 years during 2 consecutive respiratory seasons in Turku, Finland (2231 child-seasons of follow-up...
Chikungunya virus (CHIKV) emerged in the Americas in late 2013 to cause substantial acute and chronic morbidity. About 1.1 million cases of chikungunya were reported within a year, including severe cases and deaths. The burden of chikungunya is unclear owing to inadequate disease surveillance and underdiagnosis. Virus evolution, globalization, and climate change may further CHIKV...
Background. Many countries worldwide have reported increasing numbers of emm89 group A Streptococcus (GAS) infections during last decade. Pathogen genetic factors linked to this increase need assessment. Methods. We investigated epidemiological characteristics of emm89 GAS bacteremic infections, including 7-day and 30-day case-fatality rates, in Finland during 2004–2014 and...
Background. Mass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir. Methods. A cluster-randomized controlled trial in Southern Province, Zambia, was used to assess the short-term impact of 2 rounds of community-wide MDA and household-level...
Background. Preexposure prophylaxis (PrEP) is effective for preventing human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) within trial settings. Population impact will depend on clinical indications for PrEP initiation, coverage levels, and drug adherence. No modeling studies have estimated the impact of clinical practice guidelines for PrEP issued...
The digital revolution has contributed to very large data sets (ie, big data) relevant for public health. The two major data sources are electronic health records from traditional health systems and patient-generated data. As the two data sources have complementary strengths—high veracity in the data from traditional sources and high velocity and variety in patient-generated data...
Background. In the United States, >40% of people infected with human immunodeficiency virus (HIV) smoke cigarettes. Methods. We used a computer simulation of HIV disease and treatment to project the life expectancy of HIV-infected persons, based on smoking status. We used age- and sex-specific data on mortality, stratified by smoking status. The ratio of the non-AIDS-related...
Background. Treatment of Neisseria gonorrhoeae infection is empirical and based on population-wide susceptibilities. Increasing antimicrobial resistance underscores the potential importance of rapid diagnostic tests, including sequence-based tests, to guide therapy. However, the usefulness of sequence-based diagnostic tests depends on the prevalence and dynamics of the resistance...
Ninety-eight semen specimens were obtained for Ebola virus (EBOV) RNA screening from 68 men in Guinea during the convalescent phase of EBOV infection. Ten samples from 8 men were positive for EBOV up to 9 months after onset of the disease, with decreasing trends in the proportion of positive samples and the level of viral RNA. Safe sex practices should be observed after discharge...
Background. Parallel upregulation of several T-cell effector functions (ie, polyfunctionality) is believed to be critical for the protection against viruses but thought to decrease in large T-cell expansions, in particular at older ages. The factors determining T-cell polyfunctionality are incompletely understood. Here we revisit the question of cytomegalovirus (CMV)–specific T...
Background. There are several mechanisms by which global climate change may impact malaria transmission. We sought to assess how the increased frequency of extreme precipitation events associated with global climate change will influence malaria transmission in highland areas of East Africa. Methods. We used a differences-in-differences, quasi-experimental design to examine...
We report the first use of whole viral genome sequencing to identify nosocomial transmission of varicella-zoster virus with fatal outcome. The index case patient, nursed in source isolation, developed disseminated zoster with rash present for 1 day before being transferred to the intensive care unit (ICU). Two patients who had received renal transplants while inpatients in an...
Background. After decades of obscurity, Zika virus (ZIKV) has spread through the Americas since 2015 accompanied by congenital microcephaly and Guillain-Barré syndrome. Although these epidemics presumably involve transmission by Aedes aegypti, no direct evidence of vector involvement has been reported, prompting speculation that other mosquitoes such as Culex quinquefasciatus...
Background. Diagnosis of human immunodeficiency virus (HIV) infection during early infancy (commonly known as “early infant HIV diagnosis” [EID]) followed by prompt initiation of antiretroviral therapy dramatically reduces mortality. EID testing is recommended at 6 weeks of age, but many infant infections are missed. Design/Methods. We simulated 4 EID testing strategies for HIV...
Background. Human immunodeficiency virus type 1 (HIV)–infected persons are more susceptible to tuberculosis than HIV–uninfected persons. Low peripheral CD4+ T-cell count is not the sole cause of higher susceptibility, because HIV–infected persons with a high peripheral CD4+ T-cell count and those prescribed successful antiretroviral therapy (ART) remain more prone to active...
Concern has been expressed that tenofovir-containing regimens may have reduced effectiveness in the treatment of human immunodeficiency virus type 1 (HIV-1) subtype C infections because of a propensity for these viruses to develop a key tenofovir-associated resistance mutation. We evaluated whether subtype influenced rates of virological failure in a cohort of 8746 patients from...