Journal of Infectious Diseases

Conventional antibiotics have cured more diseases than all other drug classes combined. However, the pipeline of novel antibiotics is running dry while multi-drug resistance (MDR) is increasing at an alarming rate. Even though vaccines and antibodies are part of the toolkit against antimicrobial resistance, broadening the concept of 'antibiotic' is essential for innovation. Original roadmaps are needed to tackle the overwhelming MDR bacterial infections. The majority of 'in-use' antibacterial drugs derived from secondary metabolites that are produced by cultured soil microorganisms...

BACKGROUND: Cryptosporidiosis, an enteric protozoon, causes substantial morbidity and mortality associated with diarrhea in children <2 years old in low-to-middle-income countries. There is no vaccine and treatments are inadequate. A piperazine-based compound MMV665917 has in vitro and in vivo efficacy against C. parvum. Here, we evaluated the efficacy of MMV665917 in gnotobiotic piglets experimentally infected with C. hominis, the species responsible for >75% of diarrhea reported in these children...

Metabolic complications relating to complex effects of viral and immune mediated mechanisms are now a focus of clinical care among persons living with HIV (PWH) and obesity is emerging as a critical problem. To address knowledge gaps, the NIH sponsored a symposium in May 2018 entitled "Obesity and Fat Metabolism in HIV-infected Individuals." Mechanisms relating to adipose dysfunction and fibrosis, immune function, inflammation, and gastrointestinal integrity were highlighted as contributors to obesity among PWH...

BACKGROUND: Non-live vaccine approaches that are simple to deliver and stable at room temperature or 2-8°C could be advantageous in controlling future Ebola virus (EBOV) outbreaks. Using an immunopotent DNA vaccine that generates protection from lethal EBOV challenge in small animals and NHPs, we performed a clinical study to evaluate both intramuscular (IM) and novel intradermal (ID) DNA delivery. METHODS: Two DNA vaccine candidates (INO-4201 and INO-4202) targeting the EBOV glycoprotein (GP) were evaluated for safety, tolerability and immunogenicity in a Phase 1 clinical trial...

BACKGROUND: Placental malaria is a major cause of adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of parasitemia during pregnancy and placental malaria. METHODS: Data come from 637 women enrolled in a randomized controlled trial of intermittent preventive treatment of malaria in pregnancy (IPTp) from Uganda. Plasmodium falciparum parasitemia was assessed using microscopy and ultrasensitive quantitative PCR at intervals of 28 days from 12-20 weeks gestation through delivery...

BACKGROUND: This study tested the hypothesis that the immunogenicity and safety of the simultaneous administration of the combined EV71 vaccine with recombinant hepatitis B vaccine (HepB) and group A meningococcal polysaccharide vaccine (MenA) is not inferior to separate administration of each vaccine. METHODS: The study was designed as a randomized, open-label, and non-inferiority trial, and was registered at ClinicalTrials.gov (NCT03274102). A total of 775 healthy infants aged 6 months were randomized 1:1:1 to simultaneous administration (SI) or separate administration (SE1:EV71 and SE2: HepB followed by MenA)...

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While health care providers have largely turned a blind eye, the cost of health care in the US has been skyrocketing, in part as a result of rising drug prices. Patent protections and market exclusivity, while serving to incentivize targeted new drug development, have exacerbated inequitable outcomes and reduced access, sometimes fueling national epidemics. Branded drug manufacturers face few barriers to exorbitant pricing of drugs with exclusivity-as in the cases of Sovaldi, Zyvox, and Truvada. Furthermore, albendazole, pyrimethamine, and penicillin demonstrate that generic medications without patent exclusivity are not guaranteed to have durably low costs, especially where manufacturer competition is lacking...

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No abstract text is available yet for this article.

BACKGROUND: Plasmodium vivax is the main cause of malaria in Nepal. Relapse patterns have not been characterized previously. METHODS: Patients with P. vivax malaria were randomized to receive chloroquine (CQ: 25 mg base/kg given over 3 days) alone or together with primaquine (CQ+PQ: 0.25 mg base/kg/day for 14 days) and followed intensively for one month, then at 1-2 month intervals for one year. Parasite isolates were genotyped. RESULTS: 101 (49%) patients received CQ and 105 (51%) received CQ+PQ...

The restoration of CD4+ T cells, especially of Th17 cells, remains incomplete in the gut mucosa of most HIV-1-infected individuals despite sustained antiretroviral therapy (ART). Herein, we report an increase in absolute number of CXCR3+ T cells in the duodenal mucosa on ART. The frequencies of Th1 and CXCR3+ CD8+ T cells were increased and negatively correlated with CCL20 and CCL25 expression in the mucosa. Ex-vivo, we showed that IFN-γ, the main cytokine produced by Th1 and effector CD8+ T cells, down-regulates the expression of CCL20 and CCL25 by small intestine enterocytes, while it increases the expression of CXCL9/10/11, the ligands of CXCR3...

Respiratory syncytial virus-associated acute respiratory infection (RSV-ARI) constitutes a substantial disease burden in older adults aged ≥65 years. We aimed to identify all studies worldwide investigating the disease burden of RSV-ARI in this population. We estimated the community incidence, hospitalization rate, and in-hospital case-fatality ratio (hCFR) of RSV-ARI in older adults, stratified by industrialized and developing regions, using data from a systematic review of studies published between January 1996 and April 2018 and 8 unpublished population-based studies...

BACKGROUND: Infection-induced thrombocytosis is a clinically important complication of tuberculosis infection. Recent studies have highlighted the utility of aspirin as a host-directed therapy modulating the inflammatory response to infection, but have not investigated the possibility that the effect of aspirin is related to an anti-platelet mode of action. METHODS: Here we utilise the zebrafish-Mycobacterium marinum model to show mycobacteria drive host haemostasis through the formation of granulomas...

Pitting, the removal of dead parasites from their host erythrocyte, has been studied in patients with severe malaria treated parenterally with quinine or artesunate, and was recently shown to contribute to delayed hemolysis, a frequent adverse event of artesunate. We quantified pitting in 81 travelers treated with oral antimalarial therapy. Pitting rate was high (55.8%) with artemisinin-based combinations, but lower than 10% with the non-artemisinin drugs quinine, mefloquine and atovaquone-proguanil. This may, in part explain the slower parasite clearance in patients treated with antimalarial drugs lacking an artemisinin component, as well as the absence of post-treatment hemolysis with these drugs...

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Understanding Multidrug-resistant tuberculosis cases not detected by rapid phenotypic and genotypic routine clinical tests is essential to improve diagnostics and advance towards personalized TB treatments. Here, we combine WGS with single-colony phenotyping testing to diagnose a MDR strain infecting a patient over nine years. Our investigation revealed the failure of rapid testing assays and genome-based prediction tools to identify the MDR strain. The false negative outcome was caused by uncommon RIF and INH resistance mutations...

BACKGROUND: Due to global shortage of inactivated poliovirus vaccine and global withdrawal of poliovirus type-2 (PV2) containing oral vaccine in May 2016, Vietnam has not used any PV2-containing vaccine between May 2016-October 2018. We assessed population immunity gap to PV2. METHODS: A cross-sectional survey in children 1-18 months of age was carried out in January 2018: one blood sample was obtained and analysed for the presence of poliovirus neutralizing antibodies...

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