The Journal of Infectious Diseases

Wed, 10/09/2019 - 03:17
The development and implementation of rapid molecular diagnostics for tuberculosis (TB) drug-susceptibility testing is critical to inform treatment of patients and to prevent the emergence and spread of resistance. Optimal trial planning for existing tests and those in development will be critical to rapidly gather the evidence necessary to inform World Health Organization review and to support...
Mon, 04/01/2019 - 20:00
AbstractBackgroundProtective immunity against Coxiella burnetii infection is conferred by vaccination with virulent (PI-WCV), but not avirulent (PII-WCV) whole-cell inactivated bacterium. The only well-characterized antigenic difference between virulent and avirulent C. burnetii is they have smooth and rough lipopolysaccharide (LPS), respectively.MethodsMice were vaccinated with PI-WCV and PII-...
Wed, 03/20/2019 - 20:00
AbstractBackgroundEnterotoxigenic Escherichia coli (ETEC) commonly cause diarrhea in children living in developing countries and in travelers to those regions. ETEC are characterized by colonization factors (CFs) that mediate intestinal adherence. We assessed if bovine colostral IgG (bIgG) antibodies against a CF, CS17, or antibodies against CsbD, the minor tip subunit of CS17, would protect...
Sun, 02/17/2019 - 19:00
AbstractWe analyzed the virulence of pandemic H1N1 2009 influenza A viruses in vivo and in vitro. Selected viruses isolated in 2009, 2010, 2014, and 2015 were assessed using an aerosol-mediated high-dose infection model for pigs as well as air-liquid interface cultures of differentiated airway epithelial cells. Using a dyspnea score, rectal temperature, lung lesions, and viral load in the lung as...
Sun, 01/20/2019 - 19:00
AbstractBackgroundViral hepatitis epidemiological data are important for the World Health Organization plan of eliminating viral hepatitis. We aimed to document the prevalence of viral hepatitis A to E in Hong Kong.MethodsThis community-based study was open to all Hong Kong Chinese citizens aged ≥18 years. Baseline data and risk factors were collected. Hepatitis A–E serology was measured,...
Sun, 01/06/2019 - 19:00
AbstractThe resolution of Shigella flexneri infection–associated hyperinflammation is crucial for host survival. Using in vitro and in vivo models of shigellosis, we found that S. flexneri induces the expression of indoleamine 2,3-dioxygenase 1 (IDO1) through the nucleotide oligomerization domain 2 (NOD2) and epidermal growth factor receptor (EGFR) signaling pathway. Congruently, abrogation of...
Thu, 10/11/2018 - 20:00
AbstractBackgroundNontyphoidal Salmonella (NTS) organisms are a major cause of gastroenteritis and bacteremia, but little is known about maternally acquired immunity and natural exposure in infant populations residing in areas where NTS disease is highly endemic.MethodsWe recruited 503 pregnant mothers and their infants (following delivery) from urban areas in Vietnam and followed infants until...
Thu, 10/04/2018 - 20:00
AbstractBackgroundThe bacterial pathogen Vibrio vulnificus causes severe septic foodborne infections. The multifunctional autoprocessing repeats-in-toxins (MARTX) toxin is an important secreted virulence factor. The effector domain region is essential for lethal intestinal infection in mice, but the contribution of each of the 5 effector domains to infection has not been investigated.MethodsV....
Tue, 07/17/2018 - 20:00
AbstractBackgroundThe 2013–2016 outbreak of Ebola virus disease (EVD) in West Africa led to unprecedented morbidity and mortality. Although different classes of putative antiviral agents with supportive preclinical data were available for testing, and although several attempts to perform meaningful evaluation of these agents were undertaken during the epidemic, different research methods, a lack...
Sun, 04/22/2018 - 20:00
To the Editor—In response to an article by Manor et al [1], Chen et al recently reported on an outbreak of acute hepatitis A virus (HAV) in northern Taiwan that affected primarily men who have sex with men (MSM) who had human immunodeficiency virus (HIV) or other sexually transmitted infections (STIs) [2]. That outbreak started in mid-2015 and peaked with >1000 cases of acute HAV reported in...
Tue, 04/17/2018 - 20:00
AbstractBackgroundHigh-pathogenicity avian influenza viruses continue to circulate in poultry and wild birds and occasionally infect humans, sometimes with fatal outcomes. Development of vaccines is a priority to prepare for potential pandemics but is complicated by antigenic variation of the surface glycoprotein hemagglutinin. We report the immunological profile induced by human immunization...
Wed, 04/11/2018 - 20:00
AbstractBackgroundCholera is a public health problem worldwide, and the risk factors for infection are only partially understood.MethodsWe prospectively studied household contacts of patients with cholera to compare those who were infected to those who were not. We constructed predictive machine learning models of susceptibility, using baseline gut microbiota data. We identified bacterial taxa...
Mon, 03/05/2018 - 19:00
AbstractLassa fever is a viral zoonosis that can be transmitted from person to person, especially in the hospital setting. The disease is endemic to several countries in West Africa and can be a major contributor to morbidity and mortality in affected areas. There are no approved vaccines to prevent Lassa virus infection. In this work, we present a vaccine candidate that combines the scalability...
Fri, 02/16/2018 - 19:00
AbstractBackgroundTreatment with nucleos(t)ide analogues (NA) suppresses hepatitis B virus (HBV) DNA but rarely leads to functional cure of chronic hepatitis B (CHB). Following NA cessation, some hepatitis B e antigen (HBeAg)-negative CHB patients experience hepatitis B s antigen (HBsAg) loss. Cellular immune responses, including natural killer (NK) cell responses, explaining virological events...
Fri, 01/05/2018 - 19:00
AbstractBrucellaceae are stealthy pathogens with the ability to survive and replicate in the host in the context of a strong immune response. This capacity relies on several virulence factors that are able to modulate the immune system and in their structural components that have low proinflammatory activities. Lipopolysaccharide (LPS), the main component of the outer membrane, is a central...
Mon, 01/01/2018 - 19:00
AbstractBackgroundCryptosporidiosis affects all human populations, but can be much more severe or life-threatening in children and individuals with weak or weakened immune systems. However, current options to treat cryptosporidiosis are limited.MethodsAn in vitro phenotypic screening assay was employed to screen 1200 existing drugs for their anticryptosporidial activity and to determine the...
Wed, 12/20/2017 - 19:00
AbstractMost current Ebola virus (EBOV) vaccine candidates are based on viral vectors, some of which cause side effects or require complex manufacturing. Modified mRNA vaccines are easily produced, safe, and are highly immunogenic. We developed 2 mRNA vaccines based on the EBOV envelope glycoprotein, which differed by the nature of signal peptide for improved glycoprotein post-translational...
Fri, 12/15/2017 - 19:00
AbstractZika virus (ZIKV) infection during pregnancy can cause devastating congenital abnormities or fetal demise. Zika virus infection could also cause Guillain-Barré syndrome in adults. Mosquito control, vaccine, and therapeutics are 3 potential, effective means to prevent ZIKV infection. Here we review the current status of ZIKV drug discovery. Both small molecule inhibitors and therapeutic...
Tue, 12/05/2017 - 19:00
AbstractBackgroundPostdiarrheal hemolytic-uremic syndrome (D+HUS) following Shiga toxin–producing Escherichia coli (STEC) infection is a serious condition lacking specific treatment. Host immune dysregulation and genetic susceptibility to complement hyperactivation are implicated in non–STEC-related HUS. However, genetic susceptibility to D+HUS remains largely uncharacterized.MethodsPatients with...
Sun, 11/19/2017 - 19:00
AbstractBackgroundAlthough cholera is considered the quintessential long-cycle waterborne disease, studies have emphasized the existence of short-cycle (food, household) transmission. We investigated singular Danish cholera epidemics (in 1853) to elucidate epidemiological parameters and modes of spread.MethodsUsing time series data from cities with different water systems, we estimated the...
Sun, 11/12/2017 - 19:00
AbstractBackgroundWe investigated safety and immunogenicity of 1–2 doses of different bivalent virus-like particle (VLP) norovirus vaccine candidate (NoV) formulations in healthy 18- to 64-year-olds.MethodsOn days 1 and 28, participants (n = 420) randomized to 14 equal groups received intramuscular control vaccine (hepatitis A) or 1 of 11 NoV formulations containing varying dosages of GI.1 and...
Fri, 11/03/2017 - 00:00
Tuberculosis caused an estimated 1.4 million deaths in 2015 and now ranks as the leading infectious disease cause of mortality in the world [1]. An additional 1.7 billion people are currently infected with Mycobacterium tuberculosis and are at risk of developing active tuberculosis disease. The challenge to eliminate tuberculosis has never been more relevant and urgent. Unfortunately, efforts to...
Tue, 10/31/2017 - 20:00
AbstractBackgroundCampylobacteriosis is inflammation of the gastrointestinal tract as a result of Campylobacter infection. Most campylobacteriosis cases are acute and self-limiting, with Campylobacter excretion ceasing a few weeks after symptoms cease. We identified a patient with fecal specimens positive for Campylobacter jejuni (ST45) intermittently during a 10-year period.MethodsSixteen...
Thu, 09/14/2017 - 20:00
AbstractClostridium perfringens enterotoxin (CPE) causes food poisoning and antibiotic-associated diarrhea. It uses some claudin tight junction proteins (eg, claudin-4) as receptors to form Ca2+-permeable pores in the membrane, damaging epithelial cells in small intestine and colon. We demonstrate that only a subpopulation of colonic enterocytes which are characterized by apical dislocation of...
Mon, 09/11/2017 - 20:00
AbstractBackgroundAspergillus flavus is one of the most common agents of invasive aspergillosis and is associated with high mortality. The orotomides are a new class of antifungal agents with a novel mechanism of action. An understanding of the pharmacodynamics (PD) of the lead compound F901318 is required to plan safe and effective regimens for clinical use.MethodsThe pharmacokinetics (PK) and...
Fri, 09/08/2017 - 20:00
AbstractBackgroundSeasonal influenza vaccines are transitioning to quadrivalent formulations including the hemagglutinins of influenza A subtypes H1N1 and H3N2 and B lineages Yamagata and Victoria.MethodsA new quadrivalent recombinant influenza vaccine (RIV4) was compared directly with a standard-dose, egg-grown, quadrivalent-inactivated influenza vaccine (IIV4) for immunogenicity and safety in...
Fri, 08/18/2017 - 00:00
To the Editor—With great interest we read the article by Zhou and colleagues [1]. The authors intravenously inoculated Balb/c nude mice with a swine fecal preparation containing hepatitis E virus (HEV) of genotype (gt) 4 (strain KM01) and were able to detect high levels of HEV RNA in the mouse serum, liver, and brain [1].
Sat, 07/29/2017 - 00:00
To the Editor—Norovirus is a major cause of acute gastroenteritis worldwide, and chronic infections frequently occur in immunocompromised patients. However, no US Food and Drug Administration–approved specific medication is available for treating norovirus infection. Interestingly, substantial clinical evidence has suggested that nitazoxanide, originally developed as an antiprotozoal agent, is a...
Sat, 07/01/2017 - 00:00
AbstractEliminating the risk of polio from vaccine-derived polioviruses is essential for creating a polio-free world, and eliminating that risk will require stopping use of all oral polio vaccines (OPVs) once all types of wild polioviruses have been eradicated. In many ways, the experience with the global switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) can inform the eventual full global...
Fri, 06/30/2017 - 00:00
AbstractThe World Health Organization (WHO) Western Pacific Region (WPR) has maintained its polio-free status since 2000. The emergence of vaccine-derived polioviruses (VDPVs), however, remains a risk, as oral polio vaccine (OPV) is still used in many of the region’s countries, and pockets of unimmunized or underimmunized children exist in some countries. From 2014 to 2016, the region...
Mon, 04/17/2017 - 00:00
AbstractMany intracellular pathogens invade cells via endocytic organelles and have adapted to the drop in pH along the endocytic pathway. However, the strategy by which the host cell counteracts this pathogen adaptation remains unclear. βγ-CAT is an aerolysin-like pore-forming protein and trefoil factor complex in the frog Bombina maxima. We report here that βγ-CAT, as a host-secreted factor...
Thu, 03/23/2017 - 00:00
AbstractListeria monocytogenes is a major intracellular human foodborne bacterial pathogen. We previously revealed L. monocytogenes cadC as highly expressed during mouse infection. Here we show that L. monocytogenes CadC is a sequence-specific, DNA-binding and cadmium-dependent regulator of CadA, an efflux pump conferring cadmium resistance. CadC but not CadA is required for L. monocytogenes...
Fri, 02/24/2017 - 00:00
AbstractHilD, a dominant regulator of Salmonella pathogenicity island 1, can be acetylated by protein acetyltransferase (Pat) in Salmonella Typhimurium, and the acetylation is beneficial to its stability. However, the underlying mechanism of HilD stability regulated by acetylation is not clear. We show here that lysine 297 (K297) located in the helix-turn-helix motif, can be acetylated by Pat....
Mon, 01/30/2017 - 00:00
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background.</div>The presence of transmitted drug resistance mutations (TDRMs) in antiretroviral treatment (ART)–naive patients can adversely affect the outcome of ART.<div class="boxTitle">Methods.</div>Resistance testing was conducted in 6704 ART-naive subjects...
Fri, 01/27/2017 - 00:00
AbstractBackgroundTo successfully limit pathogen dissemination, an immunological link between the entry tissue of the pathogen and the underlying secondary lymphoid organs (SLOs) needs to be established to prime adaptive immune responses. Here, the prerequisite of CCR7 to mount host immune responses within SLOs during gastrointestinal Yersinia pseudotuberculosis infection to limit pathogen spread...
Mon, 12/05/2016 - 03:18
Background. In Indonesia, highly pathogenic avian influenza A(H5N1) virus has become endemic in poultry and has caused sporadic deadly infections in human. Since 2012, we have conducted fixed-point surveillance of avian influenza viruses at a live-poultry market in East Java, Indonesia. In this study, we examined the seroprevalence of avian influenza A(H5N1) virus infection among market...
Mon, 12/05/2016 - 03:18
Cryptosporidium is recognized as one of the main causes of childhood diarrhea worldwide. However, the current treatment for cryptosporidiosis is suboptimal. Calcium flux is essential for entry in apicomplexan parasites. Calcium-dependent protein kinases (CDPKs) are distinct from protein kinases of mammals, and the CDPK1 of the apicomplexan Cryptosporidium lack side chains that typically block a...
Mon, 10/31/2016 - 00:00
<span class="paragraphSection"><div class="boxTitle">Abstract</div><span style="font-style:italic;">Shigella sonnei</span> and <span style="font-style:italic;">Salmonella</span> Typhi cause significant morbidity and mortality. We exploited the safety record of the oral, attenuated <span style="font-style:italic;">S.</span> Typhi vaccine (Ty21a...
Fri, 10/28/2016 - 12:06
Vibrio cholerae, the etiological agent of cholera, is known to form biofilms to persist in the environment. It is demonstrated here that even during infection, biofilm genes are upregulated, and microscopic observation indicated that biofilm formation is initiated almost immediately after adherence of V. cholerae to intestinal cells. About 7-fold upregulation of the biofilm regulatory gene vpsT...
Fri, 10/28/2016 - 12:06
Background. Salmonella causes an estimated 100 000 antimicrobial-resistant infections annually in the United States. Salmonella antimicrobial resistance may result in bacteremia and poor outcomes. We describe antimicrobial resistance among nontyphoidal Salmonella blood isolates, using data from the National Antimicrobial Resistance Monitoring System. Methods. Human nontyphoidal...
Fri, 10/28/2016 - 12:06
Background. Universal 2-dose hepatitis A virus (HAV) vaccination of toddlers effectively controls hepatitis A. High vaccine costs, however, impede implementation in endemic countries. To test single-dose vaccination as a possible alternative, we initiated an observational, longitudinal study in Nicaragua, to assess protective effectiveness and—through challenge vaccination—...
Tue, 10/04/2016 - 00:00
AbstractCoxiella burnetii is a gram-negative bacterium that causes acute and chronic Q fever. Because of the severe adverse effect of whole-cell vaccination, identification of immunodominant antigens of C. burnetii has become a major focus of Q fever vaccine development. We hypothesized that secreted C. burnetii type IV secretion system (T4SS) effectors may represent a major class of CD8+ T-cell...
Fri, 09/23/2016 - 12:01
Giardia lamblia is a pathogen transmitted by water and food that causes infection worldwide. Giardia genotypes are classified into 8 assemblages (A–H). Assemblages A and B are detected in humans, but they are potentially zoonotic because they infect other mammalian hosts. Giardia in samples from 44 children was genotyped. Conserved fragments of the genes encoding β-giardin and...
Tue, 09/13/2016 - 11:58
With the rise of multidrug resistance, Pseudomonas aeruginosa infections require alternative therapeutics. The injectisome (iT3SS) and flagellar (fT3SS) type III secretion systems are 2 virulence factors associated with poor clinical outcomes. iT3SS translocates toxins, rod, needle, or regulator proteins, and flagellin into the host cell cytoplasm and causes cytotoxicity and NLRC4-dependent...
Tue, 08/09/2016 - 12:08
During 2013, ST278 Klebsiella pneumoniae with blaNDM-7 was isolated from the urine (KpN01) and rectum (KpN02) of a patient in Calgary, Canada. The same strain (KpN04) was subsequently isolated from another patient in the same unit. Interestingly, a carbapenem-susceptible K. pneumoniae ST278 (KpN06) was obtained 1 month later from the blood of the second patient. Next-generation sequencing (NGS)...
Tue, 08/09/2016 - 12:08
There is growing evidence that Zika virus (ZIKV) can cause devastating infant brain defects and other neurological disorders in humans. However, no specific antiviral therapy is available at present. We tested a series of 2'-C- or 2'-O-methyl–substituted nucleosides, 2'-C-fluoro-2'-C-methyl–substituted nucleosides, 3'-O-methyl–substituted nucleosides, 3'-deoxynucleosides,...
Thu, 07/21/2016 - 11:58
The PrePex circumcision device causes ischemic necrosis of the foreskin, raising concerns of anaerobic overgrowth. We compared the subpreputial microbiome of 2 men 7 days after PrePex device placement to that of 145 uncircumcised men in Rakai, Uganda, using 16S ribosomal (rRNA) RNA gene–based quantitative polymerase chain reaction analysis and sequencing. PrePex users had higher absolute...
Thu, 07/07/2016 - 12:16
Helminth-infected individuals possess a higher risk of developing tuberculosis, but the precise immunologic mechanism of Mycobacterium tuberculosis control remains unclear. We hypothesized that a perturbation of the M. tuberculosis–specific CD4+ T-cell response weakens the ability of macrophages to contain M. tuberculosis. We exposed peripheral blood mononuclear cells from M. tuberculosis...
Thu, 06/23/2016 - 12:13
Background. Tick transmission of Borrelia spirochetes to humans results in significant morbidity from Lyme disease worldwide. Serum concentrations of antibodies against outer surface protein A (OspA) were shown to correlate with protection from infection with Borrelia burgdorferi, the primary cause of Lyme disease in the United States. Methods. Mice transgenic for human immunoglobulin...
Wed, 06/08/2016 - 12:12
Background. Brucella species are facultative intracellular gram-negative bacteria that cause brucellosis, a common global zoonosis. Infection of the joints is the most common focal complication of brucellosis in humans. The purpose of this study was to identify mediators of focal inflammation during brucellosis. Methods. Wild-type (WT) mice are naturally resistant to Brucella infection...

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