Clinical Infectious Diseases

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ISSN / EISSN : 1058-4838 / 1537-6591
Published by: Oxford University Press (OUP) (10.1093)
Total articles ≅ 32,755
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, Shuk Hang Li, Jillian H Hurst, Zidanyue Yang, Donna Niedzwiecki, Genevieve G Fouda, Joanne Kurtzberg, Kyle M Walsh,
Clinical Infectious Diseases; doi:10.1093/cid/ciab627

Placentally-transferred maternal IgG protects against pathogens in early life, yet vertically-transmitted infections can interfere with transplacental IgG transfer. Although human cytomegalovirus (HCMV) is the most common placentally-transmitted viral infection worldwide, the impact of congenital HCMV (cCMV) infection on transplacental IgG transfer has been underexplored. We evaluated total and antigen-specific maternal and cord blood IgG levels and transplacental IgG transfer efficiency in a U.S-based cohort of 93 mother-infant pairs including 27 cCMV-infected and 66 cCMV-uninfected pairs, of which 29 infants were born to HCMV-seropositive non-transmitting mothers and 37 to HCMV-seronegative mothers. Controls were matched on sex, race/ethnicity, maternal age, and delivery year. Transplacental IgG transfer efficiency was decreased by 23% (95% CI 10-36%, p=0.0079) in cCMV-infected pairs and 75% of this effect (95% CI 28-174%, p=0.0085) was mediated by elevated maternal IgG levels (i.e., hypergammaglobulinemia) in HCMV-transmitting women. Despite reduced transfer efficiency, IgG levels were similar in cord blood from infants with and without cCMV infection. Our results indicate that cCMV infection moderately reduces transplacental IgG transfer efficiency due to maternal hypergammaglobulinemia; however, infants with and without cCMV infection had similar antigen-specific IgG levels, suggesting comparable protection from maternal IgG acquired via transplacental transfer.
Kevin Outterson, Ebiowei S F Orubu, John Rex, Christine Årdal, Muhammad H Zaman
Clinical Infectious Diseases; doi:10.1093/cid/ciab612

Inaccessibility of medicines in low- and middle-income countries (LMICs) is a frequent challenge. Yet it is typically assumed that high-income countries have complete access to the full arsenal of medicines. This study tests this assumption for new antibacterials, which are saved as a last resort in order to prevent the development of resistance, resulting in insufficient revenues to offset costs. Prior studies report only regulatory approval, missing the important lag that occurs between approval and commercial launch, although some antibiotics never launch in some countries. We identified all antibacterials approved and launched in the G7 and seven other high-income countries in Europe for the decade beginning January 1, 2010, using quantitative methods to explore associations. Eighteen new antibacterials were identified. The majority were accessible in only three countries (US, UK, and Sweden), with the remaining eleven high-income countries having access to less than half of them. European marketing authorization did not lead to automatic European access, as fourteen of the antibacterials were approved by EMA, but many fewer were commercially launched. There was no significant difference in access between “innovative” and “non-innovative” antibacterials. Median annual sales in the first launched market (generally the US) for these 18 antibiotics were low, $16.2M. Patient access to new antibacterials is limited in some high-income countries including Canada, Japan, France, Germany, Italy, and Spain. With low expected sales, companies may have decided to delay or forego commercialization due to expectations of insufficient profitability.
, Jade Derrick, Justin Shute, Georgina Ireland, Iain Hayden, Siew Lin Ngui, Sema Mandal, Richard S Tedder
Clinical Infectious Diseases; doi:10.1093/cid/ciab622

Surveillance programmes undertaken in infants born to hepatitis B virus (HBV) infected mothers provide an opportunity to analyse virological markers from the neonate and early infancy. These data inform on mechanisms of HBV transmission and how available interventions can be better utilised for control of HBV infections arising at the mother/child interface. Retrospective analysis of HBV serological markers was undertaken in Dried Blood Spots collected from infants born to HBV-infected mothers. In addition, molecular analysis was performed in newborn blood spot cards, collected after birth, from infants identified as HBV-infected despite receiving prophylaxis. Perinatal exposure could not account for all transmissions with at least one quarter (22%) of infants already infected in utero. All harboured a wild type HBsAg, with identical sequences noted in the neonatal and early infancy samples. In contrast, in infants infected perinatally (43%), selection of viruses harbouring amino acid changes in the HBsAg were common (80% of sequences) and divergent from the linked maternal sample. Currently considered to represent vaccine failure, it is likely that a proportion of HBV infections result from in utero acquisition. These infections are unlikely to be susceptible to post-natal prophylaxis and current recommendations for maternal antiviral treatment may be too late to prevent transmission. Consideration should be given to the earlier use of antivirals during gestation to reduce the risk of intrauterine transmission together with completion of the immunisation schedule also to reduce the perinatal risk of HBV transmission.
Patrick Sean Sullivan, Aaron J Siegler, Kayoko Shioda, Eric W Hall, Heather Bradley, Travis Sanchez, Nicole Luisi, Mariah Valentine-Graves, Kristin N Nelson, Mansour Fahimi, et al.
Clinical Infectious Diseases; doi:10.1093/cid/ciab626

Reported COVID-19 cases underestimate SARS-CoV-2 infections. We conducted a national probability survey of US households to estimate the cumulative incidence adjusted for antibody waning. From August-December 2020, a multistage random sample of US addresses were mailed a survey and materials to self-collect nasal swabs and dried blood spots. One adult household member completed the survey and mail specimens for viral detection with PCR and total (IgA, IgM, IgG) nucleocapsid antibody by a commercial, EUA-approved antigen capture assay. We estimated cumulative incidence of SARS-CoV-2 adjusted for waning antibodies and calculated reported fraction and infection fatality ratio (IFR). Differences in seropositivity among demographic, geographic and clinical subgroups were explored with weighted prevalence ratios (PR). Among 39,500 sampled households, 4,654 respondents provided responded. Cumulative incidence adjusted for waning was 11.9% (95% credible interval (CrI): 10.5-13.5%) as of October 30, 2020. We estimated 30,332,842 (CrI: 26,703,753- 34,335,338) total infections in the U.S. adult population by October 30, 2020. Reported fraction was 17% and IFR was 0.85% among adults. Non-Hispanic Black (PR: 2.2) and Hispanic (PR: 3.1) persons were more likely than White non-Hispanic to be seropositive, as were those living in metropolitan areas (PR: 2.5). One in 8 US adults had been infected with SARS-CoV-2 by late October 2020; but few had been accounted for in public health reporting. The scope of the COVID-19 pandemic is likely substantially underestimated by reported cases. Disparities in COVID-19 by race observed among reported cases cannot be attributed to differential diagnosis or reporting of infections in some population subgroups.
Frederick G Hayden, Jason Asher, Benjamin J Cowling, Aeron C Hurt, Hideyuki Ikematsu, Klaus Kuhlbusch, Annabelle Lemenuel-Diot, Zhanwei Du, Lauren Ancel Meyers, Pedro A Piedra, et al.
Clinical Infectious Diseases; doi:10.1093/cid/ciab625

Prompt antiviral treatment has the potential to reduce influenza virus transmission to close contacts, but rigorous data on the magnitude of treatment effects on transmission are limited. Animal model data indicate that rapid reductions in viral replication following antiviral treatment reduce the risk of transmission. Observational and clinical trial data with oseltamivir and other neuraminidase inhibitors indicate that prompt treatment of household index patients appears to reduce the risk of illness in contacts, although the magnitude of the reported effects has varied widely across studies. In addition, the potential risk of transmitting drug-resistant variants exists with all approved classes of influenza antivirals. A controlled trial examining baloxavir treatment efficacy to reduce transmission, including the risk of transmitting virus with reduced baloxavir susceptibility, is currently in progress. If reduced transmission risk is confirmed, modelling studies indicate that early treatment would have major epidemiologic benefits in seasonal and pandemic influenza.
, Ravina Kullar, Pierre-Jean Maziade, Ellie J C Goldstein
Clinical Infectious Diseases; doi:10.1093/cid/ciab618

Upasana Das Adhikari, George Eng, Mara Farcasanu, Laura E Avena, Manish C Choudhary, Virginia A Triant, Meaghan Flagg, Abigail E Schiff, Isabella Gomez, Leah M Froehle, et al.
Clinical Infectious Diseases; doi:10.1093/cid/ciab623

The clinical significance of SARS CoV-2 RNA in stool remains uncertain. We found that extrapulmonary dissemination of infection to the gastrointestinal (GI) tract, assessed by the presence of SARS-CoV-2 RNA in stool, is associated with decreased COVID-19 survival. Measurement of SARS-CoV-2 RNA in stool may have utility for clinical risk assessment.
, , Macy Zou, Natalie Prystajecky, John R Tyson, Eleni Galanis, Monika Naus, David M Patrick, Hind Sbihi, Shiraz El Adam, et al.
Clinical Infectious Diseases; doi:10.1093/cid/ciab616

Randomized-controlled trials of mRNA vaccine protection against SARS-CoV-2 included few elderly participants. We assess single-dose mRNA vaccine effectiveness (VE) in adults ≥70-years-old in British Columbia (BC), Canada where second doses were deferred by up to 16 weeks and where a spring 2021 wave uniquely included co-dominant circulation of Alpha (B.1.1.7) and Gamma (P.1) variants of concern (VOC). Analyses included community-dwelling adults ≥70-years-old with specimen collection between April 4 (epidemiological week 14) and May 1 (week 17) 2021. Adjusted VE was estimated by test-negative design. Cases were RT-PCR test-positive for SARS-CoV-2 and controls were test-negative. Vaccine status was defined by receipt of a single-dose ≥21 days before specimen collection, but a range of intervals was assessed. Variant-specific VE was estimated against viruses genetically characterized as Alpha, Gamma or non-VOC lineages. VE analyses included 16,993 specimens: 1,226 (7.2%) test-positive cases and 15,767 test-negative controls. Of 1,131 (92%) genetically-characterized viruses, 509 (45%), 314 (28%) and 276 (24%) were Alpha, Gamma and non-VOC lineages, respectively. At 0-13 days post-vaccination, VE was negligible at 14% (95% CI 0-26) but increased from 43% (95% CI 30-53) at 14-20 days to 75% (95% CI 63-83) at 35-41 days post-vaccination. VE at ≥21 days post-vaccination was 65% (95% CI 58-71) overall: 72% (95% CI 58-81), 67% (95% CI 57-75) and 61% (95% CI 45-72) for non-VOC, Alpha and Gamma variants, respectively. A single dose of mRNA vaccine reduced the risk of SARS-CoV-2 by about two-thirds in adults ≥70-years-old, with protection only minimally reduced against Alpha and Gamma variants.
Voahangy Andrianaivoarimanana, , Dawn N Birdsell, Birgit Nikolay, Faniry Rakotoarimanana, Lovasoa N Randriantseheno, Amy J Vogler, Jason W Sahl, Carina M Hall, Nawarat Somprasong, et al.
Clinical Infectious Diseases; doi:10.1093/cid/ciab606

Pneumonic plague (PP), caused by Yersinia pestis, is the most feared clinical form of plague due to its rapid lethality and potential to cause outbreaks. PP outbreaks are now rare due to antimicrobial therapy. A PP outbreak in Madagascar involving transmission of a Y. pestis strain resistant to streptomycin, the current recommended first-line treatment in Madagascar, was retrospectively characterized using epidemiology, clinical diagnostics, molecular characterization, and animal studies. The outbreak occurred in February 2013 in the Faratsiho district of Madagascar and involved 22 cases, including three untreated fatalities. The 19 other cases participated in funeral practices for the fatal cases and fully recovered after combination antimicrobial therapy: intramuscular streptomycin followed by oral co-trimoxazole. The Y. pestis strain that circulated during this outbreak is resistant to streptomycin resulting from a spontaneous point mutation in the 30S ribosomal protein S12 (rpsL) gene. This same mutation causes streptomycin resistance in two unrelated Y. pestis strains, one isolated from a fatal PP case in a different region of Madagascar in 1987 and another isolated from a fatal PP case in China in 1996, documenting this mutation has occurred independently at least three times in Y. pestis. Laboratory experiments revealed this mutation has no detectable impact on fitness or virulence, and revertants to wild-type are rare in other species containing it, suggesting Y. pestis strains containing it could persist in the environment. Unique AMR strains of Y. pestis continue to arise in Madagascar and can be transmitted during PP outbreaks.
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