Publications by authors named "Myron M Levine"

Poor water, sanitation, and hygiene (WASH) are the primary risks of exposure to enteric viral infection. Our study aimed to describe the role of WASH conditions and practices as risk factors for enteric viral infections in children under 5. Literature on the risk factors associated with all-cause diarrhea masks the taxa-specific drivers of diarrhea from specific pathogens, limiting the application of relevant control strategies.

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  • The study investigates the role of circulating T follicular helper cells (cT) in the immune response to Typhi infection, using data from a controlled human infection model.
  • Participants who did not develop typhoid disease (NoTD) showed higher frequencies of specific cT subsets (cT2 and cT17) compared to those who developed the disease (TD), particularly a week post-challenge.
  • The findings suggest that these cT subsets are associated with the production of anti-Typhi antibodies and could be crucial for developing effective vaccines against typhoid disease.
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  • A Controlled Human Infection Model (CHIM) with wild-type Salmonella Typhi was set up to study immunity development, revealing that about 55% of volunteers met typhoid diagnosis criteria after infection.
  • Intestinal macrophages, which play a crucial role in gut defense, are derived from circulating monocytes rather than tissue-resident progenitors, making them unique compared to macrophages in other organs.
  • Changes in circulating monocytes were tracked post-infection, showing that typhoid diagnosis participants had increased activation markers, indicating a heightened immune response, and upregulated molecules to interact with both bacterial antigens and adaptive immune cells.
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  • Enteric viruses are the main cause of diarrhea in children under 5, with rotavirus being a well-researched culprit in Mozambique, though other viruses lack data post-vaccine.
  • The study investigated the prevalence of norovirus GI and GII, adenovirus 40/41, astrovirus, and sapovirus in children with varying severity of diarrhea before and after the introduction of the rotavirus vaccine.
  • Results showed that all viruses, except norovirus GI, were detected more frequently after the vaccine's introduction, highlighting the importance of ongoing monitoring for these viruses to improve disease prevention strategies.
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Enteric viral pathogens are associated with a significant burden of childhood morbidity and mortality. We investigated the relationship between viral pathogens and child growth among under-5 children. We analyzed data from 5572/22,567 children enrolled in the Global Enteric Multicenter Study across seven study sites (2007-2011).

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Background: Quantitative molecular assays are increasingly used for detection of enteric viruses.

Methods: We compared the clinical severity using the modified Vesikari score (mVS) of enteric viruses detected by conventional assays (enzyme immunoassays [EIAs] for rotavirus and adenovirus 40/41 and conventional polymerase chain reaction for astrovirus, sapovirus, and norovirus) and a quantitative molecular assay (TaqMan Array Card [TAC]) among children aged 0-59 months in the Global Enteric Multicenter Study. For rotavirus and adenovirus 40/41, we compared severity between EIA-positive and TAC-positive cases assigned etiologies using different cycle threshold (Ct) cutoffs.

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serovar Typhi (. Typhi), a human-restricted pathogen, invades the host through the gut to cause typhoid fever. Recent calculations of the typhoid fever burden estimated that more than 10 million new typhoid fever cases occur in low and middle-income countries, resulting in 65,400-187,700 deaths yearly.

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  • Some types of bacteria can make people sick, causing problems like diarrhea and stomach issues.
  • Scientists studied 447 samples from kids in Karachi, Pakistan, to learn more about these bacteria and why some people get really sick while others don't.
  • They found lots of different kinds of bacteria and noticed some specific genes might help the bacteria be more powerful or resistant to medicines.
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  • Operation Warp Speed was a U.S. initiative aimed at speeding up the development of Covid-19 vaccines through collaboration and funding.
  • The National Institutes of Health managed a data and safety monitoring board that was responsible for overseeing the trials associated with Operation Warp Speed.
  • The article highlights the difficulties encountered in monitoring these vaccine trials and suggests strategies for improving similar efforts in the future.
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Background: In Santiago, Chile, where typhoid had been hyperendemic (1977-1991), we investigated whether residual chronic carriers could be detected among household contacts of non-travel-related typhoid cases occurring during 2017-2019.

Methods: Culture-confirmed cases were classified as autochthonous (domestically acquired) versus travel/immigration related. Household contacts of cases had stool cultures and serum Vi antibody measurements to detect chronic Salmonella Typhi carriers.

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Background: Entamoeba histolytica, Giardia, and Cryptosporidium are common intestinal protozoan parasites that contribute to a high burden of childhood morbidity and mortality. Our study quantified the association between intestinal protozoan parasites and child anthropometric outcomes among children under-5.

Methods: We analyzed data from 7,800 children enrolled in the Global Enteric Multicenter Study (GEMS) across seven study sites that were positive for intestinal protozoan parasites between December 2007 and March 2011.

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Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000).

Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch.

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Typhoid fever caused by infection with Salmonella enterica subspecies enterica serotype Typhi (S. Typhi), an important public health problem in many low- and middle-income countries, is transmitted by ingestion of water or food contaminated by feces or urine from individuals with acute or chronic S. Typhi infection.

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Background: Vibriocidal antibodies are currently the best characterised correlate of protection against cholera and are used to gauge immunogenicity in vaccine trials. Although other circulating antibody responses have been associated with a decreased risk of infection, the correlates of protection against cholera have not been comprehensively compared. We aimed to analyse antibody-mediated correlates of protection from both V cholerae infection and cholera-related diarrhoea.

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Salmonella enterica serovar Typhi (S. Typhi) is either widely distributed or proximally transmitted via fecally-contaminated food or water to cause typhoid fever. In Samoa, where endemic typhoid fever has persisted over decades despite water quality and sanitation improvements, the local patterns of S.

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For decades, the remote island nation of Samoa (population ~200,000) has faced endemic typhoid fever despite improvements in water quality, sanitation, and economic development. We recently described the epidemiology of typhoid fever in Samoa from 2008 to 2019 by person, place, and time; however, the local Salmonella enterica serovar Typhi (S. Typhi) population structure, evolutionary origins, and genomic features remained unknown.

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We have previously demonstrated that Mucosal-Associated Invariant T (MAIT) cells secrete multiple cytokines after exposure to Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever in humans. However, whether cytokine secreting MAIT cells can enhance or attenuate the clinical severity of bacterial infections remain debatable.

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  • Typhoid fever in Santiago, Chile saw a drastic reduction in cases from 128-220 per 100,000 people in the 1980s to less than 8 per 100,000 from the 1990s onwards due to targeted public health interventions.
  • Whole genome sequencing was used to compare the S. Typhi bacteria from the hyperendemic period of the 1980s to that of the nonendemic 2010s, revealing that the genotypes causing illness remained largely unchanged.
  • The persistence of certain historical genotypes suggests that chronic carriers from the 1980s may be responsible for the reoccurrence of the same strains, demonstrating a link between past and present typhoid cases
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  • Typhoid fever is primarily spread through contaminated water from carriers of Salmonella Typhi, but improved sanitation has shifted focus to chronic carriers, particularly gallbladder carriers.
  • This study developed a real-time PCR method for detecting S. Typhi in bile from patients undergoing gallbladder surgery, showing better sensitivity than traditional culture methods, especially in the presence of certain antibiotics.
  • The new detection method is important for identifying chronic carriers and can help in controlling the spread of typhoid fever as new vaccines are rolled out in endemic areas.
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Objectives: To examine the association between seroprevalence and serum pepsinogens (PGs) as markers of gastric inflammation), with high neutralizing antibody titers to poliovirus type 1 and 3 vaccine strains among children age 3-4 years, subsequent to sub-clinical infection acquired during a wild-type poliovirus type 1 outbreak in Israel.

Methods: A serosurvey was conducted among 336 children aged 5-17 years who were vaccinated with both inactivated polio vaccine and oral polio vaccines. serum IgG antibodies and PG concentrations were measured using ELISA.

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Measles is endemic in Africa; measles mortality is highest among infants. Infant measles antibody titer at birth is related to maternal immune status. Older mothers are likelier to have had measles infection, which provides higher antibody titers than vaccine-induced immunity.

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Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen-specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined.

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Approximately 90% of chronic typhoid carriers with persistent Salmonella enterica serovar Typhi (S. Typhi) gallbladder infection have gallstones. In Samoa, where typhoid fever has been endemic for many decades, risk factors predisposing to the development of gallstones are increasing among adults.

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Background: Serum IgG anti-Vi titers attained by 327 children 6-23 months of age immunized with Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar TCV®), of whom 193/327 received a booster dose 2 years post-primary vaccination, were previously reported.

Methods: Anti-Vi IgG in boosted and unboosted children 3, 5, and 7 years post-primary immunization were monitored using three different enzyme-linked immunosorbent assays (ELISAs): Vacczyme™ kit ELISA (all specimens); "Szu" ELISA (all specimens), and National Institute of Biological Standards NIBSC ELISA (subset). Endpoints analyzed included: persisting seroconversion (titer remaining ≥ 4-fold above baseline), geometric mean titer (GMT), geometric mean-fold rise post-vaccination, and percent exhibiting putative protective anti-Vi level (≥2 µg/ml) using Szu method and National Institutes of Health IgG reference standard.

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