J Infect Dis. 2021 Sep 16:jiab453. doi: 10.1093/infdis/jiab453. Online ahead of print.
INTRODUCTION: Forcibly Displaced Myanmar Nationals fled into Cox's Bazar, Bangladesh due to internal conflict. Considering the public health situation, a surveillance network was established to identify the enteric pathogens and early detection of cholera epidemics. Purpose of this manuscript is to report the clinical, epidemiological determinants of cholera and other enteric pathogens among hospitalized diarrhoeal patients from FDMNs and host community.
METHODOLOGY: A total of 11 sentinel surveillance sites were established around the camps in Ukhia and Teknaf Upazila, Cox's Bazar. Rapid diagnostic testing was conducted for immediate detection of cholera cases. Stool samples were transferred to the icddr,b laboratory for culture.
RESULT: A total of 8134 participants with diarrhea were enrolled from 2017- 2019: 4881 were FDMNs and 3253 from the Bangladeshi host community. Among the FDMNs, the proportion of V. cholerae 0.7%, ETEC 4.9% and Shigella 1.5%. The distributions from host community were 1.2% V. cholerae, 1.8% ETEC and 1.1% Shigella. Similar risk factors have been identified for the diarrhoeal pathogens for both communities.
CONCLUSION: This surveillance helped to monitor the situation of diarrheal diseases including cholera in refugee camps as well as in the neighboring host community. These findings lead policy makers to take immediate preventive measures.
Pathogens associated with linear growth faltering in children with diarrhea and impact of antibiotic treatment: The Global Enteric Multicenter Study
J Infect Dis. 2021 Sep 16:jiab434. doi: 10.1093/infdis/jiab434. Online ahead of print.
BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well-described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment.
METHODS: The Global Enteric Multicenter Study (GEMS) enrolled children seeking healthcare with moderate-to-severe diarrhea (MSD) at seven sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, ~60 days later, to calculate change in length/height for age Z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested by linear mixed effects regression models.
RESULTS: Among 8,077 MSD cases analyzed, the proportion with stunting (HAZ<-1) increased from 59% at enrollment to 65% at follow-up (p<.0001). Pathogens significantly associated with linear growth decline were Cryptosporidium (p<0.001), typical enteropathogenic Escherichia coli (p=0.013), and untreated Shigella (p=0.009) among infants (0-11 months), and enterotoxigenic E. coli encoding heat stable toxin (p<0.001) and Cryptosporidium (p=0.03) among toddlers (12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (p=0.02).
CONCLUSION: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella.
Ned Tijdschr Geneeskd. 2021 Aug 19;165:D5962.
Between 1554 and 2021, the number of and mortality from epidemics in Amsterdam decreased sharply. The decrease in epidemic outbreaks, such as those of plague, smallpox and cholera, paralleled the decrease in chronic mortality from endemic ailments and diseases, such as tuberculosis, malaria and dysentery. There are several theories about the reason for these declines, which are not necessarily mutually exclusive: better nutrition, greater prosperity, increasing altruism, and a growing understanding of cause and effect with targeted medical and public health measures. In the powder keg of chronic poverty and poor public health, a social crisis, such as war, migration, and natural disaster, usually was the spark that led to epidemic outbreaks. The nature and extent of poverty and ill health have changed and improved over the centuries, but the threat of man-made crises is unfortunately unabated.
Revenge of the Trees: Environmental Determinants and Population Effects of Infectious Disease Outbreaks On A Breeding Colony of Double-Crested Cormorants (Phalacrocorax auritus) Over A Period of 21 Years
J Wildl Dis. 2021 Sep 13. doi: 10.7589/JWD-D-20-00213. Online ahead of print.
During 16 of 21 consecutive annual breeding seasons, two diseases, Newcastle disease and avian cholera, killed approximately 50% of juvenile Double-crested Cormorants (Phalacrocorax auritus) in a large nesting colony in Canada. From 1994 to 2014, we recorded data annually on disease occurrence, causal pathogens, species and age classes affected, total number of breeding pairs of cormorants on the colony site, and other biological parameters. A mathematical model of pathogen transmission was constructed to assess the potential importance of transmission parameters and to test a hypothesis regarding the potential effect of the observed progressive loss of nest trees and the consequent shift from tree-nesting to ground-nesting behavior. The model indicated that juveniles from ground nests were 14 times more likely to die from epidemic disease (50.14% mortality) than were juveniles from nests in trees (3.57% mortality). Additive disease-related mortality of juvenile cormorants in the observed range of 40-60% would reduce a closed cormorant population over time. There was no directional change in the colony population during the study period, suggesting that immigration had compensated for disease-related mortality. Our results highlight the preeminent influence of environmental factors on pathogen transmission and the value of long-term data sets.
Socio- demographic correlates of HIV sero-discordance among couples in West Bengal, India; A cross sectional analysis
Jpn J Infect Dis. 2021 Aug 31. doi: 10.7883/yoken.JJID.2021.330. Online ahead of print.
Serodiscordant couples serves as potential source of Human Immunodeficiency Virus (HIV) transmission. Understanding demographic dynamics of serodiscordant couples plays an important role in tailoring interventions towards eliminating HIV. We conducted this cross sectional analysis in 314 Integrated Counseling and Testing Centres (ICTCs) in West Bengal, India during April 2016 to March 2020. General individuals who were detected as HIV reactive and whose spouses were also tested for HIV comprised the study population (8740 couples). Sociodemographic variables were compared across concordant and discordant arms and also between male positive (M+ F-) and female positive (F+ M-) subgroups of serodiscordant. Among the couples studied, 35.2% (95% CI: 34.2- 36.2 %) were serodiscordant. Among serodiscordant couples, the proportion of M+ F- (86.1%) was significantly higher than F+ M- (13.9%). We observed higher mean ages of couples, higher education, business & service occupations and urban residence as significantly associated with serodiscordance relationship (p < 0.05). Higher mean age of couple and lower proportion of housewives were associated with F+M- subgroup. As around 35% serodiscordant couples carry the risk of transmission to negative spouses particularly in higher age and urban residence, thus reorientation of HIV programme may be required accordingly to avert transmission in future.
Re-evaluation of population-level protection conferred by a rotavirus vaccine using the 'fried-egg' approach in a rural setting in Bangladesh
Vaccine. 2021 Sep 24;39(40):5876-5882. doi: 10.1016/j.vaccine.2021.08.048. Epub 2021 Aug 26.
BACKGROUND: Vaccine herd protection assessed in a cluster-randomized trial (CRT) may be masked by disease transmission into the cluster from outside. However, herd effects can be unmasked using a 'fried-egg' approach whereby the analysis, restricted to the innermost households of clusters, 'yolk', creates an insulating 'egg-white' periphery. This approach has been demonstrated to unmask vaccine herd protection in reanalyses of cholera and typhoid vaccine CRTs. We applied this approach to an earlier CRT in Bangladesh of rotavirus vaccine (RV) whose overall analysis had failed to detect herd protection. Herein we present the results of this analysis.
METHODS: In the study area, infants in 142 villages were randomized to receive two doses of RV with routine EPI vaccines (RV villages) or only EPI vaccines (non-RV villages). We analyzed RV protection against acute rotavirus diarrhoea for the entire cluster (P100) and P75, P50, P25 clusters, representing 75%, 50% and 25% of the innermost households for each cluster, respectively.
RESULTS: During 2 years of follow-up, there was evidence of 27% overall (95 %CI: 7, 43) and 42% total protection (95 %CI: 23, 56) in the P100 cluster, but it did not increase when moved in smaller yolks. There was no evidence of indirect vaccine protection in the yolks at any cluster size.
CONCLUSION: Our reanalysis of the CRT using the fried- egg approach did not detect RV herd protection. Whether these findings reflect a true inability of the RV to confer herd protection in this setting, or are due to limitations of the approach, requires further study.
Clinical cholera surveillance sensitivity in Bangladesh and implications for large-scale disease control
J Infect Dis. 2021 Aug 28:jiab418. doi: 10.1093/infdis/jiab418. Online ahead of print.
INTRODUCTION: A surveillance system that is sensitive to detecting high burden areas is critical for achieving widespread disease control. In 2014, Bangladesh established a nationwide, facility-based cholera surveillance system for Vibrio cholerae infection. We sought to measure the sensitivity of this surveillance system to detect cases to assess whether cholera elimination targets outlined by the Bangladesh national control plan can be adequately measured.
METHODS: We overlaid maps of nationally-representative annual V. cholerae seroincidence onto maps of the catchment areas of facilities where confirmatory laboratory testing for cholera was conducted, and identified its spatial complement as surveillance greyspots, areas where cases likely occur but go undetected. We assessed surveillance system sensitivity and changes to sensitivity given alternate surveillance site selection strategies.
RESULTS: We estimated that 69% of Bangladeshis (111.7 million individuals) live in surveillance greyspots, and that 23% (25.5 million) of these individuals live in areas with the highest V. cholerae infection rates.
CONCLUSIONS: The cholera surveillance system in Bangladesh has the ability to monitor progress towards cholera elimination goals among 31% of the country's population, which may be insufficient for accurately measuring progress. Increasing surveillance coverage, particularly in the highest risk areas, should be considered.
Serotype and genotype diversity of dengue viruses circulating in India: a multi-centre retrospective study involving the Virus Research Diagnostic Laboratory Network in 2018
Int J Infect Dis. 2021 Oct;111:242-252. doi: 10.1016/j.ijid.2021.08.045. Epub 2021 Aug 21.
OBJECTIVES: A retrospective study was undertaken to investigate the circulating dengue virus (DENV) serotypes and genotypes in India in 2018.
METHODS: In total, 4963 samples referred to virus research diagnostic laboratories (n=21), the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV) and ICMR-NIV field units (n=2) for diagnosis of dengue in 2018 were tested using a real-time reverse transcription polymerase chain reaction assay for the presence of DENV serotypes. Representative samples were sequenced for the envelope (E) gene.
RESULTS: Regional diversity was observed with regard to the dominant circulating serotypes. DENV-2 was found to be the most common serotype in many states. Thrombocytopenia, petechiae and malaise were associated with DENV-2 infection. Phylogenetic analyses of DENV E gene sequences revealed the circulation of genotypes I and V of DENV-1, two lineages of DENV-2 genotype IV, DENV-3 genotype III and DENV-4 genotype I.
CONCLUSIONS: This study found regional differences in the prevalence of circulating DENV serotypes in India, and provides baseline data for continuous molecular surveillance. Molecular surveillance may have implications for predicting large-scale outbreaks of dengue if regional shifts in the predominantly circulating serotypes and genotypes are detected during the early phase of the dengue season.
mSystems. 2021 Aug 24:e0013421. doi: 10.1128/mSystems.00134-21. Online ahead of print.
Since 1817, cholera, caused by Vibrio cholerae, has been characterized by seven distinct pandemics. The ongoing seventh pandemic (7P) began in 1961. In this study, we developed a Multilevel Genome Typing (MGT) tool for classifying the V. cholerae species with a focus on the 7P. MGT is based on multilocus sequence typing (MLST), but the concept has been expanded to include a series of MLST schemes that compare population structure from broad to fine resolutions. The V. cholerae MGT consists of eight levels, with the lowest, MGT1, composed of 7 loci and the highest, MGT8, consisting of the 7P core genome (3,759 loci). We used MGT to analyze 5,771 V. cholerae genomes. The genetic relationships revealed by lower MGT levels recapitulated previous findings of large-scale 7P transmission across the globe. Furthermore, the higher MGT levels provided an increased discriminatory power to differentiate subgroups within a national outbreak. Additionally, we demonstrated the usefulness of MGT for non-7P classification. In a large non-7P MGT1 type, MGT2 and MGT3 described continental and regional distributions, respectively. Finally, MGT described trends of 7P in virulence, and MGT2 to MGT3 sequence types (STs) grouped isolates of the same ctxB, tcpA, and ctxB-tcpA genotypes and characterized their trends over the pandemic. MGT offers a range of resolutions for typing V. cholerae. The MGT nomenclature is stable, transferable, and directly comparable between investigations. The MGT database (https://mgtdb.unsw.edu.au/) can accept and process newly submitted samples. MGT allows tracking of existing and new isolates and will be useful for understanding future spread of cholera. IMPORTANCE In 2017, the World Health Organization launched the "Ending Cholera" initiative to reduce cholera-related deaths by 90% by 2030. This strategy emphasized the importance of the speed and accessibility of newer technologies to contain outbreaks. Here, we present a new tool named Multilevel Genome Typing (MGT), which classifies isolates of the cholera-causing agent, Vibrio cholerae. MGT is a freely available online database that groups genetically similar V. cholerae isolates to quickly indicate the origins of outbreaks. We validated the MGT database retrospectively in an outbreak setting, showcasing rapid confirmation of the Nepalese origins for the 2010 Haiti outbreak. In the past 5 years, thousands of V. cholerae genomes have been submitted to the NCBI database, which underscores the importance of and need for proper genome data classification for cholera epidemiology. The V. cholerae MGT database can assist in early decision making that directly impacts controlling both the local and global spread of cholera.
Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine
PLoS One. 2021 Aug 23;16(8):e0256143. doi: 10.1371/journal.pone.0256143. eCollection 2021.
Gastrointestinal infectious diseases remain an important issue for human and animal health. Investigations on gastrointestinal infectious diseases are classically performed in laboratory animals leading to the problem that species-specific models are scarcely available, especially when it comes to farm animals. The 3R principles of Russel and Burch were achieved using intestinal organoids of porcine jejunum. These organoids seem to be a promising tool to generate species-specific in vitro models of intestinal epithelium. 3D Organoids were grown in an extracellular matrix and characterized by qPCR. Organoids were also seeded on permeable filter supports in order to generate 2D epithelial monolayers. The organoid-based 2D monolayers were characterized morphologically and were investigated regarding their potential to study physiological transport properties and pathophysiological processes. They showed a monolayer structure containing different cell types. Moreover, their functional activity was demonstrated by their increasing transepithelial electrical resistance over 18 days and by an active glucose transport and chloride secretion. Furthermore, the organoid-based 2D monolayers were also confronted with cholera toxin derived from Vibrio cholerae as a proof of concept. Incubation with cholera toxin led to an increase of short-circuit current indicating an enhanced epithelial chloride secretion, which is a typical characteristic of cholera infections. Taken this together, our model allows the investigation of physiological and pathophysiological mechanisms focusing on the small intestine of pigs. This is in line with the 3R principle and allows the reduction of classical animal experiments.
Epidemiol Mikrobiol Imunol. 2021 Summer;70(2):131-138.
Non-O1/non-O139 vibrios refer to all vibrios except toxin producing Vibrio cholerae serogroups O1 and O139. The prevalence of illness caused by non-O1/non-O139 vibrios steadily increases all over the world in the last 20 years, which is very probably related to global warming. These infections are reported year-round from tropical and subtropical climate zones, but they were also detected in the mild climate zone of the United States of America and Europe. In mild climate, they have markedly seasonal occurrence, typically peaking in May to October. A human can be infected after ingestion of contaminated food, especially seafood and fish, or water or while bathing. In Europe, non-O1/non-O139 vibrios were detected in the Baltic Sea, North Sea and Mediterranean Sea but also in ponds and rivers. Depending on the pathogen entry route, the clinical manifestation may appear as gastroenteritis, otitis, wound infection or severe up to fatal illness, predominantly in immunocompromised patients. There is no specific prevention. Non-specific prevention includes good personal and food handling hygiene practices and avoiding contact of unhealed wounds with sea or surface swimming water. Given the severity and increasing frequency of infections caused by non-O1/non-O139 vibrios, they should be considered in differential diagnosis of gastrointestinal and wound infections, especially in patients with a history of consumption of fish and seafood or with a history of contact of unhealed wounds with sea or other open swimming water.
Impact of Monovalent Rotavirus Vaccine on Rotavirus Hospitalizations among Children Younger Than 5 Years of Age in the Ouest and Artibonite Departments, Haiti, 2013 to 2019
Am J Trop Med Hyg. 2021 Aug 16:tpmd210414. doi: 10.4269/ajtmh.21-0414. Online ahead of print.
Rotavirus is responsible for 26% of diarrheal deaths in Latin America and the Caribbean. Haiti introduced the monovalent rotavirus vaccine in April 2014. The objective of this analysis is to describe the impact of the rotavirus vaccine on hospitalizations among Haitian children younger than 5 years old during the first 5 years after introduction. This analysis includes all children with diarrhea who were enrolled as part of a sentinel surveillance system at two hospitals from May 2013 to April 2019. We compare the proportion of rotavirus-positive specimens in each post-vaccine introduction year to the pre-vaccine period. To account for the potential dilution of the proportion of rotavirus-positive specimens from a waning cholera outbreak, we also analyzed annual trends in the absolute number of positive stools, fit a two-component finite-mixture model to the negative specimens, and fit a negative binomial time series model to the pre-vaccine rotavirus-positive specimens to predict the number of rotavirus diarrhea hospital admissions in the absence of rotavirus vaccination. The overall percentage of rotavirus-positive specimens declined by 22% the first year after introduction, increased by 17% the second year, and declined by 33% to 50% the subsequent 3 years. All sensitivity analyses confirmed an overall decline. We observed a clear annual rotavirus seasonality before and after vaccine introduction, with the greatest activity in December through April, and a biennial pattern, with high sharp peaks and flatter longer periods of increased rotavirus activity in alternating years, consistent with suboptimal vaccination coverage. Overall, our study shows evidence that the introduction of the rotavirus vaccine reduced the burden of severe rotavirus diarrhea.