Recent Cholera Publications on PubMed

Antimicrobial Resistance in endemic enteric infections in Kenya and the region, and efforts towards addressing the challenges

September 22, 2021

J Infect Dis. 2021 Sep 22:jiab457. doi: 10.1093/infdis/jiab457. Online ahead of print.


Resistance to commonly available antimicrobials is a major threat to the fight against endemic bacterial diseases in sub-Saharan Africa (SSA), with majority of the population unable to afford alternative effective antimicrobial options for management of these diseases. Diseases such as typhoid, cholera and invasive non-typhoidal salmonella (NTS) are among the key enteric infections endemic in most parts of SSA, especially in displaced populations and among the urban populations living in overcrowded informal settlements. Here, we explore the prevalence and the genomic epidemiology of these infections and the growing problem of multidrug resistance (MDR) including emerging resistance to the last line of treatment for these infections. Prevalence rates to commonly available antimicrobials including ampicillin, chloramphenicol, co-trimoxazole and tetracycline, now range between 65-80%, while 15-20% of recently studied isolates show reduced susceptibility to fluoroquinolones and emerging resistance to extended spectrum beta-lactams (ESBLs) mediated by the CTX-M-15 gene carried on a highly mobile genetic element. The high prevalence of MDR isolates including resistance to reserve antibiotics, calls for enhanced control and management options. It will be important for governments in the region to enhance the implementation of National Action Plans as guided by the Global Action Plan championed by the World Health Organisation (WHO) to combat the threat of antimicrobial resistance. However, these efforts will require a strong commitment and enhanced at all different levels of healthcare in order to yield meaningful results. In addition, utilization of WHO approved vaccines in the short-to-medium term and improvement of water and sanitation in the long term will reduce burden of disease and AMR in the region.

PMID:34550365 | DOI:10.1093/infdis/jiab457

Contrasting Epidemiology of Cholera in Bangladesh and Africa

September 22, 2021

J Infect Dis. 2021 Sep 22:jiab440. doi: 10.1093/infdis/jiab440. Online ahead of print.


Studies of the epidemiology of cholera in the Ganges Delta led to understanding cholera's transmission patterns, risk groups, seasonality, and the relationship of cholera with the environment. In Bangladesh and West Bengal cholera is seasonal, transmission occurs consistently every year with only brief periods without cases. By contrast, in most African countries, cholera transmission inconsistent seasonal patterns, and long periods without obvious transmission. Additional differences are observed when molecular methods are used to identify genetic lineages. Transmission patterns of cholera in Africa appear result from intermittent outbreaks followed by elimination of that genetic lineage. Later another outbreak may occur because of reintroduction of new or evolved lineages from adjacent areas, often by human travelers. These then subsequently undergo subsequent elimination. The concept of frequent elimination and reintroduction has several implications when planning for cholera's elimination. These include a) reconsidering concepts regarding the definition of elimination, b) need to enhance methods for rapid detection and response to an outbreak, c) strategies for more effective use of oral cholera vaccine and water-sanitation-hygiene interventions, d) a need to readjust estimates of the disease burden for Africa upon which cost benefit estimates are based, e) re-examination of the role of water as a reservoir for maintaining endemicity of cholera in Africa. This paper will review some of the major features of cholera's epidemiology in most endemic African countries which appear to differ from patterns in the Ganges Delta.

PMID:34549788 | DOI:10.1093/infdis/jiab440

Scoping Review on the Impact of Outbreaks on Sexual and Reproductive Health Services: Proposed Frameworks for Pre-, Intra-, and Postoutbreak Situations

September 20, 2021

Biomed Res Int. 2021 Sep 8;2021:9989478. doi: 10.1155/2021/9989478. eCollection 2021.


INTRODUCTION: Recent experiences from global outbreaks have highlighted the severe disruptions in sexual and reproductive health services that expose women and girls to preventable health risks. Yet, to date, there is no review studying the possible impact of outbreaks on sexual and reproductive health (SRH). Methodology. Studies reporting outbreaks impacting sexual and reproductive health and pregnancy outcomes were identified using MEDLINE, Embase, and ISI-WoS. Reported impacts were reviewed at systems, community, and legislative levels.

RESULTS: The initial run listed 4423 studies; the 37 studies that met all inclusion criteria were mainly from Latin America and Africa. Studies on outbreaks of diseases like Zika and Ebola have documented declines in facility-based deliveries, contraceptive use, and antenatal and institutional care due to burdened healthcare system. Service usage was also impacted by a lack of trust in the healthcare system and system shocks, including workforce capacity and availability. At the community level, poverty and lack of awareness were critical contributors to poor access to SRH services. Assessing the target population's knowledge, attitude, beliefs, and behavior and using health literacy principles for communication were fundamental for designing service delivery. Online resources for SRH services were an acceptable medium of information among young adults. In outbreak situations, SRH and pregnancy outcomes were improved by implementing laboratory surveillance, free-of-cost contraceptive services, improved screening through professional training, and quality of care. In addition, mobile health clinics were reported to be effective in remote areas. Knowledge Contribution. In outbreaks, the interventions are categorized into preoutbreak, during, and postoutbreak periods. The proposed steps can help to improve and do course correction in emergencies. Though conducted before the COVID-19 crisis, the authors believe that lessons can be drawn from the paper to understand and mitigate the impact of the pandemic on sexual and reproductive health services.

PMID:34541003 | PMC:PMC8443356 | DOI:10.1155/2021/9989478

Characterization of Pasteurella multocida isolated from ducks in China from 2017 to 2019

September 17, 2021

Microb Pathog. 2021 Sep 14:105196. doi: 10.1016/j.micpath.2021.105196. Online ahead of print.


Pasteurella multocida, an important gram-negative pathogen that mainly inhibits the upper respiratory tracts of domestic and wild animals such as chicken, duck, cattle and pig, which can cause cholera fowl, haemorrhagic septicaemia and infectious pneumonia. Currently, the prevalence and infection of Pasteurella multocida is still one of the most serious threats to the poultry industry in China, but studies on its characteristics are still insufficient. Here, this study was conducted to isolate and identify Pasteurella multocida in infected ducks and determined the leading serotypes and epidemiology of the diseases this pathogen causes. Results indicated that all the isolates were positive for KMT1 gene and the PCR amplified products were approximately 460 bp, demonstrating that these strains were all Pasteurella multocida. Moreover, all the isolated strains were identified as capsular type A and lipopolysaccharide type L1. Virulence factor identification results revealed that all strains possessed genes related to pili, adhesin, iron metabolism and uptake. In contrast, toxin coding gene (toxA) and sialidase encodes genes (nan B and nan H) were not detected in any isolates. The drug susceptibility results indicated that all the isolates were resistant to Lincomycin, Chloramphenicol, Clindamycin and Oxacillin but were sensitive to Ceftriaxone and Cefalotin. The animal experiments were also performed to further determine the pathogenicity of these isolated strains. Animal experiment revealed that the liver, kidney, and heart of infected ducks were swollen and had bleeding spots. We also observed hepatocyte hypertrophy, hepatic sinus congestion and single-cell infiltration in infected ducks through H&E staining. In summary, this study demonstrated that all the isolated strains belong to capsular A and lipopolysaccharide type L1 Pasteurella multocida, but their virulence factors, drug resistance and pathogenicity were different.

PMID:34534643 | DOI:10.1016/j.micpath.2021.105196

Association of enteropathogen detection with diarrhoea by age and high versus low child mortality settings: a systematic review and meta-analysis

September 17, 2021

Lancet Glob Health. 2021 Oct;9(10):e1402-e1410. doi: 10.1016/S2214-109X(21)00316-8.


BACKGROUND: The odds ratio (OR) comparing pathogen presence in diarrhoeal cases versus asymptomatic controls is a measure for diarrhoeal disease cause that has been integrated into burden of disease estimates across diverse populations. This study aimed to estimate the OR describing the association between pathogen detection in stool and diarrhoea for 15 common enteropathogens by age group and child mortality setting.

METHODS: We did a systematic review to identify case-control and cohort studies published from Jan 1, 1990, to July 9, 2019, which examined at least one enteropathogen of interest and the outcome diarrhoea. The analytical dataset included data extracted from published articles and supplemented with data from the Global Enteric Multicenter Study and the Malnutrition and Enteric Disease study. Random effects meta-analysis models were fit for each enteropathogen, stratified by age group and child mortality level, and adjusted for pathogen detection method and study design to produce summary ORs describing the association between pathogen detection in stool and diarrhoea.

FINDINGS: 1964 records were screened and 130 studies (over 88 079 cases or diarrhoea samples and 135 755 controls or non-diarrhoea samples) were available for analysis. Heterogeneity (I2) in unadjusted models was substantial, ranging from 27·6% to 86·6% across pathogens. In stratified and adjusted models, summary ORs varied by age group and setting, ranging from 0·4 (95% CI 0·2-0·6) for Giardia lamblia to 54·1 (95% CI 7·4-393·5) for Vibrio cholerae.

INTERPRETATION: Incorporating effect estimates from diverse data sources into diarrhoeal disease cause and burden of disease models is needed to produce more representative estimates.

FUNDING: WHO, Bill & Melinda Gates Foundation, and National Institutes of Health.

PMID:34534487 | DOI:10.1016/S2214-109X(21)00316-8

Acute watery diarrhea surveillance during the Rohingya Crisis 2017-2019 in Cox's Bazar, Bangladesh

September 16, 2021

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.

PMID:34528689 | DOI:10.1093/infdis/jiab453

Pathogens associated with linear growth faltering in children with diarrhea and impact of antibiotic treatment: The Global Enteric Multicenter Study

September 16, 2021

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.

PMID:34528677 | DOI:10.1093/infdis/jiab434

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

September 13, 2021

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.

PMID:34516647 | DOI:10.7589/JWD-D-20-00213

Socio- demographic correlates of HIV sero-discordance among couples in West Bengal, India; A cross sectional analysis

September 2, 2021

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.

PMID:34470966 | DOI:10.7883/yoken.JJID.2021.330

Clinical cholera surveillance sensitivity in Bangladesh and implications for large-scale disease control

August 28, 2021

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.

PMID:34453539 | DOI:10.1093/infdis/jiab418

Multilevel Genome Typing Describes Short- and Long-Term Vibrio cholerae Molecular Epidemiology

August 24, 2021

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 ( 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.

PMID:34427512 | DOI:10.1128/mSystems.00134-21

Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine

August 23, 2021

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.

PMID:34424915 | DOI:10.1371/journal.pone.0256143

Non-O1/non-O139 vibrios - occurrence not only in Europe in recent years

August 20, 2021

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

August 16, 2021

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.

PMID:34398813 | DOI:10.4269/ajtmh.21-0414

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

August 13, 2021

Lancet Infect Dis. 2021 Aug 9:S1473-3099(21)00050-5. doi: 10.1016/S1473-3099(21)00050-5. Online ahead of print.


BACKGROUND: Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin-gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis.

METHODS: In BARNARDS, consenting mother-neonates aged 0-60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic-pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability.

FINDINGS: Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin-gentamicin, ceftazidime-amikacin, piperacillin-tazobactam-amikacin, and amoxicillin clavulanate-amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime-amikacin than for neonates treated with ampicillin-gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14-0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin-gentamicin; 286 (73·3%) to amoxicillin clavulanate-amikacin; 301 (77·2%) to ceftazidime-amikacin; and 312 (80·0%) to piperacillin-tazobactam-amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin-gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate-amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime-amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin-tazobactam-amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis.

INTERPRETATION: Our data raise questions about the empirical use of combined ampicillin-gentamicin for neonatal sepsis in LMICs because of its high resistance and high rates of frequency of resistance and low probability of target attainment. Accessibility and affordability need to be considered when advocating antibiotic treatments with variance in economic health structures across LMICs.

FUNDING: The Bill & Melinda Gates Foundation.

PMID:34384533 | DOI:10.1016/S1473-3099(21)00050-5

Genetic characterization and evolutionary analysis of norovirus genotypes circulating among children in eastern India during 2018-2019

August 12, 2021

Arch Virol. 2021 Aug 12. doi: 10.1007/s00705-021-05197-6. Online ahead of print.


Noroviruses are significant etiological agents of acute gastroenteritis (AGE) across all age groups, especially in children under 5 years of age. Although the prevalence of norovirus infection is known to have increased in various countries, in India there are few reports pertaining to the norovirus disease burden. We investigated the epidemiology and molecular characteristics of noroviruses in children seeking health care at two hospitals in Kolkata, Eastern India. Faecal specimens were collected between January 2018 and December 2019 from 2812 children under 5 years of age with acute gastroenteritis. Noroviruses were detected in 6.04% (170/2812) of the samples, and 12.9% (22/170) of these were cases of coinfection with rotavirus. Among children (≤5 years), a higher infection rate (8.2%, n = 94/1152) was observed in the 6 to 12 month age group. GII.4 Sydney 2012 was the dominant norovirus capsid genotype (n = 75/90, 83.3%), followed by GII.3 (n = 10/90, 11.1%). Other capsid types GII.13 (n = 4/90, 4.4%) and GII.17 (n = 1/90; 1.1%) were also detected at low frequency. Phylogenetic analysis showed that the GII.P16 polymerase of strains in this region clustered with those of the phylogenetically distinct monophyletic clade of GII.P16 strains, whose members have been circulating worldwide since 2014. Inter-genotypic norovirus recombinants such as GII.P16-GII.3 (n = 10) and GII.P16-GII.13 (n = 4) were also observed among the circulating strains. In comparison to previous studies from eastern India, the present study shows a higher detection rate of norovirus infection in the paediatric population suffering from acute gastroenteritis. Continuous surveillance is required for predicting the emergence of novel genotypes and recombinant strains and for future vaccine development.

PMID:34383167 | DOI:10.1007/s00705-021-05197-6

Seroprevalence of Dengue Infection Using IgG Capture ELISA in India, 2017-2018

August 9, 2021

Am J Trop Med Hyg. 2021 Aug 9:tpmd210386. doi: 10.4269/ajtmh.21-0386. Online ahead of print.


We conducted a nationally representative population-based survey in 60 districts from 15 Indian states covering all five geographic regions during 2017-2018 to estimate the age specific seroprevalence of dengue. Of the 12,300 sera collected, 4,955 were positive for IgG antibodies against dengue virus using IgG Indirect ELISA indicating past dengue infection. We tested 4,948 sera (seven had inadequate volume) positive for IgG antibodies on indirect ELISA using anti-dengue IgG capture ELISA to estimate the proportion of dengue infections with high antibody titers, suggestive of acute or recent secondary infection. Of the 4,948 sera tested, 529 (10.7%; 95% CI: 9.4-12.1) were seropositive on IgG capture ELISA. The proportions of dengue infections with high titers were 1.1% in the northeastern, 1.5% in the eastern, 6.2% in the western, 12.2% in the southern, and 16.7% in the northern region. The distribution of dengue infections varied across geographic regions, with a higher proportion of infections with high antibody titer in the northern and southern regions of India. The study findings could be useful for planning facilities for clinical management of dengue infections.

PMID:34370710 | DOI:10.4269/ajtmh.21-0386

Microbiological survey and occurrence of bacterial foodborne pathogens in raw and ready-to-eat green leafy vegetables marketed in Tehran, Iran

August 8, 2021

Int J Hyg Environ Health. 2021 Aug 5;237:113824. doi: 10.1016/j.ijheh.2021.113824. Online ahead of print.


Fresh leafy (FL) and ready-to-eat (RTE) vegetables are recognized as an important source of foodborne disease outbreaks worldwide. Currently, there are no data available for the prevalnce of bacterial foodborne pathogens (FBPs) in raw vegetables consumed in Iran. Here, we evalated the presence of common bacterial FBPs among 366 samples of raw vegetables including 274 FL and 92 RTE collected from 21 districts of Tehran. The presence of FBPs were screened using conventional microbiological culture methods and real-time PCR assays. Overall, a higher rate of bacterial contamination was detected in FL compared to RTE samples using both detection methods. The results obtained by microbiological methods showed that Staphylococcus aureus (134/366, 36.6%), followed by Escherichia coli (85/366, 23.2%) and Clostridium perfringens (66/366, 18%) were detetcted as the most prevalent pathogens in this study. Vibrio cholerae was not detected in any of the samples either by microbiological methods or by the real-time PCR assays. There was a noticeable reduction in the proportion of Campylobacter positive samples using conventional microbiological methods (3.5%) compared to the real-time PCR assay (20.7%). The proportion of FL and RTE positive samples obtained by conventional microbiological methods was significantly different (P < 0.05) for C. perfringens, Campylobacter spp. and S. aureus. The proportion of positive samples in FL and RTE vegetables obtained by the real-time PCR assays was significantly different (P < 0.05) for C. perfringens, S. aureus, Helicobacter pylori and STEC/EHEC, the last one was found more frequently in RTE than in FL samples. Our findings indicated a contamination of FL and RTE vegetables in Iran with a range of well-known and emerging FBPs. Positivity and the distribution of bacterial species from the current data indicated different contamination sources, and overall a lack of effective decontamination steps during the production chain. Moreover, further information about the quality of the water, the hygiene measures implemented during the processing, storage and marketing are required to better identify the critical points and define the proper measures.

PMID:34365294 | DOI:10.1016/j.ijheh.2021.113824

A fructose/H(+) symporter controlled by a LacI-type regulator promotes survival of pandemic Vibrio cholerae in seawater

July 31, 2021

Nat Commun. 2021 Jul 30;12(1):4649. doi: 10.1038/s41467-021-24971-3.


The bacterium Vibrio cholerae can colonize the human intestine and cause cholera, but spends much of its life cycle in seawater. The pathogen must adapt to substantial environmental changes when moving between seawater and the human intestine, including different availability of carbon sources such as fructose. Here, we use in vitro experiments as well as mouse intestinal colonization assays to study the mechanisms used by pandemic V. cholerae to adapt to these environmental changes. We show that a LacI-type regulator (FruI) and a fructose/H+ symporter (FruT) are important for fructose uptake at low fructose concentrations, as those found in seawater. FruT is downregulated by FruI, which is upregulated when O2 concentrations are low (as in the intestine) by ArcAB, a two-component system known to respond to changes in oxygen levels. As a result, the bacteria predominantly use FruT for fructose uptake under seawater conditions (low fructose, high O2), and use a known fructose phosphotransferase system (PTS, Fpr) for fructose uptake under conditions found in the intestine. PTS activity leads to reduced levels of intracellular cAMP, which in turn upregulate virulence genes. Our results indicate that the FruT/FruI system may be important for survival of pandemic V. cholerae in seawater.

PMID:34330925 | DOI:10.1038/s41467-021-24971-3

Conflict and COVID-19 in Yemen: beyond the humanitarian crisis

July 23, 2021

Global Health. 2021 Jul 22;17(1):83. doi: 10.1186/s12992-021-00732-1.


BACKGROUND: Yemen has been left in shambles and almost destroyed by its devastating civil war, and is now having to deal with the spread of coronavirus. The Yemeni people have been are left to fend for themselves and faced many problems such as hunger, the ongoing war, infections, diseases and lack of equipment even before the COVID-19 pandemic. All together it is a humanitarian crisis. Only around 50% of the hospitals and healthcare facilities are in full working condition, and even those that are functioning are operating at nowhere near full potential. Healthcare staff and facilities lack necessary essential equipment and money.

CONCLUSION: As, sadly, is common in conflict-affected regions, the violence has brought with it a secondary disaster of infectious disease outbreaks. Yemen is not only battling COVID-19 amid a catastrophic war, but also has to deal with other diseases such as cholera, diphtheria and measles. A number of key measures are needed to support the current efforts against this deadly epidemic and its potential subsequent waves as well as to prevent further epidemics in Yemen.

PMID:34294097 | PMC:PMC8295627 | DOI:10.1186/s12992-021-00732-1