Recent Cholera Publications on PubMed

Optimizing one-dose and two-dose cholera vaccine allocation in outbreak settings: A modeling study

April 20, 2022

PLoS Negl Trop Dis. 2022 Apr 20;16(4):e0010358. doi: 10.1371/journal.pntd.0010358. eCollection 2022 Apr.


BACKGROUND: A global stockpile of oral cholera vaccine (OCV) was established in 2013 for use in outbreak response and are licensed as two-dose regimens. Vaccine availability, however, remains limited. Previous studies have found that a single dose of OCV may provide substantial protection against cholera.

METHODS: Using a mathematical model with two age groups paired with optimization algorithms, we determine the optimal vaccination strategy with one and two doses of vaccine to minimize cumulative overall infections, symptomatic infections, and deaths. We explore counterfactual vaccination scenarios in three distinct settings: Maela, the largest refugee camp in Thailand, with high in- and out-migration; N'Djamena, Chad, a densely populated region; and Haiti, where departments are connected by rivers and roads.

RESULTS: Over the short term under limited vaccine supply, the optimal strategies for all objectives prioritize one dose to the older age group (over five years old), irrespective of setting and level of vaccination coverage. As more vaccine becomes available, it is optimal to administer a second dose for long-term protection. With enough vaccine to cover the whole population with one dose, the optimal strategies can avert up to 30% to 90% of deaths and 36% to 92% of symptomatic infections across the three settings over one year. The one-dose optimal strategies can avert 1.2 to 1.8 times as many cases and deaths compared to the standard two-dose strategy.

CONCLUSIONS: In an outbreak setting, speedy vaccination campaigns with a single dose of OCV is likely to avert more cases and deaths than a two-dose pro-rata campaign under a limited vaccine supply.

PMID:35442958 | PMC:PMC9060364 | DOI:10.1371/journal.pntd.0010358

Death in a farmer with underlying diseases carrying Vibrio cholerae non-O1/non-O139 producing zonula occludens toxin

April 16, 2022

Int J Infect Dis. 2022 Jul;120:83-87. doi: 10.1016/j.ijid.2022.04.020. Epub 2022 Apr 14.


OBJECTIVES: The non-O1/non-O139 Vibrio cholerae caused outbreaks or sporadic cases of gastroenteritis that was rarely seen in good sanitary condition. It was described a case of systemic multiple organ lesions that worsened because of non-O1/non-O139 V. cholerae, suggesting that serogroups have a potential virulence in enhancing pathogenicity with patients with underlying diseases compared with a healthy population.

DESIGN OR METHODS: Samples are identified by strain culture, polymerase chain reaction (PCR) virulence identification, and whole genome sequencing.

RESULTS: A middle-aged man was diagnosed with cytotoxin-producing and nontoxin V. cholerae non-O1/non-O139 serogroups. Although lacking the CT toxin encoded by ctxAB gene, the pathogenesis of cholera relies on the synergistic action of many other genes, especially virulence genes.

CONCLUSIONS: This case suggested that the laborers engaging in agricultural production are at potential risk of V. cholerae infection by exposure of open wounds to contaminated water . However, epidemiological investigation should focus on the objective cause of the change of working environment. Furthermore, common diseases can possibly enhance the virulence of non-O1/non-O139 serogroups by attacking the tight junction of small intestinal epithelial cells, further triggering bacteremia, a process that may lead to death within 48-72 hours, which requires great attention.

PMID:35429638 | DOI:10.1016/j.ijid.2022.04.020

Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study

April 15, 2022

Lancet Glob Health. 2022 May;10(5):e661-e672. doi: 10.1016/S2214-109X(22)00043-2.


BACKGROUND: Neonatal sepsis is a primary cause of neonatal mortality and is an urgent global health concern, especially within low-income and middle-income countries (LMICs), where 99% of global neonatal mortality occurs. The aims of this study were to determine the incidence and associations with neonatal sepsis and all-cause mortality in facility-born neonates in LMICs.

METHODS: The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited mothers and their neonates into a prospective observational cohort study across 12 clinical sites from Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Data for sepsis-associated factors in the four domains of health care, maternal, birth and neonatal, and living environment were collected for all mothers and neonates enrolled. Primary outcomes were clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality in neonates during the first 60 days of life. Incidence proportion of livebirths for clinically suspected sepsis and laboratory-confirmed sepsis and incidence rate per 1000 neonate-days for all-cause mortality were calculated. Modified Poisson regression was used to investigate factors associated with neonatal sepsis and parametric survival models for factors associated with all-cause mortality.

FINDINGS: Between Nov 12, 2015 and Feb 1, 2018, 29 483 mothers and 30 557 neonates were enrolled. The incidence of clinically suspected sepsis was 166·0 (95% CI 97·69-234·24) per 1000 livebirths, laboratory-confirmed sepsis was 46·9 (19·04-74·79) per 1000 livebirths, and all-cause mortality was 0·83 (0·37-2·00) per 1000 neonate-days. Maternal hypertension, previous maternal hospitalisation within 12 months, average or higher monthly household income, ward size (>11 beds), ward type (neonatal), living in a rural environment, preterm birth, perinatal asphyxia, and multiple births were associated with an increased risk of clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality. The majority (881 [72·5%] of 1215) of laboratory-confirmed sepsis cases occurred within the first 3 days of life.

INTERPRETATION: Findings from this study highlight the substantial proportion of neonates who develop neonatal sepsis, and the high mortality rates among neonates with sepsis in LMICs. More efficient and effective identification of neonatal sepsis is needed to target interventions to reduce its incidence and subsequent mortality in LMICs.

FUNDING: Bill & Melinda Gates Foundation.

PMID:35427523 | DOI:10.1016/S2214-109X(22)00043-2

How does handwashing behaviour change in response to a cholera outbreak? A qualitative case study in the Democratic Republic of the Congo

April 12, 2022

PLoS One. 2022 Apr 12;17(4):e0266849. doi: 10.1371/journal.pone.0266849. eCollection 2022.


BACKGROUND: Handwashing with soap has the potential to curb cholera transmission. This research explores how populations experienced and responded to the 2017 cholera outbreak in the Democratic Republic of the Congo and how this affected their handwashing behaviour.

METHODS: Cholera cases were identified through local cholera treatment centre records. Comparison individuals were recruited from the same neighbourhoods by identifying households with no recent confirmed or suspected cholera cases. Multiple qualitative methods were employed to understand hand hygiene practices and their determinants, including unstructured observations, interviews and focus group discussions. The data collection tools and analysis were informed by the Behaviour Centred Design Framework. Comparisons were made between the experiences and practices of people from case households and participants from comparison households.

RESULTS: Cholera was well understood by the population and viewed as a persistent and common health challenge. Handwashing with soap was generally observed to be rare during the outbreak despite self-reported increases in behaviour. Across case and comparison groups, individuals were unable to prioritise handwashing due to competing food-scarcity and livelihood challenges and there was little in the physical or social environments to cue handwashing or make it a convenient, rewarding or desirable to practice. The ability of people from case households to practice handwashing was further constrained by their exposure to cholera which in addition to illness, caused profound non-health impacts to household income, productivity, social status, and their sense of control.

CONCLUSIONS: Even though cholera outbreaks can cause disruptions to many determinants of behaviour, these shifts do not automatically facilitate an increase in preventative behaviours like handwashing with soap. Hygiene programmes targeting outbreaks within complex crises could be strengthened by acknowledging the emic experiences of the disease and adopting sustainable solutions which build upon local disease coping mechanisms.

PMID:35413080 | PMC:PMC9004767 | DOI:10.1371/journal.pone.0266849

Impact of the SARS-CoV-2 pandemic on vaccine-preventable disease campaigns

April 10, 2022

Int J Infect Dis. 2022 Jun;119:201-209. doi: 10.1016/j.ijid.2022.04.005. Epub 2022 Apr 6.


BACKGROUND: The COVID-19 pandemic has contributed to the widespread disruption of immunization services, including the postponement of mass vaccination campaigns.

METHODS: In May 2020, the World Health Organization and partners started monitoring COVID-19-related disruptions to mass vaccination campaigns against cholera, measles, meningitis A, polio, tetanus-diphtheria, typhoid, and yellow fever through the Immunization Repository Campaign Delay Tracker. The authors reviewed the number and target population of reported preventive and outbreak response vaccination campaigns scheduled, postponed, canceled, and reinstated at 4 time points: May 2020, December 2020, May 2021, and December 2021.

FINDINGS: Mass vaccination campaigns across all vaccines were disrupted heavily by COVID-19. In May 2020, 105 of 183 (57%) campaigns were postponed or canceled in 57 countries because of COVID-19, with an estimated 796 million postponed or missed vaccine doses. Campaign resumption was observed beginning in July 2020. In December 2021, 77 of 472 (16%) campaigns in 54 countries, mainly in the African Region, were still postponed or canceled because of COVID-19, with about 382 million postponed or missed vaccine doses.

INTERPRETATION: There is likely a high risk of vaccine-preventable disease outbreaks across all regions because of an increased number of susceptible persons resulting from the large-scale mass vaccination campaign postponement caused by COVID-19.

PMID:35398300 | PMC:PMC8985404 | DOI:10.1016/j.ijid.2022.04.005


April 10, 2022

Lancet. 2022 Apr 9;399(10333):1429-1440. doi: 10.1016/S0140-6736(22)00330-0.


Cholera was first described in the areas around the Bay of Bengal and spread globally, resulting in seven pandemics during the past two centuries. It is caused by toxigenic Vibrio cholerae O1 or O139 bacteria. Cholera is characterised by mild to potentially fatal acute watery diarrhoeal disease. Prompt rehydration therapy is the cornerstone of management. We present an overview of cholera and its pathogenesis, natural history, bacteriology, and epidemiology, while highlighting advances over the past 10 years in molecular epidemiology, immunology, and vaccine development and deployment. Since 2014, the Global Task Force on Cholera Control, a WHO coordinated network of partners, has been working with several countries to develop national cholera control strategies. The global roadmap for cholera control focuses on stopping transmission in cholera hotspots through vaccination and improved water, sanitation, and hygiene, with the aim to reduce cholera deaths by 90% and eliminate local transmission in at least 20 countries by 2030.

PMID:35397865 | DOI:10.1016/S0140-6736(22)00330-0

Nontoxigenic Vibrio cholerae Challenge Strains for Evaluating Vaccine Efficacy and Inferring Mechanisms of Protection

April 7, 2022

mBio. 2022 Apr 26;13(2):e0053922. doi: 10.1128/mbio.00539-22. Epub 2022 Apr 7.


Human challenge studies are instrumental for testing cholera vaccines, but these studies use outdated strains and require inpatient facilities. Here, we created next-generation isogenic Ogawa and Inaba O1 V. cholerae challenge strains (ZChol strains) derived from a contemporary Zambian clinical isolate representative of current dominant pandemic V. cholerae. Since the primary mechanism of immune protection against cholera is thought to be antibody responses that limit V. cholerae colonization and not the diarrheagenic actions of cholera toxin, these strains were rendered nontoxigenic. In infant mice, the ZChol strains did not cause diarrhea and proved to accurately gauge reduction in intestinal colonization mediated by effective vaccination. ZChol strains were also valuable as targets for measuring vibriocidal antibody responses. Using barcoded ZChol strains, we discovered that vaccination and passive immunity in the infant mouse model tightens the infection bottleneck without restricting pathogen expansion during intestinal infection. Collectively, our findings suggest that ZChol strains have the potential to enhance the safety, relevance, and scope of future cholera vaccine challenge studies and be valuable reagents for studies of immunity to cholera. IMPORTANCE Human challenge studies are a valuable method for testing the efficacy of cholera vaccines. However, challenge studies cannot be performed in countries of cholera endemicity due to safety concerns; also, contemporary pandemic Vibrio cholerae strains are not used in current challenge studies. To facilitate cholera research, we derived nontoxigenic challenge strains of both V. cholerae serotypes from a 2016 clinical isolate from Zambia and demonstrated how they can be used to gauge cholera immunity accurately and safely. These strains were also genetically barcoded, adding the potential for analyses of V. cholerae population dynamics to challenge studies. Preclinical analyses presented here suggest that these strains have the potential to enhance the safety, relevance, and scope of future cholera vaccine challenge studies and be valuable reagents for studies of immunity to cholera.

PMID:35389261 | PMC:PMC9040834 | DOI:10.1128/mbio.00539-22

Two defence systems eliminate plasmids from seventh pandemic Vibrio cholerae

April 7, 2022

Nature. 2022 Apr;604(7905):323-329. doi: 10.1038/s41586-022-04546-y. Epub 2022 Apr 6.


Horizontal gene transfer can trigger rapid shifts in bacterial evolution. Driven by a variety of mobile genetic elements-in particular bacteriophages and plasmids-the ability to share genes within and across species underpins the exceptional adaptability of bacteria. Nevertheless, invasive mobile genetic elements can also present grave risks to the host; bacteria have therefore evolved a vast array of defences against these elements1. Here we identify two plasmid defence systems conserved in the Vibrio cholerae El Tor strains responsible for the ongoing seventh cholera pandemic2-4. These systems, termed DdmABC and DdmDE, are encoded on two major pathogenicity islands that are a hallmark of current pandemic strains. We show that the modules cooperate to rapidly eliminate small multicopy plasmids by degradation. Moreover, the DdmABC system is widespread and can defend against bacteriophage infection by triggering cell suicide (abortive infection, or Abi). Notably, we go on to show that, through an Abi-like mechanism, DdmABC increases the burden of large low-copy-number conjugative plasmids, including a broad-host IncC multidrug resistance plasmid, which creates a fitness disadvantage that counterselects against plasmid-carrying cells. Our results answer the long-standing question of why plasmids, although abundant in environmental strains, are rare in pandemic strains; have implications for understanding the dissemination of antibiotic resistance plasmids; and provide insights into how the interplay between two defence systems has shaped the evolution of the most successful lineage of pandemic V. cholerae.

PMID:35388218 | DOI:10.1038/s41586-022-04546-y

Cholera-causing bacteria have defences that degrade plasmid invaders

April 7, 2022

Nature. 2022 Apr;604(7905):250-252. doi: 10.1038/d41586-022-00871-4.


PMID:35388150 | DOI:10.1038/d41586-022-00871-4

Prevention of Typhoid Fever by Existing Improvements in Household Water, Sanitation, and Hygiene, and the Use of the Vi Polysaccharide Typhoid Vaccine in Poor Urban Slums: Results from a Cluster-Randomized Trial

April 6, 2022

Am J Trop Med Hyg. 2022 Mar 7;106(4):1149-1155. doi: 10.4269/ajtmh.21-1034.


Modest improvements in household water, sanitation, and hygiene (WASH) and typhoid vaccination can reduce typhoid risk in endemic settings. However, empiric evaluation of their combined impact is lacking. A total of 62,756 persons residing in 80 clusters in a Kolkata slum were allocated randomly 1:1 to either the typhoid Vi polysaccharide (ViPS) vaccine or hepatitis A (Hep A) vaccine. Surveillance was conducted for 2 years before and 2 years after vaccination. We classified households as having "better" or "not better" WASH, and calculated the prevalence of better WASH households in clusters using previously validated criteria. We evaluated the protection by better household WASH, better household WASH prevalence, and ViPS vaccination against typhoid in all cluster members present at baseline using Cox proportional hazard models. Overall, ViPS vaccination was associated with a 55% (P < 0.001; 95% CI, 35-69) reduction of typhoid risk and was similar regardless of better WASH in the residence. Living in a better WASH household was associated with a typhoid risk reduction of 31% (P = 0.16; 95% CI, -16 to 59) overall. The reduction was 48% (P = 0.05; 95% CI, -1 to 73) in Hep A clusters, 6% (P = 0.85; 95% CI, -82 to 51) in ViPS clusters, and 57% (P < 0.05; 95% CI, 15-78) in the population during the 2 years preceding the trial. These findings demonstrate a preventive association of better household WASH in the non-ViPS population, but, unexpectedly, an absence of additional protection from ViPS by better WASH in the ViPS population. This analysis highlights the importance of assessing the combination of WASH in conjunction with typhoid vaccines, and has implications for the evaluation of new-generation typhoid conjugate vaccines.

PMID:35385827 | DOI:10.4269/ajtmh.21-1034

A reaction-advection-diffusion model of cholera epidemics with seasonality and human behavior change

April 6, 2022

J Math Biol. 2022 Apr 6;84(5):34. doi: 10.1007/s00285-022-01733-3.


Cholera is a water- and food-borne infectious disease caused by V. cholerae. To investigate multiple effects of human behavior change, seasonality and spatial heterogeneity on cholera spread, we propose a reaction-advection-diffusion model that incorporates human hosts and aquatic reservoir of V. cholerae. We derive the basic reproduction number [Formula: see text] for this system and then establish a threshold type result on its global dynamics in terms of [Formula: see text]. Further, we show that the bacterial loss at the downstream end of the river due to water flux can reduce the disease risk, and describe the asymptotic behavior of [Formula: see text] for small and large diffusion in a special case (where the diffusion rates of infected human and the pathogen are constant). We also study the transmission dynamics at the early stage of cholera outbreak numerically, and find that human behavior change may lower the infection level and delay the disease peak. Moreover, the relative rate of bacterial loss, together with convection rate, plays an important role in identifying the severely infected areas. Meanwhile spatial heterogeneity may dilute or amplify cholera infection, which in turn would increase the complexity of disease spread.

PMID:35381862 | DOI:10.1007/s00285-022-01733-3

Identifying transferable lessons from cholera epidemic responses by Medecins Sans Frontieres in Mozambique, Malawi and the Democratic Republic of Congo, 2015-2018: a scoping review

March 30, 2022

Confl Health. 2022 Mar 29;16(1):12. doi: 10.1186/s13031-022-00445-1.


BACKGROUND: Cholera epidemics occur frequently in low-income countries affected by concurrent humanitarian crises. Evaluations of these epidemic response remains largely unpublished and there is a need to generate evidence on response efforts to inform future programmes. This review of MSF cholera epidemic responses aimed to describe the main characteristics of the cholera epidemics and related responses in these three countries, to identify challenges to different intervention strategies based on available data; and to make recommendations for epidemic prevention and control practice and policy.

METHODS: Case studies from the Democratic Republic of Congo, Malawi and Mozambique were purposively selected by MSF for this review due to the documented burden of cholera in each country, frequency of cholera outbreaks, and risk of humanitarian crises. Data were extracted on the characteristics of the epidemics; time between alert and response; and, the delivery of health and water, sanitation and hygiene interventions. A Theory of Change for cholera response programmes was built to assess factors that affected implementation of the responses.

RESULTS AND CONCLUSIONS: 20 epidemic response reports were identified, 15 in DRC, one in Malawi and four in Mozambique. All contexts experienced concurrent humanitarian crises, either armed conflict or natural disasters. Across the settings, median time between the date of alert and date of the start of the response by MSF was 23 days (IQR 14-41). Almost all responses targeted interventions community-wide, and all responses implemented in-patient treatment of suspected cholera cases in either established health care facilities (HCFs) or temporary cholera treatment units (CTUs). In three responses, interventions were delivered as case-area targeted interventions (CATI) and four responses targeted households of admitted suspected cholera cases. CATI or delivery of interventions to households of admitted suspected cases occurred from 2017 onwards only. Overall, 74 factors affecting implementation were identified including delayed supplies of materials, insufficient quantities of materials and limited or lack of coordination with local government or other agencies. Based on this review, the following recommendations are made to improve cholera prevention and control efforts: explore improved models for epidemic preparedness, including rapid mobilisation of supplies and deployment of trained staff; invest in and strengthen partnerships with national and local government and other agencies; and to standardise reporting templates that allow for rigorous and structured evaluations within and across countries to provide consistent and accessible data.

PMID:35351171 | DOI:10.1186/s13031-022-00445-1

Accessing sub-national cholera epidemiological data for Nigeria and the Democratic Republic of Congo during the seventh pandemic

March 30, 2022

BMC Infect Dis. 2022 Mar 26;22(1):288. doi: 10.1186/s12879-022-07266-w.


BACKGROUND: Vibrio cholerae is a water-borne pathogen with a global burden estimate at 1.4 to 4.0 million annual cases. Over 94% of these cases are reported in Africa and more research is needed to understand cholera dynamics in the region. Cholera data are lacking, mainly due to reporting issues, creating barriers for widespread research on cholera epidemiology and management in Africa.

MAIN BODY: Here, we present datasets that were created to help address this gap, collating freely available sub-national cholera data for Nigeria and the Democratic Republic of Congo. The data were collated from a variety of English and French publicly available sources, including the World Health Organization, PubMed, UNICEF, EM-DAT, the Nigerian CDC and peer-reviewed literature. These data include information on cases, deaths, age, gender, oral cholera vaccination, risk factors and interventions.

CONCLUSION: These datasets can facilitate qualitative, quantitative and mixed methods research in these two high burden countries to assist in public health planning. The data can be used in collaboration with organisations in the two countries, which have also collected data or undertaking research. By making the data and methods available, we aim to encourage their use and further data collection and compilation to help improve the data gaps for cholera in Africa.

PMID:35351008 | DOI:10.1186/s12879-022-07266-w

Characterization of diarrheagenic Escherichia coli with special reference to antimicrobial resistance isolated from hospitalised diarrheal patients in Kolkata (2012-2019), India

March 26, 2022

J Appl Microbiol. 2022 Mar 26. doi: 10.1111/jam.15548. Online ahead of print.


AIMS: This study analyzes the prevalence and antimicrobial resistance (AMR) of major diarrheagenic Escherichia coli (DEC) pathotypes detected in hospitalized diarrheal patients in Kolkata, India, during 2012-2019.

METHODS AND RESULTS: A total of 8,891 stool samples were collected from the Infectious Diseases Hospital, Kolkata and screened for the presence of enteric pathogens. Multiplex-PCR identified the presence of DEC in 7.8% of the samples, in which ETEC was most common (47.7%) followed by EAEC (38.4%) and EPEC (13.9%). About 54% cases were due to sole DEC infections. Majority of the mixed DEC infections was caused by the Vibrio spp. (19.1%) followed by Rotavirus (14.1%) and Campylobacter spp. (8.4%). ETEC and EAEC were associated significantly with diarrhea in children <5 years of age, whereas EPEC and also ETEC were prevalent in patients aged between 5 and 14 years. AMR profile showed high prevalence of multidrug resistance (MDR) among DEC (56.9%) in which 9% were resistant to antibiotics of six different antimicrobial classes. Screening of the AMR conferring genes of DEC showed the presence of blaCTX-M3 (30.2%) in highest number followed by blaTEM (27.5%), tetB (18%), sul2 (12.6%), strA (11.8%), aadA1 (9.8%), blaOXA-1 (9%), dfrA1 (1.6%) and blaSHV (1.2%).

CONCLUSIONS: These findings highlighted the high prevalence of MDR in major DEC pathotypes that could be considered as the leading etiologic bacterial agent responsible for diarrhea and suggests a significant public health threat.

SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study can help to improve the understanding of the epidemiology of DEC infections in patients with diarrhea. Monitoring of AMR surveillance needs special attention because the DEC isolates were highly resistant to commonly used antimicrobials in the treatment of diarrhea.

PMID:35338762 | DOI:10.1111/jam.15548

Assay for Evaluating the Abundance of Vibrio cholerae and Its O1 Serogroup Subpopulation from Water without DNA Extraction

March 26, 2022

Pathogens. 2022 Mar 16;11(3):363. doi: 10.3390/pathogens11030363.


Cholera is a severe diarrheal disease caused by Vibrio cholerae, a natural inhabitant of brackish water. Effective control of cholera outbreaks depends on prompt detection of the pathogen from clinical specimens and tracking its source in the environment. Although the epidemiology of cholera is well studied, rapid detection of V. cholerae remains a challenge, and data on its abundance in environmental sources are limited. Here, we describe a sensitive molecular quantification assay by qPCR, which can be used on-site in low-resource settings on water without the need for DNA extraction. This newly optimized method exhibited 100% specificity for total V. cholerae as well as V. cholerae O1 and allowed detection of as few as three target CFU per reaction. The limit of detection is as low as 5 × 103 CFU/L of water after concentrating biomass from the sample. The ability to perform qPCR on water samples without DNA extraction, portable features of the equipment, stability of the reagents at 4 °C and user-friendly online software facilitate fast quantitative analysis of V. cholerae. These characteristics make this assay extremely useful for field research in resource-poor settings and could support continuous monitoring in cholera-endemic areas.

PMID:35335687 | DOI:10.3390/pathogens11030363

Genetic relatedness, virulence factors and antibiotics susceptibility pattern of Vibrio cholerae isolates from various regions during cholera outbreak in Tanzania

March 25, 2022

PLoS One. 2022 Mar 25;17(3):e0265868. doi: 10.1371/journal.pone.0265868. eCollection 2022.


BACKGROUND: Cholera continues to cause morbidity and mortality in developing countries, including Tanzania. Since August 2015, Tanzania Mainland has experienced cholera outbreaks affecting 26 regions and a 1.6% case fatality rate. The current study determined the virulence factors, genetic relatedness and antimicrobial susceptibility patterns of the Vibrio cholerae isolated from different regions in Tanzania.

METHODS: A cross-sectional study that involved the genetic characterization of V. cholerae isolates from eleven regions in Tanzania was carried out. There were 99 V. cholerae isolates collected between January 2016 and December 2017. The study perfomed a Multi-locus Variable-number tandem-repeat analysis for genetic relatedness and Mismatch Amplification Mutation Analysis polymerase chain reaction for analyzing toxin genes. All the isolates were tested for antimicrobial susceptibility using the Kirby Bauer disk diffusion method. Data were generally analyzed using Microsoft excel, where genetic relatedness was analyzed using eBurst software v3.

RESULTS: All isolates were V. cholerae O1. Ogawa was the most predominant 97(98%) serotype. Isolates were genetically related with a small genetic diversity and were positive for ctxA, tcpA El Tor virulence genes. All isolates (100%) were sensitive to doxycycline, trimethoprim-sulphamethoxazole, tetracycline, ceftriaxone, and chloramphenicol, while 87.8% were sensitive to ciprofloxacin. A high resistance rate (100%) was detected towards erythromycin, nalidixic acid, amoxicillin, and ampicillin.

CONCLUSION: The V.cholerae O1 serotypes Ogawa, El Tor variant predominantly caused cholera outbreaks in Tanzania with strains clonally related regardless of the place and time of the outbreak. Most of the isolates were susceptible to the antibiotic regimen currently used in Tanzania. The high resistance rate detected for the other common antibiotics calls for continuous antimicrobial susceptibility testing during outbreaks.

PMID:35333909 | DOI:10.1371/journal.pone.0265868

Genomic Characteristics of Recently Recognized Vibrio cholerae El Tor Lineages Associated with Cholera in Bangladesh, 1991 to 2017

March 22, 2022

Microbiol Spectr. 2022 Mar 22:e0039122. doi: 10.1128/spectrum.00391-22. Online ahead of print.


Comparative genomic analysis of Vibrio cholerae El Tor associated with endemic cholera in Asia revealed two distinct lineages, one dominant in Bangladesh and the other in India. An in-depth whole-genome study of V. cholerae El Tor strains isolated during endemic cholera in Bangladesh (1991 to 2017) included reference genome sequence data obtained online. Core genome phylogeny established using single nucleotide polymorphisms (SNPs) showed V. cholerae El Tor strains comprised two lineages, BD-1 and BD-2, which, according to Bayesian phylodynamic analysis, originated from paraphyletic group BD-0 around 1981. BD-1 and BD-2 lineages overlapped temporally but were negatively associated as causative agents of cholera during 2004 to 2017. Genome-wide association study (GWAS) revealed 140 SNPs and 31 indels, resulting in gene alleles unique to BD-1 and BD-2. Regression analysis of root to tip distance and year of isolation indicated early BD-0 strains at the base, whereas BD-1 and BD-2 subsequently emerged and progressed by accumulating SNPs. Pangenome analysis provided evidence of gene acquisition by both BD-1 and BD-2, of which six crucial proteins of known function were predominant in BD-2. BD-1 and BD-2 diverged and have distinctively different genomic traits, namely, heterogeneity in VSP-2, VPI-1, mobile elements, toxin encoding elements, and total gene abundance. In addition, the observed phage-inducible chromosomal island-like element (PLE1), and SXT ICE elements (ICETET) in BD-2 presumably provided a fitness advantage for the lineage to outcompete BD-1 as the etiological agent of endemic cholera in Bangladesh, with implications for global cholera epidemiology. IMPORTANCE Cholera is a global disease with specific reference to the Bay of Bengal Ganges Delta where Vibrio cholerae O1 El Tor, the causative agent of the disease showed two circulating lineages, one dominant in Bangladesh and the other in India. Results of an in-depth genomic study of V. cholerae associated with endemic cholera during the past 27 years (1991 to 2017) indicate emergence and succession of the two lineages, BD-1 and BD-2, arising from a common ancestral paraphyletic group, BD-0, comprising the early strains and short-term evolution of the bacterium in Bangladesh. Among the two V. cholerae lineages, BD-2 supersedes BD-1 and is predominant in the most recent endemic cholera in Bangladesh. The BD-2 lineage contained significantly more SNPs and indels, and showed richness in gene abundance, including antimicrobial resistance genes, gene cassettes, and PLE to fight against bacteriophage infection, acquired over time. These findings have important epidemic implications on a global scale.

PMID:35315699 | DOI:10.1128/spectrum.00391-22

Epidemiological drivers of mother to child HIV transmission in West Bengal, India: A retrospective cohort study

March 21, 2022

Int J STD AIDS. 2022 Mar 19:9564624221076618. doi: 10.1177/09564624221076618. Online ahead of print.


BACKGROUND: HIV transmission through vertical route can be reduced to a large extent with combination of medical interventions. Apart from maternal HIV status several other epidemiological attributes determine this transmission dynamics.Objective: The objective of this study was to identify various associated factors that determine and modify the risk of HIV transmission from a mother living with HIV to her child.Materials and method: A retrospective cohort-study was conducted with 518 HIV-positive pregnant women with delivering live babies between April 2016 - September 2018. The HIV status of the children was ascertained with polymerase chain reaction. A number of socio-demographic and medical attributes were compared between HIV-positive (41) and HIV-negative babies (477) using bivariate and multivariate methods to identify disease modifying factors.

RESULTS: Maternal HIV detection during the postnatal period (AOR = 11.2; 5.2 - 23.8), low birth weight (AOR = 2.7; 1.2 - 5.9), and vaginal delivery (AOR = 2.8; 1.01 - 7.7) were significantly associated with vertical transmission of HIV. Lower duration of maternal antiretroviral treatment and higher maternal age (>25 years) were also associated in bivariate analysis.

CONCLUSION: The battery of PPTCT (Prevention of Parent to Child Transmission) interventions should be tailored in such a way to address all the epidemiological attributes influencing vertical transmission.

PMID:35306925 | DOI:10.1177/09564624221076618

Phase variation in the glycosyltransferase genes of <em>Pasteurella multocida</em> associated with outbreaks of fowl cholera on free-range layer farms

March 10, 2022

Microb Genom. 2022 Mar;8(3). doi: 10.1099/mgen.0.000772.


Fowl cholera caused by Pasteurella multocida has re-emerged in Australian poultry production since the increasing adoption of free-range production systems. Currently, autogenous killed whole-cell vaccines prepared from the isolates previously obtained from each farm are the main preventative measures used. In this study, we use whole-genome sequencing and phylogenomic analysis to investigate outbreak dynamics, as well as monitoring and comparing the variations in the lipopolysaccharide (LPS) outer core biosynthesis loci of the outbreak and vaccine strains. In total, 73 isolates from two different free-range layer farms were included. Our genomic analysis revealed that all investigated isolates within the two farms (layer A and layer B) carried LPS type L3, albeit with a high degree of genetic diversity between them. Additionally, the isolates belonged to five different sequence types (STs), with isolates belonging to ST9 and ST20 being the most prevalent. The isolates carried ST-specific mutations within their LPS type L3 outer core biosynthesis loci, including frameshift mutations in the outer core heptosyltransferase gene (htpE) (ST7 and ST274) or galactosyltransferase gene (gatG) (ST20). The ST9 isolates could be separated into three groups based on their LPS outer core biosynthesis loci sequences, with evidence for potential phase variation mechanisms identified. The potential phase variation mechanisms included a tandem repeat insertion in natC and a single base deletion in a homopolymer region of gatG. Importantly, our results demonstrated that two of the three ST9 groups shared identical rep-PCR (repetitive extragenic palindromic PCR) patterns, while carrying differences in their LPS outer core biosynthesis loci region. In addition, we found that ST9 isolates either with or without the natC tandem repeat insertion were both associated with a single outbreak, which would indicate the importance of screening more than one isolate within an outbreak. Our results strongly suggest the need for a metagenomics culture-independent approach, as well as a genetic typing scheme for LPS, to ensure an appropriate vaccine strain with a matching predicted LPS structure is used.

PMID:35266868 | DOI:10.1099/mgen.0.000772

Epidemicity of cholera spread and the fate of infection control measures

March 9, 2022

J R Soc Interface. 2022 Mar;19(188):20210844. doi: 10.1098/rsif.2021.0844. Epub 2022 Mar 9.


The fate of ongoing infectious disease outbreaks is predicted through reproduction numbers, defining the long-term establishment of the infection, and epidemicity indices, tackling the reactivity of the infectious pool to new contagions. Prognostic metrics of unfolding outbreaks are of particular importance when designing adaptive emergency interventions facing real-time assimilation of epidemiological evidence. Our aim here is twofold. First, we propose a novel form of the epidemicity index for the characterization of cholera epidemics in spatial models of disease spread. Second, we examine in hindsight the survey of infections, treatments and containment measures carried out for the now extinct 2010-2019 Haiti cholera outbreak, to suggest that magnitude and timing of non-pharmaceutical and vaccination interventions imply epidemiological responses recapped by the evolution of epidemicity indices. Achieving negative epidemicity greatly accelerates fading of infections and thus proves a worthwhile target of containment measures. We also show that, in our model, effective reproduction numbers and epidemicity indices are explicitly related. Therefore, providing an upper bound to the effective reproduction number (significantly lower than the unit threshold) warrants negative epidemicity and, in turn, a rapidly fading outbreak preventing coalescence of sparse local sub-threshold flare-ups.

PMID:35259956 | PMC:PMC8905172 | DOI:10.1098/rsif.2021.0844