scholarly journals Establishment and Validation of Pathogenic CS17+ and CS19+ ETEC Challenge Models in the New World Primate Aotus nancymaae

2020 ◽  
Author(s):  
Eric Hall ◽  
Aisling O'Dowd ◽  
Julianne E. Rollenhagen ◽  
Nereyda Espinoza ◽  
Gladys Nunez ◽  
...  
Keyword(s):  
New World ◽  
Financial Burden ◽  
Disease Model ◽  
Middle Income ◽  
E Coli ◽  
Middle Income Countries ◽  
Colonization Factor ◽  
Oral Inoculation ◽  
Etec Infection ◽  
Significant Health

Enterotoxigenic E. coli (ETEC) are a common cause of diarrheal illness in military, travelers, and children living in low to middle income countries. Increased antibiotic resistance, the absence of a licensed vaccine and the lack of broadly practical therapeutics perpetuate the significant health and financial burden resulting from ETEC infection. A critical step in the evaluation of vaccines and therapeutics is pre-clinical screening in a relevant animal disease model that closely replicates human disease. We previously developed a diarrheal model of class 5a colonization factor (CF) CFA/I expressing ETEC in the New World owl monkey species Aotus nancymaae using ETEC strain H10407. In order to broaden the use of the model, we report here on the development of A. nancymaae models of ETEC expressing the class 5b CFs CS17 and CS19 with strains LSN03-016011/A and WS0115A, respectively. For both models, we observed diarrheal attack rates of ≥ 80% after oral inoculation with 5 × 1011 CFU of bacteria. These models will aid in assessing the efficacy of future ETEC vaccine candidates and therapeutics.

scholarly journals Contribution of noncanonical antigens to virulence and adaptive immunity in human infection with enterotoxigenic E. coli

2020 ◽  
Author(s):  
FM Kuhlmann ◽  
RO Laine ◽  
S Afrin ◽  
R Nakajima ◽  
M Akhtar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Human Infection ◽  
Middle Income ◽  
Symptomatic Disease ◽  
E Coli ◽  
Middle Income Countries ◽  
Colonization Factor ◽  
Specific Antigens ◽  
Colonization Factors

AbstractEnterotoxigenic E. coli (ETEC) contribute significantly to the substantial burden of infectious diarrhea among children living in low and middle income countries. In the absence of a vaccine for ETEC, children succumb to acute dehydration as well as non-diarrheal sequelae related to these infections including malnutrition. The considerable diversity of ETEC genomes has complicated canonical vaccine development approaches focused on a subset of antigens known as colonization factors (CFs). To identify additional conserved immunogens, we mined genomic sequences of 89 ETEC isolates, bioinformatically selected potential surface-exposed pathovar-specific antigens conserved in more than 40% of the genomes (n=118), and assembled the representative proteins onto microarrays, complemented with known or putative colonization factor subunit molecules (n=52), and toxin subunits to interrogate samples from individuals with acute symptomatic ETEC infections. Surprisingly, in this open-aperture approach, we found that immune responses were largely constrained to a small number of antigens including individual colonization factor antigens and EtpA, an extracellular adhesin. In a Bangladeshi cohort of naturally infected children < 2 years of age, both EtpA and a second noncanonical antigen, EatA, elicited significant serologic responses that were associated with protection from symptomatic illness. In addition, children infected with ETEC isolates bearing either etpA or eatA genes were significantly more likely to develop symptomatic disease. These studies support a role for more recently discovered noncanonical antigens in virulence and the development of adaptive immune responses during ETEC infections, findings that may inform vaccine design efforts to complement existing approaches.

scholarly journals Contribution of noncanonical antigens to virulence and adaptive immunity in human infection with enterotoxigenic E. coli

2021 ◽  
Author(s):  
F. M. Kuhlmann ◽  
R. O. Laine ◽  
S Afrin ◽  
R Nakajima ◽  
M Akhtar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Human Infection ◽  
Middle Income ◽  
Symptomatic Disease ◽  
E Coli ◽  
Middle Income Countries ◽  
Colonization Factor ◽  
Specific Antigens ◽  
Colonization Factors

Enterotoxigenic E. coli (ETEC) contribute significantly to the substantial burden of infectious diarrhea among children living in low and middle income countries. In the absence of a vaccine for ETEC, children succumb to acute dehydration as well as non-diarrheal sequelae related to these infections including malnutrition. The considerable diversity of ETEC genomes has complicated canonical vaccine development approaches defined by a subset of ETEC pathovar-specific antigens known as colonization factors (CFs). To identify additional conserved immunogens unique to this pathovar we employed an “open-aperture” approach to capture all potential conserved ETEC surface antigens in which we mined genomic sequences of 89 ETEC isolates, bioinformatically selected potential surface-exposed pathovar-specific antigens conserved in more than 40% of the genomes (n=118), and assembled the representative proteins onto microarrays, complemented with known or putative colonization factor subunit molecules (n=52), and toxin subunits. These arrays were then used to interrogate samples from individuals with acute symptomatic ETEC infections. Surprisingly, in this approach, we found that immune responses were largely constrained to a small number of antigens including individual colonization factor antigens and EtpA, an extracellular adhesin. In a Bangladeshi cohort of naturally infected children < 2 years of age, both EtpA and a second antigen, EatA, elicited significant serologic responses that were associated with protection from symptomatic illness. In addition, children infected with ETEC isolates bearing either etpA or eatA genes were significantly more likely to develop symptomatic disease. These studies support a role for antigens not presently targeted by vaccines (non-canonical) in virulence and the development of adaptive immune responses during ETEC infections. These findings that may inform vaccine design efforts to complement existing approaches.

scholarly journals Prevalence of MDR organism (MDRO) carriage in children and their household members in Siem Reap Province, Cambodia

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Shweta R Singh ◽  
Bunsoth Mao ◽  
Konstantin Evdokimov ◽  
Pisey Tan ◽  
Phana Leab ◽  
...  
Keyword(s):  
Final Analysis ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Middle Income ◽  
E Coli ◽  
Middle Income Countries ◽  
Siem Reap ◽  
High Prevalence ◽  
Significant Public Health ◽  
History Of

Abstract Background The rising incidence of infections caused by MDR organisms (MDROs) poses a significant public health threat. However, little has been reported regarding community MDRO carriage in low- and middle-income countries. Methods We conducted a cross-sectional study in Siem Reap, Cambodia comparing hospital-associated households, in which an index child (age: 2–14 years) had been hospitalized for at least 48 h in the preceding 2–4 weeks, with matched community households on the same street, in which no other child had a recent history of hospitalization. Participants were interviewed using a survey questionnaire and tested for carriage of MRSA, ESBL-producing Enterobacterales (ESBL-E) and carbapenemase-producing Enterobacterales (CPE) by culture followed by antibiotic susceptibility testing. We used logistic regression analysis to analyse associations between collected variables and MDRO carriage. Results Forty-two pairs of households including 376 participants with 376 nasal swabs and 290 stool specimens were included in final analysis. MRSA was isolated from 26 specimens (6.9%). ESBL-producing Escherichia coli was detected in 269 specimens (92.8%) whereas ESBL-producing Klebsiella pneumoniae was isolated from 128 specimens (44.1%), of which 123 (42.4%) were co-colonized with ESBL-producing E. coli. Six (2.1%) specimens tested positive for CPE (4 E. coli and 2 K. pneumoniae). The prevalence ratios for MRSA, ESBL-producing E. coli and ESBL-producing K. pneumoniae carriage did not differ significantly in hospital-associated households and hospitalized children compared with their counterparts. Conclusions The high prevalence of ESBL-E across both household types suggests that MDRO reservoirs are common in the community. Ongoing genomic analyses will help to understand the epidemiology and course of MDRO spread.

scholarly journals The Global Burden of Surgical Disease: An Analysis on Inaccessible Surgical Care in Low and Middle Income Countries

2018 ◽  
Vol 7 (1) ◽  
pp. 8-15 ◽  
Author(s):  
Chau Huynh ◽  
Minh NQ Huynh
Keyword(s):  
Global Health ◽  
Financial Burden ◽  
Surgical Care ◽  
Anaesthetic Management ◽  
Global Burden ◽  
Political Climate ◽  
Middle Income ◽  
Surgical Interventions ◽  
Middle Income Countries ◽  
Low And Middle Income

Worldwide, 4.8 billion people do not have access to safe, adequate surgical care and anaesthetic management. Surgical care has been deemed “the neglected child of global health,” a startling reminder of the disparities in health services. The provision of surgical interventions can avert 11% of the global burden of disease and 1.5 million deaths each year. Many obstacles exist for low- and middle-income countries (LMIC) to progress towards accessible surgical care. The first challenge is delivering cost-effective surgical care despite financial constraints and political turmoil. Foreign aid was established to alleviate the financial burden and its contributions have been pivotal. However, based on the political climate in certain countries, funds are siphoned to government sectors other than health care. Moreover, the lack of infrastructure, equipment, and personnel in LMIC compound the issue. The other challenge is determining if surgery is as feasible and effective as non-surgical health interventions. Surgical care is crucial and this paper aims to assess the challenges that limit its stature in global health discussions. The paper will address the influence of financing, infrastructure, workforce, service delivery, and information management on surgical care, and the current resolutions, such as humanitarian aid missions.

scholarly journals ASSESSING THE EFFECTS OF LONG-TERM CARE INSURANCE ON EQUITY AND EFFICIENCY: A CASE STUDY OF QINGDAO CITY IN CHINA

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S300-S300
Author(s):  
Wei Yang ◽  
Shuang Chang
Keyword(s):  
Long Term Care ◽  
Financial Burden ◽  
Care Providers ◽  
Term Care ◽  
Middle Income ◽  
Middle Income Countries ◽  
Equity And Efficiency ◽  
Qingdao City ◽  
Insurance Model

Abstract The demand for equitable and efficient long-term care (LTC) has risen rapidly, and finding a suitable mechanism to finance LTC has become a pressing policy concern for many countries. A number of high income countries have chosen to use a social LTC insurance to fund the LTC system, but empirical assessments on such an insurance in low-and middle-income countries are limited. Using China as an example, this paper empirically assesses the performance of newly-piloted LTCNI by evaluating its impact on equity and efficiency in financing. We draw data from 47 in-depth interviews conducted with local government, care providers and family members of the LTCNI participants in Qingdao in 2016. We found that there remain sizable disparities in financial burden among LTCNI participants, despite of its emphasis on ensuring access to care based on people’s needs; care providers are incentivised to provide care at the least cost even this care is deemed as insufficient or inadequate due to fixed payment for their services. Our paper offers critical insights into the potential and challenges in applying LTC insurance model to a LMIC, where critical lessons can be drawn for public LTC insurance in other LMICs.

scholarly journals Salmonella grows massively and aerobically in fecal matter

2019 ◽  
Author(s):  
Teresa Guerrero ◽  
Sonia Zapata ◽  
Gabriel Trueba
Keyword(s):  
Waste Management ◽  
Animal Manure ◽  
Anaerobic Conditions ◽  
Fecal Matter ◽  
Middle Income ◽  
E Coli ◽  
Middle Income Countries ◽  
Intestinal Pathogens ◽  
Aerobic And Anaerobic ◽  
Aerobic And Anaerobic Conditions

SummaryThe use of wastewater for irrigation and animal manure as fertilizer can cause transmission of intestinal pathogens, conditions frequently observed in Low- and Middle-Income Countries (LMICs). Here we tested the ability of Salmonella to grow in the fecal matter; we inoculated freshly isolated Salmonella strains (from chickens) in chicken fecal matter and incubated for 24, 48 and 72 hrs under aerobic and anaerobic conditions. We found that both Salmonella and E. coli multiplied massively in fecal matter outside a host for 72 hrs, being their growth higher in aerobic conditions. Our results have critical implications in waste management, as we demonstrate that aerobic treatments may not be the best to reduce the number of Salmonella in the environment.

scholarly journals Globalization of national surgical, obstetric and anesthesia plans: the critical link between health policy and action in global surgery

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Paul Truché ◽  
Haitham Shoman ◽  
Ché L. Reddy ◽  
Desmond T. Jumbam ◽  
Joanna Ashby ◽  
...  
Keyword(s):  
Financial Burden ◽  
Surgical Care ◽  
Obstetric Care ◽  
Global Surgery ◽  
Health System Strengthening ◽  
Health Coverage ◽  
Middle Income ◽  
Middle Income Countries ◽  
Private And Public ◽  
Development Goals

AbstractEfforts from the developed world to improve surgical, anesthesia and obstetric care in low- and middle-income countries have evolved from a primarily volunteer mission trip model to a sustainable health system strengthening approach as private and public stakeholders recognize the enormous health toll and financial burden of surgical disease. The National Surgical, Obstetric and Anesthesia Plan (NSOAP) has been developed as a policy strategy for countries to address, in part, the health burden of diseases amenable to surgical care, but these plans have not developed in isolation. The NSOAP has become a phenomenon of globalization as a broad range of partners – individuals and institutions – help in both NSOAP formulation, implementation and financing. As the nexus between policy and action in the field of global surgery, the NSOAP reflects a special commitment by state actors to make progress on global goals such as Universal Health Coverage and the United Nations Sustainable Development Goals. This requires a continued global commitment involving genuine partnerships that embrace the collective strengths of both national and global actors to deliver sustained, safe and affordable high-quality surgical care for all poor, rural and marginalized people.

scholarly journals A Comparative Genomic Analysis of Diverse Clonal Types of EnterotoxigenicEscherichia coliReveals Pathovar-Specific Conservation

2010 ◽  
Vol 79 (2) ◽  
pp. 950-960 ◽  
Author(s):  
Jason W. Sahl ◽  
Hans Steinsland ◽  
Julia C. Redman ◽  
Samuel V. Angiuoli ◽  
James P. Nataro ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Genomic Sequence ◽  
Genomic Analysis ◽  
Genomic Diversity ◽  
Comparative Genomic ◽  
Middle Income ◽  
E Coli ◽  
Colonization Factor ◽  
Genomic Core ◽  
Genomic Regions

ABSTRACTEnterotoxigenicEscherichia coli(ETEC) is a major cause of diarrheal illness in children less than 5 years of age in low- and middle-income nations, whereas it is an emerging enteric pathogen in industrialized nations. Despite being an important cause of diarrhea, little is known about the genomic composition of ETEC. To address this, we sequenced the genomes of five ETEC isolates obtained from children in Guinea-Bissau with diarrhea. These five isolates represent distinct and globally dominant ETEC clonal groups. Comparative genomic analyses utilizing a gene-independent whole-genome alignment method demonstrated that sequenced ETEC strains share approximately 2.7 million bases of genomic sequence. Phylogenetic analysis of this “core genome” confirmed the diverse history of the ETEC pathovar and provides a finer resolution of theE. colirelationships than multilocus sequence typing. No identified genomic regions were conserved exclusively in all ETEC genomes; however, we identified more genomic content conserved among ETEC genomes than among non-ETECE. coligenomes, suggesting that ETEC isolates share a genomic core. Comparisons of known virulence and of surface-exposed and colonization factor genes across all sequenced ETEC genomes not only identified variability but also indicated that some antigens are restricted to the ETEC pathovar. Overall, the generation of these five genome sequences, in addition to the two previously generated ETEC genomes, highlights the genomic diversity of ETEC. These studies increase our understanding of ETEC evolution, as well as provide insight into virulence factors and conserved proteins, which may be targets for vaccine development.

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