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Old tools, new applications: Use of environmental bacteriophages for typhoid surveillance and evaluating vaccine impact.

ABSTRACT: Typhoid-conjugate vaccines (TCVs) provide an opportunity to reduce the burden of typhoid fever, caused by Salmonella Typhi, in endemic areas. As policymakers design vaccination strategies, accurate and high-resolution data on disease burden is crucial. However, traditional blood culture-based surveillance is resource-extensive, prohibiting its large-scale and sustainable implementation. Salmonella Typhi is a water-borne pathogen, and here, we tested the potential of Typhi-specific bacteriophage surveillance in surface water bodies as a low-cost tool to identify where Salmonella Typhi circulates in the environment. In 2021, water samples were collected and tested for the presence of Salmonella Typhi bacteriophages at two sites in Bangladesh: urban capital city, Dhaka, and a rural district, Mirzapur. Salmonella Typhi-specific bacteriophages were detected in 66 of 211 (31%) environmental samples in Dhaka, in comparison to 3 of 92 (3%) environmental samples from Mirzapur. In the same year, 4,620 blood cultures at the two largest pediatric hospitals of Dhaka yielded 215 (5%) culture-confirmed typhoid cases, and 3,788 blood cultures in the largest hospital of Mirzapur yielded 2 (0.05%) cases. 75% (52/69) of positive phage samples were collected from sewage. All isolated phages were tested against a panel of isolates from different Salmonella Typhi genotypes circulating in Bangladesh and were found to exhibit a diverse killing spectrum, indicating that diverse bacteriophages were isolated. These results suggest an association between the presence of Typhi-specific phages in the environment and the burden of typhoid fever, and the potential of utilizing environmental phage surveillance as a low-cost tool to assist policy decisions on typhoid control.

SUBMITTER: Hooda Y

PROVIDER: S-EPMC10868810 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Old tools, new applications: Use of environmental bacteriophages for typhoid surveillance and evaluating vaccine impact.

Hooda Yogesh Y Islam Shuborno S Kabiraj Rathin R Rahman Hafizur H Sarkar Himadree H da Silva Kesia E KE Raju Rajan Saha RS Luby Stephen P SP Andrews Jason R JR Saha Samir K SK Saha Senjuti S

PLoS neglected tropical diseases 20240215 2

Typhoid-conjugate vaccines (TCVs) provide an opportunity to reduce the burden of typhoid fever, caused by Salmonella Typhi, in endemic areas. As policymakers design vaccination strategies, accurate and high-resolution data on disease burden is crucial. However, traditional blood culture-based surveillance is resource-extensive, prohibiting its large-scale and sustainable implementation. Salmonella Typhi is a water-borne pathogen, and here, we tested the potential of Typhi-specific bacteriophage ...[more]

PMID: 38358956

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Project description:The constantly growing number of people suffering from bacterial, viral, or fungal infections, parasitic diseases, and cancers prompts the search for innovative methods of disease prevention and treatment, especially based on vaccines and targeted therapy. An additional problem is the global threat to humanity resulting from the increasing resistance of bacteria to commonly used antibiotics. Conventional vaccines based on bacteria or viruses are common and are generally effective in preventing and controlling various infectious diseases in humans. However, there are problems with the stability of these vaccines, their transport, targeted delivery, safe use, and side effects. In this context, experimental phage therapy based on viruses replicating in bacterial cells currently offers a chance for a breakthrough in the treatment of bacterial infections. Phages are not infectious and pathogenic to eukaryotic cells and do not cause diseases in human body. Furthermore, bacterial viruses are sufficient immuno-stimulators with potential adjuvant abilities, easy to transport, and store. They can also be produced on a large scale with cost reduction. In recent years, they have also provided an ideal platform for the design and production of phage-based vaccines to induce protective host immune responses. The most promising in this group are phage-displayed vaccines, allowing for the display of immunogenic peptides or proteins on the phage surfaces, or phage DNA vaccines responsible for expression of target genes (encoding protective antigens) incorporated into the phage genome. Phage vaccines inducing the production of specific antibodies may in the future protect us against infectious diseases and constitute an effective immune tool to fight cancer. Moreover, personalized phage therapy can represent the greatest medical achievement that saves lives. This review demonstrates the latest advances and developments in the use of phage vaccines to prevent human infectious diseases; phage-based therapy, including clinical trials; and personalized treatment adapted to the patient's needs and the type of bacterial infection. It highlights the advantages and disadvantages of experimental phage therapy and, at the same time, indicates its great potential in the treatment of various diseases, especially those resistant to commonly used antibiotics. All the analyses performed look at the rich history and development of phage therapy over the past 100 years.

Project description:BackgroundThe development of technology and information systems has led to important changes in public health surveillance.ObjectiveThis scoping review aimed to assess the available evidence and gather information about the use of digital tools for arbovirus (dengue virus [DENV], zika virus [ZIKV], and chikungunya virus [CHIKV]) surveillance.MethodsThe databases used were MEDLINE, SCIELO, LILACS, SCOPUS, Web of Science, and EMBASE. The inclusion criterion was defined as studies that described the use of digital tools in arbovirus surveillance. The exclusion criteria were defined as follows: letters, editorials, reviews, case reports, series of cases, descriptive epidemiological studies, laboratory and vaccine studies, economic evaluation studies, and studies that did not clearly describe the use of digital tools in surveillance. Results were evaluated in the following steps: monitoring of outbreaks or epidemics, tracking of cases, identification of rumors, decision-making by health agencies, communication (cases and bulletins), and dissemination of information to society).ResultsOf the 2227 studies retrieved based on screening by title, abstract, and full-text reading, 68 (3%) studies were included. The most frequent digital tools used in arbovirus surveillance were apps (n=24, 35%) and Twitter, currently called X (n=22, 32%). These were mostly used to support the traditional surveillance system, strengthening aspects such as information timeliness, acceptability, flexibility, monitoring of outbreaks or epidemics, detection and tracking of cases, and simplicity. The use of apps to disseminate information to society (P=.02), communicate (cases and bulletins; P=.01), and simplicity (P=.03) and the use of Twitter to identify rumors (P=.008) were statistically relevant in evaluating scores. This scoping review had some limitations related to the choice of DENV, ZIKV, and CHIKV as arboviruses, due to their clinical and epidemiological importance.ConclusionsIn the contemporary scenario, it is no longer possible to ignore the use of web data or social media as a complementary strategy to health surveillance. However, it is important that efforts be combined to develop new methods that can ensure the quality of information and the adoption of systematic measures to maintain the integrity and reliability of digital tools' data, considering ethical aspects.

Project description:BackgroundEnvironmental surveillance, using detection of Salmonella Typhi DNA, has emerged as a potentially useful tool to identify typhoid-endemic settings; however, it is relatively costly and requires molecular diagnostic capacity. We sought to determine whether S. Typhi bacteriophages are abundant in water sources in a typhoid-endemic setting, using low-cost assays.MethodologyWe collected drinking and surface water samples from urban, peri-urban and rural areas in 4 regions of Nepal. We performed a double agar overlay with S. Typhi to assess the presence of bacteriophages. We isolated and tested phages against multiple strains to assess their host range. We performed whole genome sequencing of isolated phages, and generated phylogenies using conserved genes.FindingsS. Typhi-specific bacteriophages were detected in 54.9% (198/361) of river and 6.3% (1/16) drinking water samples from the Kathmandu Valley and Kavrepalanchok. Water samples collected within or downstream of population-dense areas were more likely to be positive (72.6%, 193/266) than those collected upstream from population centers (5.3%, 5/95) (p=0.005). In urban Biratnagar and rural Dolakha, where typhoid incidence is low, only 6.7% (1/15, Biratnagar) and 0% (0/16, Dolakha) river water samples contained phages. All S. Typhi phages were unable to infect other Salmonella and non-Salmonella strains, nor a Vi-knockout S. Typhi strain. Representative strains from S. Typhi lineages were variably susceptible to the isolated phages. Phylogenetic analysis showed that S. Typhi phages belonged to the class Caudoviricetes and clustered in three distinct groups.ConclusionsS. Typhi bacteriophages were highly abundant in surface waters of typhoid-endemic communities but rarely detected in low typhoid burden communities. Bacteriophages recovered were specific for S. Typhi and required Vi polysaccharide for infection. Screening small volumes of water with simple, low-cost (~$2) plaque assays enables detection of S. Typhi phages and should be further evaluated as a scalable tool for typhoid environmental surveillance.

Dataset Information

Old tools, new applications: Use of environmental bacteriophages for typhoid surveillance and evaluating vaccine impact.

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Old tools, new applications: Use of environmental bacteriophages for typhoid surveillance and evaluating vaccine impact.

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