The impact of conflict on infectious disease: a systematic literature review.

BACKGROUND: Conflict situations, armed or not, have been associated with emergence and transmission of infectious diseases. This review aims to identify the pathways through which infectious diseases emerge within conflict situations and to outline appropriate infectious disease preparedness and response strategies. METHODS: A systematic review was performed representing published evidence from January 2000 to October 2023. Ovid Medline and Embase were utilised to obtain literature on infectious diseases in any conflict settings. The systematic review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis). No geographical restrictions were imposed. FINDINGS: Our review identified 51 studies covering AIDS, Hepatitis B, Tuberculosis, Cholera, Coronavirus 2, Ebola, Poliomyelitis, Malaria, Leishmaniasis, Measles, Diphtheria, Dengue and Acute Bacterial Meningitis within conflict settings in Europe, Middle East, Asia, and Africa since October 2023. Key factors contributing to disease emergence and transmission in conflict situations included population displacement, destruction of vital infrastructure, reduction in functioning healthcare systems and healthcare personnel, disruption of disease control programmes (including reduced surveillance, diagnostic delays, and interrupted vaccinations), reduced access by healthcare providers to populations within areas of active conflict, increased population vulnerability due to limited access to healthcare services, and disruptions in the supply chain of safe water, food, and medication. To mitigate these infectious disease risks reported preparedness and response strategies included both disease-specific intervention strategies as well as broader concepts such as the education of conflict-affected populations through infectious disease awareness programmes, investing in and enabling health care in locations with displaced populations, intensifying immunisation campaigns, and ensuring political commitment and intersectoral collaborations between governments and international organisations. CONCLUSION: Conflict plays a direct and indirect role in the transmission and propagation of infectious diseases. The findings from this review can assist decision-makers in the development of evidence-based preparedness and response strategies for the timely and effective containment of infectious disease outbreaks in conflict zones and amongst conflict-driven displaced populations. FUNDING: European Centre for Disease Prevention and Control under specific contract No. 22 ECD.13,154 within Framework contract ECDC/2019/001 Lot 1B.

Cost of the COVID-19 pandemic versus the cost-effectiveness of mitigation strategies in EU/UK/OECD: a systematic review.

OBJECTIVES: The economic burden of COVID-19 pandemic is substantial, with both direct and indirect costs playing a significant role. DESIGN: A systematic literature review was conducted to estimate the cost of the COVID-19 pandemic and the cost-effectiveness of pharmaceutical or non-pharmaceutical interventions. All cost data were adjusted to the 2021 Euro, and interventions compared with null. DATA SOURCES: Ovid MEDLINE and EMBASE were searched from January 2020 through 22 April 2021. ELIGIBILITY CRITERIA: Studies regarding COVID-19 outbreak or public health preparedness measures or interventions with outcome measures related to the direct and indirect costs for disease and preparedness and/or response in countries of the European Union (EU), the European Economic Area (EEA), the UK and the Organisation for Economic Co-operation and Development (OECD) of all relevant epidemiological designs which estimate cost within the selected time frame were considered eligible. DATA EXTRACTION AND SYNTHESIS: Studies were searched, screened and coded independently by two reviewers with high measure of inter-rater agreement. Data were extracted to a predefined data extraction sheet. The risk of bias was assessed using the Consensus on Health Economic Criteria checklist. RESULTS: We included data from 41 economic studies. Ten studies evaluated the cost of the COVID-19 pandemic, while 31 assessed the cost-benefit of public health surveillance, preparedness and response measures. Overall, the economic burden of the COVID-19 pandemic was found to be substantial. Community screening, bed provision policies, investing in personal-protective-equipment and vaccination strategies were cost-effective. Physical distancing measures were associated with health benefits; however, their cost-effectiveness was dependent on the duration, compliance and the phase of the epidemic in which it was implemented. CONCLUSIONS: COVID-19 pandemic is associated with substantial short-term and long-term economic costs to healthcare systems, payers and societies, while interventions including testing and screening policies, vaccination and physical distancing policies were identified as those presenting cost-effective options to deal with the pandemic, dependent on population vaccination and the Re at the stage of the pandemic.

Systematic review of outbreaks of COVID-19 within households in the European region when the child is the index case.

OBJECTIVES: This systematic review aims to identify the secondary attack rates (SAR) to adults and other children when children are the index cases within household settings. METHODS: This literature review assessed European-based studies published in Medline and Embase between January 2020 and January 2022 that assessed the secondary transmission of SARS-CoV-2 within household settings. The inclusion criteria were based on the Population, Exposure, Outcome framework for systematic reviews. Thus, the study population was restricted to humans within the household setting in Europe (population), in contact with paediatric index cases 1-17 years old (exposure) that led to the transmission of SARS-CoV-2 reported as either an SAR or the probability of onward infection (outcome). RESULTS: Of 1819 studies originally identified, 19 met the inclusion criteria. Overall, the SAR ranged from 13% to 75% in 15 studies, while there was no evidence of secondary transmission from children to other household members in one study. Evidence indicated that asymptomatic SARS-CoV-2 index cases also have a lower SAR than those with symptoms and that younger children may have a lower SAR than adolescents (>12 years old) within household settings. CONCLUSIONS: SARS-CoV-2 secondary transmission from paediatric index cases ranged from 0% to 75%, within household settings between January 2020 and January 2022, with differences noted by age and by symptomatic/asymptomatic status of the index case. Given the anticipated endemic circulation of SARS-CoV-2, continued monitoring and assessment of household transmission is necessary.

Enhancing laboratory capacity during Ebola virus disease (EVD) heightened surveillance in Liberia: lessons learned and recommendations.

INTRODUCTION: Following a declaration by the World Health Organization that Liberia had successfully interrupted Ebola virus transmission on May 9th, 2015; the country entered a period of enhanced surveillance. The number of cases had significantly reduced prior to the declaration, leading to closure of eight out of eleven Ebola testing laboratories. Enhanced surveillance led to an abrupt increase in demand for laboratory services. We report interventions, achievements, lessons learned and recommendations drawn from enhancing laboratory capacity. METHODS: Using archived data, we reported before and after interventions that aimed at increasing laboratory capacity. Laboratory capacity was defined by number of laboratories with Ebola Virus Disease (EVD) testing capacity, number of competent staff, number of specimens tested, specimen backlog, daily and surge testing capacity, and turnaround time. Using Stata 14 (Stata Corporation, College Station, TX, USA), medians and trends were reported for all continuous variables. RESULTS: Between May and December 2015, interventions including recruitment and training of eight staff, establishment of one EVD laboratory facility, implementation of ten Ebola GeneXpert diagnostic platforms, and establishment of working shifts yielded an 8-fold increase in number of specimens tested, a reduction in specimens backlog to zero, and restoration of turn-around time to 24 hours. This enabled a more efficient surveillance system that facilitated timely detection and containment of two EVD clusters observed thereafter. CONCLUSION: Effective enhancement of laboratory services during high demand periods requires a combination of context-specific interventions. Building and ensuring sustainability of local capacity is an integral part of effective surveillance and disease outbreak response efforts.

Establishing Ebola Virus Disease (EVD) diagnostics using GeneXpert technology at a mobile laboratory in Liberia: Impact on outbreak response, case management and laboratory systems strengthening.

The 2014-16 Ebola Virus Disease (EVD) outbreak in West Africa highlighted the necessity for readily available, accurate and rapid diagnostics. The magnitude of the outbreak and the re-emergence of clusters of EVD cases following the declaration of interrupted transmission in Liberia, reinforced the need for sustained diagnostics to support surveillance and emergency preparedness. We describe implementation of the Xpert Ebola Assay, a rapid molecular diagnostic test run on the GeneXpert platform, at a mobile laboratory in Liberia and the subsequent impact on EVD outbreak response, case management and laboratory system strengthening. During the period of operation, site coordination, management and operational capacity was supported through a successful collaboration between Ministry of Health (MoH), World Health Organization (WHO) and international partners. A team of Liberian laboratory technicians were trained to conduct EVD diagnostics and the laboratory had capacity to test 64-100 blood specimens per day. Establishment of the laboratory significantly increased the daily testing capacity for EVD in Liberia, from 180 to 250 specimens at a time when the effectiveness of the surveillance system was threatened by insufficient diagnostic capacity. During the 18 months of operation, the laboratory tested a total of 9,063 blood specimens, including 21 EVD positives from six confirmed cases during two outbreaks. Following clearance of the significant backlog of untested EVD specimens in November 2015, a new cluster of EVD cases was detected at the laboratory. Collaboration between surveillance and laboratory coordination teams during this and a later outbreak in March 2016, facilitated timely and targeted response interventions. Specimens taken from cases during both outbreaks were analysed at the laboratory with results informing clinical management of patients and discharge decisions. The GeneXpert platform is easy to use, has relatively low running costs and can be integrated into other national diagnostic algorithms. The technology has on average a 2-hour sample-to-result time and allows for single specimen testing to overcome potential delays of batching. This model of a mobile laboratory equipped with Xpert Ebola test, staffed by local laboratory technicians, could serve to strengthen outbreak preparedness and response for future outbreaks of EVD in Liberia and the region.

Development, Use, and Impact of a Global Laboratory Database During the 2014 Ebola Outbreak in West Africa.

Background: The international impact, rapid widespread transmission, and reporting delays during the 2014 Ebola outbreak in West Africa highlighted the need for a global, centralized database to inform outbreak response. The World Health Organization and Emerging and Dangerous Pathogens Laboratory Network addressed this need by supporting the development of a global laboratory database. Methods: Specimens were collected in the affected countries from patients and dead bodies meeting the case definitions for Ebola virus disease. Test results were entered in nationally standardized spreadsheets and consolidated onto a central server. Results: From March 2014 through August 2016, 256343 specimens tested for Ebola virus disease were captured in the database. Thirty-one specimen types were collected, and a variety of diagnostic tests were performed. Regular analysis of data described the functionality of laboratory and response systems, positivity rates, and the geographic distribution of specimens. Conclusion: With data standardization and end user buy-in, the collection and analysis of large amounts of data with multiple stakeholders and collaborators across various user-access levels was made possible and contributed to outbreak response needs. The usefulness and value of a multifunctional global laboratory database is far reaching, with uses including virtual biobanking, disease forecasting, and adaption to other disease outbreaks.

Evaluation of the enterovirus laboratory surveillance system in Denmark, 2010 to 2013.

The primary aim of the Danish enterovirus (EV) surveillance system is to document absence of poliovirus infection. The conflict in Syria has left many children unvaccinated and movement from areas with polio cases to Europe calls for increased awareness to detect and respond to virus-transmission in a timely manner. We evaluate the national EV laboratory surveillance, to generate recommendations for system strengthening. The system was analysed for completeness of viral typing analysis and clinical information and timeliness of specimen collection, laboratory results and reporting of clinical information. Of 23,720 specimens screened, 2,202 (9.3%) were EV-positive. Submission of cerebrospinal fluid and faecal specimens from primary diagnostic laboratories was 79.5% complete (845/1,063), and varied by laboratory and patient age. EV genotypes were determined in 68.5% (979/1,430) of laboratory-confirmed cases, clinical information was available for 63.1% (903/1,430). Primary diagnostic results were available after a median of 1.4 days, typing results after 17 days, detailed clinical information after 33 days. The large number of samples typed demonstrated continued monitoring of EV-circulation in Denmark. The system could be strengthened by increasing the collection of supplementary faecal specimens, improving communication with primary diagnostic laboratories, adapting the laboratory typing methodology and collecting clinical information with electronic forms.

Comparative analysis of Salmonella susceptibility and tolerance to the biocide chlorhexidine identifies a complex cellular defense network.

Chlorhexidine is one of the most widely used biocides in health and agricultural settings as well as in the modern food industry. It is a cationic biocide of the biguanide class. Details of its mechanism of action are largely unknown. The frequent use of chlorhexidine has been questioned recently, amidst concerns that an overuse of this compound may select for bacteria displaying an altered susceptibility to antimicrobials, including clinically important anti-bacterial agents. We generated a Salmonella enterica serovar Typhimurium isolate (ST24(CHX)) that exhibited a high-level tolerant phenotype to chlorhexidine, following several rounds of in vitro selection, using sub-lethal concentrations of the biocide. This mutant showed altered suceptibility to a panel of clinically important antimicrobial compounds. Here we describe a genomic, transcriptomic, proteomic, and phenotypic analysis of the chlorhexidine tolerant S. Typhimurium compared with its isogenic sensitive progenitor. Results from this study describe a chlorhexidine defense network that functions in both the reference chlorhexidine sensitive isolate and the tolerant mutant. The defense network involved multiple cell targets including those associated with the synthesis and modification of the cell wall, the SOS response, virulence, and a shift in cellular metabolism toward anoxic pathways, some of which were regulated by CreB and Fur. In addition, results indicated that chlorhexidine tolerance was associated with more extensive modifications of the same cellular processes involved in this proposed network, as well as a divergent defense response involving the up-regulation of additional targets such as the flagellar apparatus and an altered cellular phosphate metabolism. These data show that sub-lethal concentrations of chlorhexidine induce distinct changes in exposed Salmonella, and our findings provide insights into the mechanisms of action and tolerance to this biocidal agent.

Mechanisms of survival, responses and sources of Salmonella in low-moisture environments.

Some Enterobacteriaceae possess the ability to survive in low-moisture environments for extended periods of time. Many of the reported food-borne outbreaks associated with low-moisture foods involve Salmonella contamination. The control of Salmonella in low-moisture foods and their production environments represents a significant challenge for all food manufacturers. This review summarizes the current state of knowledge with respect to Salmonella survival in intermediate- and low-moisture food matrices and their production environments. The mechanisms utilized by this bacterium to ensure their survival in these dry conditions remain to be fully elucidated, however, in depth transcriptomic data is now beginning to emerge regarding this observation. Earlier research work described the effect(s) that low-moisture can exert on the long-term persistence and heat tolerance of Salmonella, however, data are also now available highlighting the potential cross-tolerance to other stressors including commonly used microbicidal agents. Sources and potential control measures to reduce the risk of contamination will be explored. By extending our understanding of these geno- and phenotypes, we may be able to exploit them to improve food safety and protect public health.

ProP is required for the survival of desiccated Salmonella enterica serovar typhimurium cells on a stainless steel surface.

Consumers trust commercial food production to be safe, and it is important to strive to improve food safety at every level. Several outbreaks of food-borne disease have been caused by Salmonella strains associated with dried food. Currently we do not know the mechanisms used by Salmonella enterica serovar Typhimurium to survive in desiccated environments. The aim of this study was to discover the responses of S. Typhimurium ST4/74 at the transcriptional level to desiccation on a stainless steel surface and to subsequent rehydration. Bacterial cells were dried onto the same steel surfaces used during the production of dry foods, and RNA was recovered for transcriptomic analysis. Subsequently, dried cells were rehydrated and were again used for transcriptomic analysis. A total of 266 genes were differentially expressed under desiccation stress compared with a static broth culture. The osmoprotectant transporters proP, proU, and osmU (STM1491 to STM1494) were highly upregulated by drying. Deletion of any one of these transport systems resulted in a reduction in the long-term viability of S. Typhimurium on a stainless steel food contact surface. The proP gene was critical for survival; proP deletion mutants could not survive desiccation for long periods and were undetectable after 4 weeks. Following rehydration, 138 genes were differentially expressed, with upregulation observed for genes such as proP, proU, and the phosphate transport genes (pstACS). In time, this knowledge should prove valuable for understanding the underlying mechanisms involved in pathogen survival and should lead to improved methods for control to ensure the safety of intermediate- and low-moisture foods.

Efficacy of biocides used in the modern food industry to control salmonella enterica, and links between biocide tolerance and resistance to clinically relevant antimicrobial compounds.

Biocides play an essential role in limiting the spread of infectious disease. The food industry is dependent on these agents, and their increasing use is a matter for concern. Specifically, the emergence of bacteria demonstrating increased tolerance to biocides, coupled with the potential for the development of a phenotype of cross-resistance to clinically important antimicrobial compounds, needs to be assessed. In this study, we investigated the tolerance of a collection of susceptible and multidrug-resistant (MDR) Salmonella enterica strains to a panel of seven commercially available food-grade biocide formulations. We explored their abilities to adapt to these formulations and their active biocidal agents, i.e., triclosan, chlorhexidine, hydrogen peroxide, and benzalkonium chloride, after sequential rounds of in vitro selection. Finally, cross-tolerance of different categories of biocidal formulations, their active agents, and the potential for coselection of resistance to clinically important antibiotics were investigated. Six of seven food-grade biocide formulations were bactericidal at their recommended working concentrations. All showed a reduced activity against both surface-dried and biofilm cultures. A stable phenotype of tolerance to biocide formulations could not be selected. Upon exposure of Salmonella strains to an active biocidal compound, a high-level of tolerance was selected for a number of Salmonella serotypes. No cross-tolerance to the different biocidal agents or food-grade biocide formulations was observed. Most tolerant isolates displayed changes in their patterns of susceptibility to antimicrobial compounds. Food industry biocides are effective against planktonic Salmonella. When exposed to sublethal concentrations of individual active biocidal agents, tolerant isolates may emerge. This emergence was associated with changes in antimicrobial susceptibilities.