Re-emerging Infectious Disease Research Articles

Isolation and molecular confirmation of leptospires from dogs in Himachal Pradesh, India

Leptospirosis is a common but largely underreported zoonotic disease in India. It has been recognized as a re-emerging infectious disease causing deaths in dogs as well as humans. Leptospires have been isolated from both clinically ill and apparently healthy animals from different geographical regions but there is no information on the presence of leptospires in various clinical conditions of animals in the northern state of Himachal Pradesh, India. Here, using dark field microscopy, culture isolation and molecular biology-based tests, we confirm leptospirosis in three clinically affected dogs with chronic renal involvement. The study reports the first isolation and molecular confirmation of leptospires from clinically affected dogs in Himachal Pradesh, India.

Zoonotic diseases: a One Health perspective

Abstract The emergence and re-emergence of infectious diseases including zoonoses and persistence of neglected zoonotic diseases threaten the global health and economy of rural societies now more than any time in the history of humanity. Animals are the main reservoirs of zoonotic disease agents, and zoonotic pathogens are transmitted to humans by direct contacts with infected animals or indirectly through animal products and the environment. A range of factors contribute in persistence and emergence of zoonoses, and globalization, climate change, and lack of proper coordination among the governmental organization responsible for human and animal health are the key indicators. Given the shared nature of zoonotic diseases and the spread, emergence, and re-emergence of zoonotic diseases in human and animal populations, integrated One Health is the only effective approach to solve this most important health issue. In this article, different aspects of zoonotic diseases, their role in incremental poverty, and the needs for integrated activities for their control and management are reviewed and discussed in detail.

Development and Evaluation of a Three-Dimensional Printer–Based DNA Extraction Method Coupled to Loop Mediated Isothermal Amplification for Point-of-Care Diagnosis of Congenital Chagas Disease in Endemic Regions

Vertical transmission of Trypanosomacruzi is the cause of congenital Chagas disease, a re-emerging infectious disease that affects endemic and nonendemic regions alike. An early diagnosis is crucial because prompt treatment achieves a high cure rate, precluding evolution to symptomatic chronic Chagas disease. However, early diagnosis involves low-sensitive parasitologic assays, making necessary serologic confirmation after 9 months of life. With the aim of implementing early diagnostic strategies suitable for minimally equipped laboratories, a T. cruzi-loop-mediated isothermal amplification (LAMP) prototype was coupled with an automated DNA-extraction device repurposed from a three-dimensional printer (PrintrLab). The whole process takes <3 hours to yield a result, with an analytical sensitivity of 0.1 to 2 parasite equivalents per milliliter, depending on the T. cruzi strain. Twenty-five blood samples from neonates born to seropositive mothers were tested blindly. In comparison to quantitative real-time PCR, the PrintrLab-LAMP dual strategy showed high agreement, while both molecular-based methodologies yielded optimal sensitivity and specificity with respect to microscopy-based diagnosis of congenital Chagas disease. PrintrLab-LAMP detected all 10 congenitally transmitted T. cruzi infections, showing promise for point-of-care early diagnosis of congenital Chagas disease.

Epidemics and Climate Change in India

As the world deals with COVID-19, there is increasing attention to the threat of emerging and re-emerging infectious diseases. India is especially vulnerable to climate-induced health risks and a hotspot for infectious diseases. In this study we use a scoping review to synthesize evidence on the impact of climate on infectious diseases. We use this to uncover gaps and understand the implications for policymaking and health system preparedness. There is a strong evidence base linking climate change to disease outbreaks, both directly and indirectly. Socio-economic factors are the modifiers that determine disease severity in different populations and locations.

Plague reservoir species throughout the world.

Plague has been known since ancient times as a re-emerging infectious disease, causing considerable socioeconomic burden in regional hotspots. To better understand the epidemiological cycle of the causative agent of the plague, its potential occurrence, and possible future dispersion, one must carefully consider the taxonomy, distribution, and ecological requirements of reservoir-species in relation either to natural or human-driven changes (e.g. climate change or urbanization). In recent years, the depth of knowledge on species taxonomy and species composition in different landscapes has undergone a dramatic expansion, driven by modern taxonomic methods such as synthetic surveys that take into consideration morphology, genetics, and the ecological setting of captured animals to establish their species identities. Here, we consider the recent taxonomic changes of the rodent species in known plague reservoirs and detail their distribution across the world, with a particular focus on those rodents considered to be keystone host species. A complete checklist of all known plague-infectable vertebrates living in plague foci is provided as a Supporting Information table.

Anti-FIM and Anti-FHA Antibodies Inhibit Bordetella pertussis Growth and Reduce Epithelial Cell Inflammation Through Bacterial Aggregation.

The pertussis vaccination is highly recommended for infants, children, and pregnant women. Despite a high coverage of vaccination, pertussis continues to be of public health concern as a re-emerging infectious disease. The mechanism by which vaccine-elicited anti-pertussis antibodies mediate direct bactericidal effects is poorly understood. In this study, we showed that the interaction of B. pertussis with A549 epithelial cells induce release of biological factors which enhance bacteria growth. Complement-depleted antisera from vaccine-immunized guinea pigs or monoclonal antibodies targeting FHA and FIM mediate bacteria aggregation and elicit bactericidal effects. Our in vitro results indicated that aggregation of bacteria through anti-FIM and anti-FHA specific antibodies is one of the major biological mechanisms to clear bacterial infections and restore epithelial cell survival in vitro. Our data also indicates that the anti-pertussis antibodies reduce secretion of proinflammatory chemokines and cytokines by preventing interaction of B. pertussis with host cells. The results of this study not only demonstrate mechanism of action of anti-FIM and anti-FHA antibodies, but also opens translational applications for potential therapeutic approaches or development of analytical assays such as in vitro potency assays.

Estimating the basic reproduction number for the 2015 bubonic plague outbreak in Nyimba district of Eastern Zambia.

BackgroundPlague is a re-emerging flea-borne infectious disease of global importance and in recent years, Zambia has periodically experienced increased incidence of outbreaks of this disease. However, there are currently no studies in the country that provide a quantitative assessment of the ability of the disease to spread during these outbreaks. This limits our understanding of the epidemiology of the disease especially for planning and implementing quantifiable and cost-effective control measures. To fill this gap, the basic reproduction number, R0, for bubonic plague was estimated in this study, using data from the 2015 Nyimba district outbreak, in the Eastern province of Zambia. R0 is the average number of secondary infections arising from a single infectious individual during their infectious period in an entirely susceptible population.Methodology/Principal findingsSecondary epidemic data for the most recent 2015 Nyimba district bubonic plague outbreak in Zambia was analyzed. R0 was estimated as a function of the average epidemic doubling time based on the initial exponential growth rate of the outbreak and the average infectious period for bubonic plague. R0 was estimated to range between 1.5599 [95% CI: 1.382–1.7378] and 1.9332 [95% CI: 1.6366–2.2297], with average of 1.7465 [95% CI: 1.5093–1.9838]. Further, an SIR deterministic mathematical model was derived for this infection and this estimated R0 to be between 1.4 to 1.5, which was within the range estimated above.Conclusions/SignificanceThis estimated R0 for bubonic plague is an indication that each bubonic plague case can typically give rise to almost two new cases during these outbreaks. This R0 estimate can now be used to quantitatively analyze and plan measurable interventions against future plague outbreaks in Zambia.

Molecular and Serological Prevalence of Leptospira spp. in Feral Pigs (Sus scrofa) and their Habitats in Alabama, USA.

Leptospirosis is a widespread zoonosis and has been recognized as a re-emerging infectious disease in humans and a variety of wild and domestic animal species. In order to understand the prevalence and diversity of Leptospira spp. in feral pig populations of Alabama, we trapped 315 feral pigs in Bullock County east-central Alabama, and collected 97 environmental samples from riparian areas in Bullock County and Macon County east-central Alabama. Two previously published PCRs followed by DNA sequencing and BLASTn were performed to identify pathogenic Leptospira species in the kidney of feral pigs (3.2%, 10/315) as well as environmental samples collected from the habitats of feral pigs (2.1%, 2/97), but not in the whole blood samples (n = 276) or spleen (n = 51). An ELISA determined that 44.2% of serum samples (122/276) were antibody-positive for Leptospira. The identification of two pathogenic Leptospira species from environmental samples and the high sero-positivity in feral pigs suggests potential pathogen shedding from feral pigs to environments, and to humans and domestic animals. In order to better understand the risk to human health associated with feral swine presence, further studies are warranted to explore the interrelationship between Leptospira spp. shedding in the urine of feral pigs and bacterial culture to explore pathogenicity. Multi-locus sequencing typing (MLST) and microscopic agglutination tests (MAT) should be performed in future studies to make a definite determination of pathogenic Leptospira in feral pigs in Alabama.

Usability and the Rapid Deployable Infectious Disease Decision Support System.

Health information technology-guided clinical decision support has demonstrated decreases in patient safety errors in the electronic health record. Unknown and re-emerging infectious diseases are a growing concern for many healthcare facilities. The purpose of this project was to develop a modular approach to integrate rapid deployment of clinical decision support for infectious diseases into the clinical workflow and evaluate the usability of the design. This article reports on the results of a quality improvement project to develop, implement, and evaluate rapid deployment of a clinical decision support module using a tuberculosis use case. Important lessons learned from the electronic health record build with previous Ebola and Zika decision support alert strategy are discussed as foundational in guiding the overall design, implementation, and evaluation of improvement strategies. Subject matter expert feedback was sought throughout the project for electronic health record design and build considerations. Usability evaluation was conducted using the classic Task, User, Representation, and Function unified framework of electronic health record usability. Usability satisfaction for both providers and nurses remained high. Tuberculosis cases pre-alert and post-alert had decreased order times for diagnostic studies. Results suggest satisfied clinicians coupled with usable systems create a more efficient workflow resulting in safer and timelier diagnostic testing.

These Are the Genes You're Looking For: Finding Host Resistance Genes.

Humanity's ongoing struggle with new, re-emerging and endemic infectious diseases serves as a frequent reminder of the need to understand host-pathogen interactions. Recent advances in genomics have dramatically advanced our understanding of how genetics contributes to host resistance or susceptibility to bacterial infection. Here we discuss current trends in defining host-bacterial interactions at the genome-wide level, including screens that harness CRISPR/Cas9 genome editing, natural genetic variation, proteomics, and transcriptomics. We report on the merits, limitations, and findings of these innovative screens and discuss their complementary nature. Finally, we speculate on future innovation as we continue to progress through the postgenomic era and towards deeper mechanistic insight and clinical applications.

Tularemia: a re-emerging tick-borne infectious disease.

Tularemia is a bacterial disease of humans, wild, and domestic animals. Francisella tularensis, which is a Gram-negative coccobacillus-shaped bacterium, is the causative agent of tularemia. Recently, an increase in the number of human tularemia cases has been noticed in several countries around the world. It has been reported mostly from North America, several Scandinavian countries, and certain Asian countries. The disease spreads through vectors such as mosquitoes, horseflies, deer flies, and ticks. Humans can acquire the disease through direct contact of sick animals, consumption of infected animals, drinking or direct contact of contaminated water, and inhalation of bacteria-loaded aerosols. Low infectious dose, aerosol route of infection, and its ability to induce fatal disease make it a potential agent of biological warfare. Tularemia leads to several clinical forms, such as glandular, ulceroglandular, oculoglandular, oropharyngeal, respiratory, and typhoidal forms. The disease is diagnosed through the use of culture, serology, or molecular methods. Quinolones, tetracyclines, or aminoglycosides are frequently used in the treatment of tularemia. No licensed vaccine is available in the prophylaxis of tularemia and this is need of the time and high-priority research area. This review mostly focuses on general features, importance, current status, and preventive measures of this disease.

A computational framework for modeling and studying pertussis epidemiology and vaccination

BackgroundEmerging and re-emerging infectious diseases such as Zika, SARS, ncovid19 and Pertussis, pose a compelling challenge for epidemiologists due to their significant impact on global public health. In this context, computational models and computer simulations are one of the available research tools that epidemiologists can exploit to better understand the spreading characteristics of these diseases and to decide on vaccination policies, human interaction controls, and other social measures to counter, mitigate or simply delay the spread of the infectious diseases. Nevertheless, the construction of mathematical models for these diseases and their solutions remain a challenging tasks due to the fact that little effort has been devoted to the definition of a general framework easily accessible even by researchers without advanced modelling and mathematical skills.ResultsIn this paper we describe a new general modeling framework to study epidemiological systems, whose novelties and strengths are: (1) the use of a graphical formalism to simplify the model creation phase; (2) the implementation of an R package providing a friendly interface to access the analysis techniques implemented in the framework; (3) a high level of portability and reproducibility granted by the containerization of all analysis techniques implemented in the framework; (4) a well-defined schema and related infrastructure to allow users to easily integrate their own analysis workflow in the framework. Then, the effectiveness of this framework is showed through a case of study in which we investigate the pertussis epidemiology in Italy.ConclusionsWe propose a new general modeling framework for the analysis of epidemiological systems, which exploits Petri Net graphical formalism, R environment, and Docker containerization to derive a tool easily accessible by any researcher even without advanced mathematical and computational skills. Moreover, the framework was implemented following the guidelines defined by Reproducible Bioinformatics Project so it guarantees reproducible analysis and makes simple the developed of new user-defined workflows.

Recent advances and challenges in electrochemical biosensors for emerging and re-emerging infectious diseases

The rise of emerging infectious diseases (EIDs) as well as the increase in spread of existing infections is threatening global economies and human lives, with several countries still fighting repeated onslaught of a few of these epidemics. The catastrophic impact a pandemic has on humans and economy should serve as a reminder to be better prepared to the advent of known and unknown pathogens in the future. The goal of having a set of initiatives and procedures to tackle them is the need of the hour.Rapid detection and point-of-care (POC) analysis of pathogens causing these diseases is not only a problem entailing the scientific community but also raises challenges in tailoring appropriate treatment strategies to the healthcare sector. Among the various methods used to detect pathogens, Electrochemical Biosensor Technology is at the forefront in the development of POC devices. Electrochemical Biosensors stand in good stead due to their rapid response, high sensitivity and selectivity and ease of miniaturization to name a few advantages.This review explores the innovations in electrochemical biosensing based on the various electroanalytical techniques including voltammetry, impedance, amperometry and potentiometry and discusses their potential in diagnosis of emerging and re-emerging infectious diseases (Re-EIDs), which are potential pandemic threats.

Diagnosis of scrub typhus: recent advancements and challenges.

Scrub typhus is a mite-borne, acute febrile illness caused by the bacterium Orientia tsutsugamushi. It is a re-emerging infectious disease of the tsutsugamushi triangle. Scrub typhus is transmitted through bites of contaminated chiggers (larval stage). Diagnosis of scrub typhus is challenging as its symptoms mimic with other acute febrile illnesses. Several methods are effectual for diagnosis of scrub typhus that includes enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), immunochromatographic test (ICT), Weil–Felix, polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP). Weil–Felix test was initially used for the diagnosis of scrub typhus in underdeveloped countries but not preferred due to a lack of both specificity and sensitivity. Other immuno-based methods like IFA and ELISA are most outrank for detection of scrub typhus due to their higher sensitivity and specificity, but not vigorous to lay bare the infection at early stages and need the convalescent sampling for verification of positive samples. On another deed, PCR based methods becoming acceptable over era due to its dexterity of early-stage diagnosis with higher specificity and sensitivity but lack its applicability in circumstances of scrub typhus due to the variegated genetic makeup of Orientia tsutsugamushi among its serotypes. The present review focused on various detection methods along with their advantages and disadvantages used in the diagnosis of scrub typhus. A comparison between available methods of diagnosis with challenges in the detection of scrub typhus is also summarized.

Detection of Emerging Infectious Disease in Cynopterus brachyotis and Rhinolopus boorneensis as Reservoirs of Zoonotic Diseases in Indonesia

Bats are mammal species that have the highest diversity. During the last two decades, various types of infections caused by microorganisms have again become epidemic in many countries, this phenomenon is known as a new infectious disease that arises and re-emerges or Re-Emerging Infectious Diseases (EID/ REID). The purpose of this study was to identify EID in bats in the karst area of South Malang. The research method of bat sampling is conducted in the karst area of South Malang, bats are identified by species, taken by blood, prepared and carried out by NGS (next generation sequencing). From the results of the research conducted, obtained 2 types of bats namely fruit-eating bats (Chiroptera brachjatis) and insect bats (Rhinolopus boorneensis). From the results of the NGS, we get specific viruses and bacteria in bats. The conclusion of this research is that bat in South Malang Karst has potential as a carrier of EID and zoonotic disease.

First Prototype of the Infectious Diseases Seeker (IDS) Software for Prompt Identification of Infectious Diseases

The rapid detection of ongoing outbreak — and the identification of causative pathogen — is pivotal for the early recognition of public health threats. The emergence and re-emergence of infectious diseases are linked to several determinants, both human factors — such as population density, travel, and trade — and ecological factors — like climate change and agricultural practices. Several technologies are available for the rapid molecular identification of pathogens [e.g. real-time polymerase chain reaction (PCR)], and together with on line monitoring tools of infectious disease activity and behaviour, they contribute to the surveillance system for infectious diseases. Web-based surveillance tools, infectious diseases modelling and epidemic intelligence methods represent crucial components for timely outbreak detection and rapid risk assessment. The study aims to integrate the current prevention and control system with a prediction tool for infectious diseases, based on regression analysis, to support decision makers, health care workers, and first responders to quickly and properly recognise an outbreak. This study has the intention to develop an infectious disease regressive prediction tool working with an off-line database built with specific epidemiological parameters of a set of infectious diseases of high consequences. The tool has been developed as a first prototype of a software solution called Infectious Diseases Seeker (IDS) and it had been established in two main steps, the database building stage and the software implementation stage (MATLAB® environment). The IDS has been tested with the epidemiological data of three outbreaks occurred recently: severe acute respiratory syndrome epidemic in China (2002–2003), plague outbreak in Madagascar (2017) and the Ebola virus disease outbreak in the Democratic Republic of Congo (2018). The outcomes are promising and they reveal that the software has been able to recognize and characterize these outbreaks. The future perspective about this software regards the developing of that tool as a useful and user-friendly predictive tool appropriate for first responders, health care workers, and public health decision makers to help them in predicting, assessing and contrasting outbreaks.

Biosafety and biosecurity approaches to restrain/contain and counter SARS-CoV-2/COVID-19 pandemic: a rapid-review.

Emergence and reemergence of infectious diseases pose significant public health risks that are continuously haunting human civilization in the past several decades. Such emerging pathogens should be considered as a high threat to humans, animals, and environmental health. The year 2020 was welcomed by another significant virus from family Coronaviridae called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the coronavirus disease 2019 (COVID-19). The disease was first reported in the city of Wuhan, Hubei province, China. Within a short time, this disease attained the status of the Public Health Emergency of International Concern. Presently, COVID-19 has spread to more than 150 countries, therefore, the World Health Organization (WHO) called it a pandemic. The Chinese government, along with WHO, other health agencies, and many nations, are monitoring the current situation closely to analyze the impact of SARS-CoV-2/COVID-19 on humans, animals, and environmental health. In the context of the current situation, biosafety and biosecurity measure that focus on One Health aspects of the disease outbreaks and the SARS-CoV-2 spread are of great importance to restrain this pathogen. Along with these efforts, standard precaution and control measures should also be taken at personal and community level to prevent the spreading of any contagion diseases, including COVID-19. Researchers are putting their very high efforts to develop suitable vaccines and therapeutics/drugs to combat COVID-19. This review aims to highlight the importance of biosafety, biosecurity, One Health approach, and focusing on recent developments and the ways forward to prevent and control COVID-19 in a useful way.

The zoonotic pathogen Leptospira interrogans mitigates environmental stress through cyclic-di-GMP-controlled biofilm production

The zoonotic bacterium Leptospira interrogans is the aetiological agent of leptospirosis, a re-emerging infectious disease that is a growing public health concern. Most human cases of leptospirosis result from environmental infection. Biofilm formation and its contribution to the persistence of virulent leptospires in the environment or in the host have scarcely been addressed. Here, we examined spatial and time-domain changes in biofilm production by L. interrogans. Our observations showed that biofilm formation in L. interrogans is a highly dynamic process and leads to a polarized architecture. We notably found that the biofilm matrix is composed of extracellular DNA, which enhances the biofilm’s cohesiveness. By studying L. interrogans mutants with defective diguanylate cyclase and phosphodiesterase genes, we show that biofilm production is regulated by intracellular levels of bis-(3′–5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) and underpins the bacterium’s ability to withstand a wide variety of simulated environmental stresses. Our present results show how the c-di-GMP pathway regulates biofilm formation by L. interrogans, provide insights into the environmental persistence of L. interrogans and, more generally, highlight leptospirosis as an environment-borne threat to human health.

Dynamical footprints enable detection of disease emergence.

Developing methods for anticipating the emergence or reemergence of infectious diseases is both important and timely; however, traditional model-based approaches are stymied by uncertainty surrounding the underlying drivers. Here, we demonstrate an operational, mechanism-agnostic detection algorithm for disease (re-)emergence based on early warning signals (EWSs) derived from the theory of critical slowing down. Specifically, we used computer simulations to train a supervised learning algorithm to detect the dynamical footprints of (re-)emergence present in epidemiological data. Our algorithm was then challenged to forecast the slowly manifesting, spatially replicated reemergence of mumps in England in the mid-2000s and pertussis post-1980 in the United States. Our method successfully anticipated mumps reemergence 4 years in advance, during which time mitigation efforts could have been implemented. From 1980 onwards, our model identified resurgent states with increasing accuracy, leading to reliable classification starting in 1992. Additionally, we successfully applied the detection algorithm to 2 vector-transmitted case studies, namely, outbreaks of dengue serotypes in Puerto Rico and a rapidly unfolding outbreak of plague in 2017 in Madagascar. Taken together, these findings illustrate the power of theoretically informed machine learning techniques to develop early warning systems for the (re-)emergence of infectious diseases.

PIN79 VACCINATION COVERAGE RATE: WHAT CAN WE EXPECT FROM BRAZIL?

The maintenance of high vaccine coverage rates is an important strategy for infectious disease control in the context of migration and tourism. The annual rate of vaccination coverage (ARVC) has decreased in Brazil in recent years. Our aim is to analyze historical ARVC data and forecast Brazilian performance in the next five years. We applied the Autoregressive Integrated Moving Average (ARIMA) model to the Brazilian ARVC time series from 1994 to 2018. Data were collected from the National Immunization Program and evaluated in four steps: (1) Data analysis: data were analyzed to identify stationarity, seasonal variation, level, cycle and trend; (2) Model Identification: this involved the estimation of the parameters p, d and q using the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) values; (3) Model checking: this step determined whether the specified model was valid based on multi-step-ahead forecasting; and (4) Forecasting: the model was tested on real data to forecast the next five years of ARVC. The data showed a growing in ARVC between 1994 and1999, random variations from 2000-2010 and irregular variations between 2011 and 2018. The largest reduction in ARVC occurred in 2016 (50.4%). The AIC automatically identified a best model with ARIMA (1, 1, 2) in software Gretl. The ARIMA (1, 1, 2) forecast showed that ARVC will increase on average by 1.53% per year and a total of 7.06% over the next 5 years to reach an ARVC of 77.07 by 2023, if no government action is taken during this period. The ARIMA model can be used for forecasting future ARVC and will help decision-makers to establish strategies for the Brazilian vaccination program. Health authorities should make every effort to reestablish ARVC greater than 90% to avoid the re-emergence of infectious diseases that were previously controlled or eliminated in Brazil.