Machine learning and deep learning techniques to support clinical diagnosis of arboviral diseases: A systematic review

Background Neglected tropical diseases (NTDs) primarily affect the poorest populations, often living in remote, rural areas, urban slums or conflict zones. Arboviruses are a significant NTD category spread by mosquitoes. Dengue, Chikungunya, and Zika are three arboviruses that affect a large proportion of the population in Latin and South America. The clinical diagnosis of these arboviral diseases is a difficult task due to the concurrent circulation of several arboviruses which present similar symptoms, inaccurate serologic tests resulting from cross-reaction and co-infection with other arboviruses. Objective The goal of this paper is to present evidence on the state of the art of studies investigating the automatic classification of arboviral diseases to support clinical diagnosis based on Machine Learning (ML) and Deep Learning (DL) models. Method We carried out a Systematic Literature Review (SLR) in which Google Scholar was searched to identify key papers on the topic. From an initial 963 records (956 from string-based search and seven from a single backward snowballing procedure), only 15 relevant papers were identified. Results Results show that current research is focused on the binary classification of Dengue, primarily using tree-based ML algorithms. Only one paper was identified using DL. Five papers presented solutions for multi-class problems, covering Dengue (and its variants) and Chikungunya. No papers were identified that investigated models to differentiate between Dengue, Chikungunya, and Zika. Conclusions The use of an efficient clinical decision support system for arboviral diseases can improve the quality of the entire clinical process, thus increasing the accuracy of the diagnosis and the associated treatment. It should help physicians in their decision-making process and, consequently, improve the use of resources and the patient’s quality of life.

Arboviral Disease Outbreaks in the Pacific Islands Countries and Areas, 2014 to 2020: A Systematic Literature and Document Review

Arthropod-borne diseases pose a significant public health threat, accounting for greater than 17% of infectious disease cases and 1 million deaths annually. Across Pacific Island countries and areas (PICs), outbreaks of dengue, chikungunya, and Zika are increasing in frequency and scale. Data about arbovirus outbreaks are incomplete, with reports sporadic, delayed, and often based solely on syndromic surveillance. We undertook a systematic review of published and grey literature and contacted relevant regional authorities to collect information about arboviral activity affecting PICs between October 2014 and June 2020. Our literature search identified 1176 unique peer-reviewed articles that were reduced to 25 relevant publications when screened. Our grey literature search identified 873 sources. Collectively, these data reported 104 unique outbreaks, including 72 dengue outbreaks affecting 19 (out of 22) PICs, 14 chikungunya outbreaks affecting 11 PICs, and 18 Zika outbreaks affecting 14 PICs. Our review is the most complete account of arboviral outbreaks to affect PICs since comparable work was published in 2014. It highlights the continued elevated level of arboviral activity across the Pacific and inconsistencies in how information about outbreaks is reported and recorded. It demonstrates the importance of a One-Health approach and the role that improved communication and reporting between different governments and sectors play in understanding the emergence, circulation, and transboundary risks posed by arboviral diseases.

Evaluation of an ivermectin-based attractive targeted sugar bait (ATSB) against Aedes aegypti in Tanzania.

Background The control of vector borne arboviral diseases such as Dengue is mainly achieved by reducing human-vector contact and controlling the vectors through source reduction and environmental management. These measures are constrained by labour intensity, insecticide resistance and pro-active community participation. The current study intended to develop and test an ivermectin-based attractive-targeted sugar bait (ATSB) against Aedes aegypti. Methods The 48hour lethal concentration (LC90) of ivermectin against Ae. aegypti was determined through serial dilution experiment where five 30cm x 30cm x 30cm cages were set; into each, a 10% sugar solution treated with ivermectin were introduced. 40 Ae. aegypti were released into each cage and observed for mortality after 4, 8, 24 and 48 hours. The ivermectin-based ATSB was evaluated in a semi field system where ATSB and attractive sugar bait (ASB) were deployed into each compartment of the semi field and 100 female Ae. aegypti were released every day and recaptured the next day through human land catch and Bio-gent sentinel trap. The developed and semi-field tested ATSB was further tested in the field by deploying them in garages. Results The ivermectin 48hr LC90 of male and female Ae. aegypti was found to be 0.03% w/v. In the semi field system, the ATSB significantly reduced a free-flying population of Ae. aegypti within 24 hours (incidence rate ratio (IRR) = 0.62; [95% confidence interval (95%CI); 0.54-0.70] and p-value < 0.001). However, in the field, the ATSBs required the addition of yeast as a carbon dioxide source to efficiently attract Ae. aegypti mosquitoes to feed. Conclusion Ivermectin is an active ingredient that can be used in an ATSB for Ae. aegypti depopulation. However, further research is needed to improve the developed and tested ATSB to compete with natural sources of sugar in a natural environment.

Tackling the global health threat of arboviruses: An appraisal of the three holistic approaches to health

Background: The rapid circulation of arboviruses in the human population has been linked with changes in climatic, environmental, and socio-economic conditions. These changes are known to alter the transmission cycles of arboviruses involving the anthropophilic vectors and thus facilitate an extensive geographical distribution of medically important arboviral diseases, thereby posing a significant health threat. Using our current understanding and assessment of relevant literature, this review aimed to understand the underlying factors promoting the spread of arboviruses and how the three most renowned interdisciplinary and holistic approaches to health such as One Health, Eco-Health, and Planetary Health can be a panacea for control of arboviruses. Methods: A comprehensive structured search of relevant databases such as Medline, PubMed, WHO, Scopus, Science Direct, DOAJ, AJOL, and Google Scholar was conducted to identify recent articles on arboviruses and holistic approaches to health using the keywords including "arboviral diseases", "arbovirus vectors", "arboviral infections", "epidemiology of arboviruses", "holistic approaches", "One Health", "Eco-Health", and "Planetary Health" Results: Changes in climatic factors like temperature, humidity, and precipitation support the growth, breeding, and fecundity of arthropod vectors transmitting the arboviral diseases. Increased human migration and urbanization due to socio-economic factors play an important role in population increase leading to the rapid geographical distribution of arthropod vectors and transmission of arboviral diseases. Medical factors like misdiagnosis and misclassification also contribute to the spread of arboviruses. Conclusion: This review highlights two important findings: First, climatic, environmental, socio-economic, and medical factors influence the constant distributions of arthropod vectors. Second, either of the three holistic approaches or a combination of any two can be adopted on arboviral disease control. Our findings underline the need for holistic approaches as the best strategy to mitigating and controlling the emerging and reemerging arboviruses.

Molecular Characterization of Associated Pathogens in Febrile Patients during Inter-Epidemic Periods of Urban Arboviral Diseases in Tapachula Southern Mexico

Emerging and re-emerging vector-borne infections are a global public health threat. In endemic regions, fever is the main reason for medical attention, and the etiological agent of such fever is not usually identified. In this study, non-specific febrile pathogens were molecularly characterized in serum samples from 253 patients suspected of arbovirus infection. The samples were collected in the southern border region of Mexico from April to June 2015, and February to March 2016. ZIKV, CHIKV, DENV, leptospirosis, and rickettsiosis were detected by qPCR and nested PCR to identify flavivirus and alphavirus genera. The results indicated that 71.93% of the samples were positive for CHIKV, 0.79% for ZIKV, and 0.39% for DENV, with the number positive for CHIKV increasing to 76.67% and those positive for ZIKV increasing to 15.41% under the nested PCR technique. Leptospira Kmetyi was identified for the first time in Mexico, with a prevalence of 3.16%. This is the first report of ZIKV in Mexico, as well the first detection of the virus in early 2015. In conclusion, the etiological agent of fever was determined in 94% of the analyzed samples.

Simbu Viruses’ Infection of Livestock in Israel—A Transient Climatic Land

Important lessons have been learned by the Israeli veterinary community regarding Simbu serogroup viruses infections. This serogroup of viruses might cause the births of neonatal malformation in susceptible ruminant’s populations. Until 2012, only Akabane virus was connected with the births of malformed ruminants in Israel. However, serological and genomic detection tests, coupled with viral isolations, revealed that more than a single Simbu serogroup serotype could be present concurrently in the same farm or even in the same animal. From 2012 to date, Aino, Shuni, Shamunda, Satuperi, Peaton, Schmallenberg, and Sango viruses have been found in Israel either by serological or genomic investigation. Israel is located in the Eastern Mediterranean Basin, a terrestrial and climatic bridge between the three old continents. The Eastern Mediterranean shores benefit from both the tropical/subtropical and the continental climatic conditions. Therefore, the Eastern Mediterranean basin might serve as an optimal investigatory compound for several arboviral diseases, acting as a sentinel. This review summarizes updated information related to the presence of Simbu serogroup viruses in Israel.

ArVirInd - a database of arboviral antigenic proteins from the Indian subcontinent

Studies on antigenic proteins for arboviruses are important for providing diagnostics and vaccine development. India and its neighbouring countries have huge burden of arboviral diseases. Data mining for country-specific sequences from existing databases is cumbersome and time-consuming. This necessitated the development of a database of antigenic proteins from arbo-viruses isolated from the countries of the Indian subcontinent. Arboviral antigenic protein sequences were obtained from the NCBI and other databases. In silico antigenic characterization was performed (Epitope predictions) and data incorporated in the database. The front end is designed and developed using HTML, CSS and PHP. For the backend of the database, we have used MySQL. A database, named ArVirInd, is created as a repository of information on antigenic proteins. This enlists sequences by country and year of outbreak or origin of the viral strain. For each entry antigenic information is provided along with functional sites, etc. Researchers can search this database by virus/protein name, country and year of collection (or in combination). It is available publicly via Internet at http://www.arvirind.co.in. ArVirInd will be useful in the study of immuno-informatics, diagnostics and vaccinology for arboviruses.

Novel Symbiotic Genome-Scale Model Reveals Wolbachia 's Arboviral Pathogen Blocking Mechanism in Aedes aegypti

Arboviral diseases such as Zika and Dengue have been on the rise mainly due to climate change, and the development of new treatments and strategies to limit their spreading is needed. The use of Wolbachia as an approach for disease control has motivated new research related to the characterization of the mechanisms that underlie its pathogen-blocking properties.

First Report of Adult Aedes aegypti (Diptera: Culicidae) Resistance to Pyrethroids in Argentina

Severe human arboviral diseases can be transmitted by the mosquito Aedes aegypti (Linnaeus), including dengue, chikungunya, Zika, and yellow fever. Adult control using spatial sprays with adulticides is recommended only when dengue outbreaks occur. In Argentina, mainly pyrethroids, like cis-permethrin, have been used as an adulticide, especially since 2008. The evolution and spread of resistance to insecticides is a major concern for vector control. This study reports for the first time pyrethroid resistance in Ae. aegypti adults from Argentina, in the city of Salvador Mazza (Salta). WHO discriminating doses of 0.75% were used for permethrin, 0.05% for deltamethrin, and 5% for malathion. Also the discriminating dose for cis-permethrin (0.6%) was calculated and evaluated for the first time. We found a resistance ratio 50 (RR50) of 10.3 (9.7–10.4) for cis-permethrin, which is considered as high resistance. Our results also indicated resistance to deltamethrin (22.6% mortality) and permethrin (53.6% mortality), and a total susceptibility to malathion (100% mortality). Results from this study highlight the importance of the correct use of insecticides within an Integrated Vector Management (IVM) approach and of early detection of resistance to enable Ae. aegypti control in Argentina. More studies are needed to determine the spread of mosquito resistance to pyrethroids.