Viral Zoonosis Research Articles

A candidate tick-borne encephalitis virus vaccine based on virus-like particles induces specific cellular and humoral immunity in mice1

Tick-borne encephalitis (TBE) is an important zoonotic viral disease transmitted by ticks. In recent decades, global climate change has increased human exposure to ticks, and mortality rates have gradually risen. Effective vaccines are essential for controlling TBE as specific antiviral treatment is unavailable. Vaccine candidates based on virus-like particles (VLPs) have previously been demonstrated to be efficient in eliciting excellent immune responses against influenza virus and SARS-CoV-2. Here, we constructed TBE virus (TBEV) VLPs containing the envelope and membrane proteins derived from the Far Eastern TBEV strain (WH2012) using an insect cell-baculovirus expression system. Induction of immune responses was investigated in mice following intramuscular injection with the TBEV VLPs vaccine candidates formulated of Poly(I:C) & Montanide ISA 201VG combination adjuvants. Mice produced memory T-cells and serum-specific IgG antibodies that averaged up to 1:104.6 and remained at 1:104 (mean) for 24 weeks after three immunizations. TBEV VLPs vaccine was able to provide long-term antibody protection against TBEV, making it a promising subunit vaccine candidate for this disease.

The Rift Valley fever (RVF) vaccine candidate 40Fp8 shows an extreme attenuation in IFNARKO mice following intranasal inoculation.

Rift Valley fever (RVF) is an important zoonotic viral disease affecting several species of domestic and wild ruminants, causing major economic losses and dozens of human deaths in various geographical areas of Africa, where it is endemic. Although it is not present in Europe, there is a risk of its introduction and spread linked to globalisation and climate change. At present, the only measure that could help to prevent the disease is vaccination of flocks in areas at risk of RVF. Available live attenuated vaccines are an effective means of controlling the disease, but their use is often questioned due to residual virulence, particularly in susceptible hosts such as pregnant sheep. On the other hand, no vaccine is currently licensed for use in humans. The development of safe and effective vaccines is therefore a major area of research. In previous studies, we selected under selective mutagenic pressure a highly attenuated RVFV 56/74 virus variant called 40Fp8. This virus showed an extremely attenuated phenotype in both wild-type and immunodeficient A129 (IFNARKO) mice, yet was still able to induce protective immunity after a single inoculation, thus supporting its use as a safe, live attenuated vaccine. To further investigate its safety, in this work we have analysed the attenuation level of 40Fp8 in immunosuppressed mice (A129) when administered by the intranasal route, and compared it with other attenuated RVF viruses that are the basis of vaccines in use or in development. Our results show that 40Fp8 has a much higher attenuated level than these other viruses and confirm its potential as a candidate for safe RVF vaccine development.

The Silent Threat: Unraveling the Impact of Rabies in Herbivores in Brazil.

Rabies, a zoonotic viral disease, poses a significant threat due to its adaptability to diverse environments. Herbivore rabies, predominantly affecting cattle, horses, and goats in Brazil, remains a concern, results in substantial losses in the livestock industry, and poses risks to public health. Rabies virus transmission, primarily through hematophagous bats in Latin America, underscores the need for effective strategies, and vaccination plays a crucial role in controlling herbivorous rabies, with systematic vaccination beingly the primary method. Efforts to control rabies in herbivores include vaccination campaigns, public awareness programs, and the enhancement of surveillance systems. Despite these initiatives, rabies persists and imposes an economic burden and a significant health risk. Economic impacts include losses in the livestock industry, trade restrictions on livestock products, and financial burdens on governments and farmers owing to control measures. Despite the considerable costs of campaigns, surveillance, and control, investing in rabies vaccination and control not only safeguards livestock, but also preserves public health, reduces human cases, and strengthens the sustainability of the livestock industry. Mitigating the impact of herbivorous rabies in Brazil requires integrated approaches and continuous investments in vaccination, surveillance, and control measures to protect public health and ensure the sustainability of the livestock industry, thus contributing to food and economic security.

Probable paralytic rabies in a dog: ante-mortem clinical diagnosis implications in limited resource settings.

Rabies is a dreadful zoonotic viral disease that affects animals and humans with a fatality rate of 100%. This report aims to create awareness among the veterinarians and general public about the paralytic form of rabies in order to understand the antemortem clinical diagnosis implications in limited resource settings, so as to follow the post-exposure prophylaxis at the golden hour period of rabies transmission. A one-year-old female dog was presented to the Ambulatory Clinic Unit, Veterinary Clinical Complex, Veterinary College and Research Institute, Theni, Tamil Nadu, India with the ailment of a dropped jaw and was unable to swallow food and water for the past three days. Epidemiological investigations revealed that the animal had dog-bitten wounds from a week ago. On clinical examination, facial distortion, changes in the vocal cord, and paralysis of the throat muscle were noticed. Based on the anamnesis, clinical, and epidemiological investigations, the animal was diagnosed to be a probable case of paralytic form of canine rabies. In the limited resource settings, antemortem clinical diagnosis was practiced to suspect rabies-infected dogs. Further, the owner was advised to implement preventive measures to safeguard against rabies infection. The dog was kept under isolation and succumbed on day two with evidence of progressive paralytic signs. This report emphasizes the importance of paralytic rabies, alongside of furious form of rabies, further creating awareness among the general public about the antemortem clinical diagnosis under limited resource settings.

A survey of the tick-borne disease Crimean-Congo hemorrhagic fever in southern Algeria: First serological evidence in the dromedary camel population

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral zoonosis caused by a Nairovirus, Crimean-Congo hemorrhagic fever virus (CCHFV). Despite its wide geographical distribution, the epidemiology of CCHF in northern Africa is incompletely understood and its occurrence in Algeria is virtually unknown. The present survey aimed to determine the prevalence of CCHF antibodies and to identify the potential risk factors associated with CCHFV seropositivity among the one-humped camel (Camelus dromedarius) in southern Algeria. A total of 269 camels selected randomly from slaughterhouses in three wilayas were employed in the study. Sera sampled were tested for the presence of CCHFV-specific IgG antibodies using enzyme-linked immunosorbent assay (ELISA). CCHFV seropositivity was recorded in 255 out of 269 camels accounting for a prevalence rate of 94.8% (95%CI = 92.14–97.45). The seroprevalence by origin was determined to be 97% (193/199) in imported camels and 86% (49/57) in local ones (p > 0.25). Tick presence (OR = 12.35, 95%CI = 1.41–107.43, p < 0.05) was recorded as the only potential risk factor for contracting CCHFV. This study shows for the first time that camels are exposed to CCHFV in Algeria with a significantly high seroprevalence. It also underlines the need for further research to investigate the broader extent of circulating CCHFV in the country, whether in humans, animals, or ticks.

The importance of a One Health approach in preventing human Rift Valley fever infections in Uganda

Rift valley fever (RVF) is an endemic viral zoonosis in Uganda that causes sporadic outbreaks. In May 2021, a 19-year-old woman from Kasaana Village, Kiruhura District, Western Uganda was diagnosed with RVF. In addition, five case patients identified from the same village were immunoglobulin (Ig) M–seropositive for RVF virus (RVFV), all with a history of contact with livestock. We interviewed farmers in Kasaana Village to find out whether their livestock had recently experienced any sign of RVF (livestock abortions and neonatal mortality). We conducted a veterinary records review at the regional animal diagnostic laboratory and a case search for livestock that had a recent history of abortion or neonatal mortality. Among 162 livestock (94 cattle and 68 goats) from four farms reporting one or more abortions during March-June 2021, 57 (33 cattle and 24 goats) were randomly selected for testing for RVFV using enzyme linked immunosorbent assay. Verbal reports from farmers and veterinary records review revealed increases in livestock abortions and neonatal mortality during March-May 2021, before the human cases occurred. Serological testing indicated that eight (14%) livestock, including three (9%) cattle and five (21%) goats, were IgM-seropositive for RVFV. The presence of anti-RVFV IgM antibodies in sera suggested current infection in livestock, corroborating livestock abortions within the same period. Hence, human RVFV infections likely resulted from contact with infected animal products. The recurring pattern of livestock abortions observed before human RVFV infections in Uganda indicates a gap in the zoonotic disease surveillance system, through which reports on such events should trigger rapid response to detect disease, control spread among animals, and prevent spillover to humans. An expanded One Health approach on collaboration and information sharing on such events could facilitate RVF risk reduction in humans in Uganda.

Enzyme immunoassay system for serological diagnosis of hemorrhagic fever with renal syndrome based on inactivated purified Puumala virus (Hantaviridae: Orthohantavirus)

Hemorrhagic fever with renal syndrome (HFRS) is the most common zoonotic human viral disease in the Russian Federation. More than 98% of the HFRS cases are caused by Puumala orthohantavirus (PUU). Effective serological tests are required for laboratory diagnosis of HFRS. Construction of an enzyme immunoassay (ELISA) test system for detection of specific antibodies using standard antigen in the form of highly purified inactivated PUU virus as immunosorbent. Preparation of PUU virus antigen, designing the ELISA for detection of specific antibodies, developing parameters of the ELISA system, parallel titration of HFRS patients sera by fluorescent antibody technique (FAT) and the new ELISA. For the first time, ELISA based on purified inactivated PUU virus as standard antigen directly absorbed onto immunoplate was developed. Parallel titration of 50 samples from HFRS patients blood sera using FAT and the developed ELISA showed high sensitivity and specificity of this ELISA, with 100% concordance of testing results and significant level of correlation between the titers of specific antibodies in the two assays. The ELISA based on purified inactivated PUU virus as an immunosorbent can be effectively used for HFRS serological diagnosis and for mass seroepidemiological studies.

Investigation of hsa-miR-1908 and hsa-miR-144 Expression Levels in Crimean-Congo Hemorrhagic Fever Patients

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic viral disease. MicroRNAs (miRNAs), which play an important role in the regulation of gene expression, are involved in many processes essential for cell life such as development, differentiation, survival, apoptosis and aging. If miRNAs fail to fulfill their functions, they cause susceptibility to many diseases, including viral infections or cause the disease to be experienced in different clinical situations, such as severe or mild. In this study, we aimed to determine the expression levels of hsa-miR-144 and hsa-miR-1908 in CCHF patients and to compare the results in different clinical courses of CCHF disease. In this study, expression levels of hsa-miR-144 and hsa-miR-1908 were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in blood samples obtained from 60 CCHF patients and 40 healthy individuals. We also investigated the differences in the expression levels of the microRNAs between patients with severe and non-severe disease or between patients who died and survived. Quantitative polymerase chain reaction data were uploaded to the "Data Analysis Center" (Qiagen, Germany) and analyzed using the ΔΔCq (ΔΔCt) method. p value was calculated according to Student's t test for genes in the study groups. The expression level of hsa-miR-144 decreased (fold change= 0.09) and the expression level of hsa-miR-1908 increased 1.44-fold in CCHF patients compared to the control group. The expression of hsa-miR-144 and hsa-miR-1908 increased 2 and 2.36-fold, respectively, in severe patients compared to non-severe patients. The expression levels of hsa-miR-144 and hsa-miR-1908 were 16.3- and 14.3-fold higher, respectively, in fatal cases compared to surviving patients and these results were statistically significant. In addition, the expression level of hsa-miR-144 was significantly decreased in patients with low leukocyte counts and the expression level of hsa-miR-1908 was significantly increased in patients with prolonged prothrombin time (PT). This is the first study in the literature investigating the expression level of hsa-miR-1908 in CCHF patients. In conclusion, the data of this study suggest that hsa-miR-144 and hsa-miR-1908 may be important biomarkers in predicting the prognosis and clinical course of CCHF disease.

Monkeypox: A Viral Zoonotic Disease of Rising Global Concern

Abstract Monkeypox (mpox) is a rare viral zoonotic disease, endemic to Central and West Africa, caused by the monkeypox virus, an orthopoxvirus similar to the variola virus (smallpox). Although sporadic travel-associated cases have historically occurred outside Africa, in May 2022, mpox began spreading globally in multiple nonendemic countries across several continents. In 2024, there has been an increase in globally reported confirmed cases of mpox and deaths from mpox, making it a public health emergency of international concern. The reasons for the unusual global spread are under investigation but likely relate to increased travel and waning population immunity to orthopoxviruses. Transmission now appears to be mainly through close, intimate contact, especially among men who have sex with men. Mpox is usually a self-limited disease. Although limited approved antiviral treatments are available, such as tecovirimat, which the European Medicines Agency approved in January 2022 for the treatment of mpox, their widespread availability and effectiveness in the current outbreak remain to be investigated. Public health control measures include surveillance, case identification/isolation, contact tracing, and targeted vaccination of contacts at high risk of exposure. However, challenges remain in curtailing the current unprecedented outbreak. Critical knowledge gaps include animal reservoir(s) responsible for initial spillover events, viral mutations that may enhance transmissibility, optimal diagnostics for noninvasive specimens, effective antiviral therapies, next-generation vaccines providing longer-term immunity, and building global capacity for outbreak response. This review summarizes the current literature on mpox virology, epidemiology, pathogenesis, clinical manifestations, diagnostics, treatment, prevention, and public health control measures. Ongoing investigation and research are needed to better understand mpox’s evolving epidemiology, pathogenicity, transmissibility, and ecology to guide strategies for containing the outbreak and preventing future global emergence.

Effect of telephone reminders on adherence to anti-rabies vaccine amongst animal bite patients in North India: A randomised, single-blind, parallel-group, single-centre, interventional superiority trial

ObjectivesRabies is a highly infectious viral zoonotic disease of the central nervous system with a near 100% fatality rate. Vaccine adherence is an integral part of achieving effective treatment. India accounts for 27% of the global deaths from rabies yearly. Rabid dog bites are responsible for 99% of these deaths. This study aimed to assess the effect of reminder calls on compliance with the anti-rabies vaccine among animal bite patients. MethodsAn interventional, randomised, single-blinded, parallel-group, single-centre study was conducted at the Anti Rabies Clinic, Rajindra Hospital, Government Medical College, Patiala, a city located in Punjab, India, with a population of approximately 19 lakhs. A sample of 400 patients was enrolled and divided into two groups by lottery method. After obtaining written and informed consent from patients, data were collected using a validated pre-tested, semi-structured proforma. The intervention group received reminder calls before each dose. At the end of the study, complete information regarding compliance was obtained from both groups and analysed. ResultsThe median age group of the animal bite patients was 21-40 years, with most being male (69.50%). Most of the bites were on the lower extremities (64.0%), followed by the upper extremities (29.0%) and the face (3.25%). Out of 153 patients who delayed the dose, 137 (89.54%) delayed a single dose. The 4th dose on the 28th day was the most frequently delayed dose (75.16%). Reminder calls increased the vaccine compliance rate from 53.5% in the non-intervention group to 70% in the intervention group (adjusted odds ratio=2.28; P=0.0002). There was no effect of gender, area, educational qualification, or marital status on the compliance. ConclusionsReminder calls were found to have significant effect on the adherence to the anti-rabies vaccine. This simple, cost-effective, and patient-friendly intervention must be integrated within the health care system to ensure timely and complete administration of the anti-rabies vaccine to reduce the risk of rabies.

Distinct Pathological Changes in Preweaning Mice Infected with Live-Attenuated Rift Valley Fever Virus Strains.

Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Middle East. Live-attenuated RVF vaccines have been studied for both veterinary and human use due to their strong immunogenicity and cost-effective manufacturing. The live-attenuated MP-12 vaccine has been conditionally approved for veterinary use in the U.S.A., and next-generation live-attenuated RVF vaccine candidates are being actively researched. Assessing the virulence phenotype of vaccine seeds or lots is crucial for managing vaccine safety. Previously, preweaning 19-day-old outbred CD1 mice have been used to evaluate the MP-12 strain. This study aimed to characterize the relative virulence of three live-attenuated RVF vaccine strains in 19-day-old inbred C57BL/6 mice: the recombinant MP-12 (rMP-12), the RVax-1, and the ∆NSs-∆NSm-rZH501 strains. Although this mouse model did not show dose-dependent pathogenesis, mice that succumbed to the infection exhibited distinct brain pathology. Mice infected with ∆NSs-∆NSm-rZH501 showed an infiltration of inflammatory cells associated with infected neurons, and focal lesions formed around virus-infected cells. In contrast, mice infected with rMP-12 or RVax-1 showed a minimal association of inflammatory cells in the brain, yet the virus spread diffusely. The preweaning model is likely useful for evaluating host responses to attenuated RVFV strains, although further refinement may be necessary to quantitate the virulence among different RVFV strains or vaccine lots.

Design of Monkeypox Disease Diagnosis Model Using Classical Machine Learning Algorithm

Monkeypox is a zoonotic viral disease that the World Health Organization (WHO) reported as an epidemic in 2022. In most nations, the rate of these illness infections started to rise over time. Monkeypox can be caught directly from an infected person or via animal contact. In this study, an artificial intelligence-based diagnostic model for early monkeypox infection detection is developed. The proposed method is based on building a model based on KNN, SVC, Random Forest, Naive Bayes and Gradient Boosting for the classification problem. A voting method was also used to determine the final diagnosis of the proposed model. The system was trained and evaluated using a dataset that represented the clinical signs of monkeypox infection. The dataset comprises one hundred twenty infected patients and 120 typical cases out of 240 probable cases. The suggested model attained 75% accuracy.

Medications used in Monkeypox Disease – A Review

Monkeypox is a zoonotic viral disease similar to smallpox, caused by the monkeypox virus. With the recent global outbreaks, there is an increasing need to understand effective treatments for this infection. This article reviews the current evidence on antiviral treatments and other therapeutic strategies for monkeypox. Keywords Monkeypox, Smallpox, Virus, Treatment

Development of immunochromatographic strip assay to detect recent infection of Japanese encephalitis virus in swine population

Japanese Encephalitis (JE) is a mosquito borne re-emerging viral zoonotic disease. Sero-conversion in swine occurs 2–3 weeks before human infection, thus swine act as a suitable sentinel for predicting JE outbreaks in humans. The present study was undertaken with the objective of developing immunochromatographic strip (ICS) assay to detect recent infection of Japanese Encephalitis virus (JEV) in swine population. The two formats of ICS assay were standardized. In the first format, gold nanoparticles (GNP) were conjugated with goat anti-pig IgM (50 μg/ml) followed by spotting of recombinant NS1 protein (1 mg/ml) of JEV on NCM as test line and protein G (1 mg/ml) as control line. In the format-II, GNP were conjugated with rNS1 protein (50 μg/ml) followed by spotting of Goat anti-pig IgM (1 mg/ml) as test line and IgG against rNS1 (1 mg/ml) as control line. To decrease the non- specific binding, blocking of serum and nitrocellulose membrane (NCM) was done using 5% SMP in PBS-T and 1% BSA, respectively. Best reaction conditions for the assay were observed when 10 μl of GNP conjugate and 50 μl of 1:10 SMP blocked sera was reacted on BSA blocked NCM followed by reaction time of 15 mins. Samples showing both test and control line were considered positive whereas samples showing only control line were considered negative. A total of 318 field swine sera samples were screened using indirect IgM ELISA and developed ICS assay. Relative diagnostic sensitivity and specificity of format-I was 81.25% and 93.0% whereas of format-II was 87.50% and 62.93%, respectively. Out of 318 samples tested, 32 were positive through IgM ELISA with sero-positivity of 10.06% while sero-positivity with format-I of ICS was 8.1%. Owing to optimal sensitivity and higher specificity of format-I, it was validated in three different labs and the kappa agreement ranged from 0.80 to 1, which signifies excellent repeatability of the developed assay to test field swine sera samples for detecting recent JEV infection.

Exosome-mediated PROTAC delivery for treatment of RNA viral infections and zoonosis

The increase in diseases caused by RNA viruses, such as influenza, severe acute respiratory syndrome-coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS), and Ebola, presents a growing global health challenge as well as the threat of zoonosis. Traditional antiviral treatments are often undermined by fast-mutating viruses, drug resistance, and newly emerging pathogens. Here, we explore proteolysis-targeting chimeras (PROTACs), a novel protein degradation machinery that has the potential to reshape the way in which RNA viral infections can be managed. PROTACs excel at specifically degrading pathogenic proteins, offering a targeted and efficient antiviral strategy. We also investigate the potential of exosome-based diagnostic technologies, which harness cell-derived nanovesicles for non-invasive sampling and early viral infection detection. Addressing the challenge of PROTAC delivery, we introduce a groundbreaking strategy utilizing exosomes to deliver PROTACs with improved precision and as a targeted delivery vehicle. Integrating these innovative strategies provides a novel approach to combat RNA zoonotic viral diseases, paving the way for a new era in antiviral therapy.

Incidence of human rabies following bite or exposure to laboratory confirmed rabid animals

Background: Rabies is one of the important endemic fatal zoonotic viral disease afflicting humans and animals in Punjab, India. The present study investigated the incidence of rabies in humans bitten/exposed to laboratory confirmed rabid animals, as well as incidence after use of vaccine or rabies immunoglobulin (RIG) and clinico-epidemiological studies. Methods: A study was conducted during August 2021 to September 2022 on forty (40) rabies suspected animals presented to diagnose rabies by direct fluorescent antibody test (dFAT) at rabies diagnostic laboratory (RDL), Guru Angad Dev Veterinary and Animal Sciences University (GADVASU), Punjab, India. A detailed questionnaire was prepared for obtaining information about exposure/bite of humans by rabid animals, death of humans, demographic and epidemiological information of victims. Results: Out of total forty (40) suspected rabies cases, 30(75%) were found positive for rabies by dFAT. Laboratory confirmed rabies (LCR) incidence was 60.80% and 21.73% in stray and pet dogs, respectively. All pet dogs were vaccinated but no stray dog was vaccinated. The LCR incidence in buffaloes and cattle was 77.77% and 100%, respectively. Further in humans exposed to rabid animals (59), males were at more risk than females. The human rabies incidence was 3.38% (2/59). Highest incidence of dog bites in adult males on lower limb was observed from urban stray dogs (60.80%) followed by children. Post exposure vaccination was given to 98.3% humans exposed to rabid animals. Human’s rabies in two cases was due to no vaccination or RIG. Conclusions: Vaccination is an important step in controlling rabies in India. There is a need for integrated and comprehensive management of street dogs and bite management.

Expanded Access Programme for the use of tecovirimat for the treatment of monkeypox infection: A study protocol for an Expanded Access Programme.

Monkeypox is a viral zoonotic disease commonly reported in humans in parts of Central and West Africa. This protocol is for an Expanded Access Programme (EAP) to be implemented in the Central African Republic, where Clade I monkeypox virus diseases is primarily responsible for most monkeypox infections. The objective of the programme is to provide patients with confirmed monkeypox with access to tecovirimat, a novel antiviral targeting orthopoxviruses, and collect data on clinical and virological outcomes of patients to inform future research. The study will be conducted at participating hospitals in the Central African Republic. All patients who provide informed consent to enrol in the programme will receive tecovirimat. Patients will remain in hospital for the duration of treatment. Data on clinical signs and symptoms will be collected every day while the patient is hospitalised. Blood, throat and lesion samples will be collected at baseline and then on days 4, 8, 14 and 28. Patient outcomes will be assessed on Day 14 -end of treatment-and at Day 28. Adverse event and serious adverse event data will be collected from the point of consent until Day 28. This EAP is the first protocolised treatment programme in Clade I MPXV. The data generated under this protocol aims to describe the use of tecovirimat for Clade I disease in a monkeypox endemic region of Central Africa. It is hoped that this data can inform the definition of outcome measures used in future research and contribute to the academic literature around the use of tecovirimat for the treatment of monkeypox. The EAP also aims to bolster research capacity in the region in order for robust randomised controlled trials to take place for monkeypox and other diseases. {2a & 2b}: ISRCTN43307947.

Evaluation of LN34 Pan-Lyssavirus RT-qPCR assay for rabies diagnosis in Brazil

Rabies, a fatal zoonotic viral disease affecting mammals, including humans, remains a significant global health concern, particularly in low-income countries. The disease, primarily transmitted through infected animal saliva, prompts urgent diagnosis for timely post-exposure prophylaxis (PEP). The gold standard diagnostic test, direct fluorescent antibody test (dFAT), while sensitive, suffers from limitations such as subjective interpretation and high costs. As a confirmatory technique, the LN34 Pan-Lyssavirus RT-qPCR assay has emerged as a promising tool for universal Lyssavirus detection. This study evaluated its performance using 130 rabies virus isolates representing eleven Brazilian variants and 303 clinical samples from surveillance operations. The LN34 assay demonstrated 100% sensitivity and 98% specificity compared to dFAT. Additionally, it detected all samples, including those missed by dFAT, indicating superior sensitivity. The assay's specificity was confirmed through Sanger nucleotide sequencing, with only a minimal false-positive rate. Comparative analysis revealed higher accuracy and concordance with dFAT than traditional rabies tissue culture infection tests (RTCIT). False-negative RTCIT results were attributed to low viral load or suboptimal sampling. These findings underscore the LN34 assay's utility as a confirmatory technique, enhancing rabies surveillance and control in Brazil. Its widespread adoption could significantly improve diagnostic sensitivity, crucial for effective PEP and public health interventions.

Severe morbidity and hospital-based mortality from Rift Valley fever disease between November 2017 and March 2020 among humans in Uganda

BackgroundRift Valley fever (RVF) is a zoonotic viral disease of increasing intensity among humans in Africa and the Arabian Peninsula. In Uganda, cases reported prior to 2016 were mild or not fully documented. We report in this paper on the severe morbidity and hospital-based mortality of human cases in Uganda.MethodsBetween November 2017 and March 2020 human cases reported to the Uganda Virus Research Institute (UVRI) were confirmed by polymerase chain reaction (PCR). Ethical and regulatory approvals were obtained to enrol survivors into a one-year follow-up study. Data were collected on socio-demographics, medical history, laboratory tests, potential risk factors, and analysed using Stata software.ResultsOverall, 40 cases were confirmed with acute RVF during this period. Cases were not geographically clustered and nearly all were male (39/40; 98%), median age 32 (range 11–63). The median definitive diagnosis time was 7 days and a delay of three days between presumptive and definitive diagnosis. Most patients (31/40; 78%) presented with fever and bleeding at case detection. Twenty-eight (70%) cases were hospitalised, out of whom 18 (64%) died. Mortality was highest among admissions in regional referral (11/16; 69%) and district (4/5; 80%) hospitals, hospitalized patients with bleeding at case detection (17/27; 63%), and patients older than 44 years (9/9; 100%). Survivors mostly manifested a mild gastro-intestinal syndrome with nausea (83%), anorexia (75%), vomiting (75%), abdominal pain (50%), and diarrhoea (42%), and prolonged symptoms of severe disease including jaundice (67%), visual difficulties (67%), epistaxis (50%), haemoptysis (42%), and dysentery (25%). Symptom duration varied between two to 120 days.ConclusionRVF is associated with high hospital-based mortality, severe and prolonged morbidity among humans that present to the health care system and are confirmed by PCR. One-health composite interventions should be developed to improve environmental and livestock surveillance, prevent infections, promptly detect outbreaks, and improve patient outcomes.

Prediction of monkeypox infection from clinical symptoms with adaptive artificial bee colony-based artificial neural network

In 2022, the World Health Organization declared an outbreak of monkeypox, a viral zoonotic disease. With time, the number of infections with this disease began to increase in most countries. A human can contract monkeypox by direct contact with an infected human, or even by contact with animals. In this paper, a diagnostic model for early detection of monkeypox infection based on artificial intelligence methods is proposed. The proposed method is based on training the artificial neural network (ANN) with the adaptive artificial bee colony algorithm for the classification problem. In the study, the ABC algorithm was preferred instead of classical training algorithms for ANN because of its effectiveness in numerical optimization problem solutions. The ABC algorithm consists of food and limit parameters and three procedures: employed, onlooker and scout bee. In the algorithm standard, artificial onlooker bees are produced as much as the number of artificially employed bees and an equal number of limit values are assigned for all food sources. In the advanced adaptive design, different numbers of artificial onlooker bees are used in each cycle, and the limit numbers are updated. For effective exploitation, onlooker bees tend toward more successful solutions than the average fitness value of the solutions, and limit numbers are updated according to the fitness values of the solutions for efficient exploration. The performance of the proposed method was investigated on CEC 2019 test suites as examples of numerical optimization problems. Then, the system was trained and tested on a dataset representing the clinical symptoms of monkeypox infection. The dataset consists of 240 suspected cases, 120 of which are infected and 120 typical cases. The proposed model's results were compared with those of ten other machine learning models trained on the same dataset. The deep learning model achieved the best result with an accuracy of 75%. It was followed by the random forest model with an accuracy of 71.1%, while the proposed model came third with an accuracy of 71%.