Arthropod-borne Infectious Diseases Research Articles

New member of Plasmodium (Vinckeia) and Plasmodium cyclopsi discovered in bats in Sierra Leone – nuclear sequence and complete mitochondrial genome analyses

Malaria remains the most important arthropod-borne infectious disease globally. The causative agent, Plasmodium, is a unicellular eukaryote that develops inside red blood cells. Identifying new Plasmodium parasite species that infect mammalian hosts can shed light on the complex evolution and diversity of malaria parasites. Bats feature a high diversity of microorganisms including seven separate genera of malarial parasites. Three species of Plasmodium have been reported so far, for which scarce reports exist. Here we present data from an investigation of Plasmodium infections in bats in the western Guinean lowland forest in Sierra Leone. We discovered a new Plasmodium parasite in the horseshoe bat Rhinolophus landeri. Plasmodium cyclopsi infections in a member of leaf-nosed bats, Doryrhina cyclops, exhibited a high prevalence of 100%. Phylogenetic analysis of complete mitochondrial genomes and nine nuclear markers recovered a close relationship between P. cyclopsi and the new Plasmodium parasite with the rodent species Plasmodium berghei, a widely used in vivo model to study malaria in humans. The data suggests that the “rodent/bat” Plasmodium (Vinckeia) clade represents a diverse group of malarial parasites that would likely expand with a systematic sampling of small mammals in tropical Africa. Identifying the bat Plasmodium repertoire is central to our understanding of the evolution of Plasmodium parasites in mammals.

Discovery and distribution of and response to arbovirus in China over the past seven decades

Arbovirus is a group of virus transmitted by blood-sucking arthropod bites, which infects both arthropods and vertebrates. More than 600 arboviruses have been characterized worldwide until now, including 65 highly pathogenic viruses, which pose a high threat to public health. The risk of arbovirus transmission is increasing due to climate change, international trade and urbanization. The review summarizes the discovery and distribution of emerging and reemerging arboviruses and novel arboviruses with potential pathogenic risks, and proposes responses to the arbovirus transmission risk, so as to provide insights into the research and management of arboviruses and arthropod-borne infectious diseases in China.

Lumpy skin disease as an emerging infectious disease.

Lumpy skin disease (LSD) is one of the most important emerging transboundary diseases. Recently, LSD has emerged in many countries in the northern hemisphere. The LSD virus has a huge genome and is highly resistant to environmental conditions. The virus is also host-specific and large ruminants, such as cattle and domestic water buffalo, are particularly susceptible. In addition, wild ruminants can serve as potential reservoirs for spreading the LSD virus. The emergence might be related to climate change in various regions because LSD is an arthropod-borne infectious disease. This disease causes enormous economic losses, such as leather damage, decreased milk production, abortion, and death in infected ruminants. The economic importance of LSD in the bovine industry has forced countries to develop and implement control strategies against the disease. With the recent global spread and the economic impact, LSD will be discussed intensively. In addition, effective preventive measures are suggested based on the presence or absence of LSD outbreaks.

Homology Modeling and Molecular Docking Approaches for the Proposal of Novel Insecticides against the African Malaria Mosquito (Anopheles gambiae).

Vector-borne infectious diseases are responsible for the deaths of over 700,000 people annually, than 400,000 of them resulting from malaria. The mosquito Anopheles gambiae is one of the dominant vector species of human malaria transmission. A significant issue of the conventional insecticides which target the arthropod borne infectious diseases is their induced resistance. To overcome this inconvenience, insecticides with new modes of action are required. One of the most promising targets for the development of new potential insecticides as evidenced by current studies is the D1-like dopamine receptor (DAR). To get a deeper understanding of the structural information of this receptor, the 3D homology model was built. The possible sites within the protein were identified and the most probable binding site was highlighted. The homology model along with a series of DAR antagonists with known activity against Anopheles gambiae larvae were used in docking experiments to gain insight into their intermolecular interactions. Furthermore, virtual screening of the natural compounds from the SPECS database led to the prediction of toxicity and environmental hazards for one potential new insecticide against the Anopheles gambiae mosquito.

Repellency of Veratraldehyde (3,4-Dimethoxy Benzaldehyde) against Mosquito Females and Tick Nymphs

Arthropod-borne infectious diseases cause many deaths and a major economic burden worldwide. Repellents play an important role in protecting people from infectious biting arthropods. The repellency of veratraldehyde, a known food additive, and the WJ-1041 formulation containing 10% veratraldehyde was tested against Aedes albopictus and Culex pipiens pallens females and Haemaphysalis longicornis nymphs using arm-in-cage, indoor or filter paper tests. Veratraldehyde exhibited repellency similar to or lower than that of n,n-diethyl-meta-toluamide (DEET) against A. albopictus, but in H. longicornis, the activity of veratraldehyde was better than that of DEET. The repellency of the 10% veratraldehyde solution was comparable to that of 20% DEET against the two mosquitoes. When comparing repellency between the WJ-1041 formulation (10% veratraldehyde) and 10% DEET against C. pipiens pallens, A. Albopictus and H. longicornis, the two showed similar repellency and complete protection time (CPT) values. However, there was a small difference depending on the tested insects. The absorption of veratraldehyde via skin was minimal, if at all. The pharmacokinetic parameters (Cmax and Tmax) of veratraldehyde in blood samples of rats were not different from those of the control group. Based on these results, veratraldehyde has high potential to be commercialized as a repellent agent against infectious disease-borne pests in the near future.

Ocular Manifestations of Emerging Arthropod-Borne Infectious Diseases.

Purpose:To review the clinical features, diagnosis, treatment modalities, and prognosis of arthropod-borne infectious diseases.Methods:This is a narrative review on arthropod-borne infectious diseases including general and ophthalmological aspects of these infectious diseases. A comprehensive literature review between January 1983 and September 2020 was conducted in PubMed database. Epidemiology, clinical features, diagnosis, treatment, and prognosis of arthropod-borne infectious diseases were reviewed.Results:Emergent and resurgent arthropod-borne infectious diseases are major causes of systemic morbidity and death that are expanding worldwide. Among them, bacterial and viral agents including rickettsial disease, West Nile virus, Dengue fever, Chikungunya, Rift valley fever, and Zika virus have been associated with an array of ocular manifestations. These include anterior uveitis, retinitis, chorioretinitis, retinal vasculitis, and optic nerve involvement. Proper clinical diagnosis of any of these infectious diseases is primarily based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. The diagnosis is confirmed by laboratory tests. Ocular involvement usually has a self-limited course, but it can result in persistent visual impairment. Doxycycline is the treatment of choice for rickettsial disease. There is currently no proven specific treatment for arboviral diseases. Prevention remains the mainstay for arthropod vector and zoonotic disease control.Conclusions:Emerging arthropod vector-borne diseases should be considered in the differential diagnosis of uveitis, especially in patient living or with recent travel to endemic countries. Early clinical diagnosis, while laboratory testing is pending, is essential for proper management to prevent systemic and ocular morbidity.

Global Governing Bodies: A Pathway for Gene Drive Governance for Vector Mosquito Control.

.Gene drive technologies represent powerful tools to develop vector control strategies that will complement the current approaches to mitigate arthropod-borne infectious diseases. The characteristics of gene drive technologies have raised additional concerns to those for standard genetically engineered organisms. This generates a need for adaptive governance that has not been met yet because of the rapid rate of progress in gene drive research. For the eventual release of gene drive insects into wild populations, an international governance network would be helpful in guiding scientists, stakeholders, public opinion, and affected communities in its use. We examined the current institutions and governing bodies among various continents that could have an impact on gene drive governance or the potential to adapt to its future use. Possible governance strategies also are proposed that seek to bridge gaps and promote an ethically sound policy framework. Ideally, governance strategies should be developed before or at the same pace as gene drive research to anticipate field releases and maximize their impact as a public health tool. However, this is not likely to happen as it takes years to develop global accords, and some countries may choose to move ahead independently on the new technology.

Obituary for Professor Michael J. Day

On 10th May 2020, Michael Day passed away at the age of 59 after a terminal illness with cancer. There have been many messages and tributes to him. He had many interests and activities as a veterinarian and was involved with the British Veterinary Small Animal Association (BSAVA), the World Small Animal Veterinary Association (WSAVA) as well as being the senior editor of the Journal of Comparative Pathology. There is an online book of condolence with many tributes at http://www.tolbc.com/MichaelDay. Michael trained as a veterinarian at Murdoch University, Perth, Western Australia. He had a profound interest in small animal immunology, infectious diseases and pathology which was focused in his residency and PhD studies performed at Murdoch. Having completed his PhD he held postdoctoral positions in Bristol and Oxford before joining the University of Bristol in 1990 as a lecturer in veterinary pathology in the Veterinary School. In 2017 he left Bristol Veterinary School as emeritus professor in veterinary pathology. Michael had been taught at Murdoch by Susan Shaw, who also joined the University of Bristol in 1990, and they forged a long-term collaborative friendship. For example, they co-authored a chapter entitled “Recent developments in atopic dermatitis of companion animals” (In: Williams HC, ed., Atopic dermatitis: the epidemiology, causes and prevention of atopic eczema. Cambridge: Cambridge University Press, 2000; 233–244). Michael was renowned for his ability to teach immunology to veterinary undergraduates and postgraduates by making the complex seem accessible. This ability was put to use helping residents of the European College of Veterinary Dermatology in their Immunology workshops in Split and ESVD members at a workshop in York. He lectured all over the world at international conferences about small animals and their immune-mediated and infectious diseases. He co-authored, with Ronald Schulz, a successful and popular textbook that has been widely used for teaching veterinary students (Veterinary immunology: principles and practice, 2nd edition. Boca Raton, FL: CRC Press, 2013). He also wrote two other books published by CRC Press, Clinical immunology of the dog and cat and (co-authored with Susan Shaw) Arthropod-borne infectious diseases of the dog and cat. Michael was extraordinarily hard-working and meticulously organised. For example, when compiling the book Veterinary Allergy (Chichester, UK: Wiley, 2014), the editors asked him to write the introductory chapter on “The immunological basis of allergic diseases”. His was, as expected, the first manuscript submitted, on time and complete with no revisions required. Michael worked on various techniques during his residency and PhD studies on the immune system of companion animals, and this is reflected in one of his earliest publications entitled “Immunodiagnosis of autoimmune skin disease in the dog, cat and horse” (Day MJ, Penhale WJ, Aust Vet J 1986; 63: 65–68). His research training in Murdoch led to the establishment of a diagnostic laboratory at the University of Bristol that enabled clinicians to investigate various diseases and conditions; it included testing for immunoglobulins, ANA titres and interpretation of immunohistochemical results for various tissues. This helped to bring him into contact with many clinicians within and outside Bristol Veterinary School and with whom he collaborated, this work helped to contribute to Michael’s large list of over 340 publications. While at Bristol Veterinary School, Michael helped to develop the application of reagents in detecting canine immunoglobulin G subclasses, and this led to a series of studies of immune responses in various skin diseases in dogs including pyoderma, hypersensitivity disorders and immune-mediated diseases. He also published detailed substantial retrospective histopathological studies looking at demodicosis, auto-immune skin diseases, pyoderma and cutaneous lymphoma. Michael will be remembered by many for his engaging and collaborative approach to all things concerning the study of infectious and immune-mediated diseases in companion animals, as well as a substantial portfolio of work on experimental autoimmunity. He supervised numerous PhD students and postdoctoral fellows, and was an external examiner for many. In later years Michael explored his family history and, interestingly, it became apparent that his family had hailed from the southwestern England, from villages in the county of Somerset, before they moved out to Australia in the 19th Century. Consequently, when he worked for the University of Bristol and made his home in Cheddar in the Mendip Hills area of Somerset, he was not far from where his ancestors had set out for Australia. Our thoughts and sympathies are extended to his wife Mary and to his family.

Babesia microti Confers Macrophage-Based Cross-Protective Immunity Against Murine Malaria.

Malaria and babesiosis, the two primary intraerythrocytic protozoan diseases of humans, have been reported in multiple cases of co-infection in endemic regions. As the geographic range and incidence of arthropod-borne infectious diseases is being affected by climate change, co-infection cases with Plasmodium and Babesia are likely to increase. The two parasites have been used in experimental settings, where prior infection with Babesia microti has been shown to protect against fatal malarial infections in mice and primates. However, the immunological mechanisms behind such phenomena of cross-protection remain unknown. Here, we investigated the effect of a primary B. microti infection on the outcome of a lethal P. chabaudi challenge infection using a murine model. Simultaneous infection with both pathogens led to high mortality rates in immunocompetent BALB/c mice, similar to control mice infected with P. chabaudi alone. On the other hand, mice with various stages of B. microti primary infection were thoroughly immune to a subsequent P. chabaudi challenge. Protected mice exhibited decreased levels of serum antibodies and pro-inflammatory cytokines during early stages of challenge infection. Mice repeatedly immunized with dead B. microti quickly succumbed to P. chabaudi infection, despite induction of high antibody responses. Notably, cross-protection was observed in mice lacking functional B and T lymphocytes. When the role of other innate immune effector cells was examined, NK cell-depleted mice with chronic B. microti infection were also found to be protected against P. chabaudi. Conversely, in vivo macrophage depletion rendered the mice vulnerable to P. chabaudi. The above results show that the mechanism of cross-protection conferred by B. microti against P. chabaudi is innate immunity-based, and suggest that it relies predominantly upon the function of macrophages. Further research is needed for elucidating the malaria-suppressing effects of babesiosis, with a vision toward development of novel tools to control malaria.

COMPARATIVE STUDY BETWEEN VISCERAL LEISHMANIASIS AND MALARIA FALCIPARUM IN CASES PRESENTED BY FEVER WITH ANEMIA IN THE REPUBLIC OF YEMEN

No doubt, both visceral leishmaniasis and malignant malaria are more or less common in many Eastern Mediterranean Countries. Both of these arthropod-borne infectious diseases have overlapping clinical presentations. This study aimed to clarify the main clinical features and laboratory diagnostic tests. A total of forty Plasmodium falciparum patients and thirty visceral leishmaniasis patients were studied. Sheets were filled on each subject included, full history taking, full clinical examination, CBC, liver and renal function tests, x-ray chest and abdominal ultrasound, bone marrow aspiration.. The results showed that jaundice and liver affection tests were more common in malaria (jaundice, 55%, high ALT & AST, 60%) than in visceral leishmaniasis (high bilirubin, 30% high ALT & AST, 40%). Besides, the malaria affected the central nervous system (coma and impaired sensorium, 30%) more than visceral leishmaniasis (coma and impaired sensorium, 5%). The effect of visceral leishmaniasis on the lymphatic system (splenomegaly, 95% & hepatomegaly, 70%) was more than malaria (70% & 60% respectively). The visceral leishmaniasis markedly affected the bone marrow (anemia, 95%, thrombocytopenia, 65% & leucopenia, 70%) more than malaria (anemia, 28%, thrombocytopenia, 50% & leucopenia, 34%). Diarrhea and cough were common in visceral leishmaniasis (80% & 55% respectively) than in malaria (20% & 5%respectively) but DIC was common in malignant malaria (20%).

A series of the studies on countermeasure for arthropod-borne infectious diseases in Japan —Focus on highly pathogenic avian influenza and dengue outbreaks in Japan—

We have faced a number of outbreaks of arthropod-borne infectious diseases in Japan and aimed to address each case appropriately. Here, I introduce two arthropod-borne infectious diseases caused by flies and mosquitoes, respectively. In 2004, the highly pathogenic avian influenza occurred in Kyoto. The H5N1 influenza A virus was isolated from the blow fly, Calliphora nigribarbis, collected around a poultry farm. Exposure experiments showed that the H5N1 virus survived in C. nigribarbis for at least 24 h. C. nigribarbis was suggested to possibly transport the H5N1 virus over a distance of 2 km, which they can access within 24 h. While in 2014, 162 autochthonous dengue cases were reported. Dengue virus was isolated from Aedes albopictus collected in the suspected locations of dengue virus infection in Tokyo. Phylogenetic analysis and virus infection experiments revealed that Ae. albopictus was a major dengue vector in Tokyo in 2014. In both cases, we first collected vector arthropods at each outbreak location to understand their biological characteristics and ecological dynamics. We then detected pathogens from the collected arthropods and conducted infection experiments in the laboratory. We can understand that obtaining data from both the field and the laboratory is necessary to confront arthropod-borne infectious diseases.

Malaria and the climate in Karachi: An eight year review.

Background and Objective:Malaria is an arthropod-borne infectious disease transmitted by the mosquito Anopheles and claims millions of lives globally every year. Reasons for failure to eradicate this disease are multifactorial. The seasonality of the malaria is principally determined by climatic factors conducive for breeding of the vector. We aimed to study the relationship between climatic variability and the seasonality of malaria over an eight-year duration.Methods:This was a retrospective medical chart review of 8,844 confirmed cases of malaria which presented to The Indus Hospital, Karachi from January 2008 to November 2015. Cases were plotted against meteorological data for Karachi to elicit monthly variation.Results:A secular incline and seasonality in malaria cases over the duration of eight years was seen. More cases were reported in the summer, rainy season compared with the other three seasons in each year. There was significant association with specific climate variables such as temperature, moisture, and humidity.Conclusion:There is a marked seasonal variation of malaria in Karachi, influenced by various environmental factors. Identification of the ‘the concentrated period’ of malaria can be helpful for policymakers to deploy malaria control interventions.

Control of arthropod-borne infectious diseases – extrapolating from the known to the unknown

Control of arthropod-borne infectious diseases – extrapolating from the known to the unknown

Co-Infection of Scrub Typhus and Human Granulocytic Anaplasmosis in Korea, 2006.

BackgroundScrub typhus, severe fever with thrombocytopenia syndrome (SFTS) and human granulocytic anaplasmosis (HGA) are important arthropod-borne infectious diseases in Korea and share a common point that they are transmitted by arthropod bites mostly during outdoor activities and there are considerable overlaps of epidemiologic and clinical features at presentation. We investigated the co-infection of these infections.MethodsThe study subjects were patients with laboratory-confirmed scrub typhus who were enrolled retrospectively in 2006. SFTS virus (SFTSV) infection was confirmed by a reverse transcriptase polymerase chain reaction (PCR) to amplify partial L segment of SFTSV for molecular diagnosis. HGA was confirmed by a nested PCR to amplify 16S rRNA gene of Anaplasma phagocytophilum. Direct sequencing of the positive PCR products was performed. Clinical features of co-infected subjects were described.ResultsOne-hundred sixty-seven patients with scrub typhus were included in the analysis. Co-infection of A. phagocytophilum was identified in 4.2% of scrub typhus patients (7/167). The route of co-infection was uncertain. The co-infected patients had not different clinical manifestations compared to the patients with scrub typhus only. All the study subjects were negative for SFTSV.ConclusionWe found retrospective molecular evidence of the co-infection of scrub typhus and HGA in Korea. HGA may be more prevalent than expected and need to be considered as an important differential diagnosis of febrile patients in Korea.

Efficacy of Mosquito Coils: Cross-resistance to Pyrethroids in Aedes aegypti (Diptera: Culicidae) From Indonesia

Aedes aegypti (L.) (Diptera: Culicidae) is the primary vector of several arthropod-borne viral infectious diseases globally. Relentless vector control efforts are performed to curtail disease transmissions, insecticides remain as the first line of defense in Indonesia. With a dearth of publication on the efficacy of mosquito coil in Indonesia, this is the first report related to mosquito coil despite its common use in households. Ae. aegypti mosquitoes were sampled from nine regencies in Indonesia and tested using the glass-chamber method against three commercially available local pyrethroid-based mosquito coils containing d-allethrin, transfluthrin, and metofluthrin. The 50% knockdown time of female Ae. aegypti tested with d-allethrin, transfluthrin, and metofluthrin containing coils ranged from 0.65 to 14.32; 0.8 to 16.4; and 0.78 to 20.57 min, respectively. Mortality rates in accordance with WHO resistance indicators showed that strains from Denpasar, Mataram, Kuningan, Padang, Samarinda, and Sumba Timur were resistant (<80% mortality rate), whereas strains from Manggarai Barat, Dompu, and Pontianak were susceptible (>98% mortality rate) to the active ingredients assayed. Moreover, the knockdown rates between d-allethrin and transfluthrin, d-allethrin and metofluthrin, as well as transfluthrin and metofluthrin displayed significant associations, portraying the presence of cross-resistance within pyrethroid insecticides. The minimal insecticidal effect of mosquito coils against some Indonesian Ae. aegypti also pointed out the development of pyrethroid resistance, prompting a revamping of the vector control system.

An efficient production of hybrid recombinant protein comprising non-structural proteins (NS 1 & NS 3) of bluetongue virus in prokaryotic expression system

Strategic design and suitable purification techniques are of paramount importance in the production of recombinant proteins, if intended for use in a diagnostic assay. However, there is no single protocol that can be universally adopted for obtaining proteins in requisite quality and quantity across various platforms. In this study, we have targeted proteins of bluetongue virus (BTV), which is the causative agent of an arthropod-borne infectious disease in ruminants. Traditionally, serological diagnosis of the disease has rested upon either virus neutralization test or on an ELISA test that employed a recombinant structural (VP1, VP7) protein. Among the non-structural (NS) proteins of BTV, NS1 and NS3, are preferred candidate antigens in development of immuno-diagnostics as these provide the option for identifying recent/ongoing infection. However, the difficulty in production/purification of recombinant full length NS proteins of BTV in sufficient quantity and quality in various expression systems, due to inherent structural complexities, have restricted their wider applicability as immunodiagnostic reagents. To circumvent the difficulties associated with production/purification, we developed a novel NS1 and NS3 fusion gene (∼1302 bp) encoding for NS1 N-terminus (1M to G252 aa) and NS3 protein containing the N- and C-termini with a deletion of two hydrophobic domains along with intervening variable central domain (118A to A182 aa) of bluetongue virus 23. This construct was cloned, over-expressed and efficiently purified by single step affinity chromatography under unique denaturing/renaturing condition. The purified fusion protein was found suitable for detection of antibodies against BTV in an indirect ELISA (iELISA).

Aedes aegypti resistance development to commonly used insecticides in Jakarta, Indonesia.

Aedes aegypti is the primary vector of various relevant arthropod-borne viral infectious diseases worldwide. The mosquito control is still mainly performed by using insecticides but their effectiveness is increasingly questioned nowadays. We here conducted a study on Ae. aegypti resistance development towards several commonly used insecticides in the capital city of Jakarta, Indonesia. In order to achieve this goal, Ae. aegypti eggs from Jakarta were collected with ovitraps and hatched in the insectary of the Gadjah Mada University, Indonesia. The F0 generations were used for WHO resistance tests and knockdown resistance (kdr) assays. Presented results clearly showed that there was resistance development of Ae. aegypti populations to the here tested pyrethroid insecticides (i. e. permethrin). Observed mortalities were less than 90% with highest resistance against 0.75% permethrin concentrations. Furthermore, a significant association of V1016G gene mutations with resistance phenotypes to 0.75% permethrin was observed. Nevertheless, the F1534C mutation did not show a significant correlation to resistance development. In conclusion, our results show that populations of Ae. aegypti mosquitoes within the city of Jakarta have developed resistance against several routinely used pyrethroid insecticides in local performed control programs. Thus, the regular verification/assessment of resistance development status will hopefully help in the future to assist local public health authorities in their mosquito control programs by recommending and managing the rotation of different routinely used insecticides with diverse effector mechanisms in order to delay Ae. aegypti resistance development.

Lure-and-Kill Yeast Interfering RNA Larvicides Targeting Neural Genes in the Human Disease Vector Mosquito Aedes aegypti

New mosquito control strategies are vitally needed to address established arthropod-borne infectious diseases such as dengue and yellow fever and emerging diseases such as Zika and chikungunya, all of which are transmitted by the disease vector mosquito Aedes aegypti. In this investigation, Saccharomyces cerevisiae (baker’s yeast) was engineered to produce short hairpin RNAs (shRNAs) corresponding to the Aedes aegypti orthologs of fasciculation and elongation protein zeta 2 (fez2) and leukocyte receptor cluster (lrc) member, two genes identified in a recent screen for A. aegypti larval lethal genes. Feeding A. aegypti with the engineered yeasts resulted in silenced target gene expression, disrupted neural development, and highly significant larval mortality. Larvicidal activities were retained following heat inactivation and drying of the yeast into tabular formulations that induced >95% mortality and were found to attract adult females to oviposit. These ready-to-use inactivated yeast interfering RNA tablets may one day facilitate the seamless integration of this new class of lure-and-kill species-specific biorational mosquito larvicides into integrated mosquito control programs.

Global Epidemiology of Dengue Outbreaks in 1990-2015: A Systematic Review and Meta-Analysis.

Dengue is an arthropod-borne infectious disease caused by dengue virus (DENV) infection and transmitted by Aedes mosquitoes. Approximately 50–100 million people are infected with DENV each year, resulting in a high economic burden on both governments and individuals. Here, we conducted a systematic review and meta-analysis to summarize information regarding the epidemiology, clinical characteristics, and serotype distribution and risk factors for global dengue outbreaks occurring from 1990 to 2015. We searched the PubMed, Embase and Web of Science databases through December 2016 using the term “dengue outbreak.” In total, 3,853 studies were identified, of which 243 studies describing 262 dengue outbreaks met our inclusion criteria. The majority of outbreak-associated dengue cases were reported in the Western Pacific Region, particularly after the year 2010; these cases were primarily identified in China, Singapore and Malaysia. The pooled mean age of dengue-infected individuals was 30.1 years; of the included patients, 54.5% were male, 23.2% had DHF, 62.0% had secondary infections, and 1.3% died. The mean age of dengue patients reported after 2010 was older than that of patients reported before 2010 (34.0 vs. 27.2 years); however, the proportions of patients who had DHF, had secondary infections and died significantly decreased after 2010. Fever, malaise, headache, and asthenia were the most frequently reported clinical symptoms and signs among dengue patients. In addition, among the identified clinical symptoms and signs, positive tourniquet test (OR = 4.86), ascites (OR = 13.91) and shock (OR = 308.09) were identified as the best predictors of dengue infection, DHF and mortality, respectively (both P < 0.05). The main risk factors for dengue infection, DHF and mortality were living with uncovered water container (OR = 1.65), suffering from hypotension (OR = 6.18) and suffering from diabetes mellitus (OR = 2.53), respectively (all P < 0.05). The serotype distribution varied with time and across WHO regions. Overall, co-infections were reported in 47.7% of the evaluated outbreaks, and the highest pooled mortality rate (2.0%) was identified in DENV-2 dominated outbreaks. Our study emphasizes the necessity of implementing programs focused on targeted prevention, early identification, and effective treatment.

A systematic review and meta-analysis for the adverse effects, immunogenicity and efficacy of Lyme disease vaccines: Guiding novel vaccine development.

Lyme borreliosis (LB) is the most prevalent arthropod-borne infectious disease in North America. Currently, no vaccine is available to prevent LB in humans, although monovalent and multivalent vaccines have been developed in the past. The aim of the current study is to conduct a systematic review and meta-analysis to evaluate and compare the findings from these two classes of vaccines for their reactogenicity, immunogenicity and efficacy, in the hope this may assist in the development of future vaccines. A search strategy was developed for online databases (PubMed, Ovid MEDLINE, and Embase). Search terms used were "vaccine/vaccination", "Lyme disease/Borreliosis", "clinical trial(s)" and "efficacy". Only seven clinical trials were included to compare the results of the monovalent vaccines to those of the multivalent one. Meta-analyses were conducted to evaluate the reactogenicity and immunogenicity of the two vaccine classes. Odds ratio (OR) for LB (and 95% confidence intervals; 95% CI) were calculated for the efficacy of the monovalent vaccine from three different clinical trials at different dose schedules. Incidence of redness (local adverse effect) and fever (systemic side effect) were, respectively, 6.8- and 2.9-fold significantly lower (p &lt; 0.05) in individuals who received multivalent vaccines compared to those receiving the monovalent one. Incidences of all other local and systemic adverse effects were non-significantly lower in the multivalent vaccine compared to the monovalent vaccines. Seroprotection was comparable among individuals who received the two vaccine classes at the 30 μg dose level. Efficacy in the prevention of LB was only evaluated for the monovalent vaccines. OR of LB ranged from 0.49 (95% CI: 0.14-0.70; p &lt; 0.005, vs. placebo) to 0.31 (95% CI: 0.26-0.63; p &lt; 0.005) for the initial and final doses respectively, with an overall OR of 0.4 (95% CI: 0.26-0.63, p &lt; 0.001). The current study further validates that the monovalent and multivalent LB vaccines result in mild local side effects and self-limiting systemic adverse effects, with the multivalent vaccine slightly more tolerable than the monovalent one. Both vaccine classes were similarly highly immunogenic. A new vaccine with high safety standards, better efficacy, low cost, and public acceptance is yet to be developed. Meanwhile, personal protection limiting exposure to ticks is recommended.