Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection.

Aedes aegypti mosquitoes are responsible for transmitting many medically important viruses such as those that cause Zika and dengue. The inoculation of viruses into mosquito bite sites is an important and common stage of all mosquito-borne virus infections. We show, using Semliki Forest virus and Bunyamwera virus, that these viruses use this inflammatory niche to aid their replication and dissemination in vivo. Mosquito bites were characterized by an edema that retained virus at the inoculation site and an inflammatory influx of neutrophils that coordinated a localized innate immune program that inadvertently facilitated virus infection by encouraging the entry and infection of virus-permissive myeloid cells. Neutrophil depletion and therapeutic blockade of inflammasome activity suppressed inflammation and abrogated the ability of the bite to promote infection. This study identifies facets of mosquito bite inflammation that are important determinants of the subsequent systemic course and clinical outcome of virus infection.

Hypersensitivity to mosquito bites: A versatile Epstein-Barr virus disease with allergy, inflammation, and malignancy.

Hypersensitivity to mosquito bites (HMB) is a rare disease characterized by transient intense skin reaction and systemic inflammation. Clinical presentation of HMB resembles other mosquito allergic responses, and it can also be difficult to clinically distinguish HMB from other severe allergic reactions. However, a distinctive pathophysiology underlies HMB. HMB belongs to a category of Epstein-Barr virus (EBV)-associated natural killer (NK) cell lymphoproliferative disorders (LPD). Hence, HMB may progress to systemic diseases, such as hemophagocytic lymphohistiocytosis, chronic active EBV disease, and EBV-associated malignancies. A triad of elevated serum IgE, NK lymphocytosis, and detection of EBV DNA in peripheral blood is commonly observed, and identification of EBV-infected NK cells usually facilitates the diagnosis. However, the effective treatment is limited, and its precise etiology remains unknown. Local CD4+ T cell proliferation triggered by mosquito bites appears to help induce EBV reactivation and EBV-infected NK-cell proliferation. These immunological interactions may explain the transient HMB signs and symptoms and the disease progression toward malignant LPD. Further research to elucidate the mechanism of HMB is warranted for better diagnosis and treatment of HMB and other forms of EBV-associated LPD.

The Optimal Age of Vaccination Against Dengue with an Age-Dependent Biting Rate with Application to Brazil.

In this paper we introduce a single serotype transmission model, including an age-dependent mosquito biting rate, to find the optimal vaccination age against dengue in Brazil with Dengvaxia. The optimal vaccination age and minimal lifetime expected risk of hospitalisation are found by adapting a method due to Hethcote (Math Biosci 89:29-52). Any number and combination of the four dengue serotypes DENv1-4 is considered. Successful vaccination against a serotype corresponds to a silent infection. The effects of antibody-dependent enhancement (ADE) and permanent cross-immunity after two heterologous infections are studied. ADE is assumed to imply risk-free primary infections, while permanent cross-immunity implies risk-free tertiary and quaternary infections. Data from trials of Dengvaxia indicate vaccine efficacy to be age and serostatus dependent and vaccination of seronegative individuals to induce an increased risk of hospitalisation. Some of the scenarios are therefore reconsidered taking these findings into account. The optimal vaccination age is compared to that achievable under the current age restriction of the vaccine. If vaccination is not considered to induce risk, optimal vaccination ages are very low. The assumption of ADE generally leads to a higher optimal vaccination age in this case. For a single serotype vaccination is not recommended in the case of ADE. Permanent cross-immunity results in a slightly lower optimal vaccination age. If vaccination induces a risk, the optimal vaccination ages are much higher, particularly for permanent cross-immunity. ADE has no effect on the optimal vaccination age when permanent cross-immunity is considered; otherwise, it leads to a slight increase in optimal vaccination age.

A mathematical model for Zika virus transmission dynamics with a time-dependent mosquito biting rate.

BACKGROUND: Mathematical modeling has become a tool used to address many emerging diseases. One of the most basic and popular modeling frameworks is the compartmental model. Unfortunately, most of the available compartmental models developed for Zika virus (ZIKV) transmission were designed to describe and reconstruct only past, short-time ZIKV outbreaks in which the effects of seasonal change to entomological parameters can be ignored. To make an accurate long-term prediction of ZIKV transmission, the inclusion of seasonal effects into an epidemic model is unavoidable. METHODS: We developed a vector-borne compartmental model to analyze the spread of the ZIKV during the 2015-2016 outbreaks in Bahia, Brazil and to investigate the impact of two vector control strategies, namely, reducing mosquito biting rates and reducing mosquito population size. The model considered the influences of seasonal change on the ZIKV transmission dynamics via the time-varying mosquito biting rate. The model was also validated by comparing the model prediction with reported data that were not used to calibrate the model. RESULTS: We found that the model can give a very good fit between the simulation results and the reported Zika cases in Bahia (R-square = 0.9989). At the end of 2016, the total number of ZIKV infected people was predicted to be 1.2087 million. The model also predicted that there would not be a large outbreak from May 2016 to December 2016 due to the decrease of the susceptible pool. Implementing disease mitigation by reducing the mosquito biting rates was found to be more effective than reducing the mosquito population size. Finally, the correlation between the time series of estimated mosquito biting rates and the average temperature was also suggested. CONCLUSIONS: The proposed ZIKV transmission model together with the estimated weekly biting rates can reconstruct the past long-time multi-peak ZIKV outbreaks in Bahia.

The Interaction between Vector Life History and Short Vector Life in Vector-Borne Disease Transmission and Control.

Epidemiological modelling has a vital role to play in policy planning and prediction for the control of vectors, and hence the subsequent control of vector-borne diseases. To decide between competing policies requires models that can generate accurate predictions, which in turn requires accurate knowledge of vector natural histories. Here we highlight the importance of the distribution of times between life-history events, using short-lived midge species as an example. In particular we focus on the distribution of the extrinsic incubation period (EIP) which determines the time between infection and becoming infectious, and the distribution of the length of the gonotrophic cycle which determines the time between successful bites. We show how different assumptions for these periods can radically change the basic reproductive ratio (R0) of an infection and additionally the impact of vector control on the infection. These findings highlight the need for detailed entomological data, based on laboratory experiments and field data, to correctly construct the next-generation of policy-informing models.

[Dengue with unusual clinical features in an infant: Case report]. / Dengue, presentación inusual en un lactante: Reporte de un caso.

The state of Yucatan, in Mexico, is an endemic area for dengue. During 2015, there was an unpredicted increase in the number of expected cases of dengue fever. OBJECTIVE: To describe and analyse the clinical presentation, progress, and management of a case of dengue infection with non-specific clinical manifestations in an infant which resulted in a dengue shock syndrome. CASE REPORT: One month old infant admitted to hospital with a generalised rash and a history of being bitten by an insect. He was diagnosed with anaphylaxis based on clinical manifestations and anamnesis. While in hospital, he developed hypotension, tachycardia, anaemia, and respiratory distress. He was transferred to the intensive care unit, but died on the fifth day. He tested positive to dengue virus in the PCR test and for IgG antibodies using Elisa. The basic cause of death was dengue shock syndrome. CONCLUSIONS: Dengue fever in young infant infections may be afebrile, so it is important to suspect them appropriately in the presence of a generalised rash, tachycardia, and hypotension, in order to avoid the deadly consequences of dengue shock.

Knowledge about the human immunodeficiency syndrome among elders in a unit for the care of the elderly. / Conhecimento sobre síndrome da imunodeficiência humana de idosos de uma unidade de atenção ao idoso.

OBJECTIVE: To analyze the knowledge of elders regarding HIV/AIDS. METHODS: Descriptive, cross-sectional, quantitative study, with 457 elders from the Unit for the Care of Elders in Uberaba - Minas Gerais, lasting 3 months. The instruments used were the Mental State Mini-exam and a questionnaire on the human immunodeficiency virus for elders, together with frequency measures for their analysis. RESULTS: Most participants were female (74%), between 60 and 69 y/o (51%). The question with the most correct answers was about syringe/needle transmission (96.2%) and the ones with the least (45.3% and 49.6%, respectively) were regarding AIDS transmission through mosquito bites and whether a person with the human immunodeficiency virus always presents symptoms (49.6%). 88.2% of participants never use condoms. CONCLUSION: The general level of knowledge can be considered good, responding to our goal. However, gaps in knowledge were identified due to the lack of campaigns aimed exclusively at such public, as well as to the lack of awareness of professionals.

First case of imported Zika virus infection in Spain.

We report a case of Zika virus (ZIKV) infection in a patient with diarrhea, fever, synovitis, non-purulent conjunctivitis, and with discreet retro-orbital pain, after returning from Colombia in January 2016. The patient referred several mosquito bites. Presence of ZIKV was detected by PCR (polymerase chain reaction) in plasma. Rapid microbiological diagnosis of ZIKV infection is needed in European countries with circulation of its vector, in order to avoid autochthonous circulation. The recent association of ZIKV infection with abortion and microcephaly, and a Guillain-Barré syndrome highlights the need for laboratory differentiation of ZIKV from other virus infection. Women with potential risk for Zika virus infection who are pregnant or planning to become pregnant must mention that fact during prenatal visits in order to be evaluated and properly monitored.

Zika Virus Disease: Case Report and Review of Literature.

Zika virus (ZIKV) infection and its associated complications have become a significant public health concern. Zika virus is a Flavivirus, and is transmitted to humans by Aedes species mosquitoes. In May 2015, the World Health Organization reported the first locally acquired transmission of ZIKV in Brazil, the first case in the Western Hemisphere. There have also been reports of increased incidence of microcephaly and other neurologic complications associated with ZIKV infection, as well as a 20-fold increase in the incidence of Guillain-Barre Syndrome during ZIKV outbreaks. In light of the clusters of microcephaly and neurologic manifestations in areas of ZIKV transmission, the World Health Organization declared ZIKV and associated complications an international public health emergency. The clinical presentations of ZIKV disease resemble many common infections, making the diagnosis of ZIKV disease a clinical challenge. Patients with ZIKV infection may have other coinfections that can distract clinicians from suspecting ZIKV disease in their patients. Complications from ZIKV, although uncommon, may be severe. Therefore, it is important for health care providers to remain alert and up to date in the efforts to control this emerging global health crisis. It is critical for physicians and other providers to know the growing list of countries and territories on the US Centers for Disease Control and Prevention list of nations with endemic ZIKV disease and to work closely with local health departments to prevent spread. In this article, we present a case of ZIKV disease in a pediatric patient and review of the current literature.

Zika--an emerging infectious disease. The risk assessment from Polish perspective.

In the last years, attention has been paid to Zika virus (ZIKV) infection, the emerging vector-borne disease. It is responsible for major outbreaks in Africa, Asia and, more recently, in previously infection-naïve territories of the Pacific area, South America and Caribbean. The etiology, epidemiology, transmission, and clinical manifestations of ZIKV disease are discussed, along with the diagnostic possibilities in the aim to assessing the risk of its introduction to Poland. ZIKV is spread by Aedes mosquitoes which are not found throughout Poland. The prevention strategies adopted by national public health authorities should be based on a surveillance of imported cases and on increasing awareness among healthcare professionals and travelers. Due to a large number of asymptomatic ZIKV infections and limitations in the availability of diagnostic tests, monitoring based on laboratory results is likely to be unreliable in Poland. There are no requirements to report ZIKV infections to the European Centre for Disease Prevention and Control. Nevertheless, the global epidemic continues to spread, and despite travels of Poles to countries in which Aedes mosquitoes are active, Polish sportsmen will be travelling to Brazil in August 2016 to participate in the Olympic Games, the will also be true of the many fans who will follow them; therefore imported cases of ZIKV infection are possible. As the awareness of the infection risk will increase among medical staff and travelers, the number of suspected cases of travel-related ZIKV infections may rise in Poland. Medical staff should be informed where and how to report such cases. Thorough surveillance, adequate assessment of possible threats, action plans, rapid and effective intervention development, spread of up to date information of ZIKV, as well as other emerging or re-emerging infectious pathogens can play a key role in guaranteeing population health.

Survival rates and prognostic factors of Epstein-Barr virus-associated hydroa vacciniforme and hypersensitivity to mosquito bites.

BACKGROUND: Epstein-Barr virus (EBV)-associated T/natural-killer lymphoproliferative disorders form a group of diseases that includes classical and systemic hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). Patients with systemic HV (sHV) and HMB often have a poor prognosis, although little is known about the prognostic factors. OBJECTIVES: To elucidate the prognostic factors of HV and HMB. METHODS: We studied clinicopathological manifestations, routine laboratory findings, anti-EBV titres, EBV DNA load and EBV-encoded gene expression, including expression of BZLF1, in 50 patients with classical HV (cHV), sHV, HMB only and HMB with HV (HMB + HV), and further analysed 30 patients who were available for follow-up. RESULTS: The median age of disease onset was 5 years (range 1-74). A follow-up study indicated that fatal outcomes were observed in three of eight patients with sHV, two of six patients with HMB only, and two of five patients with HMB + HV. The main causes of death were complications from haematopoietic stem-cell transplantation and multiorgan failure. There were no fatalities among the 11 patients with cHV. Univariate analysis revealed two poor prognostic indicators: (i) onset age > 9 years and (ii) the expression of an EBV-encoded immediate-early gene transcript, BZLF1 mRNA, in the skin lesions (P < 0·001 and P = 0·003, respectively). CONCLUSIONS: No prognostic correlation was observed in EBV-infected lymphocyte subsets, anti-EBV antibody titres or EBV DNA load. Late onset and EBV reactivation are both related to more severe phenotypes of the disease, and thus may predict a poor prognosis.

[Reemergence of Chikungunya virus]. / Chikungunya: La reemergence.

Arboviral diseases transmitted by mosquitoes such as Dengue, Chikungunya and West Nile are global health issues of growing magnitude. Their dissemination in new areas is triggered by increased mobility of persons, animal reservoirs and vectors. This article describes virological, epidemiological and clinical aspects of Chikungunya, which causes sporadic cases or epidemics, sometimes massive, such as the one spreading in the Americas since December 2013. Chikungunya should be suspected in all travellers presenting with fever, arthralgia and sometimes a rash returning from an endemic area. In the absence of vaccine, individual protection relies on the prevention of mosquito bites.

[Management of the yellow fever epidemic in 2010 in Séguéla (Côte d'Ivoire): value of multidisciplinary investigation]. / Gestion de l'épidémie de fièvre jaune en 2010 à Séguéla (Côte d'Ivoire): intérêt d'une investigation pluridisciplinaire.

INTRODUCTION: In August 2010, five positive cases of yellow fever were reported in the region of Séguéla, in the northwest of Côte d'Ivoire, affected by an armed conflict since 2002. In order to evaluate the extent of yellow fever virus circulation and the risk for local people, a multidisciplinary investigation was carried out by the Côte-d'Ivoire Ministry of Health and Public Hygiene. METHODS: Theses investigations were conducted in the villages of confirmed cases and the outpatient and hospitalization centers attended by infected patients, two weeks after the reactive immunization campaign performed in order to stop the spread of the epidemic. The search for suspects identified 16 cases, including 4 cases and 2 deaths in hospital registers and 12 cases during community interviews, including 6 deaths. RESULTS: Stegomyiens indices were relatively low. Aedes aegypti was present among adult mosquitoes. In addition, three wild vectors, varying in number from one locality to another, were detected: Ae. africanus, Ae. luteocephalus and Ae. vittatus with average biting rates of 0.3; 0.1 and 0.05 bite/man/twilight, respectively, at Soba, Ae. africanus and Ae. vittatus with average biting rates of 0.25 and 0.3 bite/man/twilight, respectively, at Yaokro and Ae. luteocephalus with one bite/man/twilight at Kaborékro. DISCUSSION: Unfortunately, the vaccine response conducted before investigations did not stop progression of the epidemic which broke out three months later in the Worofla health area, close to the Magrékros encampment.

Mosquito bite delivery of dengue virus enhances immunogenicity and pathogenesis in humanized mice.

Dengue viruses (DENV) are transmitted to humans by the bite of Aedes aegypti or Aedes albopictus mosquitoes, with millions of infections annually in over 100 countries. The diseases they produce, which occur exclusively in humans, are dengue fever (DF) and dengue hemorrhagic fever (DHF). We previously developed a humanized mouse model of DF in which mice transplanted with human hematopoietic stem cells produced signs of DENV disease after injection with low-passage, wild-type isolates. Using these mice, but now allowing infected A. aegypti to transmit dengue virus during feeding, we observed signs of more severe disease (higher and more sustained viremia, erythema, and thrombocytopenia). Infected mice mounted innate (gamma interferon [IFN-γ] and soluble interleukin 2 receptor alpha [sIL-2Rα]) and adaptive (anti-DENV antibodies) immune responses that failed to clear viremia until day 56, while a mosquito bite alone induced strong immunomodulators (tumor necrosis factor alpha [TNF-α], IL-4, and IL-10) and thrombocytopenia. This is the first animal model that allows an evaluation of human immunity to DENV infection after mosquito inoculation.

Dengue and zika viruses turn people into mosquito bait.

To spread, pathogens drive mice, people to make odorant.

Modelling the effect of temperature on transmission of dengue.

The main entomological parameters involved in the rate of dengue virus transmission include the longevity of female mosquitoes, the time interval between bites and the extrinsic incubation period of the virus. Field and laboratory data provide estimates for these parameters, but their interactions with other factors (e.g. host population density and environmental parameters) make their integration into a transmission model quite complex. To estimate the impact of these parameters on transmission, we developed a model of virus transmission by a vector population which predicts the number of potentially infective bites under a range of temperatures and entomological parameters, including the daily survival rate of females, the interval between bites and the extrinsic incubation period. Results show that in a stable population, an increase in mosquito longevity disproportionately enhances the number of potential transmissions (e.g. by as much as five times when the survival rate rises from 0.80 to 0.95). Halving the length of the biting interval with a 10- degrees C rise in temperature increases the transmission rate by at least 2.4 times. Accordingly, the model can predict changes in dengue transmission associated with short-term variation in seasonal temperature and also with potentially long-lasting increases in global temperatures.

Knowledge, beliefs, and practices regarding tick bites in the Turkish population in a rural area of the Middle Anatolian Region.

The aim of this study is to determine the knowledge, beliefs, and practices of a population living in a rural area in regards to tick bites and Crimean-Congo hemorrhagic fever (CCHF). The study was conducted in a rural area located in Central Anatolia in the region of Eskisehir. A total of 1,500 individuals aged 20 years and older chosen by a stratified random sample were enrolled. A questionnaire was administered in person. In 264 (17.4%) participants, there was a history of being bitten by a tick. This rate was higher in older persons, males, married persons, and farmers. The most commonly reported protective behavior was wearing long sleeves and long pants when wandering in rural areas (65.1% of participants). The least commonly reported behavior was using insect repellent on skin or clothes (3.3% of participants). Only 799 participants (54%) had heard about CCHF as a disease associated with ticks. Females, those with primary school education, housewives, and male farmers had a high frequency of having heard about CCHF. Tick bites and CCHF are important public health problems, yet the current knowledge of these problems is not sufficient in populations living in rural areas of the Middle Anatolian Region of Turkey.

Zika virus transmission by Brazilian Aedes aegypti and Aedes albopictus is virus dose and temperature-dependent.

BACKGROUND: Zika virus (ZIKV) emerged in the Pacific Ocean and subsequently caused a dramatic Pan-American epidemic after its first appearance in the Northeast region of Brazil in 2015. The virus is transmitted by Aedes mosquitoes. We evaluated the role of temperature and infectious doses of ZIKV in vector competence of Brazilian populations of Ae. aegypti and Ae. albopictus. METHODOLOGY/PRINCIPAL FINDINGS: Two Ae. aegypti (Rio de Janeiro and Natal) and two Ae. albopictus (Rio de Janeiro and Manaus) populations were orally challenged with five viral doses (102 to 106 PFU / ml) of a ZIKV strain (Asian genotype) isolated in Northeastern Brazil, and incubated for 14 and 21 days in temperatures mimicking the spring-summer (28°C) and winter-autumn (22°C) mean values in Brazil. Detection of viral particles in the body, head and saliva samples was done by plaque assays in cell culture for determining the infection, dissemination and transmission rates, respectively. Compared with 28°C, at 22°C, transmission rates were significantly lower for both Ae. aegypti populations, and Ae. albopictus were not able to transmit the virus. Ae. albopictus showed low transmission rates even when challenged with the highest viral dose, while both Ae. aegypti populations presented higher of infection, dissemination and transmission rates than Ae. albopictus. Ae. aegypti showed higher transmission efficiency when taking virus doses of 105 and 106 PFU/mL following incubation at 28°C; both Ae. aegypti and Ae. albopictus were unable to transmit ZIKV with virus doses of 102 and 103 PFU/mL, regardless the incubation temperature. CONCLUSIONS/SIGNIFICANCE: The ingested viral dose and incubation temperature were significant predictors of the proportion of mosquito's biting becoming infectious. Ae. aegypti and Ae. albopictus have the ability to transmit ZIKV when incubated at 28°C. However Brazilian populations of Ae. aegypti exhibit a much higher transmission potential for ZIKV than Ae. albopictus regardless the combination of infection dose and incubation temperature.

Immunobiology of Acquired Resistance to Ticks.

Ticks are blood-sucking arthropods of great importance in the medical and veterinary fields worldwide. They are considered second only to mosquitos as vectors of pathogenic microorganisms that can cause serious infectious disorders, such as Lyme borreliosis and tick-borne encephalitis. Hard (Ixodid) ticks feed on host animals for several days and inject saliva together with pathogens to hosts during blood feeding. Some animal species can acquire resistance to blood-feeding by ticks after a single or repeated tick infestation, resulting in decreased weights and numbers of engorged ticks or the death of ticks in subsequent infestations. Importantly, this acquired tick resistance (ATR) can reduce the risk of pathogen transmission from pathogen-infected ticks to hosts. This is the basis for the development of tick antigen-targeted vaccines to forestall tick infestation and tick-borne diseases. Accumulation of basophils is detected in the tick re-infested skin lesion of animals showing ATR, and the ablation of basophils abolishes ATR in mice and guinea pigs, illustrating the critical role for basophils in the expression of ATR. In this review article, we provide a comprehensive overview of recent advances in our understanding of the cellular and molecular mechanisms responsible for the development and manifestation of ATR, with a particular focus on the role of basophils.