Climate-driven variation in mosquito density predicts the spatiotemporal dynamics of dengue.

Dengue is a climate-sensitive mosquito-borne disease with increasing geographic extent and human incidence. Although the climate-epidemic association and outbreak risks have been assessed using both statistical and mathematical models, local mosquito population dynamics have not been incorporated in a unified predictive framework. Here, we use mosquito surveillance data from 2005 to 2015 in China to integrate a generalized additive model of mosquito dynamics with a susceptible-infected-recovered (SIR) compartmental model of viral transmission to establish a predictive model linking climate and seasonal dengue risk. The findings illustrate that spatiotemporal dynamics of dengue are predictable from the local vector dynamics, which in turn, can be predicted by climate conditions. On the basis of the similar epidemiology and transmission cycles, we believe that this integrated approach and the finer mosquito surveillance data provide a framework that can be extended to predict outbreak risk of other mosquito-borne diseases as well as project dengue risk maps for future climate scenarios.

Evolutionary transition from blood feeding to obligate nonbiting in a mosquito.

The spread of blood-borne pathogens by mosquitoes relies on their taking a blood meal; if there is no bite, there is no disease transmission. Although many species of mosquitoes never take a blood meal, identifying genes that distinguish blood feeding from obligate nonbiting is hampered by the fact that these different lifestyles occur in separate, genetically incompatible species. There is, however, one unique extant species with populations that share a common genetic background but blood feed in one region and are obligate nonbiters in the rest of their range: Wyeomyia smithii Contemporary blood-feeding and obligate nonbiting populations represent end points of divergence between fully interfertile southern and northern populations. This divergence has undoubtedly resulted in genetic changes that are unrelated to blood feeding, and the challenge is to winnow out the unrelated genetic factors to identify those related specifically to the evolutionary transition from blood feeding to obligate nonbiting. Herein, we determine differential gene expression resulting from directional selection on blood feeding within a polymorphic population to isolate genetic differences between blood feeding and obligate nonbiting. We show that the evolution of nonbiting has resulted in a greatly reduced metabolic investment compared with biting populations, a greater reliance on opportunistic metabolic pathways, and greater reliance on visual rather than olfactory sensory input. W. smithii provides a unique starting point to determine if there are universal nonbiting genes in mosquitoes that could be manipulated as a means to control vector-borne disease.

Insect pathogenic fungus interacts with the gut microbiota to accelerate mosquito mortality.

The insect gut microbiota plays crucial roles in modulating the interactions between the host and intestinal pathogens. Unlike viruses, bacteria, and parasites, which need to be ingested to cause disease, entomopathogenic fungi infect insects through the cuticle and proliferate in the hemolymph. However, interactions between the gut microbiota and entomopathogenic fungi are unknown. Here we show that the pathogenic fungus Beauveria bassiana interacts with the gut microbiota to accelerate mosquito death. After topical fungal infection, mosquitoes with gut microbiota die significantly faster than mosquitoes without microbiota. Furthermore, fungal infection causes dysbiosis of mosquito gut microbiota with a significant increase in gut bacterial load and a significant decrease in bacterial diversity. In particular, the opportunistic pathogenic bacterium Serratia marcescens overgrows in the midgut and translocates to the hemocoel, which promotes fungal killing of mosquitoes. We further reveal that fungal infection down-regulates antimicrobial peptide and dual oxidase expression in the midgut. Duox down-regulation in the midgut is mediated by secretion of the toxin oosporein from B. bassiana Our findings reveal the important contribution of the gut microbiota in B. bassiana-killing activity, providing new insights into the mechanisms of fungal pathogenesis in insects.

A Mathematical Model for the Transmission Dynamics of Lymphatic Filariasis with Intervention Strategies.

This manuscript considers the transmission dynamics of lymphatic filariasis with some intervention strategies in place. Unlike previously developed models, our model takes into account both the exposed and infected classes in both the human and mosquito populations, respectively. We also consider vaccinated, treated and recovered humans in the presented model. The global dynamics of the proposed model are completely determined by the basic ([Formula: see text]) and effective reproduction numbers ([Formula: see text]). We then use Lyapunov function theory to find the sufficient conditions for global stability of both the disease-free equilibrium and endemic equilibrium. The Lyapunov functions show that when the basic reproduction number is less than or equal to unity, the disease-free equilibrium is globally asymptotically stable, and when it is greater than unity then the endemic equilibrium is also globally asymptotically stable. Finally, numerical simulations are carried out to investigate the effects of the intervention strategies and key parameters to the spread of lymphatic filariasis. The numerical simulations support the analytical results and illustrate possible model behavioral scenarios.

Chemical Compositions, Mosquito Larvicidal and Antimicrobial Activities of Essential Oils from Five Species of Cinnamomum Growing Wild in North Central Vietnam.

Members of the genus Cinnamomum (Lauraceae) have aromatic volatiles in their leaves and bark and some species are commercially important herbs and spices. In this work, the essential oils from five species of Cinnamomum (C. damhaensis, C. longipetiolatum, C. ovatum, C. polyadelphum and C. tonkinense) growing wild in north central Vietnam were obtained by hydrodistillation, analyzed by gas chromatography and screened for antimicrobial and mosquito larvicidal activity. The leaf essential oil of C. tonkinense, rich in ß-phellandrene (23.1%) and linalool (32.2%), showed excellent antimicrobial activity (MIC of 32 µg/mL against Enterococcus faecalis and Candida albicans) and larvicidal activity (24 h LC50 of 17.4 µg/mL on Aedes aegypti and 14.1 µg/mL against Culex quinquefasciatus). Cinnamomum polyadelphum leaf essential oil also showed notable antimicrobial activity against Gram-positive bacteria and mosquito larvicidal activity, attributable to relatively high concentrations of neral (11.7%) and geranial (16.6%). Thus, members of the genus Cinnamomum from Vietnam have shown promise as antimicrobial agents and as potential vector control agents for mosquitoes.

GWAS of self-reported mosquito bite size, itch intensity and attractiveness to mosquitoes implicates immune-related predisposition loci.

Understanding the interaction between humans and mosquitoes is a critical area of study due to the phenomenal burdens on public health from mosquito-transmitted diseases. In this study, we conducted the first genome-wide association studies (GWAS) of self-reported mosquito bite reaction size (n = 84,724), itchiness caused by bites (n = 69,057), and perceived attractiveness to mosquitoes (n = 16,576). In total, 15 independent significant (P < 5×10-8) associations were identified. These loci were enriched for immunity-related genes that are involved in multiple cytokine signalling pathways. We also detected suggestive enrichment of these loci in enhancer regions that are active in stimulated T-cells, as well as within loci previously identified as controlling central memory T-cell levels. Egger regression analysis between the traits suggests that perception of itchiness and attractiveness to mosquitoes is driven, at least in part, by the genetic determinants of bite reaction size.Our findings illustrate the complex genetic and immunological landscapes underpinning human interactions with mosquitoes.

Advances in Zika Virus⁻Host Cell Interaction: Current Knowledge and Future Perspectives.

Emerging mosquito-transmitted RNA viruses, such as Zika virus (ZIKV) and Chikungunya represent human pathogens of an immense global health problem. In particular, ZIKV has emerged explosively since 2007 to cause a series of epidemics in the South Pacific and most recently in the Americas. Although typical ZIKV infections are asymptomatic, ZIKV infection during pregnancy is increasingly associated with microcephaly and other fetal developmental abnormalities. In the last few years, genomic and molecular investigations have established a remarkable progress on the pathogenic mechanisms of ZIKV infection using in vitro and in vivo models. Here, we highlight recent advances in ZIKV-host cell interaction studies, including cellular targets of ZIKV, ZIKV-mediated cell death mechanisms, host cell restriction factors that limit ZIKV replication, and immune evasion mechanisms utilized by ZIKV. Understanding of the mechanisms of ZIKV⁻host interaction at the cellular level will contribute crucial insights into the development of ZIKV therapeutics and vaccines.

Local Transmission of Zika Virus in Miami-Dade County: The Florida Department of Health Rises to the Challenge.

As early as 2015, Florida and Centers for Disease Control and Prevention (CDC) public health officials recognized the potential danger of Zika for US residents and visitors. The Zika virus, a mosquito-borne flavivirus, is transmitted through the bite of the Aedes aegypti mosquito. A physician in Miami-Dade notified the Florida Department of Health (DOH) of the first non-travel-related Zika case in the United States. A 23-year old pregnant woman had presented on July 7, 2016, at 23 weeks of gestation, with a 3-day history of fever, widespread pruritic rash, and sore throat. Three more cases, involving men, were reported in Dade and Broward counties. These notifications set into motion additional activities from the DOH's Zika Playbook: increased mosquito surveillance; collaboration with the CDC on recommendations for mosquito abatement techniques; and increased awareness of the risks of Zika. In August, the department reported that active transmission of Zika virus was occurring in one small area in Miami-Dade County known as Wynwood. Mosquito trapping in the area with local transmission identified large numbers of the Zika vector, Aedes aegypti females and a large number of mosquito larval sites. Control efforts included larviciding, eliminating standing water, and backpack and truck spraying of insecticides. A communication strategy was developed that addressed risk mitigation, public concerns over application of noxious pesticides, loss of tourist revenue, and reproductive issues. It was reported on December 28, 2016, that there had been 256 locally acquired cases of infection of Zika, 1011 travel-related cases, and 208 pregnant women with laboratory evidence of Zika. At the end of 2018, 2 years after active Zika virus transmission was controlled in Florida, there have been 101 reported cases of Zika during 2018 but none have been linked to local transmission.

Zika Virus: What Do Emergency Physicians Need to Know?

BACKGROUND: Zika virus currently dominates headlines, creating public fear due to its complications. With the ease of worldwide travel, this disease has spread rapidly to the U.S. OBJECTIVES: To provide physicians with an updated clinical review of the epidemiology, pathogenesis, diagnosis, management, and mimics of zika virus. DISCUSSION: This flavivirus is spread by the bite of the Aedes mosquito during daylight. The ease of worldwide travel has allowed the virus to spread to Mexico and the U.S. Main transmission route is via blood contact or sexual activity involving mucous membranes. Incubation ranges from 2 to 12 days, but only 20% of patients experience symptoms. Fever is low grade with conjunctivitis, arthralgias, myalgias, and a maculopapular rash. Chikungunya and Dengue Fever differ in that patients experience higher fever and no conjunctivitits. The dreaded complication of Zika virus is microcephaly in infants born to infected mothers. Guillain-Barre Syndrome is also linked to the virus. Historical factors including travel history are paramount, and diagnosis includes PCR or serology. No current treatment regimen exists beyond symptom control. The emergency physician must seek to rule out other similar diseases such as malaria, chikungunya, and dengue fever. CONCLUSION: Zika virus has created public fear due to complications, and this flavivirus spread by the Aedes mosquito presents similarly to Chikungunya and Dengue Fever. The dreaded complication of Zika virus is microcephaly in infants born to infected mothers. This review provides key information concerning the disease and management.

No Evidence of Gouléako and Herbert Virus Infections in Pigs, Côte d'Ivoire and Ghana.

A recent report suggested that 2 novel bunyaviruses discovered in insects in Côte d'Ivoire caused lethal disease in swine in South Korea. We conducted cell culture studies and tested serum from pigs exposed to mosquitoes in Côte d'Ivoire and Ghana and found no evidence for infection in pigs.

Chikungunya outbreak in Garo Hills, Meghalaya: An epidemiological perspective.

BACKGROUND & OBJECTIVES: Chikungunya (CHIK) fever is a mosquito-borne disease caused by chikungunya virus (CHIKV). Chikungunya infection was first reported from India in 1963 from Kolkata. We report the serological and molecular evidence of an outbreak of chikungunya in northeast India that occurred in Tura, a hilly and forested terrain in Garo Hills district of Meghalaya. METHODS: Blood samples (3 ml) collected from hospitalized patients during the outbreak were tested for IgM antibodies against CHIKV and followed up four months later. A repeat survey was carried out in the same area after four months from where cases had been reported. Blood samples were also collected from people with history of fever and body ache in the last four months. Persons showing IgM positivity against CHIKV in the repeat survey were followed up one and a half years later. All samples were also processed by RT-PCR assay for CHIK Envelope (E) 1 gene. Immature mosquitoes were collected, link reared and identified with standard keys. Virus incrimination studies were done on Aedes aegypti and Ae. albopictus mosquitoes collected during the survey. RESULTS: Fever, headache and joint pain were the primary clinical presentations. Twenty three (35.93 %) of 64 samples reported during the outbreak were IgM positive for CHIK. Three samples showed PCR amplification. All these were IgM positive. The sequenced E1 gene revealed that the strains belonged to East Central South African (ECSA) genotype. INTERPRETATION & CONCLUSIONS: Field survey done after four months revealed that some individuals still had joint pain associated with episodes of headache and fever. It could be inferred that these persons might have contracted infection during the CHIK outbreak four months ago or during the intervening period which caused persistence of sequelae. ECSA genotype was found to be involved in the outbreak. Aedes albopictus was the predominant mosquito species collected during the outbreak.

A three year retrospective study on the increasing trend in seroprevalence of dengue infection from southern Odisha, India.

BACKGROUND & OBJECTIVES: In Odisha, several cases of dengue virus infection were detected for the first time in 2010, the importance of dengue as a serious mosquito-borne viral infection was felt only in 2011 with the reporting of many more positive cases. This retrospective three year study was done to find out the seroprevalence of dengue Ig m0 antibody and to know the predominant serotype of dengue virus among the patients suspected to have dengue virus infection in a tertiary care hospital in southern Odisha, India. METHODS: Blood samples from clinically suspected dengue cases admitted in the Medicine and Paediatrics departments of a tertiary care hospital were collected. These were processed for detection of dengue specific IgM antibody, carried out by the ELISA method. Dengue IgM antibody positive serum samples were tested for serotypic identification. RESULTS: Of the 5102 samples tested, 1074 (21.05%) were positive for dengue IgM. Maximum numbers of cases were found in 2012. Majority (47.86%) of cases were detected in the month of September. The most common affected age group was 11 to 20 yr. DENV1 and DENV2 were the detected serotypes. INTERPRETATION & CONCLUSIONS: Rapid increase in the dengue cases in 2012 became a public health concern as majority of cases were affecting the young adolescents. Most of the cases were reported in post-monsoon period indicating a need for acceleration of vector control programmes prior to arrival of monsoon.

Entomological investigations into an epidemic of Japanese encephalitis (JE) in northern districts of West Bengal, India (2011-2012).

BACKGROUND & OBJECTIVES: Japanese encephalitis (JE) is one of the most important arboviral diseases of human beings with outbreaks in many parts of Southeast Asia including India. We present the entomological findings of an outbreak occurred in northern part of West Bengal during 2011-2012 with special emphasis on the role of JE vectors in different seasons. METHODS: Adult mosquito collections were made with the help of mouth aspirators, aided by flash lights during day time resting inside human and animal habitations as indoor, and resting outside field grasses, bushes, underneath of culverts and bridges as outdoor, and in and around the pig enclosures and cattle sheds during dusk period in JE affected villages from Cooch Behar, Dakshin Dinajpur, Darjeeling and Jalpaiguri districts in North West Bengal. In all study villages, a long handled with enamel bowl dipper was used to obtain immature stages of mosquitoes from various breeding habitats. RESULTS: A total of 19 different types of mosquito breeding habitats were examined for vectors of JE. From these habitats, 23.7 per cent were positive for breeding during the study period. Overall, nine different species were recorded through emergence, but none was positive for JE virus when subjected for detection of virus. Adult mosquitoes of more than 50 per cent of the potential JE vector species obtained through dusk and the rest through indoor and outdoor collections in all seasons. Altogether, 27 different species were recorded. Most of these were JE vectors. INTERPRETATION & CONCLUSIONS: Our results showed that in addition to Cx. vishnui subgroup, detection of JE virus antigen in Cx. quinquefasciatus indicated the possible maintenance of JE virus in nature through poor vector mosquitoes throughout the year. Since, all potential vector species reported elsewhere in India were also found in this region and fluctuated in density in different seasons, a proper integrated vector control programme needs to be implemented to control JE transmission.

Survival of diurnally sub periodic Wuchereria bancrofti in Downsiomyia nivea (Diptera: Culicidae): a density dependent factor from Andaman & Nicobar Islands.

BACKGROUND & OBJECTIVES: In India, diurnally sub periodic Wuchereria bancrofti transmitted by Downsiomyia nivea is prevalent only in the Nicobar district of Andaman and Nicobar Islands. The ongoing LF elimination programme aims at transmission interruption by bringing down the microfilarie (mf) load in the community, which has implication on the parasite load in mosquito vector. Therefore, understanding density dependent constraints on transmission assumes significance from control perspective. The present study was undertaken in Teressa Island to understand the density dependent parasite mortality and survival probability of the parasite Do. nivea. METHODS: The entomological data collected from Teressa Island, endemic for the diurnally sub periodic form of W. bancrofti were used to examine the parasite loss and its survival up to infectivity. Patterns of parasite distribution in Do. nivea were examined. RESULTS: Distribution patterns of microfilariae were found to be over dispersed in Do. nivea. The later stages of the parasite in the vector were randomly distributed. Distribution pattern of various filarial larval stages suggested that the loss of parasites occurred as development progressed and was maximal between the first and second stages. Further, both the prevalence of infection and the degree of parasite aggregation in the vector population have fallen significantly with development of parasite stage. INTERPRETATION & CONCLUSIONS: Results indicate the operation of parasite density dependent mortality of vectors or parasite loss or combination of both. The present study with Aedes transmitted filariasis conducted before launching LF elimination programme in the study area indicates a comparable level of parasite regulation in the vector which has similar implications on the transmission threshold. Thus, the consideration of Aedes with Culex in deriving the critical level of antigen positive for making decisions on cessation of mass drug administration (MDA) can be justified. However, with MDA aiming at reducing parasite load in the community, the operation of density dependent factor in the transmission becomes less pronounced in the subsequent rounds of MDA.

[Mosquitoes as vectors for exotic pathogens in Germany]. / Stechmücken als Überträger exotischer Krankheitserreger in Deutschland.

As a result of intensified globalization of international trade and of substantial travel activities, mosquito-borne exotic pathogens are becoming an increasing threat for Europe. In Germany some 50 different mosquito species are known, several of which have vector competence for pathogens. During the last few years a number of zoonotic arboviruses that are pathogenic for humans have been isolated from mosquitoes in Germany including Usutu, Sindbis and Batai viruses. In addition, filarial worms, such as Dirofilaria repens have been repeatedly detected in mosquitoes from the federal state of Brandenburg. Other pathogens, in particular West Nile virus, are expected to emerge sooner or later in Germany as the virus is already circulating in neighboring countries, e.g. France, Austria and the Czech Republic. In upcoming years the risk for arbovirus transmission might increase in Germany due to increased occurrence of new so-called "invasive" mosquito species, such as the Asian bush mosquito Ochlerotatus japonicus or the Asian tiger mosquito Aedes albopictus. These invasive species are characterized by high vector competence for a broad range of pathogens and a preference for human blood meals. For risk assessment, a number of mosquito and pathogen surveillance projects have been initiated in Germany during the last few years; however, mosquito control strategies and plans of action have to be developed and put into place to allow early and efficient action against possible vector-borne epidemics.

ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans.

The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63 (ChAd63) followed by the attenuated orthopoxvirus MVA is safe and immunogenic in healthy adults. Here, we report on vaccine efficacy against controlled human malaria infection delivered by mosquito bites. The blood-stage malaria vaccines were administered alone, or together (MSP1+AMA1), or with a pre-erythrocytic malaria vaccine candidate (MSP1+ME-TRAP). In this first human use of coadministered ChAd63-MVA regimes, we demonstrate immune interference whereby responses against merozoite surface protein 1 (MSP1) are dominant over apical membrane antigen 1 (AMA1) and ME-TRAP. We also show that induction of strong cellular immunity against MSP1 and AMA1 is safe, but does not impact on parasite growth rates in the blood. In a subset of vaccinated volunteers, a delay in time to diagnosis was observed and sterilizing protection was observed in one volunteer coimmunized with MSP1+AMA1-results consistent with vaccine-induced pre-erythrocytic, rather than blood-stage, immunity. These data call into question the utility of T cell-inducing blood-stage malaria vaccines and suggest that the focus should remain on high-titer antibody induction against susceptible antigen targets.

Climate change & infectious diseases in India: implications for health care providers.

Climate change has the potential to influence the earth's biological systems, however, its effects on human health are not well defined. Developing nations with limited resources are expected to face a host of health effects due to climate change, including vector-borne and water-borne diseases such as malaria, cholera, and dengue. This article reviews common and prevalent infectious diseases in India, their links to climate change, and how health care providers might discuss preventive health care strategies with their patients.

DDT & deltamethrin resistance status of known Japanese encephalitis vectors in Assam, India.

BACKGROUND & OBJECTIVE: Japanese encephalitis (JE) outbreaks are common in Assam, northeastern State of India. Information on resistance in known JE vectors in the affected area is important for effective control measures. This study was undertaken to determine the species abundance of JE vectors endemic to Sibsagar district of Assam, and their susceptibility against DDT and deltamethrin. METHODS: Adult mosquitoes were collected using CDC light trap and aspirators from human dwellings from 13 endemic villages falling under three Primary Health Centres. Collected mosquitoes were identified and unfed female mosquitoes were used for DDT and deltamethrin sensitivity bioassay. The bioassay was performed following WHO protocol using standard susceptibility test kit. Knockdown time (KDT) was monitored at every 10 minutes intervals, whereas mortalities were recorded 24 h post-exposure. Vector density and resistance status were mapped using geographic information system (GIS) technique. RESULTS: A total of 7655 mosquitoes were sampled under three genera, i.e. Anopheles, Culex and Mansonia, and nine species, the JE vector Cx. vishnui group (31.78%) was the most predominant species, followed by Ma. uniformis (16.81%) and Ma. indiana (16.45%). All vector species were suspected to be resistant to DDT and sensitive to deltamethrin, except Ma. indiana, which was suspected to deltamethrin resistant. The KDT50 and KDT95 values of vector mosquitoes for DDT were significantly higher as compared to deltamethrin. The probit model used to estimate KDT50 and KDT95 values did not display normal distribution of percentage knockdown with time for all the vectors tested for DDT and deltamethrin, except for Ma. indiana for deltamethrin assay and Cx. gelidus for the DDT assay. INTERPRETATION & CONCLUSION: Differences in insecticide resistance status were observed between insecticides and vector species. The results of this study provided baseline data on insecticide resistance in known JE vectors of Sibsagar, Assam. The maps generated may allow better communication in control operations and comparison of changes in susceptibility status of these vectors over time.

Nonconsensus West Nile virus genomes arising during mosquito infection suppress pathogenesis and modulate virus fitness in vivo.

West Nile virus (WNV) is similar to other RNA viruses in that it forms genetically complex populations within hosts. The virus is maintained in nature in mosquitoes and birds, with each host type exerting distinct influences on virus populations. We previously observed that prolonged replication in mosquitoes led to increases in WNV genetic diversity and diminished pathogenesis in mice without remarkable changes to the consensus genome sequence. We therefore sought to evaluate the relationships between individual and group phenotypes in WNV and to discover novel viral determinants of pathogenesis in mice and fitness in mosquitoes and birds. Individual plaque size variants were isolated from a genetically complex population, and mutations conferring a small-plaque and mouse-attenuated phenotype were localized to the RNA helicase domain of the NS3 protein by reverse genetics. The mutation, an Asp deletion, did not alter type I interferon production in the host but rendered mutant viruses more susceptible to interferon compared to wild type (WT) WNV. Finally, we used an in vivo fitness assay in Culex quinquefasciatus mosquitoes and chickens to determine whether the mutation in NS3 influenced fitness. The fitness of the NS3 mutant was dramatically lower in chickens and moderately lower in mosquitoes, indicating that RNA helicase is a major fitness determinant of WNV and that the effect on fitness is host specific. Overall, this work highlights the complex relationships that exist between individual and group phenotypes in RNA viruses and identifies RNA helicase as an attenuation and fitness determinant in WNV.