Global genetic diversity of Aedes aegypti.

Mosquitoes, especially Aedes aegypti, are becoming important models for studying invasion biology. We characterized genetic variation at 12 microsatellite loci in 79 populations of Ae. aegypti from 30 countries in six continents, and used them to infer historical and modern patterns of invasion. Our results support the two subspecies Ae. aegypti formosus and Ae. aegypti aegypti as genetically distinct units. Ae. aegypti aegypti populations outside Africa are derived from ancestral African populations and are monophyletic. The two subspecies co-occur in both East Africa (Kenya) and West Africa (Senegal). In rural/forest settings (Rabai District of Kenya), the two subspecies remain genetically distinct, whereas in urban settings, they introgress freely. Populations outside Africa are highly genetically structured likely due to a combination of recent founder effects, discrete discontinuous habitats and low migration rates. Ancestral populations in sub-Saharan Africa are less genetically structured, as are the populations in Asia. Introduction of Ae. aegypti to the New World coinciding with trans-Atlantic shipping in the 16th to 18th centuries was followed by its introduction to Asia in the late 19th century from the New World or from now extinct populations in the Mediterranean Basin. Aedes mascarensis is a genetically distinct sister species to Ae. aegypti s.l. This study provides a reference database of genetic diversity that can be used to determine the likely origin of new introductions that occur regularly for this invasive species. The genetic uniqueness of many populations and regions has important implications for attempts to control Ae. aegypti, especially for the methods using genetic modification of populations.

Epidemiology of Mosquito-Borne Viruses in Egypt: A Systematic Review.

There are at least five common mosquito-borne viruses (MBVs) recorded in Egypt, including dengue virus (DENV), Rift Valley fever virus (RVFV), West Nile virus (WNV), Chikungunya virus, and Sindbis virus. Unexpected outbreaks caused by MBVs reflect the deficiencies of the MBV surveillance system in Egypt. This systematic review characterized the epidemiology of MBV prevalence in Egypt. Human, animal, and vector prevalence studies on MBVs in Egypt were retrieved from Web of Science, PubMed, and Bing Scholar, and 33 eligible studies were included for further analyses. The monophyletic characterization of the RVFV and WNV strains found in Egypt, which spans about half a century, suggests that both RVFV and WNV are widely transmitted in this nation. Moreover, the seropositive rates of DENV and WNV in hosts were on the rise in recent years, and spillover events of DENV and WNV to other countries from Egypt have been recorded. The common drawback for surveillance of MBVs in Egypt is the lack of seroprevalence studies on MBVs, especially in this century. It is necessary to evaluate endemic transmission risk, establish an early warning system for MBVs, and develop a sound joint system for medical care and public health for managing MBVs in Egypt.

Molecular Phylogenetics and Population Genetics of the Dengue Vector Aedes aegypti From the Arabian Peninsula.

Aedes aegypti mosquito is the principal dengue vector in the Kingdom of Saudi Arabia (KSA); however, no study has addressed its ecology and population structure yet. Therefore, we report on Ae. aegypti phylo- and population genetics using three DNA markers: COI, ND4, and rDNA-ITS2. Sampling the immature stages of Ae. aegypti revealed that water storage tanks (34.3% of habitats) were the most productive and contained 33% of immatures stages. Other important habitats included containers for wastewater drainage (including air-conditioning and water cooler trays) and containers associated with ornamentation. Shallow water leakage spots (2.7% of habitats, 8% of immatures) can be considered rare-but-epidemiologically-important containers. Neighbor-joining (NJ) phylogenetic analysis of Ae. aegypti identified 8, 14, and 9 haplotypes of COI, ND4, and ITS2, respectively, and revealed high levels of genetic variation in Ae. aegypti populations of KSA. Global distribution of haplotypes also indicated multiple gene introductions into these populations, with high levels of intra-population genetic variation and continuous gene exchange. The neutrality values indicated a deficiency of alleles and suggested that the KSA Ae. aegypti loci tested did not follow a neutral model of molecular evolution. Fst values and AMOVA indicated that most of the genetic variation in the KSA Ae. aegypti populations is due to intra- rather than inter-population differences. This is the first comprehensive report on the phylo- and population genetics of Ae. aegypti from the Arabian Peninsula. This information expands our understanding of the ecology and population dynamics of this important arboviral vector for informed control efforts.

Molecular Analysis of Targeted Insecticide Resistance Gene Mutations in Field-Caught Mosquitos of Medical Importance From Saudi Arabia.

Gene mutations on target sites can be a valuable indicator of the status of insecticide resistance. Jeddah, a global commercial and major port-of-entry city, is bearing the brunt of dengue disease burden in Saudi Arabia. In the current study, six genotypes of three codon combinations (989, 1016, and 1534) were observed on voltage-gated sodium channel (VGSC) gene in Jeddah's Aedes aegypti population, with PGF/PGC as the dominant one. Two types of introns between exon 20 and 21 on VGSC have been identified for the first time in Ae. aegypti in Saudi Arabia. Statistical and phylogenetic analyses showed that the intron type was significantly associated with the 1016 allele and may reflect the history of insecticide treatment in different continents. In addition, fixation of the L1014F allele on VGSC and G119S on acetylcholinesterase 1 gene was detected in local Culex quinquefasciatus populations, with frequencies of 95.24 and 100%, respectively. To the best of our knowledge, this is the first report of resistant-associated mutations in field-caught Cx. quinquefasciatus in Saudi Arabia. The high prevalence of insecticide resistance gene mutations in local primary mosquito vector species highlights the urgent need to carry out comprehensive insecticide resistance surveillance in Saudi Arabia.

Detection of DENV-2 and Insect-Specific Flaviviruses in Mosquitoes Collected From Jeddah, Saudi Arabia.

Background: Mosquito-borne diseases are rapidly spreading due to increasing international travel and trade. Routine mosquito surveillance and screening for mosquito-borne pathogens can be early indicators for local disease transmission and outbreaks. However, arbovirus detection in mosquito vectors has rarely been reported in Saudi Arabia. Methods: A total of 769,541 Aedes and Culex mosquitoes were collected by Black Hole traps during routine mosquito surveillance in the first half of 2016. Culex. quinquefasciatus and Ae. aegypti were the most prevalent species observed. Twenty-five and 24 randomly selected pools of Ae. aegypti and Cx. quinquefasciatus, respectively, were screened for arboviruses by RT-PCR. Results: Dengue 2 (DENV-2) and four strains of insect-specific flaviviruses, including one of cell-fusing agent virus (CFAV) and three of Phlebotomus-associated flavivirus (PAFV) were detected in pools of Ae. aegypti. We also detected 10 strains of Culex flavivirus (CxFV) in pools of Cx. quinquefasciatus. Phylogenetic analysis using whole genome sequences placed the DENV strain into the cosmopolitan 1 sub-DENV-2 genotype, and the CxFVs into the African/Caribbean/Latin American genotype. These analyses also showed that the DENV-2 strain detected in the present study was closely related to strains detected in China in 2014 and in Japan in 2018, which suggests frequent movement of DENV-2 strains among these countries. Furthermore, the phylogenetic analysis suggested at least five introductions of DENV-2 into Saudi Arabia from 2014 through 2018, most probably from India. Conclusions: To our knowledge, this study reports the first detection of four arboviruses DENV, CFAV, PAFV, and CxFV in mosquitoes in Saudi Arabia, which shows that they are co-circulating in Jeddah. Our findings show a need for widespread mosquito-based arbovirus surveillance programs in Saudi Arabia, which will improve our understanding of the transmission dynamics of the mosquito-borne arboviruses within the country and help early predict and mitigate the risk of human infections and outbreaks.

Enhanced surveillance and response approaches for pilgrims and local Saudi populations against emerging Nipah, Zika and Ebola viral diseases outbreaks threats.

Increasing emergence and spread of Nipah, ZIKV and Ebola case and potential outbreaks threats have been reported in several regions around the globe. Yet, emerging Nipah, Ebola and Zika viral diseases outbreaks have been indirectly linked to substantially globalization of trade and travel, climate change and intense urbanization impact, healthcare and socioeconomic inequities as well in affected community settings. Although no case has been documented in Saudi Arabia, there is a great risk of sudden emergence of any of these viruses and others via introducing among pilgrims coming from endemic regions during ritual ceremonies of mass gatherings. Consequently, promoting and investing on new and sensitive proven effective and innovative surveillance and monitoring approaches, including enhanced risk communication, improved integrated vectors surveillance in addition to improved sustainable highly pathogens surveillance control programs to human motility and environmental sanitation strategies all represent 'One Health' approach implementation strategic core. Initiation, development and implementation leaded by Saudi government and international stakeholders' of new partnership, coordinated response leadership and resource mobilization for multidisciplinary and intersectorial advocacy on emerging viral disease outbreaks, accompanied with R&D roadmap and taskforce is crucial. More efforts in epidemiological and laboratory early screening and surveillance of highly pathogenic germs/microbes, and confirmation of asymptomatic and syndromic cases amongst suspected Hajj and Umrah pilgrims, local vulnerable populations and expatriate workers is vital in generating reliable data and data sharing platform for timely risk communication and tourist information update, appropriate immunization campaigns or safe and efficacious care delivery implementation. Moreover, increase Hajj/Umrah mass gathering emergency outbreak preparedness, pilgrims health education and engagement outreach, pre-, during and post programs coverage and effectiveness is needed through One Health approach integration in attaining pilgrims and local population health safety and security, in advancing Saudi sustainable health development goals.

Innovative Preventive and Resilience Approaches Against Aedes-linked Vector-borne Arboviral Diseases Threat and Epidemics Burden in Gulf Council Countries.

Facing the local and imported borderless Aedes-linked vector-borne viral diseases threat and epidemics burden, the Health Committee of the Gulf Cooperation Council (GCC), including the Saudi Arabian government, announced that all Gulf countries are still free from the threat of a Zika virus epidemic. This article provides a vision of integrated eco-friendly and sustainable behavioral communication change (BCC), biological control preparedness and resilience approaches, and innovations implementation in Saudi Arabia and GCC for the purpose of controlling the threat of Aedes-linked vector-borne viral diseases. Implementing innovative Aedes-linked arboviral preventive and resilient control measures is pivotal in improving community-based surveillance-response systems, BCC multidisciplinary and empowerment methods, and in enhancing community social mobilization and risk communication strategies. Moreover, boosting social, cultural and ecological preparedness, and prompt management approaches are necessary against the threat of local and global zoonotic epidemics and pandemics. Nurturing evidence and proven tick or mosquito vector populations' reduction, planned urbanization, climate change and waste management systems, and implementing data sharing and tailored mitigation solutions are crucial against the persisting Aedes competence and the public health threat of dengue, MERS-CoV, and influenza outbreaks. Sustained investment and ample financial allocation are needed to improve Muslim pilgrimage (Hajj and Umrah mass gathering) including point of entry screening and treatment, community-based education and awareness campaigns, and increasing mosquito vector viral pathogens surveillance interventions. Increasing evidence-based population participation and resilient emergency community preparedness and rapid response programs integration are critical to reduce mosquito breeding sites, dengue, and other arboviral infections.

Ethical, legal and societal considerations on Zika virus epidemics complications in scaling-up prevention and control strategies.

Much of the fear and uncertainty around Zika epidemics stem from potential association between Zika virus (ZIKV) complications on infected pregnant women and risk of their babies being born with microcephaly and other neurological abnormalities. However, much remains unknown about its mode of transmission, diagnosis and long-term pathogenesis. Worries of these unknowns necessitate the need for effective and efficient psychosocial programs and medical-legal strategies to alleviate and mitigate ZIKV related burdens. In this light, local and global efforts in maintaining fundamental health principles of moral, medical and legal decision-making policies, and interventions to preserve and promote individual and collectiveHuman Rights, autonomy, protection of the most vulnerable, equity, dignity, integrity and beneficence that should not be confused and relegated by compassionate humanitarian assistance and support. This paper explores the potential medical and ethical-legal implications of ZIKV epidemics emergency response packages and strategies alongside optimizing reproductive and mental health policies, programs and best practice measures. Further long-term cross-borders operational research is required in elucidating Zika-related population-based epidemiology, ethical-medical and societal implications in guiding evidence-based local and global ZIKV maternal-child health complications related approaches and interventions. Core programs and interventions including future Zika safe and effective vaccines for global Zika immunization program in most vulnerable and affected countries and worldwide should be prioritized.

Deciphering emerging Zika and dengue viral epidemics: Implications for global maternal-child health burden.

Since its discovery in 1947 in Uganda and control and eradication efforts have aimed at its vectors (Aedes mosquitoes) in Latin America in the 1950s, an absolute neglect of Zika programs and interventions has been documented in Aedes endemic and epidemic-prone countries. The current unprecedented Zika viral epidemics and rapid spread in the Western hemisphere pose a substantial global threat, with associated anxiety and consequences. The lack of safe and effective drugs and vaccines against Zika or dengue epidemics further buttresses the realization from the West Africa Ebola outbreak that most emerging disease-prone countries are still poorly prepared for an emergency response. This paper examines knowledge gaps in both emerging and neglected arthropod-borne flavivirus infectious diseases associated with poverty and their implications for fostering local, national and regional emerging disease preparedness, effective and robust surveillance-response systems, sustained control and eventual elimination. Strengthening the regional and Global Health Flavivirus Surveillance-Response Network (GHFV-SRN) with other models of socio-economic, climatic, environmental and ecological mitigation and adaptation strategies will be necessary to improve evidence-based national and global maternal-child health agenda and action plans.

Outwitting dengue threat and epidemics resurgence in Asia-Pacific countries: strengthening integrated dengue surveillance, monitoring and response systems.

Dengue is still a substantial vector-borne viral disease threat and burden of public health importance worldwide. This situation is complicated by dengue virus unprecedented resurgence and persistence of varied serotypes in endemic-prone areas, and man-made and natural activities consequences that promote vector emergence, transmission dynamics and spread across the Asia-Pacific region. There is an urgent need to strengthen operational and contextual surveillance-response research in improving early detection of active reservoir detection, novel drug in case management and quality evidence-based response including the deployment of dengue mass vaccination. Moreover, sustained mapping and watching of dengue risk factors or determinants, performance and outcome indicators of control or elimination programs effectiveness in defining minimum effective data towards community knowledge-based decision-making policy and effective response packages is imperative. Moreover, implementation of a robust, integrated dengue early warning surveillance, monitoring and response systems metrics is required for evidence-based, timely and cost-effective contextual mitigation strategies, and innovative interventions.

Nobel prize for the artemisinin and ivermectin discoveries: a great boost towards elimination of the global infectious diseases of poverty.

The Millennium Development Goals (MDGs) made a marked transformation for neglected and vulnerable communities in the developing countries from the start, but infectious diseases of poverty (IDoPs) continue to inflict a disproportionate global public health burden with associated consequences, thereby contributing to the vicious cycle of poverty and inequity. However, the effectiveness and large-scale coverage of artemisinin combination therapy (ACT) have revolutionized malaria treatment just as the control of lymphatic filariasis (LF) and onchocerciasis have benefitted from harnessing the broad-spectrum effect of avermectin-based derivatives. The paradigm shift in therapeutic approach, effected by these two drugs and their impact on community-based interventions of parasitic diseases plaguing the endemic low- and middle-income countries (LIMCs), led to the Nobel Prize in Physiology or Medicine in 2015. However, the story would not be complete without mentioning praziquantel. The huge contribution of this drug in modernizing the control of schistosomiasis and also some intestinal helminth infections had already shifted the focus from control to potential elimination of this disease. Together, these new drugs have provided humankind with powerful new tools for the alleviation of infectious diseases that humans have lived with since time immemorial. These drugs all have broad-spectrum effects, yet they are very safe and can even be packaged together in various combinations. The strong effect on so many of the great infectious scourges in the developing countries has not only had a remarkable influence on many endemic diseases, but also contributed to improving the cost structure of healthcare. Significant benefits include improved quality of preventive and curative medicine, promotion of community-based interventions, universal health coverage and the fostering of global partnerships. The laudable progress and benefits achieved are indispensable in championing, strengthening and moving forward elimination of the IDoPs. However, there is an urgent need for further innovative, contextual and integrated approaches along with the advent of the Sustainable Development Goals (SDGs), replacing the MDGs in ensuring global health security, well-being and economic prosperity for all.

Potency and persistence of the bacterial mosquitocide Bacillus sphaericus against culicine mosquitoes under field conditions.

The biopesticide Bacillus sphaericus represents one of the important tools used in the control of mosquito larvae after chemical insecticides. The present study was conducted to investigate the efficacy B. sphaericus 2362 (VectoLex) in two different technical powders, ABG-6232 and ABG-6491 against larvae of two mosquitoes, Culex pipiens and Aedescaspius in El-Arish city, North Sinai, Egypt. The mosquito larvae were collected from polluted and fresh water (Cx. pipiens) and saline water (Ae. caspius). The physicochemical characteristics of larval breeding water sites were measured as salinity, conductivity, pH values and temperature. Susceptibility bioassays showed that Cx. pipiens larvae from polluted water sites have high susceptibility to B. sphaericus 2362 formulation ABG-6232 (LC50 0.150.33 ppm, LC90: 0.73-9.68 ppm). In case of ABG-6491 formulation, the values were LC50: 0.15-0.33 ppm and LC90: 1.73-9.83 ppm. Cx. pipiens larvae collected from fresh water habitat in ElQusiema, outside El-Arish city, susceptibility to B. sphaericus 2362 ABG-6232 had LC50 values ranging between 0.12 and 0.28 ppm, while LC90 ranged between 1.59 and 4.13 ppm. In case of ABG-6491, the LC50 values ranged between 0.13 and 0.28 ppm, while LC90 values ranged between 1.46 and 8.93 ppm. For Ae. caspius larvae from saline water and treated with B. sphaericus 2362 ABG-6232, LC50 values ranged between 0.31 &1.36 ppm, while LC90 ranged between 1.92 & 9.75 ppm. In case of ABG- 6491, the LC50 values ranged between 0.34 & 0.59 ppm, while LC90 values ranged between 1.79 and 11.56 ppm.

Morphometrics and protein profiles of the salivary glands of Phlebotomus papatasi and Phlebotomus langeroni sand flies.

Sand fly salivary fluid contains numerous proteins that modulate host immune responses to infection and facilitate blood-feeding and establishing Leishmania infection. Salivary proteins are differentially expressed in adaptation to the host, the meal type and ecological factors. We report on the morphometrics and protein composition of salivary glands of colonised Phlebotomus papatasi and P. langeroni sand flies from Egypt. Female glands were dissected at day 1 (D1, unfed), day 2 (D2, sugar-fed), day 3 (D3, blood-fed) and day 7 (D7, blood-digested). The salivary glands are composed of two lobes: heterogeneous in P. papatasi and homogeneous in P. langeroni. Lobe sizes varied considerably with fly age and feeding state; D3 flies had the largest lobe sizes and protein content. The P. papatasi flies had larger lobes and higher protein content than the P. langeroni flies. The P. papatasi D1 flies had 15 protein bands that decreased in the D2, D3 and D7 flies to 10 bands in the Sinai flies and 9 bands in the Alexandria flies. All P. langeroni flies had 12 protein bands but with different intensities. The results reveal inter-specific variation between P. papatasi and P. langeroni, while no intra-specific variation between P. papatasi strains. These results increase our understanding of salivary gland protein composition and blood-feeding behaviour in Old World sand flies with implications for leishmaniasis epidemiology and control.

The biological effects of the insect growth regulators; pyriproxyfen and diflubenzuron on the mosquito Aedes aegypti.

The biological effects of two insect growth regulators (IGRs), pyriproxyfen and diflubenzuron against larvae of the mosquito Aedes aegypti (L.) have been evaluated. Mosquitoes were collected from Jeddah governorate, west of the Kingdom of Saudi Arabia and maintained in the laboratory. According to IC50 values obtained (concentrations which inhibit the emergence of 50% of adults), diflubenzuron (0.00036 ppm) proved to be more effective by 11.4 fold of pyriproxyfen (0.0041 ppm). In addition to the delayed lethal action, larval treatment with the two IGRs, pyriproxyfen and diflubenzuron led to pronounced reduction in the reproductive potential of mosquito adults that emerged from these treatments. Pyriproxyfen caused a 33.2% decrease in egg production compared to 25.5% for diflubenzuron. The reduction in egg hatchability was by 40.6 and 36.2% for pyriproxyfen and diflubenzuron, respectively, with up to 4 fold higher reduction rates than in the control tests. These results shed light on the extended biological effects of IGRs on mosquitoes and encourage further testing of IGRs for wider use in the control of Ae. aegypti and other important disease vectors in Arabia and the world.

Potential of medicinal plants in mosquito control.

Medicinal plants have long history as important components in traditional medicine, and food of humans since ancient Egyptians and Chinese. Naturally occurring botanical compounds contain a broad range of chemical active ingredients can intervene in all biological processes of the mosquito, thus interrupt its life cycle and dispersal and reduce harms to humans and animals. Many medicinal plants were tested for their pesticide and repellent potential, as crude material, essential oils or individual active ingredients. This article reviewed studies on the efficacy of many well known and commonly used safe medicinal plants or their products in controlling the mosquitoes; Aedes aegypti, Anopheles gambiae, An. stephensi and Culex quinquefasciatus and the ticks, Dermacentor variabilis, Amblyomma americanum, Ixodes scapularis and I. ricinus. Promising and encouraging results were obtained against these arthropod-vectors of zoonotic diseases.