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Fulltext Pyrethroid resistance in the dengue vector Aedes aegypti in Southeast Asia: present situation and prospects for management

Amelia-Yap ZH, Chen CD, Sofian-Azirun M, Low VL

Parasit Vectors, 2018 Jun 04;11(1):332.
PMID: 29866193 DOI: 10.1186/s13071-018-2899-0

Human arboviral diseases transmitted by Aedes aegypti such as dengue, Zika, chikungunya and yellow fever remain global public health threats to date. Of these diseases, dengue fever is particularly prevalent in Southeast Asia. Relentless vector control efforts are performed to curtail disease transmissions through which pyrethroid insecticides are broadly used as the first line of defense to control Ae. aegypti, especially in the course of disease outbreaks. Here, we compile the largest contemporary database for susceptibility profiles and underlying mechanisms involved in Ae. aegypti resistant to pyrethroids in Southeast Asia. The extensive use of pyrethroids inevitably elicit different levels of resistance to numerous populations despite the presence of geographical isolation. The most common mechanisms of pyrethroid resistance that have been identified in Ae. aegypti includes mutations in the voltage sensitive sodium channel gene (Vssc gene) and metabolic-mediated insecticide resistance. Aedes aegypti develops resistance to pyrethroids by acquisition of one or several amino acid substitution(s) in this Vssc gene. Enzymes involved in metabolic-mediated detoxification (i.e. monooxygenases, glutathione-S-transferases and esterases) have been reported to be related to pyrethroid resistance but many specific contributory enzymes are not completely studied. An inadequate amount of data from some countries indicates an urgent need for further study to fill the knowledge gaps. Perspectives and future research needs are also discussed.

Matched MeSH terms: Zika Virus Infection/transmission*
Fulltext Willingness to Participate and Associated Factors in a Zika Vaccine Trial in Indonesia: A Cross-Sectional Study

Harapan H, Mudatsir M, Yufika A, Nawawi Y, Wahyuniati N, Anwar S, et al.

Viruses, 2018 11 18;10(11).
PMID: 30453663 DOI: 10.3390/v10110648

One of the crucial steps during trials for Zika and other vaccines is to recruit participants and to understand how participants' attitudes and sociodemographic characteristics affect willingness to participate (WTP). This study was conducted to assess WTP, its explanatory variables, and the impact of financial compensation on WTP in Indonesia. A health facility-based cross-sectional study was conducted in eleven regencies in the Aceh and West Sumatra provinces of Indonesia. Participants were recruited via a convenience sampling method and were interviewed. The associations between explanatory variables and WTP were assessed using a two-step logistic regression analysis. A total of 1,102 parents were approached, and of these 956 (86.8%) completed the interview and were included in analysis. Of those, 144 (15.1%) were willing to participate in a Zika vaccine trial without a financial compensation. In the multivariate analysis, WTP was tied to an age of more than 50 years old, compared to 20⁻29 years (odds ratio (OR): 5.0; 95% confidence interval (CI): 2.37⁻10.53), to being female (OR: 2.20; 95% CI: 1.11⁻4.37), and to having heard about Zika (OR: 2.41; 95% CI: 1.59⁻3.65). Participants' WTP increased gradually with higher financial compensation. The rate of WTP increased to 62.3% at the highest offer (US$ 350.4), and those who were still unwilling to participate (37.7%) had a poorer attitude towards childhood vaccination. This study highlights that pre-existing knowledge about Zika and attitudes towards childhood vaccination are important in determining community members being willing to participate in a vaccine trial. Financial incentives are still an important factor to enhance participant recruitment during a vaccine trial.

Matched MeSH terms: Zika Virus Infection/prevention & control*
Polysulfonate suramin inhibits Zika virus infection

Tan CW, Sam IC, Chong WL, Lee VS, Chan YF

Antiviral Res, 2017 07;143:186-194.
PMID: 28457855 DOI: 10.1016/j.antiviral.2017.04.017

Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log10 PFU viral reduction with IC50value of ∼2.5-5 μg/ml (1.93 μM-3.85 μM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor.

Matched MeSH terms: Zika Virus Infection/prevention & control*; Zika Virus Infection/virology; Zika Virus/drug effects*; Zika Virus/physiology
The distribution of important sero-complexes of flaviviruses in Malaysia

Kumar K, Arshad SS, Toung OP, Abba Y, Selvarajah GT, Abu J, et al.

Trop Anim Health Prod, 2019 Mar;51(3):495-506.
PMID: 30604332 DOI: 10.1007/s11250-018-01786-x

Flaviviruses (FVs) are arthropod-borne viruses of medical and veterinary importance. Numerous species of FVs have been isolated from various host; mainly humans, animals, ticks, and mosquitoes. Certain FVs are extremely host-specific; at the same time, some FVs can infect an extensive range of species. Based on published literatures, 11 species of FVs have been detected from diverse host species in Malaysia. In humans, dengue virus and Japanese encephalitis virus have been reported since 1901 and 1942. In animals, the Batu Cave virus, Sitiawan virus, Carey Island, Tembusu virus, Duck Tembusu virus, and Japanese encephalitis viruses were isolated from various species. In mosquitoes, Japanese encephalitis virus and Kunjin virus were isolated from Culex spp., while Zika virus and Jugra virus were isolated from Aedes spp. In ticks, the Langat virus was isolated from Ixodes spp. One of the major challenges in the diagnosis of FVs is the presence of sero-complexes as a result of cross-reactivity with one or more FV species. Subsequently, the distribution of specific FVs among humans and animals in a specific population is problematic to assess and often require comprehensive and thorough analyses. Molecular assays such as quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and digital droplet RT-PCR (ddRT-PCR) have been used for the differentiation of flavivirus infections to increase the accuracy of epidemiological data for disease surveillance, monitoring, and control. In situations where sero-complexes are common in FVs, even sensitive assays such as qRT-pCR can produce false positive results. In this write up, an overview of the various FV sero-complexes reported in Malaysia to date and the challenges faced in diagnosis of FV infections are presented.

Matched MeSH terms: Zika Virus
Idiopathic ileal volvulus with multiple concomitant infections in a starving man

Tan LJ, Othman MS, Hiu J, Wong KT, Lai SK

Malays J Pathol, 2021 Apr;43(1):81-85.
PMID: 33903310

BACKGROUND: Small bowel volvulus is defined as the torsion of the small intestine, potentially leading to bowel obstruction, gangrene and perforation. It is a rare condition, especially in adults.
CASE PRESENTATION: A 30-year-old man was retrieved from the jungle with severe weight loss and abdominal symptoms. He succumbed to death despite 22 days of intensive medical treatment. An autopsy revealed a ruptured gangrenous ileal volvulus with peritonitis and subdiaphragmatic abscess. Further laboratory analysis detected systemic Candida tropicalis and intestinal gramnegative bacterial sepsis, systemic Zika virus viremia, leptospirosis complicating rhabdomyolysis and disseminated intravascular coagulopathy, Type I Herpes Simplex virus infection of the tongue and upper gastrointestinal tract. The cause of death was the ruptured ileal volvulus, complicated with upper gastrointestinal bleeding due to Herpes simplex virus esophagitis in a malnourished patient with resolving leptospirosis and underlying Zika virus co-infection.
CONCLUSION: Rare clinical scenarios of adult-onset intestinal volvulus with concomitant multiple infections precludes clinical diagnosis and early treatment, leading to devastating consequences of clinical outcome. The positive clinical and postmortem correlation is a good learning lesson in many disciplines of medicine and science.

Matched MeSH terms: Zika Virus
Mosquito control with green nanopesticides: towards the One Health approach? A review of non-target effects

Benelli G, Maggi F, Pavela R, Murugan K, Govindarajan M, Vaseeharan B, et al.

Environ Sci Pollut Res Int, 2018 Apr;25(11):10184-10206.
PMID: 28755145 DOI: 10.1007/s11356-017-9752-4

The rapid spread of highly aggressive arboviruses, parasites, and bacteria along with the development of resistance in the pathogens and parasites, as well as in their arthropod vectors, represents a huge challenge in modern parasitology and tropical medicine. Eco-friendly vector control programs are crucial to fight, besides malaria, the spread of dengue, West Nile, chikungunya, and Zika virus, as well as other arboviruses such as St. Louis encephalitis and Japanese encephalitis. However, research efforts on the control of mosquito vectors are experiencing a serious lack of eco-friendly and highly effective pesticides, as well as the limited success of most biocontrol tools currently applied. Most importantly, a cooperative interface between the two disciplines is still lacking. To face this challenge, we have reviewed a wide number of promising results in the field of green-fabricated pesticides tested against mosquito vectors, outlining several examples of synergy with classic biological control tools. The non-target effects of green-fabricated nanopesticides, including acute toxicity, genotoxicity, and impact on behavioral traits of mosquito predators, have been critically discussed. In the final section, we have identified several key challenges at the interface between "green" nanotechnology and classic biological control, which deserve further research attention.

Matched MeSH terms: Zika Virus
Fulltext Assessment of Aedes albopictus reference genes for quantitative PCR at different stages of development

Dzaki N, Azzam G

PLoS One, 2018;13(3):e0194664.
PMID: 29554153 DOI: 10.1371/journal.pone.0194664

Members of the Aedes genus of mosquitoes are widely recognized as vectors of viral diseases. Ae.albopictus is its most invasive species, and are known to carry viruses such as Dengue, Chikugunya and Zika. Its emerging importance puts Ae.albopictus on the forefront of genetic interaction and evolution studies. However, a panel of suitable reference genes specific for this insect is as of now undescribed. Nine reference genes, namely ACT, eEF1-γ, eIF2α, PP2A, RPL32, RPS17, PGK1, ILK and STK were evaluated. Expression patterns of the candidate reference genes were observed in a total of seventeen sample types, separated by stage of development and age. Gene stability was inferred from obtained quantification data through three widely cited evaluation algorithms i.e. BestKeeper, geNorm, and NormFinder. No single gene showed a satisfactory degree of stability throughout all developmental stages. Therefore, we propose combinations of PGK and ILK for early embryos; RPL32 and RPS17 for late embryos, all four larval instars, and pupae samples; eEF1-γ with STK for adult males; eEF1-γ with RPS17 for non-blood fed females; and eEF1-γ with eIF2α for both blood-fed females and cell culture. The results from this study should be able to provide a more informed selection of normalizing genes during qPCR in Ae.albopictus.

Matched MeSH terms: Zika Virus/genetics