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INFORMATION ON EMERGING DRUG RESISTANT PATHOGENS AND DEVELOPMENTS OF NEW DRUGS

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INFORMATION ON EMERGING DRUG RESISTANT PATHOGENS AND DEVELOPMENTS OF NEW DRUGS

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As these pathogens change, spread and infect more individuals, our infectious disease firefighters need new antibiotic fire hydrants to do their work.The emerging drug resistant of this virus has not been reported yet. However, it has been reported that the virus might come to resist and change genetically based on the surrounding condition such as temperate climate. For examples  the Ae. albopictus mosquitoes from a humid subtropical climate (Central Florida, United States) were infected with the Asian ZIKV genotype involved in the large South American outbreak, and the other one from a tropical rainforest climate (Singapore) which were infected with an Ugandan ZIKV genotype.

In spite of that,  A. aegypti mosquitoes and the development of mosquitoes that are resistant to arbovirus infection had been approached.  The mosquitoes are genetically modified to express a repressible lethal gene that will activate the virus activities. During their rearing in insectaries, the mosquitoes were provided with a dietary supplement not present in nature (eg, tetracycline), and this supplement represses the lethal gene activation. The off springs do not survive to the adult stage because they do not receive the dietary additive in the wild and have minimal fitness costs.An alternative approach is the use of endosymbiotic bacteria to prevent arboviruses replicating within the mosquito.

Discussing the development of new drugs, the threat is already here and will only grow over time. The development of new drugs have not yet been proven. However, many experiments had been done including results of the vaccine on mice. Experts say the developing of a useable preventative shot against the disease will not be simple, particularly due to concerns surrounding the safety of vaccinating pregnant women.

For example, an experimental vaccine to protect against the Zika virus has shown promising results in mice, experts said. Developers said the drug induced 'robust and durable immune responses'. While in India, India's Bharat Biotech presumed the experimental vaccine would start pre-clinical trials in animals imminently. in addition, Inovio's DNA-based vaccine is being developed with South Korea's GeneOne Life Sciences Inc and academic collaborators.

Furthermore, a crystal structure of Zika virus helicase which is the prior basis for antiviral drug design had been studied. A high-resolution structure of ZIKV helicase which is an important drug target was successfully presented by some reseachers.
The structure has revealed critical substrate-binding pockets for antiviral drug design. The other promising study is about "A Screen of FDA-Approved Drugs
for Inhibitors of Zika Virus Infection". The FDA-approved drugs that can inhibit ZIKV infection in several human cells, including those of genitourinary and neural origin had been identified, and suggest that these drugs be carefully considered for expedited trials among Zika patients. Although it is difficult to extrapolate from in vitro models to in vivo activity, it is promising that the preclinical testing discovered anti-ZIKV activity for several drugs within a range reasonably achievable in humans.

In conclusion, the zika virus has yet been identified as an emerging drug resistant but it might become one considering other factors. The development of new drugs have also not officially been approved since the scientist all over the world are still trying to find other factors that helps to inhibit the virus infection.

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HERE I ATTACHED THE LINK OF THE JOURNAL ON HOW ZIKA VIRUS TRANSFER OR INFECT HUMANS.

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HERE I ATTACHED THE LINK OF THE JOURNAL ON HOW ZIKA VIRUS TRANSFER OR INFECT HUMANS.

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http://jvi.asm.org/content/89/17/8880.short

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The suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficiently infects human neural progenitor cells (hNPCs) derived from induced pluripotent stem cells. Infected hNPCs further release infectious ZIKV particles. Importantly, ZIKV infection increases cell death and dysregulates cell-cycle progression, resulting in attenuated hNPC growth. Global gene expression analysis of infected hNPCs reveals transcriptional dysregulation, notably of cell-cycle-related pathways. Our results identify hNPCs as a direct ZIKV target. In addition, we establish a tractable experimental model system to investigate the impact and mechanism of ZIKV on human brain development and provide a platform to screen therapeutic compounds

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https://coggle.it/diagram/WMFbKu9C5gABXlK2

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*DEAR MEMBERS, I NEED YOUR HELP IN THIS QUESTION* Is Zika an opportunistic infection?

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*DEAR MEMBERS, I NEED YOUR HELP IN THIS QUESTION* Is Zika an opportunistic infection?

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An opportunistic infection is when the immunes system is weakened or has an abnormal distribution, then bacteria, viruses, fungi, or protozoa take advantage and cause an infection.

So for ZIka virus, I can't find the appropriate materials to exactly state that its opportunistic or not. So from my understanding in general, its not considered opportunistic because even in a healthy immune system, a person can still get infected wit ZIka.

So what are your opinions and points?

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In response to the link between Zika virus infection during pregnancy and microcephaly, the World Health Organization (WHO) declared Zika virus a Public Health Emergency of International Concern, February 1, 2016. Vector control, personal protection against mosquitoes, and pregnancy prevention are currently the only available approaches to reduce the risk of fetal infection in Zika-endemic areas. A majority priority of the global public health community is the development of a safe and effective Zika virus vaccine to address the dire need for additional prevention and control methods.

Important considerations for Zika virus vaccine development are
(1) the target population for vaccination

(2) the number of doses required to induce an immune response

(3) the effect of previous Flavivirus exposure on Zika virus vaccine safety and immunogenicity

(4) previous human experience with related types of vaccines/adjuvants

(5) sustainability

One of the potential vaccine against Zika virus is GLS-5700 vaccine. This vaccine is a synthetic DNA vaccine being developed by Inovio Pharmaceuticals from Pennsylvania and GeneOne Life Sciences of South Korea.

In preclinical testing this vaccine induced robust antibody and T cell responses in small and large animal models, demonstrating the product’s potential to prevent infection from this harmful pathogen in humans.

After receiving approval by the US Food and Drug Administration (FDA) on 26 July 2016, it begins a Phase 1 clinical trial in approximately 40 volunteers in the United States and Canada in Q3 2016 with safety and immunogenicity results expected by the end of the year. Now the research is still ongoing under clinical trials in US.

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1. Through mosquito bites

Zika virus is transmitted to people primarily through the bite of an infected Aedes species mosquito (Ae. aegypti and Ae. albopictus).
2. From mother to child (vertical transmission)

A pregnant woman infected with Zika virus can pass this virus to her fetus.
3. Through sex
It can be passed from a person with Zika before their symptoms start, while they have symptoms, and after their symptoms end.

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Symptoms of patient infected with Zika Virus

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Symptoms of patient infected with Zika Virus

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Many people infected with Zika virus are asymptomic or will only have mild symptoms which last for several days or one week. The most common symptoms of Zika are

Fever

Rash

Joint pain

Conjunctivitis (red eyes)

Headache

Muscle pain

Symptoms of Zika are similar to other viruses spread through mosquito bites, like dengue and chikungunya.

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https://www.khanacademy.org/science/biology/biology-of-viruses/virus-biology/a/what-is-zika-virus

http://www.sciencedirect.com/science/article/pii/S0166354216301206

https://worldwide.promega.com/resources/pubhub/features/zika-history-biology-research/

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Zika belongs to a group of viruses called the flaviviruses is spread by mosquitoes of the Aedes family which includes dengue, West Nile, and yellow fever. Flaviviruses are tiny structures made up of protein, RNA (a molecule related to DNA), and a lipid membrane. Each viral particle consists of a single-stranded RNA genome tucked inside a protein shell called a capsid, surrounded by an external sphere of membrane known as the envelope.

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Zika virus diagnosis is primarily based on detection of viral RNA by reverse transcription polymerase chain reaction (PCR) from clinical samples. Individual assays have been issued for Asian and African Zika viral strains targeting the envelope gene or NS5 region. There are several commercial assays available for Zika virus genome detection.

Using molecular technique will allow detecting Zika virus within 5 days of infection. However, the viral RNA presence depends on how much of it is present during the acute phase of infection.

The Trioplex rRT-PCR is a laboratory test designed to detect Zika virus, dengue virus, and chikungunya virus RNA.This test is not approved for protocol use unless its an emergency. It is used to differentiate between the RNA of Zika, Dengue and Chikungunya virus.Positive results indicate an ongoing infection. However, a negative result does not rule out infection.

The duration and level of viraemia(presence of virus) in asymptomatic patients are still unknown. Because viraemia decreases over time, a negative PCR test in blood collected 5–7 days after symptom onset does not exclude flavivirus infection.To confirm the infection serological testing.In a serological testing detection of anti-Zika IgM is tested.The Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA) is used for the qualitative detection of Zika virus IgM antibodies.This is used once onset symptoms up to until 12 weeks after infection. However serological testing can not confirm the infection by Zika, we must include symptoms, patient history, epidemiological information, and further testing and monitoring.

List of samples used for testing for Zika:
Serum
Urine
plasma
whole blood
cerebrospinal fluid (CSF)
amniotic fluid

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The first line of defense and immune response involved

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The first line of defense and immune response involved

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There are 4 type of targeted cells by Zika virus, which are fibroblasts, kerantinocytes, dendritic cells and monocytes. Zika use the C-type lectin receptor, DC-SIGN (a kind of receptor present on both macrophages and dendritic cell's surface) and phosphatetidylserine receptors on host cell surface to gain access to the cytoplasm via the receptor-mediated endocytosis.  Scientist also identified the cell receptor enabling the virus to enter fibroblasts. It is a protein called “AXL”.

The researchers demonstrated that the virus uses autophagy to replicate, a mechanism consisting of the partial degradation of cyctoplasm by the cell itself. This phenomenon eventually leads to cellular apoptosis, or death by breaking up, and in this way boosts dissemination of the pathogenic agent.

Infection of fibroblasts by Zika virus induces the expression pathogen recognition receptor, including toll-like receptor (TLR)3, RIG-I and MDA-5, which subsequently trigger the expression of type I interforon, interferon stimulated genes, including OAS2, ISG15 and MX1, and inflammatory chemokines, while the infection of monocytes triggers robust proinflammatory cytokine and chemokine responses upon infection.

Type I and type II interferon are known to be important for control of other flavivirus infections. Replication of ZIKV in human fibroblasts is inhibited by both types of interferons.

The adaptive immunity also involved in fighting the Zika Virus. Both anti-ZIKV IgG and IgM and neutralization antibodies , which were shown to provide partial protection in adult. Scientists replicate her experiments in T cell-competent mice confirmed that both mouse models mount a robust CD8+ T cell response to Zika infection.

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http://www.webmd.com/a-to-z-guides/news/20160829/3-drugs-identified-to-potentially-fight-zika-virus#1

http://www.hopkinsmedicine.org/news/media/releases/new_hope_for_zika_treatment_found_in_large_scale_screen_of_existing_drugs

https://www.nih.gov/news-events/nih-research-matters/finding-compounds-inhibit-zika

http://www.healio.com/infectious-disease/emerging-diseases/news/online/%7B9d3d5d95-89fa-4070-9cf8-42b03c3ed8c9%7D/various-compounds-may-help-advance-zika-treatments

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Burden of zika virus for Global and Malaysia.

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Burden of zika virus for Global and Malaysia.

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-Zika Virus Infection in Pregnant Women in Rio de Janeiro-

A total of 345 women were enrolled from September 2015 through May 2016.
Out of 182 women (53%) tested positive for ZIKV in blood, urine, or both.
The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation
Predominant maternal clinical features included:-
- maculopapular rash
- arthralgias
- conjunctival injection
- and headache
- 27% had fever (short-term and low-grade).

By July 2016,  among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly.
Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV
- 55% of pregnancies had adverse outcomes after maternal infection in the first trimester,
- 52% after infection in the second trimester,
- 29% after infection in the third trimester).

-Zika Virus Outbreak on Yap Island, Federated States of Micronesia-

In April and May 2007, physicians on Yap Island, Federated States of Micronesia, noted an outbreak of illness characterized by rash, conjunctivitis, subjective fever, arthralgia, and arthritis.

Although three patients tested positive with a commercially available dengue IgM kit, the physicians had the impression that this illness was clinically distinct from dengue, which had been detected on Yap in two previous outbreaks.

In June 2007, serum from acutely ill patients was sent to the Centers for Disease Control and Prevention (CDC) Arbovirus Diagnostic and Reference Laboratory in Fort Collins, Colorado.

Ten of 71 samples (14%) were found to contain Zika virus RNA according to reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay. RT-PCR assays with the use of consensus primers for nucleic acid of other arboviruses, including dengue, chikungunya, o'nyong-nyong, Ross River, Barmah Forest, and Sindbis viruses, were all negative.

They conducted an investigation to define the epidemiologic features of the outbreak and to describe the clinical manifestations of Zika virus disease.
The burden is that, this virus gives the abnormalities in newborns.

-Potential exposure to Zika virus for foreign tourists during the 2016 Carnival and Olympic Games in Rio de Janeiro, Brazil-
Statistical associations of Zika virus infections with Guillain–Barré syndrome underpin the additional serious threat of this new emerging Zika virus to everyone.

Therefore, it is very important for travellers to Zika virus-affected areas or countries to estimate the risk for acquiring a Zika virus infection. Such risk estimates have particular importance for tourists during the Carnival events in February 2016 or those planning to attend the Olympic Games in August 2016, with both events occurring in Rio de Janeiro.

However, for risk estimations one would need to know the true burden of Zika virus disease and quantify the force of infection in Rio de Janeiro over the time periods of the Carnival and the Olympic Games. At this stage, however, such data are still preliminary, the reasons of which are many: Zika virus is a flavivirus, therefore serologically based diagnostic tests are highly cross-reactive with dengue viruses.

Zika virus and dengue virus infections have one thing in common that may help to indirectly estimate the risk of Zika virus infections: both are transmitted by the same Aedes mosquitoes, and hence the potential exposure to Zika and dengue viruses can be calculated through mathematical modelling based on Aedes mosquito bites. In other words, the primary research question is the calculation of the risk of a tourist receiving a bite from an Aedes mosquito in Rio. Some preliminary estimation of the risk of acquiring Zika virus infection are presented.

They  set out to calculate the risk of foreign tourists being bitten by an Aedes aegyptii mosquito, the predominant species in Rio, during the carnival week (7–13 February) and the Olympic Games (5–20 August) 2016 in Rio de Janeiro.

-Malaysia reports first case of pregnant woman with Zika virus-

PUTRAJAYA - Malaysia on Wednesday (Sept 7) reported its first case of Zika infection in a pregnant woman, whose husband works in Singapore where authorities have already recorded 275 cases.

The 27-year-old Chinese patient is 3 to 4 months pregnant and lives in Taman Desa Harmoni, Minister of Health Subramaniam Sathasivam told reporters.

"She showed signs and symptoms before the husband. She was tested earlier and found positive," he said.

Datuk Seri Dr Subramaniam advised people with spouses who have been infected with the Zika virus to avoid sex or to take precautions to avoid pregnancy for at least six months.

He said the health ministry will hospitalise all pregnant Zika patients who will be treated by specialists.

Zika infections in pregnant women have been shown to cause microcephaly in the foetus, a severe birth defect in which the head and brain are undersized, besides other brain abnormalities.

The health minister also clarified that Malaysia is not spraying in-coming vehicles at the land checkpoints with disinfectant and insect repellent as a safety precaution. Instead, authorities are asking that drivers spray their vehicles before entering Malaysia.

But he acknowledged it's impossible for enforcement officers to ensure that all vehicles are sprayed.

Dr Subramaniam said given the close proximity of Johor Bahru to Singapore, the increasing number of Zika cases in Malaysia is to be expected. Aedes control measures have been increased in Johor Bahru and around the house of the patient, he added.

Conclusion

The Zika virus does give the burden to the global and even in Malaysia. A few steps can be done to avoid the Zika virus attacked.

1. Clean our house.
Make sure there is no water reservoirs inside and outside of the house.Just one tablespoon of water can serve as a mosquito breeding ground and produce up to 300 mosquitoes. The insects can breed in the bottom of a glass in the bathroom (like one you use to brush your teeth with) or in a film of water next to the sink. Therefore eliminate standing water throughout the home, including in flower pots, bottles, and accumulating garbage.

2. Exercise indoors

Break a sweat inside. Mosquitoes are attracted to carbon dioxide and heat. Your body naturally emits both, but cranks up the volume when you work out.

3. Travel smart

The best way to avoid Zika virus is to avoid affected areas. Check the CDC’s regularly updated list of countries and territories with active Zika virus transmission. If you must travel to an affected country, stay in air-conditioned areas, sleep under bed nets if your room may have mosquitoes, and use mosquito repellent vigilantly.

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Emerging Drug-resistant and Development of New Drugs

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Emerging Drug-resistant and Development of New Drugs

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https://www.thenation.com/article/from-zika-to-antibiotic-resistant-superbugs-welcome-to-the-new-age-of-contagions/

http://www.dailymail.co.uk/health/article-3455381/Experimental-Zika-promising-New-drug-induces-robust-durable-immune-responses-against-virus.html

https://wwwnc.cdc.gov/eid/article/21/10/pdfs/15-0847.pdf

http://www.ghtcoalition.org/blog/research-roundup-treating-drug-resistant-infections-ebola-virus-mutations-and-zika-vaccine-clinical

http://www.medscape.com/viewarticle/869249#vp_2

http://www.deseretnews.com/article/865671147/My-view-Drug-resistant-bacteria-poses-a-serious-threat.html

Tian, Hongliang, Xiaoyun Ji, Xiaoyun Yang, Wei Xie, Kailin Yang, Cheng Chen, Chen Wu et al. "The crystal structure of Zika virus helicase: basis for antiviral drug design." Protein & cell 7, no. 6 (2016): 450-454.

Barrows, Nicholas J., Rafael K. Campos, Steven T. Powell, K. Reddisiva Prasanth, Geraldine Schott-Lerner, Ruben Soto-Acosta, Gaddiel Galarza-Muñoz et al. "A screen of FDA-approved drugs for inhibitors of Zika virus infection." Cell Host & Microbe 20, no. 2 (2016): 259-270.

Musso, D., & Gubler, D. J. (2015). Zika virus: following the path of dengue and chikungunya?. The Lancet, 386(9990), 243-244.

Mansuy, J. M., Dutertre, M., Mengelle, C., Fourcade, C., Marchou, B., Delobel, P., & Martin-Blondel, G. (2016). Zika virus: high infectious viral load in semen, a new sexually transmitted pathogen. Lancet Infect Dis, 16(4), 405.

Guzzetta G, Poletti P, Montarsi F, Baldacchino F, Capelli G, Rizzoli A, Rosà R, Merler S. Assessing the potential risk of Zika virus epidemics in temperate areas with established Aedes albopictus populations. Euro Surveill. 2016;21(15):pii=30199.

Yakob, L., Thomas W..2016. Zika virus outbreak in the Americas: the need for novel mosquito control methods. The Lancet Global Health , Volume 4 , Issue 3 , e148 - e149.

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1) https://www.cdc.gov/zika/symptoms/symptoms.html
2) https://www.cdc.gov/zika/transmission/

3) http://www.nejm.org/doi/full/10.1056/NEJMc1610613?query=featured_zika

4) http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002157

5) http://intjinfection.com/?page=article&article_id=37354

6) https://www.esciencecentral.org/journals/emergence-of-zika-virus-2327-5073-1000222.php?aid=61298#38

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References - The first line of defense and the immune response involved

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References - The first line of defense and the immune response involved

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1)http://www.springernature.com/gp/group/zika-virus/zika-virus-and-host-immunity/7823114

2) https://en.ird.fr/the-media-centre/scientific-newssheets/483-how-the-zika-virus-infects-human-cells

3)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774925/pdf/pntd.0004530.pdf

4)https://www.researchgate.net/publication/304531221_Mechanisms_of_Zika_Virus_Infection_and_Neuropathogenesis

5) https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0036-1592071

6) http://www.lji.org/news-events/news/post/t-cells-join-the-fight-against-zika/

7) Below is a short brief review about the innate immunity of Zika Virus

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http://www.drugdevelopment-technology.com/projects/gls-5700-dna-vaccine-for-prevention-of-infection-from-zika-virus/

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http://ecdc.europa.eu/en/publications/Publications/zika-virus-guidance-healthcare-providers-and-laboratory-diagnosis.pdf

https://www.cdc.gov/zika/hc-providers/types-of-tests.html

https://www.sciencedaily.com/releases/2016/05/160512102626.htm

https://www.glynncounty.org/DocumentCenter/View/54527

https://www.gov.uk/guidance/zika-virus-and-immunocompromised-patients

https://www.glynncounty.org/DocumentCenter/View/54527

https://www.cdc.gov/zika/symptoms/treatment.html