Posts Tagged “malaria”

So you drive over to the lab to have your blood work? In the near future, that would totally be ‘old-school’. Even if you so much as consider making that journey, you have GOT to be tempted to please think again! Time has been proven, repeatedly, to be of the essence, both for the sake of the diagnosis & treatment and the patient’s quality of life. For instance, imagine the convenience it will provide for an HIV-infected patient, who is what a lab technician would probably call a regular customer, due to the regular follow-up tests needed to monitor the development and treatment. Through a $10 piece of hardware connected to your cell phone, you will have your medical test results ready on the go. All you’d have to do is insert a slide containing a drop or two of your blood and leave the rest of the work up to the chip, as demonstrated on a prototype. I will even bet that, those who choose not to use it, would be charged extra for lab work!!!

The Ozcan Research Group at UCLA will already begin their field tests in Africa concerning the new cell phone/microscope gadget. I had to see to believe. Aside from all the engineering & technological aspects, which I am sure are quite many, if this were to be actually implicated worldwide, the possibilities of its application are endless, including, but not necessarily limited to, pretty much all of the blood-borne diseases. For instance, malaria, which is fairly common in many African countries, can be instantly diagnosed. The hospital would get the patient’s blood picture, through the cellular networks for analysis by physicians and there you have it.

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“It’s an honor to announce that we’ve successfully discovered, cloned & characterized the densonucleosis virus (DNV) Antigen, which will be able to infect Anopheles gambiae. That will hinder its ability to transmit Malaria parasite, Plasmodium or, at least, reduce its lifespan. I’ve to tell you this: This will be the latest in Malaria control.” Well.. those are my words but, of course, it is not my discovery. It’s the team of researchers from Johns Hopkins who discovered it. To realize how big it’s; we first need to know the previous approaches & trials in Malaria control.

To think, just think, about control/ prevention of any of those vector-borne parasites; automatically researchers think about these:
1- Prevent infection – disease – transmission.
2- By looking at: the parasite’s life cycle – the mosquito – the human immune system.
3- So, it’ll look like that: get humans vaccinated – develop genetically modified mosquitoes incapable of transmitting the parasite or simply “I was so naive to think that it’s simple” kill them with insecticides (anti-vector measures) – target the parasite at any stage of its life cycle.

For decades, DDT (dichloro-diphenyl-trichloroethane) & Chloroquine were successfully used in eradication of Anopheles & Plasmodium respectively, “I do like this word, makes me sound like a pro”. Chloroquine was used in treatment as well as prevention, till the emergence of chloroquine-resistant Plasmodium parasites and DDT-resistant Anopheles mosquitoes. Yes, they overcame the humans’ arsenal. So, preventing spread of resistant parasites is the #1 priority.

We can’t talk about all control strategies today, so we’ll talk about anti-vector measures. What do they use in control programs as anti-vector measures?
1- Insecticide-treated bednets (ITNs) & long-lasting ITNs (LLINs) it helped kids to survive. The only allowed insecticides to be used in ITNs are pyrethroid insecticides, so when the pyrethroid resistance emerged, as usual, it was really bad.
2- Indoor residual spraying (IRS) using DDT
One word about the mechanism of action of DDT & pyrethroids, both target voltage-gated Na-channels. So, when a set of mutations change the protein structure; Congratulations! It’s resistance to both DDT & pyrethroids.
3- New approach: Molecular talk; Know more about “blood meal” host selection. Yes, Anopheles smells the host, so researchers want to identify that pathway.
4- Another new approach: They are investigating genes which encode proteins that may interrupt the development of the parasite in the Anopheles.

The latest as an anti-vector measure is using Paratransgenesis or “the genetic manipulation of insect symbiotic (mutualistic, commensal or parasitic) microorganisms”, I can’t get the term or the definition. I’ll say it like that: “Any other m.o. has a relationship with the vector”. The steps are:
1- Know the Ag (Pick the gift)
2- Get the gene(s) engineered to be successfully expressed (Wrap the gift)
3- Delivery to Anopheles (Deliver the gift)
So the gift will be the non-enveloped ssDNA virus called (DNV). Its genome is very small, when they say for a viral genome that it’s small, so it has to be small (4–6 kb). The entire genome can be placed in a plasmid.

Back to the story of the discovery, they were doing a totally unrelated experiment when they found that strange band/ zone. They isolated it from the gel, cloned, sequenced, ran through BLAST which showed that it looks like DNV of Aedes aegypti (AeDNV) but not the man himself. They did multiple tests to identify the Ag, e.g. Immunofluorescence assay. There was a trial to infect Anopheles gambiae with DNV of Aedes aegypti which wasn’t successful in infecting adults from Anopheles gambiae. But the novel “AgDNV is highly infectious to An. gambiae larvae, disseminates to adult tissues, and is passed on to subsequent generations.”

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It’s hard for me, as a patriot, to read an article in EID about Plasmodium falciparum in ancient Egypt & shut up. The first emergence of Malaria in literature was when Hippocrates described the typical undulated fever which is highly characteristic for Malaria infection. Scientists made studies to identify P. falciparum‘s DNA in remains of a Roman infant (5th century) and another study on remains from 100-400 years ago.

They made their studies on 4000 years old mummies from Abydos, the Middle Kingdom tomb in Thebes West. Also samples from two different tombs from the New Kingdom until the Late Kingdom were taken. How did they know that those mummies had malarial infection? They simply searched for mummies had osteopathic evidence for chronic anemia. They ran PCR, a special technique called heminested PCR, using 18S rDNA primers. 2 of the 91 tested samples had chloroquine-resistance transporter (pfcrt) gene. I don’t know how, there wasn’t even chloroquine back there. They also ran immunological test which came positive for the P. falciparum histidine-rich protein-2 antigen.

Another thing came to my mind about Malaria. We must celebrate the launch of MalHaploFreq, the computer program which is designed for estimation of malaria haplotype frequencies in blood samples. Two awful facts about Malaria: There’s always drug resistance & multiple infections (the person can be infected by more than one type each one is resistant to an anti-malarial agent). All I know that they used Algorithm; this is really bad because I can’t stand math, and molecular markers to trace the spread of the drug-resistance & to predict the frequency of mutations.

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