Mass drug administration for the control and elimination of Plasmodium vivax malaria: an ecological study from Jiangsu province, China

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Recent progress in malaria control has caused renewed interest in mass drug administration (MDA) as a potential elimination strategy but the evidence base is limited. China has extensive experience with MDA, but it is not well documented.
Methods

An ecological study was conducted to describe the use of MDA for the control and elimination of Plasmodium vivax in Jiangsu Province and explore the association between MDA and malaria incidence. Two periods were focused on: 1973 to 1983 when malaria burden was high and MDA administered to highly endemic counties province-wide, and 2000 to 2009, when malaria burden was low and a focal approach was used in two counties. All available data about the strategies implemented, MDA coverage, co-interventions, incidence, and adverse events were collected and described. Joinpoint analysis was used to describe trends in incidence and the relationship between MDA coverage and incidence was explored in negative binomial regression models.
Results

From 1973 to 1983, MDA with pyrimethamine and primaquine was used on a large scale, with up to 30 million people in target counties covered in a peak year (50% of the total population). Joinpoint analyses identified declines in annual incidence, -56.7% (95% CI -75.5 to -23.7%) from 1973–1976 and -12.4% (95% CI -24.7 to 2.0%) from 1976–1983. Population average negative binomial models identified a relationship between higher total population MDA coverage and lower monthly incidence from 1973–1976, IRR 0.98 (95% CI 0.97 to 1.00), while co-interventions, rainfall and GDP were not associated. From 2000–2009, incidence in two counties declined (annual change -43.7 to -14.0%) during a time when focal MDA using chloroquine and primaquine was targeted to villages and/or individuals residing near passively detected index cases (median 0.04% of total population). Although safety data were not collected systematically, there were rare reports of serious but non-fatal events.
Conclusions

In Jiangsu Province, China, large-scale MDA was implemented and associated with declines in high P. vivax malaria transmission; a more recent focal approach may have contributed to interruption of transmission. MDA should be considered a potential key strategy for malaria control and elimination.

AUTHORS: Michelle S Hsiang, Jimee Hwang, Amy R Tao, Yaobao Liu, Adam Bennett, George Dennis Shanks, Jun Cao, Stephen Patrick Kachur, Richard GA Feachem, Roly D Gosling and Qi Gao

Source: Malaria Journal 2013, 12:383 doi:10.1186/1475-2875-12-383
http://www.malariajournal.com/content/12/1/383/abstract
Published: 1 November 2013

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Ranbaxy Drug Synriam Receives Indian Government Approval to Treat Plasmodium Vivax

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Single treatment for both Plasmodium vivax and Plasmodium falciparum malaria Permission received to conduct Phase III clinical trials for pediatric formulation

Gurgaon, India,: Ranbaxy Laboratories Limited (Ranbaxy) today announced that the company has received approval from the Central Drugs Standard Control Organisation (CDSCO), Government of India to manufacture and market Synriam (arterolane maleate and piperaquine phosphate tablet 150+750 mg) in India for the treatment of uncomplicated malaria in adults caused by Plasmodium vivax parasite.

Phase III clinical trials for the drug conducted in India, successfully demonstrated the efficacy and tolerability of Synriam as comparable to chloroquine.

Last year on World Malaria Day, April 25, Ranbaxy had launched India’s first new drug, Synriam for the treatment of uncomplicated Plasmodium falciparum malaria in India. Since its launch, Synriam has successfully treated around one million patients.

The company has also received permission to conduct Phase III clinical trials for the pediatric formulation in pediatric patients of uncomplicated Plasmodium falciparum malaria.

Commenting on the approval, Arun Sawhney, CEO & Managing Director, Ranbaxy, said, “Synriam is a new age cure for malaria and is fast emerging as the preferred option in the hands of doctors. This approval makes Synriam one of the few therapies in the world that successfully treats both, Plasmodium vivax and Plasmodium falciparum malaria. Ranbaxy remains committed in its fight against malaria and we are making all efforts to make this new therapy accessible to patients around the world.”

Ranbaxy is working to make this new treatment available in African, Asian and South American markets where malaria is rampant. The company has filed New Drug Applications (NDAs) for marketing Synriam in some African countries and will be filing more applications during the year. Once approved, the product will be launched in these markets.

Synriam provides quick relief from most malaria-related symptoms, including fever, and has a high cure rate of over 95%. It conforms to the recommendations of the World Health Organization (WHO) for using combination therapy in malaria.

As the dosage regimen for Synriam is simple, it leads to better compliance. A patient is required to take just one tablet per day, for three days, compared to other medicines where two to four tablets are required to be taken, twice daily, for three or more days. The drug is also independent of dietary restrictions for fatty foods or milk, as is the case with older anti-malarial therapies. Since Synriam has a synthetic source, unlike artemisinin-based drugs, production can be scaled up whenever required and a consistent supply can be maintained at a low cost.

According to the World Malaria Report 2012 published by WHO, India sees about 1.3 million confirmed cases of malaria each year, about 50% of which are caused by Plasmodium vivax, the second most important species after Plasmodium falciparum. Worldwide, 40% of total malaria burden globally is due to Plasmodium vivax , which shows the vast potential of Synriam in India and globally.

Traditional drugs are proving ineffective against the deadly malarial parasite because it has progressively acquired marked resistance to available drugs. Availability of plant based Artemesinin, a primary ingredient in established anti-malarial therapies is finite and unreliable. This leads to price fluctuations and supply constraints, which is not the case with a synthetic drug like Synriam.

Source: Ranbaxy

Is it Malaria Relapse?

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QUESTION

WHILE IN VIETNAM, I HAD VIVAX AND FACIPRIUM MALARIA. THE OLDER I GET I COME DOWN WITH THE CHILLS, FEVER AND PROFUSE SWEATING. BLOOD TEST NEVER DOES SHOW ANY MALARIA BUT DOES SHOW THE VIVAX ANTIBODIES. DOES THIS MEAN I STILL HAVE MALARIA OR HOW LONG DO THE ANTIBODIES REMAIN IN MY BODY AND WHY NO MALARIA CELLS?

ANSWER

Antibodies to malaria can persist in the body for years after the malaria infection, so if blood tests are not showing up malaria parasites but do show you have antibodies, then you probably don’t have malaria now, and it is just showing that you once had malaria, but it could have been many years ago. You should talk to your doctor about other possible infections that might be causing your symptoms.

Can the PCR blood test identify hypnozoites?

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QUESTION

I have never been diagnosed with malaria but returned from Turkey in 2007 (P. Vivax endemic area; Diarbykar & Mardin areas). My symptoms were consistent with malaria and I have now had 5 relapses since then, averaging one occurrence per year. I now have impaired kidney functioning and I am uncertain if this could be because of undiagnosed malaria? Would the PCR blood test at anytime be an option to conclusively rule out malaria or would blood need to be drawn during an actual relapsing event?

ANSWER

You have certainly done your research! It’s great to hear from someone who is so well informed about the risk areas they traveled too and the diagnostic options. You’re right in thinking that PCR is only appropriate during an active relapse; while the malaria parasites are dormant in the liver (called hypnozoites, in that form), they are extremely hard to detect. One option could be to investigate the possibility of taking a test to look for antibodies to the P. vivax parasite. These tests are often referred to as ELISAs (enzyme-linked immunosorbent assays) and they can sometimes be useful for testing for malaria in between relapses because the antibodies your body produces against the malaria parasite during the relapse phase can stick around in the blood for weeks, or even months or years. Therefore these tests are not very useful for people in endemic areas (who may always have these antibodies, regardless of their current infection status) but for travelers who have been exposed a limited number of times, this test may be able to say whether you have at some stage been infected with P. vivax; together with your clinical history, this will provide strong evidence to your doctor that you might need to discuss the possibility of taking primaquine, the drug which can kill the dormant hypnozoites and prevent further relapse.

Testing for Dormant Malaria

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QUESTION

When malaria is dormant in the body can it be detected in a blood test?

ANSWER

Not directly, no. A normal malaria blood test consists of a thick or thin smear, which is often stained and then looked at under a microscope; with these tests, you would not be able to see any sign of the malaria which is lying dormant in the liver. However, there is another type of blood test, known as serology, which looks for the body’s antibodies against malaria. These are proteins produced by the immune system when the patient becomes infected with malaria. These antibodies are specific to the type of malaria the person was infected with, and can persist for many months and even years. As such, if a patient was infected with one of the types of malaria which can become dormant (i.e. P. vivax and P. ovale), a serology test might be able to tell whether the patient had ever been infected with one of these two types, and then suggest that they might continue to have a dormant infection.

Malaria or Kidney Infection?

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QUESTION

Two months ago my daughter was in Uganda working and when came back to the States she was hospitalized for 4 days with Malaria symptoms. Her tests came back negative they really didn’t act like they knew how to treat this. They kept telling her they didn’t know how to diagnosis Malaria. So they treated her for it. She now after 2 months is once again hospitalized with the same symptoms. They are telling her they think it is a kidney infection. Can malaria be misdiagnosed as a kidney infection. She once again has all the symptoms as malaria?

ANSWER

What tests did the doctors do to try to diagnose malaria in your daughter when she first got back to the States? Usually, malaria is diagnosed by a blood test, whereby a trained technician will look at the patient’s blood under a microscope. The technician looks for signs of the malaria parasite in the patient’s blood, and if seen, can determine the intensity of the infection as well as the species of malaria. This is important information for accurate treatment. Alternatively, rapid diagnostic tests, which utilize a droplet of blood in a device which looks similar to a pregnancy test, and can very quickly determine whether someone is infected with malaria. It is important to know that malaria cannot be diagnosed by looking at standard blood parameters. If you don’t think your doctors know what is afflicting your daughter, you should take her to a clinic which specializes in tropical or travel medicine. There, they will certainly know how to effectively diagnose your daughter.

Given that your daughter experienced a resurgence of symptoms two months after returning, if she did have malaria, then there are two kinds which she might have: Plasmodium ovale and Plasmodium vivax. The other types of malaria, including the most deadly kind, P. falciparum, are not able to come back and relapse once they are treated. However, in order to prevent future relapses, your daughter may also have to be treated with another form of medication called primaquine. I will emphasize again, however, that it is crucial to gain an accurate diagnosis before taking any form of treatment for malaria.

Recurrence of Malaria

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QUESTION

If a person treated for malaria after being infected from a malaria endemic country of West Africa and cured then he travel back to his country which does not known for malaria endemic region of the world. Question is: Is there any chance of re-occurrence even he is not being exposed to malaria spreading mosquito for some time may be year?
Is it true Malaria parasites stays in liver as hibernation for a long period and attack after many months or year?
If so what treatment can prevent it?

Please advise.

ANSWER

There are several different types of malaria which are found in West Africa, and the most common and deadly form, Plasmodium falciparum, is not able to hibernate in the liver. However, two other types of malaria are able to lay dormant in the liver – these two kinds are called Plasmodium vivax and P. ovale. Both are not nearly as common as P. falciparum in West Africa, though P. ovale has been reported at prevalences of over 10% in some areas, which is double its usual prevalence elsewhere in the world. Weeks, months or even years after an initial infection with P. vivax or P. ovale, the patient may experience what is known as a relapse, which is when the dormant liver forms become active again and re-invade the blood stream, causing a renewal of malaria symptoms. These relapses can be treated with normal anti-malarial drugs (even chloroquine, in many cases), but a different drug is required to kill the dormant liver forms and prevent future relapse. This drug is called primaquine, and may not be suitable for people with certain types of G6DP deficiencies, so you should talk to your doctor about having a test for this condition before taking primaquine.

Positive RDT After Malaria Treatment

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QUESTION

I have Pv malaria repeated 2 times in two month then doctor give arthemether, lumefantrine tablet for three days twice in a day and primaquine tablet for 14 days..after this treatment malaria show positive on rapid test by a faint line….what is this?

ANSWER

It sounds like your doctor has treated you appropriately. What the line on the rapid test means depends a bit on the type of test it was. Some of these rapid tests look for parts of the malaria parasite which the body recognizes as causing disease (called antigens)—sometimes, these antigens can persist a bit in the body even after the malaria infection has been cured. Therefore, that could explain a slight positive result in a  rapid test soon after treatment. It will be important to follow this up with a second rapid test, maybe in a week, just to make sure you do not have an active infection. You should also be aware that Plasmodium vivax can remain dormant in the liver (primaquine is used to kill these dormant forms), and if primaquine treatment does not work, you will still be ay risk of relapse but you will not have any malaria parasites in the blood, and thus even a rapid test will be negative.

Vivax or Falciparum Malaria?

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QUESTION:
I live in Pucallpa, Peru. I recently went on a trip to a remote jungle location in amazon jungle of Peru, and now I have malaria, but I’m not sure if it’s Vivax or falciparum. How could I know the difference? It seems like vivax is more common here in the jungle region of Peru, or am I wrong? Also, if it is Vivax, is Chloroquine with primaquine the best thing to take? I heard vivax is starting to develop a resistance to Chloroquine, but is there any evidence of a resistance to chloroquine + primaquine? Thanks.

ANSWER:
The symptoms of malaria infection with P. vivax vesus P. falciparum are similar. P. vivax has fewer severe complications and is almost never fatal. The two strains can be distinguished in the laboratory where the diagnosis of malaria is confirmed, either by their appearance under a microscope or by more sophisticated molecular approaches. In your region of South America, P. vivax is far more common that P. falciparum. Yes, there is a small risk of chloroquine resistance, but it is low in this region and the combination of chloroquine and primaquine remains a standard treatment. The combination of chloroquine plus primaquine helps overcome chloroquine resistance in P. vivax and P. falciparum. The primaquine is also effective in eliminating the form of vivax that can “hibernate” in the liver for months or years and resurface, causing relapse. Despite this, there are rare cases of relapse after a full course of standard chloroquine and primaquine and close medical follow up during and after treatment will be important.

Malareich and Pregnancy

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QUESTION

Hi , am 31 weeks pregnant and had to take Malareich as my Anti malaria drug. I did not take the drug until I felt I had malaria, because I had body pains and headaches. Please advise if I will be ok after taking the malareich.

ANSWER

Malareich is a combination drug comprising of sulfadoxine and pyrimethamine, which is one of the medications recommended for treatment of malaria in pregnant women. However it sounds like you took the medication because you thought you had malaria – it is really important to be diagnosed by a doctor. For example, they will be able to ensure that you get the correct type of treatment for the kind of malaria you have. Malareich, for example, is probably not as effective against P. vivax malaria as P. falciparum malaria, but P. vivax is still susceptible to chloroquine, which is another drug that is suitable for the treatment of malaria in pregnant women.