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Virus-based malaria vaccine shows promise in early trial

By Sungano Mharakurwa Moderator | 01 Jun, 2015

Please see abstract below and accompanying link.
After at least 90 years of hard work and unfulfilled anticipation for a malaria vaccine, could this be finally it? Is there really light at the end of the tunnel now? We welcome perspectives and thoughts on this time-honoured challenge.

ABSTRACT
Prime-boost vaccination with chimpanzee adenovirus and modified vaccinia Ankara encoding TRAP provides partial protection against Plasmodium falciparum infection in Kenyan adults

Caroline Ogwang,1* Domtila Kimani,1* Nick J. Edwards,2,3 Rachel Roberts,2,3 Jedidah Mwacharo,1 Georgina Bowyer,3 Carly Bliss,3 Susanne H. Hodgson,2,3 Patricia Njuguna,1 Nicola K. Viebig,4 Alfredo Nicosia,5,6,7 Evelyn Gitau,1 Sandy Douglas,2,3 Joe Illingworth,3 Kevin Marsh,1,2
Alison Lawrie,2 Egeruan B. Imoukhuede,2,4 Katie Ewer,3 Britta C. Urban,8* Adrian V. S. Hill,2,3* Philip Bejon,1,2*† the MVVC group9

Protective immunity to the liver stage of the malaria parasite can be conferred by vaccine-induced T cells, but no subunit vaccination approach based on cellular immunity has shown efficacy in field studies. We randomly allocated 121 healthy adult male volunteers in Kilifi, Kenya, to vaccination with the recombinant viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia Ankara (MVA), both encoding the malaria peptide sequence ME-TRAP (the multiple epitope string and thrombospondin-related adhesion protein), or to vaccination with rabies vaccine as a control. We gave antimalarials to clear parasitemia and conducted PCR (polymerase chain reaction) analysis on blood samples three times a week to identify infection with the malaria parasite Plasmodium falciparum. On Cox regression, vaccination reduced the risk of infection by 67% [95% confidence interval (CI), 33 to 83%; P = 0.002] during 8 weeks of monitoring. T cell responses to TRAP peptides 21 to 30 were significantly associated with protection (hazard ratio,0.24; 95% CI, 0.08 to 0.75; P = 0.016).

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Replies

 

Sungano Mharakurwa Moderator Replied at 8:03 AM, 2 Jun 2015

The malaria vaccine has been really elusive for decades. When the real answer finally comes, it would not be surprising if we could well be too habituated to notice by then.

Pierre Bush, PhD Moderator Replied at 9:22 PM, 2 Jun 2015

This would be a good development. Based on the fact that the sample was not large enough (120), and the malaria transmission was lower during the study period, we can just wait and see. But there is definitely some hope.

Sungano Mharakurwa Moderator Replied at 8:19 AM, 3 Jun 2015

Thanks Dr. Pierre. So it is back to waiting again in anticipation. Hopefully there will be more success from larger field trial in peak transmission period. I remember an excellent book "Malaria: waiting for the vaccine" (1991), edited by Prof G. Targett. One has to earn respect for the malaria parasite.

Rajib Sengupta Replied at 9:29 AM, 3 Jun 2015

So at this point, when this vaccine seems to gone in a waiting state, I
thought to ask a candid question, which I was itching to ask for a while -

Malaria prevention has been a MDG goal and millions if not billions dollar
has been poured in and being poured in - every now and then I see new
innovation, new intervention - But in many countries (most developed
countries) malaria has not only been prevented but eradicated.

So why the same cannot be done in countries with high malaria rate? now,
the public health experts will come up with the dreaded
socio-cultural-economic paradigm type of answers of why this is not
possible in developing countries etc etc..

I will remind them that 60 years ago in US malaria was eradicated - and the
area where this happened , specifically the rural southeast US , at that
point of time, was very much comparable to many developing countries with
malaria - In-fact, with current modes of transportation, new ways of
logistics, new technologies and improved hygiene supplies (and many more
other things and expertise obtained), we are in a much much better
position compared to what these guys has gone through ..

http://www.cdc.gov/malaria/about/history/elimination_us.html

- the point is, the effort was sincere, efficient and done in a war like
fashion with a singular focus - and that's why it succeeded -(obviously it
surely helped with no corruption and vested interests)

So, my request to all is don't waste any more money in R&D, clinical
trials, new technoloies blad blah blah.. Set aside all interest - Pull all
the money together - prioritize countries/regions - and go on a war like
manner to NOT prevent BUT eradicate malaria using tried and tested method ..

I know , it's not going to happen for one reason or another .. but at the
end of the day, we all know the real reason - too many eggs in different
baskets with too much vested interest.. ..

Michael Gayle Replied at 1:22 PM, 3 Jun 2015

Rajib,

Thanks for your input on this matter. I am Medical Director for a missionary hospital in Togo, West Africa, and we have become a referral hospital for much of Togo and surrounding countries. We have seen our share of malaria including cerebral malaria and its complications including death--particularly in kids <5 yoa. As we know, malaria contributes to around 500,000 deaths per year and half of those coming in sub-Saharan Africa. I had read before the details of the elimination of malaria is SE USA around the mid-20th century, and their use of DDT. I realize that DDT has not been used for some time--it was banned in the US in 1972 because it had the potential to wipe out bald eagles, pelicans, and other bird species. WHO approved its use in 2006, but many scientists feel that it should be used only if first line efforts fail. Well, in developing countries such as Togo and many other countries in sub-Saharan Africa, primary efforts are failing and uncontrolled use in spraying houses has its effects physically, but I can only imagine the effects of not using DDT in house spraying and the increase number or deaths due to malaria. As people wait for new developments in the fight against malaria, more that 500,000 people die each year from malaria. Why not push DDT to the point of not only elimination of malaria in Togo but also eradication of malaria around the world?

William Jobin Replied at 4:18 PM, 3 Jun 2015

Dear Colleagues,

You both refer to the early suppression of malaria in the US, and wish it could be done in the rest of the world. It can, if the same pathway is followed, which had been followed in the southern US. That pathway included FIRST reduction of mosquito breeding sites by drainage, and filling of swamps, reservoir shorelines, and areas frequently flooded. Then, houses were improved and metallic screens added, thus protecting people from biting mosquitoes. Thus the first two steps on this pathway involved permanent ecological changes - in mosquito ecology, and then in human ecology. After this was done, it was fairly easy to further reduce transmission with temporary insecticides and drugs.

But notice that the current approach by Roll Back Malaria, WHO and the US Malaria Initiative, is to start with the temporary methods and skip the permanent ones. These temporary methods (DDT lasts a month or two) require continual repetition, with continuous costs. Thus it takes a huge effort just to maintain suppression in one area. In contrast, - the First Pathway which starts with permanent improvements - can be expanded each year with the same budget.

Thus the use of permanent methods is necessary, and they must be used first, if we are to achieve suppression in our lifetime.

This First Pathway was followed in the US, Puerto Rico, the Holy Land, and Turkmenistan, all of which are now free from malaria. The WHO approach, which I consider backward, has not achieved successful suppression anywhere.

Bill Jobin
Director
Blue Nile Associates
(I started with CDC in Puerto Rico as they were just finishing off the malaria, and have continued to work on malaria and other vector-borne diseases in Africa for 50 years. We need to study history, and learn).

Pierre Bush, PhD Moderator Replied at 2:21 AM, 4 Jun 2015

Hi Jobin,
You are absolutely right. Permanent pathway is the one that is required first. Ecological management is the primary method of getting rid of mosquitoes and then using insecticides can be complementary. In many countries they lake proper water drainage, and many villages are surrounded by huge bushes that are the source of mosquito breeding. The improvement of housing style is also a requirement for getting rid of mosquitoes. Spraying DDT alone will not by itself help in mosquito control. It will take a combination of these two pathways you correctly described to eliminate malaria and ultimately eradicate it by the beginning of the next century.

Margaret Chirgwin Replied at 10:05 AM, 4 Jun 2015

The present focus on very personal prevention which requires convincing every individual to use an impregnated mosquito net has always troubled me - the vested interests involved are obvious but I think it is more that people have watched malaria be pushed back by organised programmes of clearing and draining and then when governments have changed or war has come etc very quickly (in same cases somewhat slowly) disappeared back to square one. England and Italy both had malaria and still have the required mosquitos but no malaria. We drained the Fens in England. I guess the question is can we/should we plan to change the natural environment to the extent we will get rid of malaria. I used to work in Ratanakiri in northeastern Cambodia - I am told the amount of malaria (it was cerebral malaria - the pattern of a country with only moderate transmission) has diminished significantly since they cut the rain forest down. A sad but effective solution.

I have worked in Nigeria as well as Cambodia and have seen two diseases - they are profoundly different where transmission is high and all year vs season and moderate- I did not realise that this was the case until I arrived in Nigeria from Cambodia thinking I was quite an expert on malaria....!

I worry that we are using very personal and temporary solutions and reducing immunity which will tend to move west African malaria from anaemia and huge livers and spleens with little or no cerebral malaria (yes lots of death) to one where we will have pregnant women in comas of cerebral malaria and then if we have a war we will get large numbers with out nets and lots of death. I know the numbers over all work out better but cerebral malaria is a much more frightening disease killing very quickly and often the most productive.

Hence the desire for a vaccine but we are not getting this to work yet! I have always wondered if there was any mileage in trying to stop the cycle by treating everyone at the same time - not sure what the logistics are but we could in theory have the mosquitos but none infected.... I wonder if anyone has tried this anywhere?

Manuel Lluberas Replied at 4:25 PM, 4 Jun 2015

One of the most troubling and frustrating things I have ever encountered in the three decades I have worked as a public health entomologist is the 2nd Global Malaria Action Plan for 2015 through 2030 (2GMAP). In it, as glorious as it sounds and as good as WHO, RBM and the others want it to make it sound, the mosquito plays no role. I wrote a note to WHO RBM and others and sent it as far as I could to see if anyone would listen, but I am afraid it seems to have landed on deaf ears or blind eyes. This proves what my grandmother would say, which loosely translated from Spanish would go: “There is no worse blind person than he who does not want to see and no worse deaf person that he who does not want to hear.” My note to RBM board, with copy to the Vector Control Working Group follows.


As the template for malaria control with the strong possibility of being used as a guide for vector-borne disease control campaigns around the world, the 2nd Global Malaria Action Plan comes very short of the proposed mark. In fact, though malaria is a mosquito-borne disease, the words “mosquito” and “control” are never used together.

While portraying itself as the template for integrated vector management (IVM) for malaria control, it continues to place way too much emphasis on the use of mosquito nets with IRS as a supplementary intervention and gives little credence to proven mosquito control methods deployed around the globe that eradicated malaria from over one hundred countries over sixty years ago.

A quick search of the term “larviciding,” for instance, produced one result in reference to the use of Bti, leaving out all the other materials or methods used in a comprehensive Larval Source Management (LSM) component of mosquito control programs around the world. Moreover, searching the words “repellents,” “space sprays,” “ultra low volume,” “ULV,” “environmental manipulation,” “Insect Growth Regulator,” “IGR,” or any mosquito control tool or method used in active mosquito control programs yielded negative results.

A search for the term “IVM” resulted in a reference to “WHO handbook” on the subject. This is troubling, as the WHO definition of IVM reads: “IVM can be considered as the utilization of all appropriate technological and management techniques to bring about an effective degree of vector suppression.” This definition leaves out all mosquito control tools and methods and opens vector control to interpretation. To correct this, the 10th Vector Control Working Group meeting, which convened in February, 2015 has proposed changing WHO’s definition of IVM to one modified from the 1983 WHO Expert Committee on Vector Biology & Control that would read:

"Integrated Vector Management is a rational decision-making process to determine the most appropriate mix of interventions drawing on resources beyond health, both public and private. These include LLIN, IRS, larviciding, environmental manipulation, housing improvements, Information Education and Communication, space spraying, personal protection, etc. Otherwise, suboptimal use of available resources will continue and millions of people will remain vulnerable.”

The GMAP2 directs malaria control program managers to make sure beneficiaries “optimize their involvement in their response” to malaria control. This, however, must go far beyond just promoting what has been done during the past decade. To be effective, GMAP2 must fully endorse and implement active mosquito population suppression methods –including larviciding with agents beyond Bti- and make sure all mosquito control methods and procedures (LSM, LLINs, IRS, space spraying or ULV spraying, environmental management, protecting water supplies, housing improvements, personal protection, etc.) are placed in the malaria control tool bag.

As it stands, GMAP2 reads as an attempt to continue to justify and promote what has been done in the past decade or so and leaves little room for the introduction of active mosquito control interventions. It is obvious that it had limited input from mosquito control professionals. A more robust and comprehensive document that includes mosquito population suppression methods, tools and procedures could be produced if mosquito control professionals were engaged in drafting it.

It is not a matter of considering traditional mosquito control methods, whatever that means. It is a matter of providing all the tools in the mosquito population suppression bag as options and letting mosquito control professionals, not pediatricians or epidemiologists design a mosquito control plan tailored to the country’s needs and parameters. In that light, we need to add all the tools available, from biological to chemical tools targeting all the mosquito’s developmental stages (IRS, ULV, barriers, LSM, etc.) to environmental management, housing improvements and legal interventions. As you know, mosquito control is not a one-size-fits-all. If the tools are not in the tool bag for professionals in the field to select, they will never be used or considered. Unfortunately, very few other public health professionals understand their use and limitations.

Perhaps more significantly, GMAP2 must not be just a plan for Africa; it NEEDS to be a GLOBAL plan. There are many other vectors of malaria around the globe than just An. gambiae and her siblings. Limiting the mosquito control tools to mosquito nets, which are NOT a mosquito control interventions, does little for malaria vectors in South America, Haiti and the rest of the Caribbean, and Asia. Though a large portion of the malaria burden is in Africa, we need to stop thinking so parochially and start thinking more globally; like a Global plan should. What works in Africa will not work in the Americas or Asia and vice versa. A global plan NEEDS to place all tools in the bag; not just LLINs and IRS. Not doing so will only continue to promote treating the World as if it was all just like Africa and program managers outside the continent will continue to fail to have adequate tools for their specific country parameters.

Let us be the change we want to see and start promoting a better approach to global malaria vector control. Malaria was eradicated from over 100 countries over 60 years ago through active vector control –mostly LSM- and without the benefit of a vaccine. Remember the work of Fred Soper, William Gorgas, the Tennessee Valley Authority, Israel Kligler, Carlos Finlay, Le Prince, and a handful of others. We need to place their methods in the vector control tool bag and explore ways to apply some version of them, or combination thereof, in today’s programs.

I know we can do this, but there are many who continue to resist the change.

Sean Dimond Replied at 8:15 PM, 4 Jun 2015

Perhaps for somewhat different reasons, I too have been mystified by the WHO Global Malaria Action Plan. I honestly do not understand its theoretical basis for success given three questions:

1.Resistance. We all know of the work of Drs Nosten and White in SE Asia, and their persistent call for increased action to prevent the possibility of a global pandemic of untreatable malaria. The mechanism of artemisinin resistance is complicated, but with the historical precedent of past resistance episodes, and the emergence of nearly untreatable malaria in Cambodia, etc... I do not understand the absence of a MUCH more vigorous, global response. We also know that there is increasing vector resistance in 64 countries to all four existing classes of approved insecticides, and a new class of WHO approved insecticide will likely not be on the scene until when... 2022 or 2023?

Can anyone confidently predict that both insecticide and artemisinin resistance will not significantly compromise progress over the next 15 years?

2. Absence of political will in high burden countries. Rajib's observation of malaria eradication success in the US is spot-on when he says it was conducted in a war-like manner. But a war requires a government to make a declaration of war. The world's rural families who bear a majority of the malaria burden are not empowered to advocate and push for proven transmission reduction strategies. There are multiple proven protocols to reduce transmission, but sustainable transmission reduction requires strong health Ministries, and sustained national government leadership and will at the highest levels. In other words, in-country advocacy that leads to sustained political will matters a great deal. Will it emerge in mid and high burden countries? Particularly if resistance begins to erode past gains? Or to be more blunt, if a pandemic of artemisinin resistance leads to mass graves in Africa?

3. Funding. I understand the strategic necessity to celebrate the gains achieved over the last year. I am not an expert here, but I hear rumors of donor fatigue, and understand that donors want to know that increased investments will in fact work. ROI, evidence-based funding, and all that. But we know that malaria kills so very many people -- still -- due to an absence of not just moral imagination, but also economic imagination. In international diplomacy there is a technique called 'stacking the deck' -- when you work across multiple points of influence to achieve a stated goal. RE: point #2 above, I see the benefits of a much more vigorous and sustained argument of the long-term economic benefits of malaria reduction being championed as much as IRS and swamp drainage, etc....

As long as there are in fact proven methods to significantly reduce malaria, then as I see it the prevalence of the disease is as much a human and political problem as it is a technical, or scientific problem.

Menyanga Abu Replied at 5:01 AM, 5 Jun 2015

There is going to be ilght at the end of the tunnel, however more work needs to be done on the larger sample. While we are waiting, we shoul have it at the back of our mind that all hope is not lost. we are getting to the end of malaria, all we need is to keep up the push. Menyanga Abu

William Jobin Replied at 8:34 AM, 5 Jun 2015

Hello Manuel and colleagues,

I share your frustration at the blind approach of WHO and others. However I think the inertia of the current folks in charge is so great, that we will not be able to get them to make improvements, until their entire global program collapses. Sad to say, but it is true. So in the meantime, we should work on reviving and improving the permanent, durable methods used successfully in the past.

William Jobin

Manuel Lluberas Replied at 9:39 AM, 5 Jun 2015

Bill and All:

Bulgaria is celebrating 50 years of being malaria-free (see http://www.euro.who.int/en/countries/bulgaria/news2/news/2015/05/bulgaria-50-...). The site states that one of the three main reasons for their success was "Sustainable solutions for vector control, including the permanent draining of mosquito breeding sites, as well as improved living standards of human habitations, were introduced. Entomological surveillance was continued in areas with a high risk of malaria." I continue to be amazed, somewhat amused and always perplexed that this kind of statement is part of WHO and others but the methods continue to be rejected as viable today.

Lovemore Gwanzura Replied at 12:17 PM, 5 Jun 2015

Hi Manuel!
Its all about money Money. If Malaria was eradicated completely as you have done in Bulgaria people would have no jobs Manuel.
can we share the details methods used out there for adoption consideration in Africa. They sound easy but may be add extra information on cost? budgets etc

Manuel Lluberas Replied at 12:42 PM, 5 Jun 2015

It is about money. Money to do other things besides buying drugs that may or may not work. Money not earned when a family needs to stop working to take children to a doctor or to wait for the wage earners to recover. Money to develop the country and provide a better standard of living for all. Money to see your children grow and enjoy their life and become good citizens. Any other way of looking at it completely misses the point. The funding used to eliminate malaria in the US, Bulgaria and the rest of Europe has been be reallocated to surveillance, reducing the impact of other vector-borne diseases (in humans, livestock, and domestic animals) and keeping the mosquito population at a point where outdoor activities are possible. This, in turn, has created other markets and other ways of making a decent living while keeping malaria and other vector-borne diseases in check.

The issue is not money. The world has spent about a billion US dollars per year (that is 1 with 9 zeroes before the decimal) during the past decade or so and we still have half the world's population at risk.

Forgive my frankness, but those who continue to believe that reducing mosquito populations or eliminating malaria vectors -or any vector- will end up without a job need to rethink their position and perhaps do something else.

Go back to the Tennessee Valley Authority in the US and the work of Fred Soper in Brazil -to name just two. Soper eliminated An. gambiae from a 54K square kilometer area -the size of Togo!- with US$6 million in 2014 in today's currency and in 18 months between 1938 and 1940; with none of today's technology. He did it mostly with LSM.

The world NEEDS to rethink malaria control and stop thinking that it can be done without including the mosquito.

Rajib Sengupta Replied at 5:13 PM, 6 Jun 2015

Thanks all for a great discussion. I knew that my question is going to
churn up a heated debate , but never thought that most (in-fact all) of you
have the same opinion of the current way of Malaria prevention -

First let me state that, I am just a public health enthusiast and no way an
expert of Malaria prevention - compared to all of you guys knowledge, I
stand humbled !!!

But as a regular common person, let me provide a very personal experience -


I have been born and brought up in Kolkata ( the national capital of
Malaria in India where Sir Ronald Ross did his seminal Nobel winning work
on Malaria - http://en.wikipedia.org/wiki/Ronald_Ross) - I still remember
the extent of malaria during the monsoon seasons in 80s and everyone
getting inside the mosquito net as soon as the evening starts - The
different repellent (mosquito coils, burning coconut husks etc) , helped
but was not that effective. Then I left India for 20 long years, working
primarily in US in the health-care domain - Then the motherland called and
am back in Kolkata in 2013 to work on multiple public health project !!! I
was really amazed to see that the extent of malaria is reduced
significantly - yes, few incidents are reported but it's not at-all severe
and mosquito net is used rarely, primarily at night only :-) So what they
did really? It obviously seems to be not anyway comparable to US/Bulgaria
or any developed country where malaria was eradicated in a focused, war
like effort - Here it's done mostly in a semi-organized, local municipalty
effort where the central theme was and is mosquito eradication - I heard
the municipal workers used to spray DDT but now they spray Pyrethroid and
while spraying they inspect each house to confirm that there is no stagnant
water - and yes, urbanization helped a lot - such as underground drainage,
regular garbage collection etc etc..


With this small real life anecdote, I go back to my original
post/request/suspicion which is just confirmed by all of you learned
experts experience -

That enough money and resources are being spent for Malaria but for certain
reasons (I withdraw the "vested interest" reasoning just as I don't have
any direct proof :-) ) , the right things, which are proven and
time-tested, is not being done in a determined manner to completely
eradicate Malaria.



We need a global movement to pool all resources together and do the right
thing - which is to bring mosquito as the central theme and DO WHATEVER IS
REQUIRED TO NOT CONTROL OR PREVENT BUT ERADICATE MALARIA -


If the top doesn't listen, it's the duty of the bottom to take the fight to
them and the fight can happen as a bottoms up approach - push your local
government, push your local municipalty, push your local village council
and the almighty will come begging !!!

Sungano Mharakurwa Moderator Replied at 5:46 PM, 8 Jun 2015

Thank you Rajib for stimulating remarks and many thanks to all for such a frank, thorough and thought-provoking discussion. There seems indeed a feeling that maybe the available tools that eliminated malaria are available and could be used with greater zeal and rigour. Many points were raised and, interestingly, everything is borne out by evidence. Meanwhile, the wait for a malaria vaccine is starting to feel eternal and it is not surprising if many were already disappointed along the way.
Maybe the challenge is that the malaria problem is one big one but the perhaps the effective solutions may have to be diverse and locally customized. As Manuel said, a whole tool bag is required to address the global malaria problem. Hopefully there will be an efficacious vaccine that can also be included in the armamentarium one day. What is most inspiring, especially for some of us from endemic countries, is that the current feeling is to no longer tolerate the malaria scourge.
Since the Gates Foundation challenged the world to the "e-word" again, a lot of progress has actually thankfully been made in reducing preventable illness and deaths. Standards of living are slowly starting to improve in many countries as well. Donor fatigue would be a real disaster, but rather more commitment is needed for lock-on effect to finish off the final push and not lose all the hard-earned progress so far.
Great discussion once again thanks very much to all.

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