The London School of Hygiene & Tropical Medicine has made available a series of podcasts from the MIM conference. They may be accessed on the School’s Audio News site. The podcasts include the following.

Professor Brian Greenwood discusses the presentation he gave to the conference, in which he explained that combined prophylactic and therapeutic use of malarial drugs can play an important part in programmes to control the disease.

Epidemiologist Diadier Diallo, co-ordinator of a trial of intermittent preventive treatment (IPT) for children in Burkina Faso and Mali, discusses what has been learned from this project. In another podcast, Dr Harry Tagbor describes his IPT work in Ghana.

Geoffrey Targett Professor of Parasitology says the prospects for malaria elimination are good in many regions.

There is also an interview with Bianca D’Souza, Manager of the ACT Consortium. Other interviews focussing on the Consortium involve Ugandan Health Ministry Commissioner Dr Anthony Mbonye and - from the School - Professor David Schellenberg and Dr Harparkash Kaur.

Dr Roma Chilengi, head of clinical trials at the KEMRI/Wellcome Trust Research Programme in Kilifi, Kenya discusses the way forward for malaria elimination

Elimination means reducing to zero the incidence of a specified disease in a defined geographical area as a result of deliberate efforts. For malaria, this means a situation where incidence of the disease is reduced to zero in a given area, and this should be demonstrable by sensitive diagnostic tests.

The accepted definition of elimination is however a sobering reality for the bulk of sub-Saharan Africa. The depth from which certain places have to be lifted is daunting, as they are still way behind in malaria “control” benchmarks. Unfortunately, the health systems infrastructure, which is critical to achievement of malaria elimination, is very poor or non-existent in most places.

Since the problem of malaria also does not follow political borders, variation in the burden and transmission intensity cuts across national boundaries. For example, the malaria burden within Kenya varies, such that the problem is declining on the coast while it is still a substantial problem in the western parts. Therefore, to attain elimination, health systems need to be sufficiently capable of establishing the correct burden, identifying proper interventions, deploying them, and monitoring and evaluating the process.

This is why many may be pessimistic about malaria elimination as a target, believing it to be way beyond the reach of some places. Some countries will realise elimination, while others may not be able to do so within the foreseeable future, given the currently available tools.

There is therefore a great need to sharpen and develop new tools altogether to help in the fight against malaria. A malaria vaccine offers a great hope of achieving significantly improved malaria control, particularly in Africa, where the ecological habitat is such that effective mosquito control has proved difficult or impossible to maintain.

The success of other vaccination campaigns within Africa demonstrate that the control of major infectious diseases is achievable on a global scale: smallpox has been eradicated as a result of vaccination, polio seems close to being eliminated, and measles is virtually under control in many African countries.

Ashley Birkett, director of pre-clinical development at the PATH Malaria Vaccine Initiative discusses their strategy towards new vaccine development
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We’re eager at MVI to build on the progress that we’ve achieved with RTS,S. Even as we look forward to taking this first vaccine candidate through a large Phase 3 clinical trial with GlaxoSmithKline Biologicals and African scientists, we’re also moving ahead with a strategy for developing a next-generation vaccine that includes candidates that can block transmission of the parasite.

A key part of our strategy is to build on current progress. RTS,S, which is a pre-erythrocytic candidate that aims to protect against the early stage of Plasmodium falciparum malaria infection, was found to be 53 percent effective against clinical disease in Phase 2 trials. As we test this candidate in phase 3 trials at 11 sites in seven African countries, we’re already working on approaches that should help us to achieve the 2025 goal of a product that is at least 80 percent effective against clinical malaria for at least four years.

How do we plan to do this? Our approach involves a number of aspects. Our focus on pre-erythrocytic vaccine candidates—those that target the parasite on its journey to the liver or while it matures in an infected person’s liver cells—will continue. However, we plan to target other stages of the parasite’s development as well. 
In addition to widening our focus to include transmission-blocking vaccines and other approaches, we’re also pursuing candidates that target the less deadly but more widespread P. vivax malaria. These steps to further diversify our portfolio of vaccine candidates are helping to set the stage for the malaria community’s push to control malaria and to eliminate the disease in the long term.

Transmission-blocking vaccine candidates typically seek to interrupt the life cycle of the parasite by inducing antibodies that prevent the parasite from maturing in the mosquito after being taken up during a blood meal from a vaccinated person. Further, MVI has had an increasing interest in multi-stage, multi-antigen vaccines. We believe that a highly effective pre-erythrocytic, transmission-blocking vaccine that could block the parasite’s lifecycle, to reduce transmission in endemic areas, as well as provide protection from clinical disease would be a key tool in the global effort to beat back the disease.

Eradication was on everybody’s lips yesterday, though not everyone agrees on how to move forward with this enormous challenge. Some, like the Malaria Eradication Agenda’s (malERA) Pedro Alonso believe we must look beyond the short-term goal of control and shift our focus to eradication (see TropIKA’s Q&A with Pedro Alonso on this topic). Alonso also has the backing of several key players in malaria: Fred Binka of the INDEPTH –Network/MCTA, Ghana; Brian Greenwood at the London School of Hygiene and Tropical Medicine, UK; and Marcel Tanner of the Swiss Tropical Institute, Switzerland, to name a few.

Alonso and others are rightly worried about repeating the mistakes of the past, when over-optimism and complacency led to a subsequent massive resurgence of the disease. Those fighting against malaria, as with other diseases of the poor, must continuously battle for funding that is not only sufficient but sustainable.

Understandably then, some MIM delegates told TropIKA that they were concerned that a push towards eradication – especially with the might of the Gates foundation, which often drives the direction of research, behind it – would divert funds from urgent control measures.

But it should be possible to focus both on control and access to drugs as well as the long-term prize of eradication. After all, the global health community now has more funding and support than ever before; if we don’t move towards eradication, or at least think about how and when we might achieve it, when will we? It seems the least that those suffering with the burden of malaria on a daily basis deserve.

As Editor of TropIKA.net, I read many new research papers on the infectious diseases of poverty, the majority of which are about malaria. Identifying which are the most important is no easy task, but some do attract my particular attention. I have just written an article about seven such papers.

Issues raised in my personal selection include:
- the need to protect older children (i.e. those aged 5-18 years) from mosquito bites
- what is the best way to prevent malaria in children with sickle cell disease
- the growing popularity of window screens and ceilings as a way to prevent mosquito entry to homes
- the factors that determine what sort of treatment mothers seek when their child has malaria.

You can read my article here and use the TropIKA.net “Comment” facility to add your own views on my selection. (Six of the seven papers I have chosen are available with open access, so you can also read the full papers yourself.)

Paul Chinnock
Editor, TropIKA.net

Kevin Marsh, director of the Wellcome-KEMRI-Oxford Collaborative Research Programme, discusses malaria vaccines on this MVI guest blog:

Deciding when it’s a good time to take a malaria vaccine into African countries for testing in children is not always straightforward. It’s a real issue for vaccine developers and funders and one that is the subject of debate here at MIM and in the wider malaria vaccine community. There are no absolute criteria for these decisions.

For malaria vaccines, the ability to challenge—with the bites of infected mosquitoes—healthy adult volunteers who have not previously been exposed to malaria is a critical way for developers to decide whether or not a candidate vaccine has potential and should therefore move to African trials.

For pre-erythrocytic vaccine candidates—those designed to prevent the parasite from getting past the liver and into the blood stream—this model has proven to be extremely valuable. One good example is RTS,S, the vaccine candidate developed by GlaxoSmithKline Biologicals and supported by the PATH Malaria Vaccine Initiative that is now being tested in the region.

On the other hand, for vaccines that target the parasite later in its life cycle, during its development in human red blood cells, the human challenge model has been seen to have limitations. However, many researchers now believe these limitations can be overcome and that challenge models should form part of the selection pathway for blood-stage vaccines. Without this crucial decision point, a major question is, how do developers decide which blood-stage vaccines should go into the field?

An added complication for these blood-stage vaccine candidates is the fact that adults tend to develop immunity as a result of previous exposure to the parasite. Therefore, young children who have had limited exposure and limited immunity to malaria are really the best population for evaluating whether these vaccines work.

These factors create ethical dilemmas for developers and funders, given that vaccine candidates that have limited human proof-of-concept data may need to be evaluated in large numbers of children.

All the important challenge models exist in developed countries. So it’s time to ask why such models are not found in developing regions, such as Africa. In Kenya, there are active discussions among ethical and research institutions to examine whether this country could take a lead in developing challenge models. There’s a strong positive feeling that this is important.

In the meantime, there needs to be broad consensus among scientists, including African scientists, about when vaccines should be tested in Africa. It’s also important that African institutions and scientists are meaningfully involved throughout the process of vaccine development.

Research ethics occupies an uncomfortable place in investigators’ hearts. On one hand, it’s at the core of their work – no clinical trial could, or should, be conducted without a strong ethical framework. But researchers also want to get their trials up and running as soon as possible, and waiting for ethics review can be immensely frustrating. In a small basement room at the MIM conference today, it became clear just how relevant these issues are for a disease like malaria.

Malaria trials often involve the vulnerable segments of a population –pregnant women and children and so there are sensitive ethics issues. But the trials are almost always done in Africa, where ethics review is patchy across the region. Clearly, there is a need to mesh these conflicting factors.

The members of review panels, however, have a hard time of things. They are often volunteers who have full-time jobs, few resources, and little training.

So what’s the solution? Collaborative efforts by organisations like PABIN/SIDCER help tremendously by offering much needed training and funding. For their part, African scientists involved in bioethics will have to think about the issues in a broad, perhaps moral, context, rather than just ticking ethics review boxes. This is a tough challenge, but one that African scientists are more than capable of. Watch this space for a Q&A with Aceme Nyika, AMANET’s ethics coordinator.

Yvette Collymore of the Malaria Vaccine Initiative talks to MIM Professor Wen Kilama, AMANET: Managing Trustee, African Malaria Network Trust (host of MIM):

The Product Development Partnership model has seen a number of achievements since they began developing drugs, vaccines, and vector control solutions in 1999. However, from an African perspective, these product development partnerships (PDPs) that receive funding to address neglected diseases create a number of challenges. As I said at a session on PDPs organized by the PATH Malaria Vaccine Initiative as well as the Medicines for Malaria Venture and the Innovative Vector Control Consortiumm at the MIM conference, the PDP model addresses one disease problem with one approach.

The model does not take a holistic approach to the development of these products. But a product on its own does not solve the problem. You need to go beyond that and make a product accessible. There may be hindrances to do with weak public health systems, lack of political will, poor infrastructure, corruption, traditional norms and beliefs, and prescribing practices. All these issues impinge on access.

Some argue that the PDP model cannot do all things. I agree. At the same time, these PDPs can build good working relations with national and local researchers and scientists instead of relying on so-called CROs (contract research organizations)—small companies perhaps contracted through ads on the Internet who come in, do the job, and leave without contributing whatsoever to local capacity building. They come back, do the same thing, over and over again.

We need to work hand-in-hand with PDPs: plan together, implement together, build up local capacity, so that local researchers can eventually carry on, without much outside input. I do not see PDPs carrying on implementation research, long-term follow-up, for example, of chronic adverse events, or disease rebound effects, pharmacovigilance—following a study population to detect rare adverse events.

Another area of concern is that PDPs are not likely to analyze data inside the country of testing. The issue of data sharing is crucially important, as is that of transferring materials or specimens for analysis abroad. And when results are obtained, they are often not fed back to the country of origin, in order to benefit the national health care system. Local manufacturing and related aspects such as technological transfer are also major concerns. The local researchers and research participants might inadvertently be creating markets for foreign products.

Would you take a drug not knowing whether it was safe or not? Whether it could kill you? For a whole host of reasons, this is exactly what many people with malaria do. The reasons are not as simple as ignorance or a lack of education.

In a session on ‘pharmacovigilance’ today, Ogobara Doumbo, the director of the Malaria Research and Training at Bamako talked about some of the reasons why people still take drugs that are unsafe, and what can be done to prevent it.

Some people are so used to getting medicine from their local pharmacies or shops that they don’t question the validity of the medicines. Fake drugs can enter the market in many ways; in some countries with no local manufacturers, imported drug can have questionable provenance. Some companies sell antimalarials even when after the expiration date.

The consequences are serious. Some fake drugs do contain some active ingredient, but not being prescribed properly, the drugs can lead to the development of resistance in parasites – effectively working as an immunization for the parasite. In the worst cases, the drugs kill people. Doumbo said, for example, that 2500 people died in Niger in 1995.

So what is the solution? Regions need to coordinate on quality assurance, and they need to educate people about the importance of getting hold of safe drugs. More importantly, and something that will be a challenge for policymakers and governments, is to ensure that safe antimalarials are available to those who need them. Until then, people with malaria may well feel that desperate times call for desperate measures.

Welcome to the 5th MIM Pan-African Malaria Conference. Please see the official meeting site for a complete schedule.