Malaria: a time to take stock?

9 Feb 2009

Paul Chinnock

Source: TropIKA

Comments

Recent weeks have seen the publication of a number of review and opinion articles on the subject of malaria. It is no doubt the appearance of new (and in most cases encouraging) data on the impact of scaling up control efforts, particularly in Africa, which has prompted a number of malaria specialists to try to take stock of the situation and ask what have we learned – where do we go from here?

In the Lancet

Laurence Slutsker and Robert Newman (1) point out that, in 2007, 90 million children in stable malaria endemic areas were still not protected by insecticide-treated bednets. Yet, overall, coverage has increased about six-fold since 2000. So, they ask, is the glass half-empty or half-full for malaria scale-up progress?

Other interventions, as they authors remind us, lag further behind in their implementation. The use of artemisinin combinations in children with fever is less than six per cent in 14 African countries. They argue that the scaling-up malaria interventions must be accompanied by better surveillance, stronger health systems and local ownership.

The authors of a letter (2), also in the Lancet argue that: “Most of the successful African examples [of control scale-up] are from islands, fringes of endemic areas, or smaller countries with substantial external support. Whether progress can be expected to be comparable in most sub-Saharan African countries ... remains doubtful.”

Malaria Journal

This open-access publication is now recognized as one of the most important journals focusing on infectious diseases of poverty. A supplement comprising nine review articles addresses the theme ‘Towards a research agenda for global malaria elimination’. Introducing the supplement the journal’s editor Marcel Hommel (3) (http://www.malariajournal.com/content/7/S1/S1) comments that, “The decreasing pattern of incidence is encouraging and, by giving funding agencies a first impression of success, it has helped enormously in the advocacy for further increases in the global funding effort, which are considered necessary to achieve malaria control.”

The topics dealt with are:

Clearly it is impossible to discuss all of these detailed reviews here. Some of the conclusions reached by the authors may surprise some readers and indeed could prove controversial. Here are some direct quotes from a few of the articles:

“Obsessive emphasis on ‘global warming’ as a dominant parameter is indefensible; the principal determinants are linked to ecological and societal change, politics and economics (4)."

“Without wide implementation of accurate and discriminating diagnostic testing, and reporting of results, most fever will be inappropriately managed, millions of doses of ACT will be wasted, and malaria control programmes will be blindfolded to the impact of their efforts (6).”

“Most of those who need the drugs do not get them. Simultaneously, a high proportion of those who are given antimalarials do not in fact have malaria (8).”

“The key operational question now is whether primaquine should be added to artemisinin combination treatments for the treatment of falciparum malaria to reduce further the transmissibility of the treated infection (9).”

“The malaria research community is becoming more aware and concerned about the widespread spectrum of illness and death caused by up to a couple of hundred million cases of vivax malaria each year (10).”

“Research on malaria vaccines is currently directed primarily towards the development of vaccines that prevent clinical malaria. Malaria elimination ... requires a different vaccine strategy, since success will depend on killing all parasites in the community in order to stop transmission completely. (11).”

Awa Marie Coll-Seck, Executive Director of the Roll Back Malaria Partnership (13), has welcomed the Malaria Journal supplement saying that, “If there ever was a golden age for malaria research and innovation, it is now.”

Children and pregnancy

Other review articles on malaria that have appeared recently include an update on severe malaria in children and pregnancy (14). This article outlines new understanding of the pathogenesis of severe malaria complications. It goes on to discuss the use of new drugs such as intravenous artesunate and oral artemisinin combinations, noting that – combined with increased access to insecticide-treated bed nets – this is resulting in improved outcomes and a reduction of malaria deaths. The authors say that several research groups are now identifying the characteristics of parasite var genes associated with cerebral malaria, and that understanding of the interactions between malaria and other diseases in causing severe anaemia and cerebral malaria has increased substantially. At the cellular level, the disturbances leading to coma or other complications are becoming clearer. Discussing the challenges for continuing research, they note that: “The role of ACTs, in particular, needs to be evaluated in detail, given their widespread adoption for malaria treatment.”

Acquired immunity

A further review article (15) focuses on acquired immunity to falciparum malaria. Naturally acquired immunity to malaria protects millions of people routinely exposed to infection from severe disease and death, but there is no clear understanding of how this protection works. There is no consensus as to the rate of onset of acquired immunity or what constitutes the key determinants or the mechanism of protection. This review discusses the new insights provided by biotechnology and places these insights in the context of historical, clinical, and epidemiological observations. Controversially perhaps, the authors argue that naturally acquired immunity is virtually 100% effective against severe disease and death among heavily exposed adults and that even the immunity that occurs in exposed infants may exceed 90% effectiveness. They conclude that: “The induction of an adult-like immune status among high-risk infants in sub-Saharan Africa would greatly diminish disease and death caused by P. falciparum. The mechanism of naturally acquired immunity that occurs among adults living in areas of hyper- to holoendemicity should be understood with a view toward duplicating such protection in infants and young children in areas of endemicity.”

India too

And finally a letter from India (16), recently published in Trans R Soc Trop Med Hyg, reminds us that Asia too still faces the challenge of malaria control. A writer from the National Institute of Malaria Research (ICMR) says that in several Indian states “...there is increased risk of development and spread of multidrug-resistant strains of Plasmodium falciparum, particularly in marginalised population groups living in poverty and remote forest fringe areas”. Outbreaks of malaria in India often lead a high morbidity and death rates. A stepping up of control efforts, using tools already available, is called for here too. It is not only Africa that has a malaria problem.

References

1. Slutsker L, Newman (2009). Malaria scale-up progress: is the glass half-empty or half-full? Lancet; 373(9657):58-67. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19019423

2. Müller O, Yé M, Louis VR, Sié A (2009). Malaria in sub-Saharan Africa. Lance; 373(9658)122. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19135609

3. Hommel M (2008). Towards a research agenda for global malaria elimination. Malaria Journal; 7(Suppl 1):S1. Available from: http://www.malariajournal.com/content/7/S1/S1/abstract

4. Reiter P (2008). Global warming and malaria: knowing the horse before hitching the cart. Malaria Journal; 7(Suppl 1):S3. Available from: http://www.malariajournal.com/content/7/S1/S3/abstract

5. Beier JC, Keating J, Githure JI, Macdonald MB, Impoinvil DE, Novak RJ (2008). Integrated vector management for malaria control. Malaria Journal; 7(Suppl 1):S4. Available from: http://www.malariajournal.com/content/7/S1/S4/abstract

6. Perkins MD, Bell DR (2008). Working without a blindfold: the critical role of diagnostics in malaria control. Malaria Journal; 7(Suppl 1):S5. Available from: http://www.malariajournal.com/content/7/S1/S5/abstract

7. Brabin BJ, Wasame M, Uddenfeldt-Wort U, Dellicour S, Jenny, Gies S (2008). Monitoring and evaluation of malaria in pregnancy – developing a rational basis for control. Malaria Journal;7(Suppl 1):S6. Available from: http://www.malariajournal.com/content/7/S1/S6/abstract/

8. Whitty CJM, Chandler C, Ansah E, Leslie T, Staedke SG (2008). Deployment of ACT antimalarials for treatment of malaria: challenges and opportunities. Malaria Journal; 7(Suppl 1):S7. Available from: http://www.malariajournal.com/content/7/S1/S7/abstract

9. White NJ (2008). The role of anti-malarial drugs in eliminating malaria. Malaria Journal; 7(Suppl 1):S8. Available from: http://www.malariajournal.com/content/7/S1/S8/abstract

10. Galinski MR, Barnwell JW (2008). Plasmodium vivax: who cares? Malaria Journal; 7(Suppl 1):S9. Available from: http://www.malariajournal.com/content/7/S1/S9/abstract

11. Targett GA, Greenwood BM (2008). Malaria vaccines and their potential role in the elimination of malaria. Malaria Journal; 7(Suppl 1):S10. Available from: http://www.malariajournal.com/content/7/S1/S10/abstract

12. Mills A, Lubell Y (2008). Malaria eradication: the economic, financial and institutional challenge. Malaria Journal; 7(Suppl 1):S11. Available from: http://www.malariajournal.com/content/7/S1/S11/abstract

13. Coll-Seck AM (2008). A golden age for malaria research and innovation. Malaria Journal; 7(Suppl 1):S2. Available from: http://www.malariajournal.com/content/7/S1/S2/abstract

14. Milner DA Jr, Montgomery J, Seydel KB, Rogerson SJ (2008). Severe malaria in children and pregnancy: an update and perspective. Trends Parasitol; 24(12):590-595. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18848498

15. Doolan DL, Dobaño C, Baird JK (2009). Acquired immunity to malaria. Clin Microbiol Rev; 22(1):13-36. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19136431

16. ev V (2009). Rolling back malaria initiative in India. Trans R Soc Trop Med Hyg; 103(2):210. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19056099