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CDC tests new malaria tools

7 Jan 2010

Tatum Anderson

Source: TropIKA.net

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Dr Laurence Slutsker.

Dr Laurence Slutsker, chief of the malaria branch at the Centers for Disease Control, USA talks to TropIKA.net about CDC’s major contributions to malaria research and describes its current work in evaluating potential new tools to fight the disease.

The Centers for Disease Control and Prevention (CDC) has been a byword for malaria control for decades. CDC grew out of efforts to control malaria around domestic military installations and prevent returning servicemen from importing malaria back into the US after World War II. Later, it spearheaded an eradication programme focused on 13 south-eastern US states. Over 4,650,000 house-sprays later, by 1951, it had eradicated the disease from American shores.

Although CDC’s public health remit has expanded to cover a broad range of communicable and non-communicable diseases, its role in malaria control continues. Of course, the priority is to advise US travellers and to prevent malaria from being imported, because American mosquitoes are still capable of spreading the disease. (CDC says it still occasionally deals with mini-outbreaks; in 2007 there were 1,505 cases of malaria in the US.)

But CDC is also tasked with participating in international malaria control, which has increased substantially with funding from the US President’s Malaria Initiative. It helps other countries to plan, implement and monitor national malaria control programmes and routinely places CDC officials within ministries of health in three endemic countries (Kenya, Malawi, and Tanzania).

As well as national programmes, CDC looks into operational research. According to Dr Laurence Slutsker, chief of the malaria branch at CDC, that means studying how new tools work in the field, as well as how existing tools might be improved or integrated with others. In the past, that has meant developing strategies to deal with malaria in pregnancy, delivering older drugs in new ways – including intermittent preventative treatment for malaria in infants (IPTi) – and drug resistance work.

Today, operational research means looking at how IPTi might be incorporated within routine immunization programmes (the so-called Expanded Programme on Immunization [EPI]) or how IPT for pregnant women (IPTp) might be combined with existing antenatal health services, for instance.

Field research

“Although we do bench research – such as looking at parasite biology in animal models – our effort is on applied research in the field,” says Slutsker.

This kind of operational field research has led to much knowledge that the health community now takes for granted, says Slutsker. A research station – a 30-year-old collaboration between CDC and the Kenya Medical Research Institute (KEMRI) that Slutsker headed for five years – completed one of the first studies to demonstrate that insecticide-treated nets (ITNs) could reduce malaria-related illness and death in an area of very intense, year-round malaria transmission in Kisumu, western Kenya. Before that, evidence of bednet efficacy in Africa came from areas where transmission was either moderate or seasonal. “At the time, there was not a general belief that they would be effective in [a high-transmission] setting and that they would lead to rebound mortality and morbidity as children who were not exposed then became exposed later,” he says.

Other CDC studies established the impact of HIV infection on malaria in pregnancy – how it increases the transfer of malaria parasites to newborn babies, and reduces the effectiveness of anti-malarial prophylactic drugs.

Today the laboratories at CDC are involved in a number of evaluations. For instance, the agency is a WHO collaborating centre for the ITN certification process, as part of the WHO Pesticide Evaluation Scheme (WHOPES). Specifically, this agency is evaluating new and existing insecticides used for impregnating bed nets. Today, manufacturers market their nets on the basis that they can be washed more times than their competitors while remaining effective. However, few claims have been confirmed by independent tests. CDC’s role is to test the claims.

CDC is testing a number of new tools that could become tomorrow’s commodities, from various methods of larval control to alternatives to ITNs. Under investigation currently is an insecticide-treated wall lining. If it can be hung like wallpaper, it might remove the need for indoor residual spraying every six months. (It has an added advantage over bednets in that it would be handled far less and might therefore be more effective says Slutsker.)

Moving into malaria

A generalist in public health when he first joined CDC, Slutsker became interested in malaria after working with its malaria experts. He later worked in a range of areas from food and diarrhoeal disease surveillance, especially looking into household water systems purification and in Kisumu, focused on a wide variety of topics from HIV/AIDS and diarrhoeal diseases to general tropical public health. When he returned to CDC ten years ago, he returned to malaria.

“I came back to my first love, malaria, although I think diarrhoeal disease is a fascinating topic too,” he says. “Malaria’s got just about everything you could hope for – a pathogen with fascinating properties, a complex interaction with vectors and people and health systems and cultures, the anthropology and the pharmacology.”

Today, evaluating malaria tools in the field is not just about determining which tools work and which do not, says Slutsker (1). It’s about assessing which overall strategies are making a difference and pinpointing the gaps.

That’s increasingly important because evaluations can help pinpoint precisely where malaria control, and later elimination efforts, could be focused. In other words there is a need to improve overall malaria surveillance, far beyond the limited reach of sentinel research sites like the station in Kisumu. “There’s a lot of talk about getting transmission way down,” He says. “But to have any hope of staying on top of things and all the interventions being proactive, surveillance of malaria will be the key,” he says.

Surveillance will be needed to establish whether or when IPT strategies for pregnant women need to be re-evaluated as transmission drops and the epidemiology alters, for instance. “At some point it may be more strategic to do something else such as find women who might be infected and treat them, rather than give preventative drugs to all women,” says Slutsker.

The problem is that such a comprehensive and efficient surveillance system does not exist.

New strategies needed

In the past, malaria drugs were typically dished out – without laboratory diagnosis – to patients with fever in high transmission areas. This method, called presumptive treatment, has been used because, with cheap drugs and widespread malaria, the assumption that the patient has malaria was not unreasonable.

But the game has changed for a range of reasons. A fever may not necessarily predict malaria; new anti-malarial drugs are expensive too, so giving them to people who may not have malaria is not only wasteful but increases the likelihood of drug resistance developing.

WHO guidelines have changed accordingly – presumptive treatment is no longer recommended (2). However, decent, broad-ranging malaria surveillance to establish where controls might or might not be working, is severely lacking (for instance, although the right drugs exist in many areas, only a fifth of fever cases get the right treatment within 20 hours.)

“The challenge increasingly is to do better and better measurements of where we are and where we are heading. We need really to improve surveillance such that we understand what’s going on and the areas that need attention. We don’t do a very good job of that now,” says Slutsker.

That is why CDC is looking at a number of strategies, including studies on rapid diagnostic tests (RDTs), the handheld malaria tests that – in theory – could be used in rural areas and in the absence of laboratories and trained lab staff.

The health workers, and ostensibly a basic health system should be able to use such tests for surveillance. “We need people to be using tests properly and recording the results properly so information can be aggregated, analysed and sent back out to the field. That includes the people needed to operate and interpret data,” he says. “That’s what a surveillance system is supposed to do and we don’t have examples of that in a lot of places.”

RDTs, however, are not yet widely used – they do not form part of many national strategies and studies have shown that the RDTs currently available vary considerably in their accuracy – see TropIKA.net article.

Plenty of existing studies have focused more on how well the tests work, says Slutsker, but fewer look at how the good ones are used by healthcare workers. CDC has been looking at how tests are used by health workers in routine patient care as a result.

For instance, there is some evidence to suggest that the more training people have, the less they adhere to the results of the tests (3). A CDC study in rural Tanzania found that, despite training and supervision, some health workers did not perform the tests correctly or use the results to influence treatment decisions. Another study in Kenya showed that use of RDTs did not improve treatment of malaria cases. CDC reckons far more research is needed to help explain why health workers are not using RDTs and how best to encourage more appropriate use.

Improved case management – especially for surveillance – has become so important that a Case Management Working Group (CMWG) was re-started within the Roll Back Malaria partnership last year. (When it was first formed there was little consensus on what combination therapies for malaria should include and it therefore ceased to function for some time.) Co-chaired by Slutsker, the group will also focus on new case management strategies, such as those to prevent the spread of ACT resistance and scaling up diagnostics.

“We thought it was about time to reconstitute [the working group]. There are big challenges that are coming up in treatment,” says Dr Sylvia Meek of the Malaria Consortium which has been intimately involved with working group since its inception in 2003.

Indeed, it is thought that one major up-coming issue will address the AMFm, a global subsidy mechanism for artemisinin-based drugs, and whether it might be expanded to fund diagnostic tests too. Certainly, there is a feeling that promoting treatment without diagnosis within such a major international strategy may be untenable in the longer term.

Key questions

Briefly, what are the priority concerns of your organization?

CDC domestic activities include: epidemiologic surveillance, investigations of outbreaks of locally transmitted malaria and of other occurrences (e.g., transfusion malaria), advice to international travellers, consultations with clinicians, advice to blood collection centres, diagnostic assistance.

They could have an enormous effect on malaria control strategies. It is now absolutely essential to know whether someone has malaria before giving the malaria tablets. So, it is essential that the right diagnostics have been used. But as well as helping to treat correctly, those tests will yield results that could be vital for epidemiology. However, the problem with these sites is that they can only take information from a limited area.

And, more precisely, what goals have you set?

Work in malaria-endemic countries with the ministry of health and local disease prevention and control partners (e.g., the national malaria control programme, the reproductive health program responsible for maternal health, the child health programme)

Work in malaria-endemic regional settings (e.g., the Mekong River region; the Amazon River basin region).

Which other organizations will you be working with most closely?

CDC currently has staff posted at the Global Fund to Fight AIDS, Tuberculosis, and Malaria; UNICEF; and the World Bank; as well as in three African malaria-endemic countries (Kenya, Malawi, and Tanzania). It works with Roll Back Malaria (RBM) partners (WHO, UNICEF, the World Bank, USAID).

It runs the following collaborating centres:

References

1. Gimnig JE, Slutsker L (2009). House screening for malaria control. Lancet; 374(9694): 954-955. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61078-3/fulltext?_eventId=login

2. WHO (2006). Guidelines for the Treatment of Malaria. Global Malaria Programme. World Health Organization (WHO/HTM/MAL/2006.1108). Available from: http://whqlibdoc.who.int/publications/2006/9241546948_eng_full.pdf

3. CDC (2009). With Findings from CDC Research, Africans Use Rapid Diagnostic Tests to Effectively Treat Malaria. CDC Global Health E-Brief, 3rd Quarter 2009. http://www.cdc.gov/washington/EGlobalHealthEditions/eGlobalHealth3rd0909.htm#five