Global Health Policy
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March 08, 2007
Combining Interventions to Prevent Malaria While Fighting Resistance
Posted by Mead Over at 12:08 PM
Last week, the New York Times reported on recent findings that the combination of one inexpensive antibiotic pill each day and sleeping under an insecticide-treated mosquito net can reduce the incidence of malaria by 97 percent in HIV-positive children in Uganda. If the results hold up to further analysis and critical review, this study can be understood as further support for the proposition that a combination of malaria interventions can do substantially better against malaria than any single intervention by itself. A non-experimental study that I and co-authors performed on data from the Solomon Islands similarly showed that mosquito bednets worked much better in combination with indoor DDT spraying and other interventions than by themselves.
It's not surprising that bednets need help in protecting children from malaria. They protect children against (most) bites while the child is under the net, but anyone who has tried a bednet has had the experience of being bitten through the net if it has any holes or even if you just roll too closely against it in your sleep. So even under the net, protection is not perfect. Furthermore, children will always be outside of their bednets and exposed to mosquitoes for a part of the evening hours when biting is most frequent. The DDT spraying in the Solomon Islands and the cotrimoxazole in Uganda both serve to prevent malaria infection from the bites that the child will get regardless of bednet use.
Like all chemical interventions, both cotrimoxazole and insecticide can stimulate the appearance and speed the spread of resistant forms of disease agents. The NY Times article mentions the possibility that increased use of cotrimoxazole will might lead to cotrimoxazole-resistant strains of pneumonia and the other illnesses against which it protects. Some of these illnesses infect people without HIV as well as those with it. Thus, heavy use of cotrimoxazole to prevent malaria must be balanced against the possible loss of the efficacy of this highly beneficial and inexpensive drug. Similarly DDT and other insecticides engender the development of insecticide-resistant varieties of mosquitoes. (DDT has additional harmful effects on the environment, but those are minimized when the spraying is restricted to the interiors of houses, close to the floor.)
It's not clear whether the combination of bednets plus insecticide spraying was assessed as an alternative to bednets plus cotrimoxazole. In a separate study on the resistance of the malaria parasite to anti-malarials, Laxmaman Ramanayan, David Smith and I suggested that one way to slow the development of resistance would be to alternate between two interventions over time in the same local area. For example, the public health authority could combine the bednets with cotrimoxazole for a year or two and then, as soon as resistance begins to appear, drop the cotrimoxazole and replace it with insecticide spraying. When the mosquitoes start to become resistant, the public health authority can investigate whether the cotrimoxazole-resistant microbes have been supplanted by the re-emergent, wild, non-resistant strains. If that is so, the government can again switch away from bednets plus insecticide spraying back to bednets plus preventive cotrimoxazole, at least until the reappearance of cotrimoxazole resistance.
Such a strategy is not a perfect solution to resistance. Once drug-resistance has appeared in a population, it is likely to remain, lurking in the genetic assets of the population, ready to re-emerge rather quickly in response to a renewal of selective pressure from the drug that encouraged it in the first place. However, in the endless arms race between man and disease agent, switching can be a useful tactic for keeping the diseases off-balance until new drugs or vaccines can be developed and distributed.
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Comments
There has also been some discussion within the global health community around the role of switching in the effective use of chloroquine.
Posted by: Jessica Pickett at March 8, 2007 12:31 PM
My reading of the research suggests that any public health policy that accepts continuing reinfection of the population, partial treatment of the patients, and partial intervention against the mosquito vector is doomed to failure.
Worse there is also going to be more and more resistance over time in both the malaria parasite and the mosquito. The solution, it would appear are programs where many interventions are active at the same time and the goal is to break the cycle of reinfection ... How much will this cost? Probably much less than any of the single approach strategies on their own.
Peter Burgess
Posted by: Peter Burgess at March 13, 2007 12:08 AM
Combinations of malaria interventions (better yet combining them with other community-based MCH interventions, such as C-IMCI and Intermittent Presumptive Therapy (IPT) in pregnancy that include early recognition and care-seeking for danger signs) will definitely be more effective than single "magic bullet" interventions. In high to medium transmission areas where malaria is the major cause of the high post neonatal infant and child mortality (particularly Sub-Saharan Africa) when we have looked at Indoor Residual Spraying (IRS) versus Insecticide Impregnated Nets (ITNs) esp Long-life nets (LLIN) the major deterrents for IRS were cost ($9 per spraying per household every 6 months) versus $3-$15 per net offering up to 5 years of protection),so there doesn't seem to be the long term, sustainable funding for IRS at scale. Even if justified, encouraging dual protection of ITN and IRS would be unlikely to have widespread long-term financial support in Africa where health sector budgets are less than $5 per person per year, and in many situations considerably less. One might say that driving down parasitemia in the population using both strategies would reduce costs, but that remains to be proven. Medium income countries, or defined geographic areas (such as island countries) may be able to sustain long-term IRS and it makes sense to consider it there. That is without the consideration of technical capacity, quality assurance, supervision and worker safety considerations for handling insectides over time. There is no question that IRS in controlled situations is effective, but the sustainable implementation challenges are formidable.
The issues of whether or not to include widespread cotrimoxazole, regardless of HIV status have important long-term implications and should definitely be studied by the overall MCH and HIV/AIDS communities before the policies and programs are changed. Addressing the dual disease issues of HIV and malaria are extremely important. Therefore, the programmatic issues must be taken into consider within the overall epidemiologic profile of the population at large. One must remember that the next highest killer of children in the same countries is pneumonia and cotrimoxazole remains the most cost-effective antibiotic for treatment in those children, regardless of whether or not they are HIV+.
Jean Capps
MCH consultant
Posted by: Jean Capps at March 21, 2007 04:01 PM
well, the authour of this article seems to have put his/her ideals in the right pespective.Yes I agree there is need for a combination of malaria interventions with the cost in mind.Cost is why most developing countries are failing to impliment these interventions.So if cheap alternative could be found, well and good.
However I smile a rut, why focusing much on cotrimoxazole than any other equally cheap but effective antibiotics?Ths brings me to another question.Is this not meant to be a marketing deffence and opportunity for Cotrimoxazole.
Joseph
Posted by: JOSEPH SINDAWA at October 30, 2007 10:19 AM