Friday, February 23, 2007

Occam's Razor and the Silver Bullet Gambit

Entia non sunt multiplicanda praeter necessitatem (Entities should not be multiplied beyond necessity.) - William of Ockham, 14th C philosopher

It began in the early New Year when I traveled to England on family business. Within 48 hours of landing in cold, crowded Heathrow I had a nasty Upper Respiratory Tract Infection (URTI). Notwithstanding my brother and I discovering our recently deceased father’s stash of old and distinguished whiskies, and consuming a plentiful amount in his memory, I felt increasingly miserable and the cough got worse.

After ten days in wintry England I began my two day journey back to northern Uganda, feeling very sorry for myself, convinced my URTI was morphing into pneumonia and regretting not seeing a doctor before leaving. The first night back in Lira I spiked a temperature of 101F and alternately sweated and shivered the night away, resolving to find a doctor, have a chest x-ray, whatever other diagnostic procedure was available and start industrial strength antibiotics post haste. The following day I felt better and convinced myself my ‘chest-cold’ had been exacerbated by the long journey and the abrupt change in climate. That night I spiked another fever and all the alarm bells rang…well, at least with my wife who insisted I get a test for malaria in the morning.

At 8am we were in a small mission clinic in town, sat amongst a group of fifty or so patients, mainly women with babies or pregnant or both; the nurse told me, most probably had malaria. Eventually I took my turn to be stabbed in the finger by a young laboratory technician called Fred, who explained what he was doing and how he would reach a diagnosis. Half an hour later he emerged from the lab to announce “ Mzee (respectful title for elder male) you are a strong man, you have over 50 parasites to 100 WBC!”

My immediate reaction was in character, I was overwhelmed with self-pity. Malaria? Why me? How? I am so careful and have never had it before in my life. Etc etc. The next 36 hours is a bit of a fog. I know well enough the standard treatment protocol and always have a stock of Co-ArtemÒ (a combination of artemether and lumefantrine) in the fridge. I have used it on patients in the middle of no-where and it works like magic. Given that I had a weapons-grade dose of the disease, I embarked on a ‘take-no-prisoners’ counter-attack: a full course of 20/120 Co-ArtemÒ plus 100mgs of Doxycycline twice daily as insurance, analgesics and gallons of water. My wife nursed me diligently. My temperature see-sawed around 101F to 105F, I crawled to the shower, ached in places I did not know I could and was visited by very strange creatures which walked the bedroom walls . After 72 hours, I emerged from my bed an old man. It took a further week to nurture my appetite and get out and about.

“If you hear hoof beats behind you, look for horses not zebras” - Dr Jay Sanders, an old friend and mentor.

My purpose in recounting this story is not self-indulgence. It raises some very clear issues for me. The first is how easily I reached a [wrong] conclusion as to what ailed me. In my defense, I had strong circumstantial and symptomatic evidence to support my ‘diagnosis’. Though I don’t take prophylactic antimalarial medicine – it’s neither feasible nor affordable over years – I do take every other precaution, covering up in the evening, use insect repellents and always sleep under an Insecticide Treated Net (ITN). I am rarely bitten and have never before had malaria.

My initial symptoms where of an URTI and I contracted that in the UK. The cough and chest pain became the focus of my illness. It was 13 days from the time I left Uganda and 2 days after I returned before I suffered my first classic malaria rigor and by that time I had a very high level of parasites in my blood. The malaria is long gone but I still have a hacking cough. I had followed the age-old saw of medicine drawn from Occam’s premise, to suspect the obvious and commonplace – horses not zebras. I made two errors, I was living in a part of Africa where there are no horses only zebras and I had ignored another famous medical saw, Hickam’s Dictum, “a patient can have as many diseases as he damn well pleases.” I had both an URTI and malaria, a disease from each continent and one masking the other. It’s not a mistake I will make readily again.

No-one who lives in Africa can ignore malaria, and I have written about it on a number of occasions; now I have first-hand knowledge of the illness. It is not something I wish to repeat. But I was lucky, I had the education and resources to protect me and to be diagnosed and treated when prevention failed. For most of my neighbors in Lira and Uganda in general, there is scant help and many die. About 400 Ugandans die every day from malaria, mostly children under five and pregnant mothers. The data for other countries in sub-Saharan Africa are similar. Despite the efforts of international organizations, governments and non-government organizations (NGOs) nothing seems to be making a dent in the death toll, to the contrary, it is inexorably rising.

In 1998 the UN, WHO, a host of governments and NGOs launched a program, Roll Back Malaria (RBM), aimed at halving deaths from malaria by 2010 – almost 90% of these deaths are in sub-Saharan Africa. With less than three years to go the annual number of deaths worldwide from malaria is higher now than in 1998, rising from 5.5m in 1998 to a staggering 16m in 2004. If ever there was a failure of an international initiative, one that has been trumpeted around the world in every manner of global forum, and funded to the tune of hundreds of millions of dollars, the Roll Back Malaria is the classic example. It is a damp squib. Why? If Uganda is any example, the impending demise of RBM is a result of broken promises, ineptitude, misplaced reliance on ‘silver-bullet’ solutions and the defeat of science by soap opera. In theory Uganda has the three tools needed to curb malaria deaths—effective combination treatment based on artemisinin, ITNs and insecticides. A glance at each might throw some light on why Uganda is losing the fight.

The reality is that most Ugandans consider malaria like Americans view a common cold, hardly something you visit a physician for unless it gets really bad. The parallels between the US and Uganda in this regard are striking. Americans, with colds, rather than navigate the complexities and costs of a physician consult, will self-medicate or at most, seek the advice of a pharmacist. Ugandans do the latter. But they rarely have access to trained pharmacists and they have to pay out of pocket. They opt for the cheapest plan. This can be anything from traditional herbal medicine through dangerously ineffective but cheap combination therapies like chloroquine and fansidar, to effective but hugely painful intra-muscular quinine. Combination treatments based on artemisinin, that rescued me from who-knows-what, are being made available through the WHO and Global Fund but given the ineptitude of the Ugandan healthcare system, are only slowly permeating down to the ‘village’. As in all matters Ugandan though, there is always a way for those who can pay.

Talk to any member of the malaria prevention cognoscenti and they will wax lyrical about the ITN and its life saving properties. It is the ‘killer app’, the ‘silver bullet’ of modern malaria intervention, single-handedly able to reduce malaria deaths by over 60%. Despite what Sharon Stone and other glitterati would have us believe, ITNs have been around a long time and yet have not made a significant impact on malaria. Why? The ITN lobby insists it is a problem of supply, not enough are available. But there are more complex issues that the ‘silver bullet’ theorists downplay. ITNs cost more to distribute than to make and distribution is complex business, fraught with issues of local politics and economics. Then there are some banal practical facts: you cannot live 24/7 under an ITN, mosquitoes bite most in early evening and morning, when ordinary folks are up and about. They are hot to sleep under, particularly when there are eight people living in a small hut, and they are a fire hazard in huts where the only means of illumination is a candle or paraffin lamp. This is not a dismissal of ITNs, I swear by mine; rather a recognition that ITNs alone cannot beat malaria.

The third leg of the triad, vector control with insecticides, is the most contentious, mainly because it involves a dirty word, Dicophane or DDT. This is not the time or place for a history lesson on DDT, most readers are well aware of Silent Spring and the American experience with agricultural use of DDT. I have also expressed my bias in previous articles. For anyone who wants a serious scientific opinion on the issue, I recommend, “Balancing Risks on the Backs of the Poor” by Amir Attaran et al Nature.

The plain fact is that in terms of cost and effectiveness, DDT has no rival as an insecticide in vector control of insect-borne disease. Despite libraries of research, much conducted during and immediately after the time when DDT was used on a huge scale in the USA and elsewhere, there is no science to support the claim that DDT harms human health. Moreover, the strategy for DDT use in vector control, is to spray, small amounts of oil-based liquid inside selected homes and buildings once or twice a year in a tactic called Indoor Residual Spraying (IRS). To put this in perspective, back in the old days, US farmers would spray 1,100kgs of DDT on 100 hectares of cotton in four weeks. IRS would use this much to spray every building in northern Uganda in a year. It is not surprising therefore that the Stockholm Convention on Persistent Organic Pollutants (POPs) in 2004, exempted DDT for use in control of insect borne disease. Nor that in September 2006 the WHO announced their support for IRS using DDT in malaria control.

When, shortly after the WHO announcement, Uganda announced it would embark on IRS using DDT as the third leg of its RBM initiative, the reaction and rhetoric from activists, local and international, resembled a soap opera. Every well-worn cliché and threat was rolled out, ranging from the disastrous impact on agricultural exports to ‘recent studies that showed massive IQ loss in children whose mothers were exposed to DDT’. Even if tiny amounts of DDT from IRS, leached into agriculture it’s a stretch to see how this would destroy the nations principal exports, cut-flowers, tea and coffee. My favorite warning of agricultural Armageddon resulting from DDT use in Uganda came from the British American Tobacco company, delivered without a hint of irony!

As to IQ loss in children, I have not researched the study quoted, but I doubt that the damage, if any, could match the destruction of children’s brains inflicted by malaria every year here. As a small measure, my wife plans to fund a project for care of epilepsy patients ( there seems to be a correlation between infantile malaria and epilepsy) in Lira; there are an estimated 1,000 plus – in a population of less than100,000. No rational argument seems to sway the activists in Physicians for Social Responsibility (PSR) or the Pesticide Action Network (PAN), maybe because it threatens their funding and their salaries. But every day they succeed in delaying the implementation of IRS, they need to explain why hundreds of Ugandans must continue to die.

What Uganda needs is a coherent, well resourced and managed plan to ‘Roll Back Malaria’; by every measure, the current plan is not working and I am a recent victim. The Plan must include all three legs of the triad, effective treatment, nation-wide distribution and use of ITNs and IRS, using the best insecticide currently available, DDT. Over-reliance on ITNs will fail. As to the siren calls of PSR and PAN so concerned about our future but with no solutions for today, I have only one comment. Close down your expensive offices in malaria-free San Francisco, Washington DC and Nairobi and open them in Lira. Bring your families, leave behind your expensive malaria prophylaxis and designer insect repellants. Come and sleep under an ITN and work here for a couple of years. Then you will have a credible voice at the table.

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