Un­cov­er­ing why malaria drugs fail

Sci­en­tists fo­cus on a Cam­bo­dian re­gion where treat­ments lose their ef­fect, re­ports Robin McKie

The Guardian Weekly - - Discovery -

Pailin is a small set­tle­ment nestling in trop­i­cal rain­for­est near Cam­bo­dia’s bor­der with Thai­land. It is an unas­sum­ing town that lies at the cen­tre of one of the coun­try’s main log­ging ar­eas. Pailin har­bours se­crets, how­ever. It was in this town, in the late 1970s, that the Kh­mer Rouge set up one of its main strongholds and ruled Cam­bo­dia with a fe­roc­ity that caused at least 2 mil­lion deaths. It is a grim legacy, by any stan­dards.

But Pailin has an­other un­wanted claim to fame, one that is also as­so­ci­ated with wide­spread death. The town, it tran­spires, lies at the heart of a re­gion that has seen suc­ces­sive waves of re­sis­tance to malaria drugs arise in lo­cal peo­ple and then spread across the globe. The re­sult­ing death tolls can be mea­sured in mil­lions of lives, say sci­en­tists.

Just why malar­ial drug re­sis­tance has arisen here is not clear. Nev­er­the­less, sci­en­tists are em­phatic: the re­gion has seen the cre­ation of sev­eral mu­ta­tions in malaria par­a­sites that have al­lowed them to shrug off medicines that once pro­tected hu­mans. Even worse, they have dis­cov­ered that a new wave of malar­ial drug re­sis­tance has re­cently ap­peared in this tiny area and has al­ready spread into Thai­land, Laos and Viet­nam, and be­gun to move into Myan­mar and travel to­wards In­dia and Bangladesh.

“The prob­lem is that we are pussy­foot­ing around,” said Prof Sir Nicholas White, of the Mahi­dol Ox­ford Trop­i­cal Medicine Re­search Unit. “The World Health Or­ga­ni­za­tion (WHO) has not pro­vided the nec­es­sary lead­er­ship. We need very firm di­rect ac­tion and at present we are not get­ting that.”

Re­sis­tance to ma­jor malaria drugs first ap­peared in the late 1950s when chloro­quine – then a highly ef­fec­tive suc­cess­ful treat­ment for the dis­ease – be­gan to lose its ef­fi­cacy. Cru­cially, this re­sis­tance first ap­peared in Pailin on the Cam­bo­dian-Thai bor­der and then spread to Africa by the early 1980s. Sev­eral mil­lion deaths were added to the al­ready grim toll of lives lost to the dis­ease as a re­sult.

Sci­en­tists have re­cently dis­cov­ered once more that re­sis­tance to key malar­ial drugs – in this case, the artemisinins – has evolved – and in ex­actly the same place as be­fore: the farms and vil­lage that sur­round Pailin. Just why this tiny re­gion of south­east Asia has proved to be such a fer­tile zone for the emer­gence of deadly re­sis­tance to malar­ial medicine is not clear, a point stressed by Do­minic Kwiatkowski, di­rec­tor of the cen­tre for ge­nomics and global health at Ox­ford Univer­sity.

“We would love to know the an­swer, but it is not ob­vi­ous,” Kwiatkowski said.

“One idea is that re­sis­tance keeps aris­ing here for his­tor­i­cal rea­sons. Maybe it has some­thing to do with the way that malar­ial medicines are ad­min­is­tered here. But how ex­actly?” In fact, this the­ory is just one of a great many other sug­ges­tions that have been put for­ward to ex­plain why this re­sis­tance is ap­pear­ing here first.

The lo­cal strain of malaria par­a­sites may have some spe­cial prop­er­ties, or the ecol­ogy of the re­gion may have fea­tures that boost the rise of re­sis­tance. “The cru­cial point is that we need to do some­thing about it and once we have, we need to mon­i­tor the sit­u­a­tion very, very care­fully,” said Kwiatkowski.

One fac­tor that has re­cently be­come clear is that malar­ial drug re­sis­tance ap­peared very quickly in the re­gion. Writ­ing in Lancet In­fec­tious Dis­eases in Fe­bru­ary, re­searchers from the Well­come Sanger In­sti­tute and col­lab­o­ra­tors re­ported that re­sis­tance to com­bi­na­tion ther­a­pies that in­cluded artemisinins arose al­most as soon as the treat­ment was in­tro­duced as a first-line malar­ial drug. How­ever, that this loss of ef­fi­cacy was not spot­ted, for a va­ri­ety of rea­sons, un­til sev­eral years had passed.

The im­pli­ca­tions of this fail­ure were stressed by Ben Rolfe, head of the Asia Pa­cific Lead­ers Malaria Alliance. “On our watch, drug re­sis­tant strains have spread al­most un­no­ticed,” he told the Bri­tish jour­nal BMJ re­cently. “As a re­sult, we now risk a global resur­gence of the dis­ease.”

The ques­tion fac­ing sci­en­tists – and heads of state and health lead­ers – is straight­for­ward: what can be done? White is em­phatic. “We have a win­dow of op­por­tu­nity but it is clos­ing rapidly,” he said.

What is needed is a cam­paign, run with mil­i­tary ef­fi­ciency, to use cur­rent drugs – while they still have some ef­fi­cacy – not only on peo­ple who

al­ready have malaria but on those in­di­vid­u­als who have been in­fected but who have not suc­cumbed or shown symp­toms of the dis­ease.

“These in­di­vid­u­als carry small num­bers of par­a­sites and al­though they don’t get ill they are sources of new in­fec­tions,” said White. “Mos­qui­tos bite them, take their blood and spread it to oth­ers. They are the source of new in­fec­tions.”

The plan, pro­posed by White and other sci­en­tists, is that ev­ery­one in a vil­lage in a malaria hotspot should be treated with anti-malar­ial drugs – re­gard­less of their symp­toms. “It is called mass drug ad­min­is­tra­tion. It is very con­tro­ver­sial but it works – if it is done as part of a con­certed strat­egy. If you do it badly you will only make the prob­lem of re­sis­tance worse, so this has to be done right. But if we don’t do it we won’t be able to elim­i­nate malaria quickly enough, and if re­sis­tance wors­ens it may be­come un­treat­able,” says White.

WHO of­fi­cials say that the dan­gers posed by the new malaria su­per­bug are ex­ag­ger­ated and that bet­ter preven­tion, mon­i­tor­ing and treat­ments will limit its spread from the Mekong re­gion. Oth­ers are not so sure, how­ever.

White said: “We are run­ning out of time and un­less we act rapidly, peo­ple will suf­fer and the peo­ple who will suf­fer most will be the chil­dren of Africa.”

Paula Bron­stein/Getty

Pre­cau­tion ... Pailin prov­ince res­i­dents sleep under pro­tec­tive nets

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