Malaria’s deadly come­back

Financial Mirror (Cyprus) - - FRONT PAGE -

The dra­matic drop in malaria deaths since the be­gin­ning of the cen­tury is one of the great public-health suc­cess sto­ries of re­cent years. Thanks to con­certed in­vest­ments in pre­ven­tion, di­ag­no­sis, and treat­ment, the num­ber of peo­ple killed by the dis­ease each year has de­clined 60% since 2000, sav­ing more than six mil­lion lives.

And yet, even as the dream of elim­i­nat­ing malaria seems closer to be­com­ing re­al­ity, grow­ing drug re­sis­tance is threat­en­ing these re­mark­able gains. Re­sis­tance to the most ef­fec­tive an­ti­malar­ial medicine, artemisinin, has emerged in Cam­bo­dia and is spread­ing across the Mekong Delta re­gion.

With­out ef­fec­tive and timely action, this new, re­sis­tant form of malaria will be­come wide­spread – a pat­tern that has al­ready oc­curred twice with older malaria medicines. Govern­ments, in­ter­na­tional or­gan­i­sa­tions, civil-so­ci­ety groups, and com­pa­nies must take ur­gent steps to prevent an epi­demic of re­sis­tant malaria and stop a painful episode from re­cur­ring.

In or­der to de­lay the spread of re­sis­tance long enough to al­low new drugs to come on­stream, an ur­gent short-term ob­jec­tive must be achieved: pre­vent­ing re­sis­tance from tak­ing hold in South and South­east Asia and spread­ing else­where. If his­tory is any guide, artemisinin re­sis­tance could move into In­dia and on­ward to Sub-Sa­ha­ran Africa and the rest of the world, putting mil­lions of lives at risk and jeop­ar­diz­ing decades of progress.

In the 1950s, re­sis­tance to an­other medicine, chloro­quine, emerged along the Thai-Cam­bo­dia bor­der. The same thing then hap­pened in the 1970s with sul­pha­dox­inepyrimethamine (SP). From South­east Asia, re­sis­tance to chloro­quine and SP spread to In­dia, and from there to Africa and much of the rest of the world. Mil­lions have died as a re­sult, most of them young African chil­dren.

The con­se­quences of wide­spread artemisinin re­sis­tance would be sim­i­larly dev­as­tat­ing. Even the most con­ser­va­tive es­ti­mates paint a grim pic­ture. One study found that its spread could re­sult in more than 116,000 ad­di­tional deaths each year and roughly $417 mil­lion in as­so­ci­ated med­i­cal costs and pro­duc­tiv­ity losses – above and be­yond the $12 bil­lion in pro­duc­tiv­ity losses malaria al­ready costs SubSa­ha­ran Africa each year.

De­spite broad-based concern over the past eight years, artemisinin re­sis­tance has not been con­tained. On the con­trary, it has now been de­tected in Cam­bo­dia, Vietnam, Laos, Thailand, and Myan­mar, on In­dia’s east­ern bor­der.

There has been a wel­come in­crease in donor sup­port, no­tably the Regional Artemisinin-re­sis­tance Ini­tia­tive, funded by a $100-mil­lion grant from The Global Fund to Fight AIDS, Tu­ber­cu­lo­sis, and Malaria. But the slow strength­en­ing of con­ven­tional con­trol in­ter­ven­tions is not prov­ing ca­pa­ble of out­pac­ing the spread of re­sis­tance.

To end malaria, we need a united global front against the driv­ers of re­sis­tance. In ad­di­tion to ef­forts to con­tain artemisinin re­sis­tance in the Greater Mekong sub-re­gion, action is needed farther afield. Ac­cord­ing to the World Health Or­gan­i­sa­tion, as of Novem­ber 2015, na­tional health au­thor­i­ties in six African coun­tries and Colom­bia had not yet with­drawn their mar­ket­ing au­tho­riza­tions for oral artemisinin monother­a­pies – an im­por­tant driver of re­sis­tance.

Stronger com­mit­ments from the private sec­tor will be needed as well. As of De­cem­ber 2015, 21 drug man­u­fac­tur­ers con­tacted by the WHO had not yet agreed to stop pro­duc­ing oral artemisinin monother­a­pies. More than two-thirds of these com­pa­nies are lo­cated in Asia.

Re­search-based phar­ma­ceu­ti­cal com­pa­nies must also in­vest in the next generation of an­ti­malar­ial medicines. While many artemisinin-based treat­ments re­main ef­fec­tive, at some point they will need to be re­placed – or risk be­com­ing part of the prob­lem.

Through a public-private part­ner­ship with the Sin­ga­pore Eco­nomic De­vel­op­ment Board, the No­var­tis In­sti­tute for Trop­i­cal Dis­eases has led the for­ma­tion of a re­search con­sor­tium with this pre­cise aim. The ef­fort has al­ready yielded two promis­ing new an­ti­malar­ial drug can­di­dates cur­rently in Phase 2 clin­i­cal tri­als – new classes of com­pounds that treat malaria in dif­fer­ent ways from cur­rent ther­a­pies and thus have the po­ten­tial to com­bat emerg­ing drug re­sis­tance.

More broadly, prod­uct de­vel­op­ment part­ner­ships, such as the Drugs for Ne­glected Dis­eases ini­tia­tive and the Medicines for Malaria Ven­ture, are bringing to­gether aca­demic, phar­ma­ceu­ti­cal, and fund­ing part­ners to de­liver po­ten­tial new treat­ments for ne­glected dis­eases. These col­lab­o­ra­tions can shep­herd promis­ing com­pounds through the lengthy and ex­pen­sive process of drug de­vel­op­ment and ap­proval.

Two other an­ti­malar­ial com­pounds in Phase 2 clin­i­cal tri­als are cur­rently be­ing de­vel­oped with sup­port from Medicines for Malaria Ven­ture – one with Takeda Phar­ma­ceu­ti­cals and the US Na­tional In­sti­tutes of Health, and an­other with the French phar­ma­ceu­ti­cal com­pany Sanofi.

We may be win­ning many bat­tles against malaria, but fa­mil­iar warn­ing signs in­di­cate we could lose the war. The spread of artemisinin re­sis­tance in Asia to­day threat­ens the lives of chil­dren in Africa to­mor­row. That’s why we need ef­fec­tive action to prevent the spread of artemisinin re­sis­tance, in­clud­ing ur­gent in­vest­ments in the next generation of an­ti­malar­ial treat­ments. If we do not heed the his­tory of malaria, we may be doomed to re­peat it.

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