Saturday, 20 August 2016

River blindness - a big challenge

The Beloved's grand-mother lived out the last 10 of her 104 years in the same darkness as Milton (When I consider how my light is spent / E're half my days, in this dark world and wide, etc.) and thereby helped our girls to realise at an early age that there were people who needed their help. Too many young people today live for 25 years or more continually on the take: it does not make them richer or better people. Despite living most of her life in tropical West Africa, the cause of her blindness was not Onchocerca volvulus, which infests upwards of 130 million people in sub-Saharan Africa. The disease is commonly known as river blindness [horrible pictures: you have been warned] because it is spread by Simulium spp. flies which prefer to breed in faster flowing streams. This contrasts with puddle-breeding yellow fever- zika- and dengue- & malaria-carrying mosquitoes like Aedes [prev and prevlier and prevlievier] and Anopheles [prev and prevlier]. At some stage the family got on the mailing list for charities giving it to river blindness, so we've been presented with lots of pictures of poor, sick, and unproductive black people [R above blind man being led by child who isn't yet blind herself].

You can treat onchocerciasis by interrupting the life-cycle in the larval stage with an anthelminthic drug called Ivermectin, which was developed 35 years ago by Merck. It was isolated from the bacterium Streptomyces avermitilis: it is chemically too complicated [see L] to imagine it having been deliberately constructed by chemists: where would you start?? That's why tapping into the delivery pipeline of evolution has been so productive and why it is worth investing in the discovery of weirder and wonderfuller killers. Satoshi Ōmura and William Campbell >!huzzah, born in Donegal, wears a green jersey!< co-discoverers of the avermectin chemical family, shared half the 2015 Nobel Prize in Physiology and Medicine. The other half went to Tu Youyou for her work in malaria.

Those of you who listen to the advertisements during Irish farming programmes on the wireless will get a tinkle of recognition at the name, because Ivermectin is effective against various parasitic worms, mites and ticks of livestock. In 1992, Merck undertook to donate as many Ivermectin doses as it took to rid Latin America of river blindness and this has been markedly successful. 600,000 cases at the start of the program have been reduced to a mere 24,000 according to a recent survey. 600,000 doses can probably be taken out of petty cash for a multinational pharmaceutical company like Merck: wholesale cost of a treatment course in the third world is 12c/US (and $30 in US, so I guess this is subsidising the good will from Merck). But it requires a different war chest in Africa - Nigeria alone has 30 million cases: 50x more than the whole of South America. Nevertheless in conjunction with the Carter Center [bloboprev], which is moving on to other Neglected Tropical Diseases NDTs having given the Guinea-worm Dracunculus medinensis a drubbing, they are making headway in Uganda and other tropical African countries. Usually the ivermectin program runs in parallel with a much more environmentally destructive, because less precisely targetted, attack on the flies. The government in Uganda just got fed up with Onchocerca's drain on the economy: in areas where river blindness has been eliminated, the production of tea, coffee and bananas has bounced back; and school attendance has started to recover as well. Bonus benefits are that other nematode diseases like lymphatic filariasis aka elephantiasis are also susceptible to ivermectin.

But here's the rub.  In tropical Africa, you might carry more than one loathsome and debilitating disease. River blindness and malaria; dengue fever and sleeping sickness, for example. That usually means that you just double the number of pills the unfortunate sufferers have to take. But IF you have both Onchocerca volvulus AND Loa loa, the eye-worm AND you take ivermectin THEN you are likely to suffer a violent and often fatal inflammatory response. Nobody seems to know the details of the mechanism, but it means that, before you start a community-wide ivermectin drive in areas where Simulium flies are endemic, you need to check who has already contracted Loa loa lest you have a case of the treatment was successful but the patient died. Loa loa doesn't exist (yet) in the New World which is another reason why the river blindness program has been so successful in Latin America. Another oddity is that collie dogs have a mutation in the multi-drug resistance gene MDR1 which puts them open to ivermectin poisoning: not all drugs suit all cases - that's why the FDA is so scrupulous in requiring testing testing testing before new products can be marketed.

Now hear this. Onchocerca volvulus, like many nematodes, harbours endosymbiotic bacteria of the genus Wolbachia, a group that we've met before [vs Zika; vs Dengue] as part of an elegant precisely targetted solution to other tropical diseases. The presence of Wolbachia is seemingly essential for the correct development of the Onchocerca larvae. It is not impossible to imagine an antibiotic which selectively kills Wolbachia and thus causes the propagation of Onchocerca to fizzle and die.  Maybe the protocol that isolated Eleftheria terrae and teixobactin is a place to start? Or talk to Satoshi Ōmura, he seems to know what to do to. There's a final year undergraduate research project in here somewhere!

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