The publication of the latest malaria mortality estimates in the Lancet this week was remarkable for two things: 1 - the substantial increase on previous estimates and 2 - the uncertainty it introduces in terms of how close we are to eradicating the disease. Contrast this paper with another important event earlier in the week where Bill Gates and representatives from a good number of big pharmaceutical and global health agencies signed the so-called 'London Declaration' on Neglected Tropical Diseases (NTDs). The discussion and subsequent press releases offered nothing but certainty and an end to suffering, backed up with hundreds of millions of dollars and collaborative commitments.
Malaria is not classified as an NTD because relatively large amounts of attention and funding have been pitted against the parasite. But if we now have to rethink malaria control strategies, then how confident can we be about controlling or eradicating any of the 17 NTDs identified by the World Health Organisation - a collection of infectious viruses, bacteria and parasites that collectively infected many hundreds millions in the Global South There is no easy answer, but what we can do is look at the factors that create uncertainty and re-assess what needs to be done.
A relevant place to start for this process is to examine the 5 key strategies against NTDs as recommended by W.H.O: preventive chemotherapy; vector and intermediate host control, veterinary public health at the human-animal interface; provision of safe water, sanitation and hygiene. These five strategies, if integrated, executed well and made sustainable, could spell the end of many of the 17 so-called Neglected Tropical Diseases (NTDs).
Whether any of these strategies is implemented or not first comes down to money. Low-income country governments don't have enough to prioritise every infectious disease threatening their inhabitants. So when the Gates Foundation and many other highly-prominent pharmaceutical and global health organisations commit to putting hundreds of millions of pounds into the control and elimination of NTDS, heads turn and we should all celebrate. Such events put NTDs on the front pages of national newspapers.
As I joined in the discussion surrounding the Gates event on Monday, I could not help patterning my thoughts with personal images of in a village in Uganda where exposure to bilharzia, a disease caused by exposure to parasitic worms, is particularly high. The most relevant of the W.H.O strategies in the context of bilharzia are chemotherapy, intermediate host control, provision of safe water, sanitation and hygiene. I last visited this village in October 2011 as part of research project investigating the impact of climate change on the transmission of the parasite that causes bilharzia. I've been there many times before and can report that preventive chemotherapy is by far the most effective strategy at reducing levels of infection. This is true of many other NTDs because it is the only one of the 5 strategies that promises a high degree of certainty.
But the one major weakness of this approach is that preventive chemotherapy is not quite what it says on the tin. Chemotherapy alleviates the burden of disease by killing the parasite. If applied often enough it may prevent the conditions which can result from long-term infection (e.g., bladder cancer, hepatic fibrosis), but a single or multiple doses will not prevent infection per se. Anybody receiving a dose of, say, albendazole for their hookworm infection can leave their local health centre and become re-infected moments later when they step on some faecally-contaminated soil containing the larvae of the hookworm parasite for which they have just received treatment. We know that if people are already infected they are likely to become re-infected unless something significant happens to their environment.
What needs to happen to prevent them becoming re-infected is that the environment must be made resistant to the natural history of the parasite. This is where the water-sanitation strategy comes into play. But in adding water-sanitation to chemotherapy we now rely on heavily on changing human behaviour and attempting to modify other environmental variables that may be less tenable to manipulation than the behaviour of a patient in a medical setting. In other words, we increase the uncertainty.
The village I visited in Uganda has a number of water-sanitation initiatives in place. It is a requirement of Ugandan law that every compound should have a latrine. There are pumps providing safe water and even public latrines for anyone caught short whilst away from their compound.
As a research scientist interested in the epidemiology of infectious disease I am interested in how infections impact on the health of populations and how interventions benefit that population. I know that chemotherapy works in the short term but I also know that it requires a long-term commitment because the parasites simply keep coming back if the environment is suitable. I know that people move with their parasites from one location to another, spreading infection as a result of economic migration. I know that not all drugs currently in use are particularly effective against all their target infections (Trichuris trichiura is not particularly susceptible to albendazole, but no other drug is commonly available). I know that even if there is no sign of infection, someone might get sick, and I know that certain genetic factors predispose to protection from infection, whilst others are either protective or maladaptive depending on the recombination events in heterozygous parents.
I know that environmental variables are key to the transmission of NTDs, but I don't know what the future holds. Climate change is having and will have a profound effect on food availability, water availability, local as well as international climate and ecology. We sometimes cannot detect infection properly because the diagnostic tests are insensitive or non-specific. Sometimes the drugs aren't available, sometimes the latrines collapse in the mud, sometimes people prefer to use open water sources rather than a paid-for latrine. Most of the time the extreme pragmatism that accompanies extreme poverty understandably diverts infected people away from attending to their health and thinking more about the small but significant difference in their economic situation that accompany a decision to buy a bed-net, or a set of waders, or rebuilding that collapsed latrine.
There was something made of the passion of the people attending the event in London. One senses this passion was based on their sense of certainty, that finally NTDs are about to receive the attention they deserve, that they will finally face their executioner. My own passion, along, I suspect, with many of my scientific research colleagues is more tempered but no less intense. We find our passion in revealing, explaining and adapting to uncertainty. No agenda that projects into the future is certain. So although we know many things about parasites and their response to drugs there are many other things we don't know about, and can only find out about through rigorous scientific research.
Much of the money donated by the Gates Foundation will be put towards operational research. This is good. But let us ensure that research spreads far beyond the operational and that every aspect of relevant scientific research addressing uncertainty is accepted as valid. The consortium of partners signed up to the London declaration is comprised primarily of pharmaceutical companies. A few academic institutions heavily involved in the control of NTDS (e.g. Liverpool School of Tropical Medicine) are also signed up to the declaration. To really make a sustainable difference that can address uncertainties proactively, we need to have a flexible partner structure that recognises the value of expertise in key areas, irrespective of sector. A multi-disciplinary, multi-agency, multi-country approach that tackles the social component of bilharzia with equal passion as the molecular biology of rabies.
Scientific research is the key to understanding unintended consequences, uncovering the counter-intuitives, investigating uncertainty. When the drugs no longer work, when the statistics overwhelm us, when climate change creates new epidemics, when health doesn't seem to matter in the face of economic hardship, when false diagnosis leads to poor healthcare, when mosquitoes change their behaviour to avoid bed-nets, when corruption destroys supply chains, when health systems breakdown or need building from scratch - someone, somewhere in research community rises to the challenge. Let their interests, their passion and their commitment be declared.
Let's accept uncertainty and run with it.