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Hotez hooks high-fliers for neglected diseases
1 Apr 2010
Tatum Anderson
Source: TropIKA.net
Dr Peter Hotez.
Peter J Hotez is pushing to get neglected tropical diseases (NTDs) recognized on the international stage. Now research professor and chair of the Department of Microbiology, Immunology and Tropical Medicine at George Washington University, he is not far from the US seat of power.
The mobilization of several different NTD organizations under the Global Network for Neglected Tropical Diseases
banner is helping, he says. This lobby group is dedicated to raising awareness, political will, and funding for NTDs and was launched at the Clinton Global Initiative Annual Meeting in 2006. The Sabin Institute, a non-profit organization that researches new vaccines amongst other activities, hosts the Global Network and now counts members among the various public–private partnerships and academic institutions that have for years worked on NTDs. (Hotez is president of the Institute). A few include the Schistosomiasis Control Initiative and the International Trachoma Initiative.
The profile of NTDs has certainly been raised; UN Secretary General Ban Ki-moon has highlighted these diseases as did the G-8, for the very first time, last year. The Obama administration has committed around $65m to NTDs this year. Hotez says it has promised much more next year and will make the diseases one of four key pillars in its Global Health Initiative.
Pushing NTDs up the agenda has been difficult, says Hotez. Politicians have been difficult to convince because these diseases don’t cause headline death-rates like AIDS, TB and malaria. That they keep people in poverty is more difficult to explain, he says.
“We don’t have a good elevator speech (where you get two to three minutes with a high-profile individual),” he says. “We have a more complicated message and it has taken time for people to realise. But now they are understanding.”
Persistence
For his part, Hotez has persisted with messages designed to resonate with politicians and voters, especially in the US.
One such message is that NTD treatment is one of the best buys in public health. It offers a massive return on investment compared with other interventions. Another message is the economic argument, that treating NTDs lifts people out of poverty and reduces dependency on the rest of the world for aid. That requires being able to cite evidence; controlling intestinal worms alone would avoid 16 million cases of mental retardation and 200 million years of lost primary schooling; deworming in Kenya could raise per capita earning by 30% and controlling lymphatic filariasis in India would add almost $1 billion to the country’s GNP; chronic hookworm infection in childhood reduces a person’s lifetime earning power by more than 40 percent [1]. Indeed Hotez-style advocacy is likely to link NTDs with security in the Middle East and fragile states, lymphatic filariasis (LF) with the food crisis, or Gandhi with hookworm.
His conviction is a life-long one. A 14- year-old Hotez begged his parents to buy him a microsope after reading a book called Microbe Hunters, by Paul De Kruif published in 1926.
At university, he was also inspired by Norman Stoll, a distinguished Rockefeller Institute scientist who helped to establish human parasitology research in North America and looked at hookworm almost 40 years ago [2].
Integration of treatment for the big seven
Today, Hotez’s aim is to convince donors to give more money to scale up dramatically the number of people treated for the seven most prevalent NTDs: three major intestinal worms infections, also known as helminths (ascariasis, trichuriasis and hookworm); as well as lymphatic filariasis, onchocerciasis, schistosomiasis and trachoma.
But rather than treat each disease separately, as has historically been the case, the plan is to provide a rapid impact package of four drugs that treat all seven diseases at the same time. They are to be provided by mass drug administration to hundreds of millions of people, annually. Annual treatments can both treat the diseases in those who have them and, ultimately, arrest transmission too.
The drug package would comprise praziquantel, azithromycin, either albendazole or mebendazole and finally, either diethylcarbamazine or ivermectin. (The drugs also treat trongyloidiasis,trematodiases, taeniasis and scabies.)
Integrating drug administration would avoid the enormous overlaps that have been seen now for many years – different public–private partnerships have run concurrent programmes in the same places with no coordination (in some cases giving out the same drugs.)
It would also address the mismatch between the coverage of drugs for different diseases. Some programmes, such as those for LF and onchocerciasis, have made huge strides with coverage rates of 50% in some cases. The African Programme for Onchocerciasis Control (APOC) reached more than 62 million people in 19 countries in 2006, for instance. In contrast, coverage with schistosomiasis treatments has reached only 10% of the populations who need them, says Hotez [3].
But that is partly a function of time. LF and onchocerciasis programmes have been running for a few decades, while a resolution by the World Health Assembly to tackle intestinal worms came only in 2001. It is also a question of scale. Onchocerciasis affects far fewer people(18–37 million), while intestinal worms affect a staggering 600–800 million.
Eyebrows have been raised as to why only seven diseases have been focused on by the Global Network. After all, diseases such as dengue and cholera are counted as NTDs by many including the US government (which classifies 16 diseases as NTDs), WHO and TDR. Chagas disease, human African trypanosomiasis and leishmaniasis are not covered by the Global Network either.
Hotez says treatment for the top seven can be done with mass drug administration, whilst the other NTDs require different strategies – Chagas requires mainly vector control, he says.
That said, there’s room to expand the Global Network’s reach in future. “In time there will be opportunity to bring in additional neglected diseases,” he says. “The original seven were chosen on their high prevalence, the disease burden and geographical overlap and high rates of co-infection.”
Bringing the package to the people
Today’s package of four drugs is being rolled out using different strategies determined by recipient countries. They may be combined with existing community-directed treatment with ivermectin (CDTI) programmes. They could also be delivered to school-age children at school, by training teachers, or even on child health days when pre-school children are given vitamin A tablets and bednets.
Cooperation is already beginning to happen, says Professor Moses Bockarie, director of one member of the Global Network – the Centre for Neglected Tropical Diseases. (In a spirit of integration, CNTD has subsumed the Lymphatic Filariasis Support Centre).
Donors, such as USAID and DFID are providing funds on condition that there is integration. The Global Network’s member vertical organizations are beginning to work together. (APOC is dipping its toes into the water, piloting integrated projects in DRC and Tanzania.) They are also, for example, helping countries put together integrated strategies that they can use to approach donors. Today, some countries, such as Burkina Faso, are organizing fully integrated programmes through their ministries of health. Ghana and Sierra Leone are good examples too, says Bockarie. “The ministry of health is the leader of the programme and pools all funding,” he says.
There are no figures yet on how many rapid impact packages have so far been rolled out as a proportion of all programmes; there is too much flux as USAID ramps up its programmes this year, and countries are devising national integration plans says Hotez.
He reckons, however, that there must be even more participation from endemic countries. “We want to build in some sustainability and ownership by disease endemic countries by having them pay in some cases, but building technical capacity as well,” he says.
Countries could help with mapping, monitoring and evaluation of the seven diseases. That is important, he says, because determining how and when the integrated package should be used is crucial. “What do you do if not all seven diseases are present and you only have two or three?”
Integrating projects means funding must change too; the Global Network is creating four regional funding bodies to which they can apply for scale-up money using a US$34m Gates grant.
The first, a Latin American fund, is in the process of being formed with the help of the Inter-American bank and PAHO. Asian and sub-Saharan African funds are still under discussion and another is planned for Middle Eastern countries. Hotez says he is loath to compare them to the Global Fund for AIDS, TB and Malaria but the analogy exists nevertheless. Indeed whether the Global Fund should expand to cover more health issues is a recurring question within the global health community [4].
Those funds should help circumvent the logjam in funding for NTDs from the largest donor, the US. Previously, the US government has provided funding through a private company called Research Triangle International (RTI). Observers have expressed dissatisfaction with the way it has awarded funds in the past. (USAID was unavailable for comment.)
Challenges
But the Global Network faces a host of challenges. Securing enough money to roll out the impact package will not be easy in an economic recession and with other strong global health lobbies jockeying for prominence.
Indeed, getting a prominent position on this year’s G8 agenda in Canada this summer – the complex intricacies of diplomacy, international negotiations and agendas – is likely to be difficult too.
There is not as much support from many G8 countries for NTDs beyond the US and UK says Hotez. (When the previous US administration promised $350m to NTDs for five years, in 2008, it was made on the assumption that other rich countries would match funds and bring the total figure to $1bn. That never happened).
Secondly, despite NTDs receiving the largest drug donations in history, not all drugs are donated to the level that is required (see graphic). So while some donations have enabled the cost of treatment programmes to plummet, the lack of others ramps it up again.
Needs and supply levels of four drugs used to treat neglected tropical diseases.
The drug used to treat schistosomiasis, praziquantel, is an example. “We have only a small percentage of what is needed,” says Hotez. “We don’t have a pharmaceutical company stepping up. And it is devastating not having an adequate amount of praziquantel donated.” Albendazole and mebedazole are less than 50% covered too.
Thirdly, getting vertical programmes to work together is not necessarily easy, says the Liverpool School’s Bockarie. Many programmes and funders have committed to a certain course of action and specific goals for their chosen diseases and are loath to deviate, he says. Some are reluctant to cede power to other agencies where there is overlap in any one country. “Now the whole struggle is who will be the lead agency,” he says.
And finally, the longevity of the impact package is a worry. Research into new drugs, vaccines and diagnostics is absolutely critical because, although many of these drugs work extremely well, there is always the risk of resistance.
Signs are already emerging. A single dose of mebendazole is much less effective against hookworm than previously thought. The other drug in the same class, albendazole, may be useful but there is evidence of resistance when used in cattle and livestock. “Now we have one drug albendazole to treat 600 million people,” he says. “So what is the backup?”
That is why the Sabin Institute has formed a product development partnership to put a recombinant hookworm vaccine into clinical trials this year and is researching a schistosomiasis vaccine too.
But Hotez says he became involved with access to drugs and the Global Network precisely because these vaccines take so long to develop and interim solutions are needed. So he calls for more drug research. “We are trying to encourage WHO/TDR to expand a business line for the purpose of developing new anti-helminthic drugs,” he says. “The rapid impact package a decade from now will look very different from the rapid impact package of today.”
Peter Hotez: education
BA degree in Molecular Biophysics Phi Beta Kappa from Yale University (1980).
MD and PhD medical scientist-training programme at Weill Cornell Medical College and the Rockefeller University.
Residency at Massachusetts General Hospital.
Dr Hotez returned to Yale University where he was on the faculty for 12 years
George Washington University (2000).
References
1. Bleakley H (2007). Disease and Development: Evidence from hookworm eradication in the American . Quarterly Journal of Economics; 122(1)73-117. Available from: http://www.mitpressjournals.org/doi/abs/10.1162/qjec.121.1.73
2. Stoll NR (1962). On endemic hookworm, where do we stand today? Exp Parasitol; 12: 241-252. Available from: http://www.ncbi.nlm.nih.gov/pubmed/13917420
3. Hotez PJ, Fenwick A (2009). Schistosomiasis in Africa: An Emerging Tragedy in Our New Global Health Decade. PLoS Negl Trop Dis; 3(9):e485. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19787054
4. Editorial [no authors listed] (2010). The Global Fund: replenishment and redefinition in 2010. Lancet; 375(9718):865. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20226967
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