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The global burden of neglected tropical diseases

The global burden of neglected tropical diseases School of Public Health, Imperial College, London The first comprehensive study on the global burden of disease and risk factors was commissioned by the World Bank in 1992. A follow-up study was performed in 2005, and another iteration was commissioned by the World Health Organization in 2010, due forpublication in 2011. The author suggests that the global burden of neglected tropical diseases (NTDs) has been seriously underestimated. The way forward is the integration of control efforts, with programmes coming together to deliver a package of drugs against NTDs. Barriers to continent-wide coverage of drugs against NTDs are political will (missing in those countries with poor governance), funding (approximately half of the $1.5e2 billion is needed) and human resources. However, if the donors who give so much to malaria, tuberculosis and human immunodeficiency virus would share just 10% of the amountallocated to the big three, the most common NTDs could become diseases of the past. Thiscould well happen within 7 years, and the targets of GET2020 (Global Elimination ofTrachoma by 2020) to eliminate trachoma and GAELF (the Global Alliance to EliminateLymphatic Filariasis) to eliminate lymphatic filariasis by 2020 are achievable.
ª 2011 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
The first comprehensive study on the global burden of disease In the first study on the global burden of disease and risk and risk factors was commissioned by the World Bank in factors, the weightings allocated to the various neglected tropical diseases (NTDs), listed in were significantly another iteration was commissioned by the World Health lower than these diseases merited in the opinion of NTD Organization (WHO) in 2010, due for publication in experts. Several peer reviewed publications have subse- Disability-adjusted life years (DALYs) represent an attempt quently attempted to make the case for a significant increase to quantify the burden of each disease, calculated as the sum in the disability Indeed, since 2006, the investi- of life years lost through early death (YLL) plus the years lost to gators working on many of these NTDs have come together disability (YLD). YLL is estimated for each disease. The thanks to a WHO initiative. By combining their global burden, disability caused by each disease is allocated a value from 0 to the result is that the combined burden of disease due to NTDs 1, and YLD is calculated as the years lived with the disability has been estimated at 56.6 DALYs, compared with malaria at Morbidity and mortality due to NTDs were underestimated as long-term disabilities were not always attributed to an early Unfortunately, the DALY allocation, which forms the basis NTD infection, nor were they given a high rating, thus leading for research and controls funding allocations, is considered by to low YLD. Almost all deaths which are known to be due to some to be somewhat arbitrary, and therefore is not always longstanding parasitic infections were, in fact, not recognized as such and so were not attributed to the childhood infection 0033-3506/$ e see front matter ª 2011 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
MDG6 calls for treatment of human immunodeficiency Table 1 e The core 13 neglected tropical diseases.
virus (HIV), malaria and other diseases. NTDs are an impor- tant constituent of the ‘other diseases’.
Estimates of those infected with intestinal worms suggest that over 800 million individuals worldwide harbour Ascaris infections, 600 million have Trichuris worms, and 600 million have one or another of the hookworm species. The worms infect children from 2 years of age, but the consequences of infection can be prevented by early treatment with either albendazole or mebendazole. Regular treatment during childhood may be needed in areas where sanitation and human hygiene is poor in order to prevent long-term effects, especially those suffered by the 10% of individuals who harbour heavy infections.
Interestingly, hookworm tends to infect adults as well as children, whereas the other worms are not usually found inadults. A meta-analysis by Smith and showed that which led to the patient’s death some 25 soil-transmitted helminths cause significant weight loss and reality, the visual impact of the appalling stigma, disfigure- anaemia, while Miguel and Kremer showed that treated chil- ment, blindness and disabilities caused by NTDs only needs to dren soon achieve a better attendance record at be seen to convince most people of the importance of these Another study showed that a single round of deworming led diseases. It is shameful that their public health importance has not already attracted more effort to reduce the horrific Since 1973, publications on schistosomiasis have quoted a worldwide prevalence of approximately 200 million.Today, Seven NTDs listed (marked with a star) in infect this is likely to be the minimum because the stool examination many millions of the poorest of the poor (‘the bottom billion’), and urine test which leads to these figures are so insensitiv and many infected individuals suffer the indignity of co- Since 1971, the global distribution of schistosomiasis has changed because China, Egypt and Brazil have all embarked on The G8 and G20 have committed to reaching the Millen- effective control programmes. The numbers infected in these nium Development Goals (MDGs) by 2015, but how three countries have declined sharply. Sadly, as the population can these goals be achieved when so many people suffer in Sub-Saharan Africa has increased, so has the number of parasitic infestaHow can poverty be reduced (MDG1) infected people on this continent. In 2011, approximately 85% when a billion people are caught in the cycle of poverty and of all cases of schistosomiasis (over 200 million) are found in disease: NTDs promote poverty and poverty promotes NTDs.
Sub-Saharan A very strong and convincing case has How can universal primary education be achieved (MDG2) been made for an upward revision of the disability weighting when millions of children are undernourished and stunted? Many children are hungry and anaemic, and have their The subtle morbidity caused by early and low-intensity long- cognitive ability impaired because they are infected with one term infections has previously been ignored but is significant.
or more intestinal worms. Children suffer because the worms Equally, several more serious conditions (bladder fibrosis, liver consume the food that the child eats and/or feed off blood fibrosis, portal hypertension) and deaths that occur many years from the Infected children are too weak to go to school after infection (bladder cancer, haematemesis) are often not or unable to concentrate when they are there. These children recognized as being due to childhood infection with schistoso- are frequently labelled as ‘lazy’ or ‘unintelligent’ when in fact miasis. Finally, urogenital schistosomiasis causes cervical they have been parasitized since an early age.
lesions which may lead to higher infections with HIV among How can child mortality be reduced (MDG4) and maternal younger women; all this when schistosomiasis is preventable health be improved (MDG5) when one of the major causes of poor birth outcomes is anaemia, caused in turn by the para- Two NTDs (trachoma and onchocerciasis) cause blindness e sitic infections carried by millions of women of childbearing the former simply because after a Chlamydia infection and conjunctivitis, the eyelashes turn down and scrape the cornea.
This is so easily prevented, yet an estimated 8 million peopletoday are unnecessarily visually impaired. Today, eliminationcampaigns are being led by governments and non-government organizations (NGOs) using the SAFE strategy and drugs donated by Pfizer through the International Trachoma Initiative 1. Eradicate extreme poverty and hunger.
). Onchocerciasis (river blindness) does not 2. Achieve universal primary education.
3. Promote gender equality and empower women.
cause anywhere near as much blindness today compared with 60 years ago thanks to two programmes e the Onchocerciasis Control Project, and its successor, the African Programme for the 6. Combat HIV/AIDS, malaria and other diseases.
Control of Onchocerciasis (APOC). Meanwhile, in the Americas, 7. Ensure environmental sustainability.
onchocerciasis is close to elimination because of the Oncho 8. Develop a global partnership for development.
Elimination Programme for the Americas. This success is due to Force for Global Health (in Atlanta), several drug donation pro- Table 3 e More accurate estimation of disability-adjusted grammes are now in place ). As such, the pharmaceu- life years (DALYs) attributed to neglected tropical tical industry has laid the foundation for either disease elimination or morbidity control of six of the seven diseases All that is needed is the funding for in-country logis- tics: mapping; planning; training, information, education and communication materials; drug distribution; and monitoring and evaluation. It has been estimated that, on average, a cost of $0.50 per person per year would fund the programmes in full, and even less would be needed in areas free of schistosomiasis.
In Uganda, the overall economic cost per child treated in six districts was US$0.54, and the cost-effectiveness was US$3.19per case of anaemia avertedFor Sub-Saharan Africa witha total target population of approximately 500 million, an esti- the donation of ivermectin (Mectizan) by Merck. Back in 1960, mated $1.5e2 billion over the next 7 years would probably be people living and working on vast tracts of land near the major enough to take these diseases off the burden of disease list.
rivers in Africa were so heavily infected that over 50% of middle- Already, thanks to WHO’s leadership and financial donations aged adults were blind due to the migrating larvae of the from the US Agency for International Development (USAID), the onchocerciasis worm. What disability weighting do these NTDs UK Department for International Development, and the Bill and Melinda Gates Foundation, progress has been made. By 2010, 600 Lymphatic filariasis (LF) does not kill, but for many years, million people were receiving albendazole every year against LF.
the millions of sufferers with grossly deformed limbs and the In Africa, almost 100 million every year also receive Mectizan, men with hydrocoeles probably wished that they were not while in the Far East and Indian subcontinent, albendazole is forced to live with their afflictions. For different reasons, both given with diethylcarbamazine. Within 6 years of these annual men and women were denied marriage and were unable to drug distributions, LF transmission should cease, as has been work. They hid their shame caused by their swollen, infected achieved in Egypt and on Zanzibar. Surgery for hydrocoeles and and disfigured limbs and scrotum. Globally, approximately more washing of deformed limbs is needed to complete the 600 million individuals are still at risk of contracting LF, an elimination of LF. One word of warning for areas where the estimated 120 million are infected and some 40 million suffer filarial worm Loa Loa is prevalent e albendazole and Mectizan can cause serious adverse events if dispensed to an individual This article has not touched upon the horrific consequences infected with L. Loa. This has delayed national coverage of LF of some other NTDs, including leprosy, Chaga’s disease, rabies, control in several countries in Africa, including Cameroon and sleeping sickness, leishmaniasis and buruli ulcer.
the Democratic Republic of the Congo.
Returning to the seven NTDs described in detail, their APOC with NGO partners is helping the governments of 19 contribution to the 56.6 DALYs is so unnecessary. There are safe countries to deliver 40 million doses of Mectizan every year to oral drugs that, if delivered annually, can remove these diseases prevent onchocerciasis. The elimination of onchocerciasis by as a major public health problem. However, these drugs are increasing the frequency of drug deliveries is currently being unaffordable for the billion people who are infected, who live on tested. In the Americas, the elimination of onchocerciasis is less than $2 per day. The pharmaceutical industry has now almost complete thanks to the efforts of the gvernments, the recognized this fact, and in conjunction with WHO and the Task CarterCenter and Mectizan donations.
Table 4 e Contribution of the pharmaceutical industry to the control of neglected tropical diseases.
Reconfirmed their commitment to donate Mectizan for as long as neededfor both onchocerciasis and filariasis in Africa.
Already donated almost 2 billion tablets of albendazole for lymphatic filariasisand will continue until elimination is achieved.
In October 2010, they committed an additional 400 million tablets per year for5 years to deworm school-aged children in Africa.
Donated up to 50 million tablets of mebendazole per year for intestinal wormsfor several years. Next year, this will be increased to 200 million tablets per year.
Committed to provide doses of azithromycin for trachoma.
In 2009 alone, they donated 50 million. In 2011, that number will reach 70 million.
Committed to provide multidrug treatment for leprosy.
In October 2010, EISAI committed to provide 2 billion tablets of diethylcarbamazinefor lymphatic filariasis which is used with albendazole outside of Africa.
Both Medpharm (a generic manufacturer) and E. Merck have donated praziquantel. E. Merckhave committed to provide 200 million tablets over 10 years.
Meanwhile, the International Trachoma Initiative acts as the agent to assist Pfizer with their donation of Zithromaxagainst trachoma. In 2011, it is estimated that 70 million doseswill reach populations with trachoma, and elimination after 3 1. World Bank. World Development Report 1993: investing in health.
years of treatment is possible as proven in Morocco.
New York: Oxford University Press; 1993.
The prevalence and intensities of intestinal worms have 2. Murray CJL, Lopez AD, editors. The global burden of disease: already been reduced by the LF elimination campaign because a comprehensive assessment of mortality and disability fromdiseases, injuries and risk factors in 1990 and projected to 2020.
albendazole is a deworming drug. However, from 2012, an even Cambridge, MA: Harvard University Press on behalf of the greater effort will be made to deworm children after Glax- World Health Organization and the World Bank; 1996.
oSmithKlein pledged to make 400 million albendazole tablets 3. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJL.
available per year for school-aged children in Africa, and Global burden of disease and risk factors. New York: Oxford Johnson & Johnson increased their donation to 200 million mebendazole tablets per year for other parts of the world.
4. World Health Organization. Available at: Merck Serono have pledged 200 million praziquantel tablets to treat children against schistosomiasis over 10 years. However, 5. King CH, Bertino AM. Asymmetries of poverty: why global as this is only enough to treat 8 million children per year, there is burden of disease valuations underestimate the burden of a huge gap for widespread treatment of schistosomiasisFrom neglected tropical diseases. PLoS Negl Trop Dis 2008;2:e209.
2003 to 2007, the Bill and Melinda Gates Foundation funded the 6. Hotez PJ, Fenwick A, Savioli L, Molyneux DH. Rescuing the Schistosomiasis Control Initiative (SCI) at Imperial College to bottom billion through control of neglected tropical diseases.
deliver over 50 million doses of praziquantel to six countries in 7. Hotez P, Daar AS. The CNCDs and the NTDs: blurring the lines Africa, and Geneva Global/Legatum have funded control in dividing noncommunicable and communicable chronic Burundi and Rwanda. Both USAID and the UK Department for diseases. PLOS Neg Trop Dis 2008;2:1e3.
International Development have awarded contracts for NTD 8. Fenwick A, Molyneux D, Nantulya V. Achieving the control, and SCI will deliver 75 million treatments over the next 5 Millennium development goals. Lancet 2005;365:1029e30.
years to eight countries. The World Bank is supporting control in 9. Hall A, Hewitt G, Tuffrey V, de Silva N. A review and Yemen. USAID funding may well double that number provided meta-analysis of the impact of intestinal worms on child growth and nutrition. Matern Child Nutr 2008;4(Suppl. 1):118 The way forward now is the integration of control efforts 10. Smith JL, Brooker S. Impact of hookworm infection and with the different programmes coming together to deliver deworming on anaemia in non-pregnant populations: a package of drugs against NTDs. Barriers to continent-wide a systematic review. Trop Med Int Health 2010;15:776e95.
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Schistosomiasis and water resources development:systematic review, meta-analysis, and estimates of people atrisk. Lancet Infect Dis 2006;6:411.
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17. Stoever K, Molyneux D, Hotez P, Fenwick A. HIV/AIDS, The author is very grateful to Professor Charles King, Professor schistosomiasis, and girls. Lancet 2009;373:2025e6.
Peter Hotez, Dr Wendy Harrison and Dr Simon Brooker for 18. Brooker S, Kabatereine NB, Fleming F, Devlin N. Cost and cost-effectiveness of nationwide school-based helminthcontrol in Uganda: intra-country variation and effects of scaling-up. Health Policy Plann 2008;23:24e35.
19. Fenwick A. Waterborne infectious diseasesdcould they be consigned to history? Science 2006;313:1077e81.
20. Hotez PJ, Engels D, Fenwick A, Savioli L. Africa is desperate for 21. Molyneux DH, Hotez PJ, Fenwick A. Rapid-impact interventions: how a policy of integrated control for Africa’s neglected tropical diseases could benefit the poor. PLoS Med2005;2:1064e70.
22. Hotez PJ, Molyneux DH, Fenwick A, Kumaresan J, Sachs SE, Sachs JD, Savioli L. Control of neglected tropical diseases. N


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