Neglected diseases

A young boy from Panama suffering from Chagas disease. It has manifested as an acute infection with swelling of one eye (chagoma).

The neglected diseases are a group of tropical infections which are especially endemic in low-income populations in developing regions of Africa, Asia, and the Americas. Different organizations define the set of diseases differently. In sub-Saharan Africa, the impact of these diseases as a group is comparable to malaria and tuberculosis.^[1] Some of these diseases have known preventive measures or acute medical treatments which are available in the developed world but which are not universally available in poorer areas. In some cases, the treatments are relatively inexpensive. For example, the treatment for schistosomiasis is USD $0.20 per child per year.^[2] Nevertheless, control of neglected diseases is estimated to require funding of between US$2 billion to US$3 billion over the next five to seven years.^[3]

These diseases are contrasted with the big three diseases (HIV/AIDS, tuberculosis, and malaria), which generally receive greater treatment and research funding. The neglected diseases can also make HIV/AIDS and tuberculosis more deadly.^[4] However, some pharmaceutical companies have committed to donating all the drug therapies required and mass drug administration has been successfully accomplished in several countries.^[5]

List of diseases

Neglected tropical diseases include in order of decreasing prevalence:^[6]

• Soil transmitted helminths, including:
  • roundworms such as Ascaris lumbricoides which causes ascariasis;
  • whipworm which causes trichuriasis;
  • hookworms which, depending on the species, cause necatoriasis and ancylostomiasis.
• Snail fever (schistosomiasis)
• Elephantiasis (Lymphatic filariasis)
• Trachoma
• River blindness (onchocerciasis)
• Kala-azar black fever (and other clinical forms of leishmaniasis)
• Chagas disease (American trypanosomiasis)
• Leprosy
• African sleeping sickness (Human African Trypanosomiasis)
• Guinea-worm (dracunculiasis)
• Buruli ulcer

The World Health Organization (WHO) list of neglected tropical diseases also adds the following additional diseases: Cysticercosis, Dengue/dengue haemorrhagic fever, Echinococcosis, Fascioliasis, Rabies , Yaws; and includes two other 'neglected' conditions’: Podoconiosis (also known as elephantiasis) and Snakebite.^[7]

Trypanosomal parasites

• Kala-azar (visceral leishmaniasis, a severe form of leishmaniasis) - Treatments exist, most of them costly and/or toxic. Resistance to pentavalent antimonials is spreading in parts of India. Disease is fatal if untreated. Vaccines are under development as of 2006. Infection is spread by the bite of sandflies.
• African sleeping sickness (African trypanosomiasis) - In 2009, the reported number of new cases of this disease fell below 10,000 for the first time in 50 years.^[8] Treatments exist, but have not changed much since colonial times due to lack of further research. The current forms of treatment are ineffective, highly toxic and resistance is spreading. This disease is always fatal if untreated but the outcome is often the same with the existing treatment. Infection is spread by the bite of the tsetse fly.
• Chagas disease (American trypanosomiasis) - No vaccine exists for Chagas disease. Treatment for early infection exists but is uneconomical and not authorized as such, current drugs have severe side effects. Chagas disease does not kill victims rapidly, instead causing years of debilitating chronic symptoms. Bites from South American assassin bugs allow the disease to spread.

Worm (helminth) parasites

• Schistosomiasis - Inexpensive praziquantel can treat this disease, but cannot prevent reinfection. Other treatments are harder to obtain in the developing world. Multiple vaccines are under development. Schistosoma species have a complex life cycle that alternates between humans and freshwater snails; infection occurs upon contact with contaminated water. This disease is unique in that damage is not caused by the worms themselves, but rather by the large volume of eggs that the worms produce.^[9]
• Lymphatic Filariasis (causes elephantiasis) - Effective antihelminthic treatments have been widely used in a cost-effective manner ^[10]
• Onchocerciasis (river blindness) - Antihelminthic treatment exists, prevention may also involve insect control.
• Drancunculiasis (guinea worm) - Preventable by water filtration, case containment, and increased access to safe water. An eradication program has been under way since 1989. So far, all but 4 countries worldwide have eliminated transmission and annual cases have been reduced from ~3,500,000 in 1986 to 3,190 in 2009.^[11]

Soil-transmitted helminthiases

• Ascariasis (roundworm) - Antihelminthic treatments exist, prevention involves food and sewage sanitation
• Trichuriasis (whipworm) - Antihelminthic treatments exist, prevention involves food and sewage sanitation
• Hookworm - Antihelminthic treatments exist, prevention involves food and sewage sanitation
• Strongyloidiasis - Antihelminthic treatments exist, prevention involves sewage sanitation and prevention of malnutrition

Bacterial infections

• Leprosy - Antibiotic treatments exist which can clear the infection; BCG vaccine has some preventative effect.
• Buruli ulcer - Surgical and antibiotic interventions are recommended
• Noma - Antibiotics in early phase prevents spreading of Noma. After 2–3 weeks, surgical interventions become necessary.
• Trachoma - Antibiotic treatments exist, prevention involves interpersonal hygiene
• Cholera - Cholera is caused by Vibrio cholerae bacteria living in contaminated drinking water. The disease presents with severe, watery diarrhea after a short incubation period lasting from zero to five days. Cholera is especially dangerous because it can kill patients in less than 24 hours from rapid dehydration. Antibacterial treatments can cure the disease, but most effective is isotonic fluid replacement therapy, which reduces deaths to 1% of cases. Cholera can be prevented with limited efficacy by two oral vaccines, but access to clean drinking water provides a guarantee of prevention.

Viral infections

• Yellow fever - A vaccine exists for Yellow fever. Yellow fever, like some other neglected diseases, is caused by a flavivirus. It is not generally transmissible between humans except presumably through fluid transfer, so patient isolation is not required. In a minority of cases it is hemorrhagic. Thus, due to increased tendency to bleed, and possible blood in the vomitus, standard precautions for caregivers (like gloves and washing with soap) should be applied.
• Dengue fever - Dengue fever is also caused by a flavivirus, and is spread by the bite of the A. Aegypti mosquito. Dengue fever is not usually fatal, but infection with one of four serotypes can increase later susceptibility to other serotypes, resulting in the highly dangerous Dengue hemorrhagic fever (DHF). No treatment for either type of disease exists beyond palliative care.
• Japanese Encephalitis - A vaccine exists for Japanese Encephalitis. Japanese Encephalitis is caused by a flavivirus. The disease is spread by Culex tritaeniorhynchus mosquitoes. It is not transmissible between humans, except presumably through fluid transfer, so patient isolation is not required.

Incentives for research and development

The U.S. Food and Drug Administration priority review voucher is an incentive for companies to invest in new drugs and vaccines for tropical diseases. A provision of the Food and Drug Administration Amendments Act (HR 3580) awards a transferable “priority review voucher” to any company that obtains approval for a treatment for one of the listed diseases. The voucher can later be used to accelerate review of an unrelated drug. This program is for all tropical diseases and includes medicines for malaria and tuberculosis. The first voucher given was for Coartem, a malaria treatment.^[12] It does not use or define the term "neglected" though most of the diseases listed are often included on lists of neglected diseases.

The prize was proposed by Duke University faculty Henry Grabowski, Jeffrey Moe, and David Ridley in their 2006 Health Affairs paper: "Developing Drugs for Developing Countries."^[13] In 2007 United States Senators Sam Brownback (R-KS) and Sherrod Brown (D-OH) sponsored an amendment to the Food and Drug Administration Amendments Act of 2007. President George W. Bush signed the bill in September 2007.

Biotechnology companies in the developing world have targeted neglected tropical diseases due to need to improve global health.^[14]

Anacor Pharmaceuticals, located in Palo Alto, California, is a biopharmaceutical company with a unique chemistry platform using the element boron in its therapeutic compounds. Its boron chemistry platform appears to be well suited for the treatment of neglected diseases therefore Anacor has partnered with several not-for-profit organizations to discover therapies for these diseases. Anacor currently has partnerships with Drugs for Neglected Diseases Initiative to develop new therapeutics for African Sleeping Sickness, Visceral Leishmaniasis, and Chagas Disease; Medicines for Malaria Venture to develop new therapeutics for the treatment of malaria; the TB Alliance to explore therapeutics for tuberculosis; UCSF's Sandler Center to identify a drug candidate for River Blindness; and the Institute for OneWorld Health to identify antibacterial compounds to treat shigellosis, or bloody diarrhea.

See also

• Contagious disease
• Drugs for Neglected Diseases Initiative
• Global Network for Neglected Tropical Diseases
• Neglected Tropical Disease Research and Development
• Orphan diseases

References

1. ^ P. J. Hotez, A. Kamath. "Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence, Distribution, and Disease Burden". Public Library of Science. http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000412. Retrieved 11 December 2009. 
2. ^ "Making the Case to Fight Schistosomiasis". National Public Radio. http://www.npr.org/templates/story/story.php?storyId=7806977. Retrieved 2008-12-01. 
3. ^ P.J.Hotez. "How To Cure 1 Billion People? -- Defeat Neglected Tropical diseases". Scientific American. http://www.scientificamerican.com/article.cfm?id=a-plan-to-defeat-neglected-tropical-diseases. Retrieved 1 January 2010. 
4. ^ Mike Shanahan (31 January 2006). "Beat neglected diseases to fight HIV, TB and malaria". SciDev.Net. http://www.scidev.net/News/index.cfm?fuseaction=readNews&itemid=2629&language=1. 
5. ^ Reddy M, Gill SS, Kalkar SR, et al. Oral drug therapy for multiple neglected tropical diseases.JAMA 2007;298(16):1911-1924 [1]
6. ^ World Health Organization, apud Reddy M et al.:"Key Features of 13 Neglected Tropical Diseases Listed by Prevalence - 2007". The Journal of the American Medical Association. http://jama.ama-assn.org/content/298/16/1911/T1.large.jpg. Retrieved 2011-09-17. 
7. ^ World Health Organisation: Diseases covered by NTD Department. http://www.who.int/neglected_diseases/diseases/en/
8. ^ "Human African Trypanosomiasis: number of new cases falls to historical low in 50 years". http://www.who.int/neglected_diseases/integrated_media/integrated_media_hat_june_2010/en/index.html 
9. ^ "Schistosomiasis Fact Sheet". CDC, Division of Parasitic Diseases. http://www.cdc.gov/ncidod/dpd/parasites/schistosomiasis/factsht_schistosomiasis.htm. Retrieved 2008-12-03. 
10. ^ Mohammed KA, Hail HJ, Gabrielli AF. et al. (2008). Utzinger, Juerg. ed. "Triple Co-Administration of Ivermectin, Albendazole and Praziquantel in Zanzibar: A Safety Study". PLoS Negl Trop Dis 2 (1): e171. doi:10.1371/journal.pntd.0000171. PMC 2217668. PMID 18235853. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2217668. 
11. ^ World Health Organisation. Weekly Epidemiology Record 85, no 19, p. 166: Dracunculiasis eradication - global surveillance summary, 2009. World Health Organization. http://www.who.int/entity/wer/2010/wer8519.pdf. Retrieved 2010-05-14 
12. ^ "FDA Approves Coartem Tablets to Treat Malaria". USFDA. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149559.htm. Retrieved 11 December 2009. 
13. ^ Developing Drugs For Developing Countries - Ridley et al. 25 (2): 313 - Health Affairs
14. ^ Frew SE, Liu VY, Singer PA (2009). "A business plan to help the 'global South' in its fight against neglected diseases". Health Aff (Millwood) 28 (6): 1760–73. doi:10.1377/hlthaff.28.6.1760. PMID 19887417. http://siteresources.worldbank.org/EDUCATION/Resources/278200-1099079877269/547664-1099079975330/Peter_Singer_Neglected_Tropical_Diseases.pdf. 

External links

• Global Network for Neglected Tropical Diseases
• Neglected Tropical Disease Control Program RTI/USAID $100,000,000 Program to Treat 40,000,000 People
• The Global Network for Neglected Tropical Diseases (Sabin Vaccine Institute)
• Taking on The Neglected Diseases, WorldChanging
• Nigeria's Neglected Disesaes, National Public Radio, 3-part series. March 12–13, 2007.
• International Trachoma Initiative,
• Cure for Neglected Diseases: Funding
• Malaria, the Mostly Forgotten Killer
• Whose health revolution?
• Public Library of Science NTDs, open-access journal on Neglected Tropical Diseases
• Drugs for Neglected Diseases initiative, a non-profit product development partnership for the R&D of new treatments for the most neglected diseases
• BVGH Global Health Primer, a detailed analysis of the pipeline for new drugs, vaccines, and diagnostics for NTDs