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PHP 2013: Visceral Leishmaniasis: Good Value for Money in Saving Lives

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Epidemiology

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File:Geographical distribution of visceral leishmaniasis in the Old and New world.jpg
Geographical distribution of visceral leishmaniasis in the Old and New world.jpg

Disease Leishmaniasis is caused by several species of protozoan parasites, Leishmania, and is transmitted to humans through sandflies which are very small insect vectors with a range of habitats.[1] The disease comes in three forms: cutaneous, mucocutaneous and visceral. The first two result in severe skin or muco-membranous lesions and high morbidity, and consequently high DALYs (Disability Adjusted Life Years). Visceral Leishmaniasis (VL), also known as kala azar, rarely results in long-term illnesses, however, if left untreated, patients have a fatality rate of 100% within two years.[2] The symptoms are high fever, substantial weight loss, swelling of the spleen and liver, and anaemia. However, these symptoms are frequently confused with malaria and/or other tropical diseases, which overlap in endemic regions. [3] Co-infection with HIV can deteriorate the health conditions of patients very quickly, as HIV progression to AIDS is accelerated, and VL patients are particularly vulnerable to HIV infections. [4] [5]

Diagnosis and Treatment


The standard test in diagnosis is visualisation of amastigotes from bone marrow or splenic aspirates. This procedure is inconvenient and requires professionally trained personnel.[6] [7] A dipstick test, recombinant K39, based on antigen recognition has been developed for VL and tested in VL-endemic regions. It was compared against direct agglutination test(DAF), a less convenient and more expensive test, and was found to be more sensitive and confirmed results from bone marrow positive patients. [8] Antimonials are the primary drugs used to treat visceral Leishmaniasis. The application requires several weeks’ hospital admission and has many adverse side-effects including nausea and abdominal pains; long term use may also lead to cardiotoxicity. Drug resistance has become a severe problem. An alternative is amphotericin B, which also have limited range of application, many side-effects and is about five-times more expensive. However, it is highly effective against VL. [9] There are no vaccines currently available against human VL, but vaccines against canine leishmaniasis have been devised and shown to be effective.[10]

Global burden of disease

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VL is the second biggest parasitic killer worldwide and is responsible for an estimate of 500,000 annual deaths. [11] Over 90% of VL cases are found in six countries, Bangladesh, Brazil, India, Nepal, Sudan and Ethiopia. [12] Despite the high fatality rates, the disease is severely under-reported, and disease mapping has thus been both difficult and inaccurate. [13] VL can cause large-scale epidemics. [14] In 1989, VL struck an area in Sudan where no immunity was present against a background severe malnutrition, one of the factors associated with heavy VL burdens in developing countries. Mortality rate was estimated to be over 90%.[15] Dense populations are a prerequisite for the disease to persist and circulate. Newly emerged cities in South America, e.g., Brazil and Argentina, have witnessed an increase in VL cases. [16]

Current funding situation

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The neglected tropical diseases impact on the world’s poorest people[17] , and receive a disproportionately low amount of funding for the DALYs and mortalities. In 2008, IDRI (Infectious Disease Research Institute) awarded grant of 3-year, $7 million to fight visceral Leishmaniasis in Africa to develope new methods for diagnosis and care management for patients. [18] Preventative measures through applying currently available technologies can help reduce mortalities and DALYs.


Good Value for Money in Saving Lives

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Background

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Cost-effectiveness analysis (CEA) and realisability CEA has rarely been considered as a priority for fund raising on disease budgets. It is a measure of the number of life years averted per US dollar spent.[19] VL is ranked the third most cost-effective infectious disease in low to medium-income countries to manage. [20] In Sudan, it also showed a cost-effectiveness ratio of US$18.4 (a ratio below US$25 is considered “a very good value for money”). [21]

Justification

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CEAs can vary considerably among different local communities, however, where VL are endemic, labour costs more likely to be low. We also feel that the WHO’s “five approaches to reduce incidences rates in endemic countries” [22] need specification, therefore we are focussed on two aspects, diagnosis and education, that can potentially bring huge change.

Proposal

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Diagram of the interplay of factors that affect risk of kala-azar and asymptomatic Leishmania donovani infection in South Asia

Intensify efforts in disease diagnosis and mapping Leishmaniasis used to be difficult to diagnose. Professional knowledge was required for identification through slide-reading. However, currently available dipstick tests are cheap (about 1/5 price compared to DAT) and sensitive.[23] This will help reduce the uncertainties in disease diagnosis and hopefully lower the ratio of actual (estimated) and reported disease incidence. [24] Yet, the dipstick test is limited when used in disease endemic regions or when co-infection with HIV occurs, therefore professional personnel are still needed to correctly read and interpret results from slides. In this plan, we expect to divert budget on training so that diagnostic accuracy could be raised. We also propose to establish an automated reporting system in developing countries through utilising the internet and mobile networks. The precedent in malaria has witnessed a great success which helped accurate mapping and concentration of resources.

Education and public awareness Sandflies are too small to be kept out with bed nets. Indoor residual spraying (IRS) is a much more effective approach that kills the disease vector, though the attitude many households have is not very welcoming. Leishmaniasis also shows a high gender bias, with females much more likely to suffer from the disease but much less likely to seek medical help due to cultural or traditional reasons. Besides, isolation from domestic animals such as cattle or dogs reduces transmission significantly. Education on those aspects are urgently needed, and can be highly cost-effective.

Goals

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Our goal is, through coordinated system in automated reporting, to diagnose and treat newly emerged VL cases in early stages to reduce mortality. We expect to combine the information and map VL globally. We also expect to raise public awareness of VL and basic preventative measures. We hope to educate people, particularly in conservative societies where getting infected with VL is stigmatised, to recognise the disease critically and encourage them to seek medical help.

References

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  1. ^ "Parasite, Leishmaniasis, Centers for Disease Control and Prevention".
  2. ^ "Epidemiology & Risk Factors, Leishmaniasis-Parasites, Centers for Disease Control and Prevention".
  3. ^ "The disease and its epidemiology, Leishmaniasis, World Health Organisation".
  4. ^ Guerin; et al. (2002). "Visceral leishmaniasis: current status of control, diagnosis and management, and a proposed research and development agenda" (PDF). The Lancet. 2. {{cite journal}}: Explicit use of et al. in: |last= (help)
  5. ^ "Leishmaniasis and HIV co-infection, World Health Organisation".
  6. ^ "Diagnosis, Leishmaniasis, Centers for Disease Control and Prevention".
  7. ^ "Resources for health professionals, Leishmaniasis, Centers for Disease Control and Prevention".
  8. ^ Bern; et al. (2000). "Use of the recombinant K39 dipstick test and the direct agglutination test in a setting endemic for visceral leishmaniasis in Nepal". Am. J. Trop. Med. Hyg. {{cite journal}}: Explicit use of et al. in: |last= (help)
  9. ^ Guerin; et al. (2002). "Visceral leishmaniasis: current status of control, diagnosis and management, and a proposed research and development agenda" (PDF). The Lancet. 2. {{cite journal}}: Explicit use of et al. in: |last= (help)
  10. ^ "Resources for health professionals, Leishmaniasis, Centers for Disease Control and Prevention".
  11. ^ Desjeux P. (2001). "The increase of risk factors for leishmaniasis worldwide". Transactions of the Royal Society of Tropical Medicine and Hygiene. 95 (3): 239–43. doi:10.1016/S0035-9203(01)90223-8. PMID 11490989. {{cite journal}}: Cite has empty unknown parameter: |month= (help)
  12. ^ Alvar; et al. (2012). "Leishmaniasis Worldwide and Global Estimates of Its Incidence". PlosOne. 7 (5). {{cite journal}}: Explicit use of et al. in: |last= (help)
  13. ^ "Magnitude of the problem, Leishmaniasis, World Health Organisation".
  14. ^ "Response, Leishmaniasis, World Health Organisation".
  15. ^ Greekspoor; et al. (1999). "Cost-Effectiveness Analysis of Humanitarian Relief Interventions: Visceral Leishmaniasis Treatment in the Sudan". Health Policy and Planning. 14 (1). {{cite journal}}: Explicit use of et al. in: |last= (help)
  16. ^ "Response, Leishmaniasis, World Health Organisation".
  17. ^ Feasey; et al. (2009). "Neglected tropical diseases". British Medicine Bulletin. 93 (1). {{cite journal}}: Explicit use of et al. in: |last= (help)
  18. ^ "IDRI Awarded Grant to Fight Visceral Leishmaniasis in Africa".
  19. ^ Greekspoor; et al. (1999). "Cost-Effectiveness Analysis of Humanitarian Relief Interventions: Visceral Leishmaniasis Treatment in the Sudan". Health Policy and Planning. 14 (1). {{cite journal}}: Explicit use of et al. in: |last= (help)
  20. ^ (Editor) Jamison; et al. Disease Control Priorities in Developing Countries, 2nd edition. ISBN 0-8213-6179-1. {{cite book}}: |last= has generic name (help); Explicit use of et al. in: |last= (help)
  21. ^ Greekspoor; et al. (1999). "Cost-Effectiveness Analysis of Humanitarian Relief Interventions: Visceral Leishmaniasis Treatment in the Sudan". Health Policy and Planning. 14 (1). {{cite journal}}: Explicit use of et al. in: |last= (help)
  22. ^ "Surveillance and control of leishmaniasis, World Health Organisation".
  23. ^ Bern; et al. (2000). "Use of the recombinant K39 dipstick test and the direct agglutination test in a setting endemic for visceral leishmaniasis in Nepal". Am. J. Trop. Med. Hyg. {{cite journal}}: Explicit use of et al. in: |last= (help)
  24. ^ Guerin; et al. (2002). "Visceral leishmaniasis: current status of control, diagnosis and management, and a proposed research and development agenda" (PDF). The Lancet. 2. {{cite journal}}: Explicit use of et al. in: |last= (help)