Some perspectives of dynamics of leishmaniasis infection in poor nations by

1. Some perspectives of dynamics of leishmaniasis infection in poor nationsby J.Y.T. Mugisha* & Ibrahim M.ELmojtaba+ *Biomathematics Group, Makerere University +University of Khartoum, Faculty of Mathematical Sciences A paper presented at DIMACS Workshop on Economic epidemiology, Makerere University, 3 – 5 August, 2009 Department of Mathematics, www.math.ac.ug

2. What is Leishmaniasis • parasitic disease Transmitted by a bite of the infected female sand fly, that is usually infected with one species of Leishmania • About 30 species of sand flies can become infected when taking a blood meal from a reserviour host. • Most of the leshmaniasises are zoonotic (transmitted from to human from animals esp. dogs) • The human becomes a sole reservoir if the transmission is anthroponotic Department of Mathematics, www.math.ac.ug

3. Forms of the disease • Visceral leishmaniasis, (also known as kala-azar) the most severe form in which the parasites migrate to vital organs, and potentially fatal if un treated • Cutaneous leishmaniasis, the most common form which causes a sore on the site of bite which heals in few months to a year leaving unpleasant scar • Diffuse cutaneous leishmaniasis that produces wide spread skin lesions (similar to leprosy) and very difficult to treat, never heals spontaneously and tends to relapse after treatment • Mucocutaneous leishmaniasis that starts with an ulcer which spreads causing tissue damage esp. nose, mouth There is also the Post-kala- azar dermal leishmaniasis (PKDL) that is an illness condition got after cutaneous (with depigmented eruptions mainly on the face, arms, feet, upper part of the trunk etc) Department of Mathematics, www.math.ac.ug

4. Symptoms-V Leishmaniasis In children Vomiting, Diarrhea, Fever, Cough In adults Fever for 2 weeks to 2 months, along with fatigue, Weakness, Night sweats, Weight loss etc… Department of Mathematics, www.math.ac.ug

5. Symptoms-C Leishmaniasis • Skin sores • Skin ulcer • Erosion of tissue on the mouth, tongue, gums, lips, nose and inner nose • Swallowing difficulty • Stuffy nose, runny nose, nosebleeds Department of Mathematics, www.math.ac.ug

6. The disease • The disease begins as an erythematous papule at the site of the sand fly bite on exposed parts of the body. The papule increases in size and becomes a nodule. It eventually ulcerates and crusts over. The border is usually raised and distinct. There may be multiple lesions, especially when the patient has encountered a nest of sand flies. • The ulcer is typically large but painless unless there is secondary bacterial or fungal infection Department of Mathematics, www.math.ac.ug

7. Disease… • The mucosal form usually occurs after an initial cutaneous infection and they usually begin in the nose or palate (WHO fact sheet, 2003). • Lesions progress to destruction of mucosa and even cartilage. They result in scarring and disfigurement and can cause pulmonary aspiration and death. Department of Mathematics, www.math.ac.ug

8. Deformities • Cutaneous leishmaniasis can become disseminated (diffuse cutaneous leishmaniasis), especially in immunosuppressed persons. This can result in deformities and disfiguring of the face • This illness can go on for years. Patients with human immunodeficiency virus (HIV) infection are particularly susceptible. Department of Mathematics, www.math.ac.ug

9. Distribution • Although cutaneous leishmaniasis can be traced back many hundreds of years, one of the first and most important clinical descriptions was made in 1756 by Alexander Russell following an examination of a Turkish patient • Mainly a disease of Developing world and rarely known in developed world • Now endemic in 88 countries on five continents. Bangladesh, Brazil, India,, Nepal, Sudan, Peru, Saudi Arabia, Syria, Afghanistan, Iran (check WHO sheet for numbers) Department of Mathematics, www.math.ac.ug

10. CutaneousLeishmaniasisdistribution Department of Mathematics, www.math.ac.ug

11. Distribution examples cont… Distribution of cutaneous leishmaniasis causedby L. major with a rodent reservoir Department of Mathematics, www.math.ac.ug

12. Distribution Cont… • Distribution of Leishmania species causingcutaneous Leishmaniasis in Central and South America Department of Mathematics, www.math.ac.ug

13. Public Health Concerns • WHO estimated that the global prevalence of all forms of these diseases is 12 million cases and that the annual incidence is 1.5 - 2 million cases. • Of human diseases caused by protozoan parasites, visceral leishmaniasis alone comes second in public health importance (after malaria) as measured by DALYs (Disability Adjusted Life Years) (Markle & Makhoul (2004) ). Department of Mathematics, www.math.ac.ug

14. Public concerns… • Cutaneous leishmaniasis occurs throughout the Americas from Texas to Argentina, and in the Middle East and North Africa. The condition is diagnosed every year in travelers, immigrants, and military personnel. It is endemic in 88 countries throughout Africa, Asia, Europe, and North and South America (Dedet and Pratlong, 2003). • There are an estimated 12 million cases worldwide, with 1.5 to 2 million new cases each year. Leishmaniasis is a disease associated with rural areas and poverty, but it has adapted to the urban environment as well. Department of Mathematics, www.math.ac.ug

15. Public Concerns… • As a disease very closely associated with poverty, leishmaniasis usually affects the poorest people of the poorest countries; 72 of 88 countries affected are developing and 13 of them are among the least developed. It is here where more than 80% of the population earns less than US$2 per day (Davis et al 2003). Department of Mathematics, www.math.ac.ug

16. Control of Leishmaniasis • No effective vaccine exists against the disease and no prophylactic drugs. • Treatment is expensive and frequently followed by a relapse. • Current means of control are aimed at the sand fly vectors • No preventive vaccines or drugs (Reithinger, 2007) Department of Mathematics, www.math.ac.ug

17. Control… Vector control • Insecticide spraying • Genetic control • Biological control • Chemical control Are these manageable in poor countries? Department of Mathematics, www.math.ac.ug

18. Intervention targets • Control of animal reservoirs • Drugs • Vaccine • Personal protection • Vaccine • Repellents • Early diagnosis and treatment Department of Mathematics, www.math.ac.ug

19. Exams and Tests Tests include:- • Biopsy of the spleen and culture • Bone marrow biopsy and culture • Direct agglutination assay • Skin Biopsy • Complete blood count • Montenegro skin test Department of Mathematics, www.math.ac.ug

20. Possible complications • Deadly infection due to immune system damage • Disfiguration • Hemorrhage (bleeding) • Treatment: Medicines called antimony –containing compounds, Amphotericin B, Pentamidine often expensive • Treatment cycle cost $30 - $120. • In case of relapse, patient needs to be treated with far more toxic second line medicine $60-$70 • Amphotericin B has no side effects but costs > $1500 • Plastic surgery unmanageable in developing countries • Removal of spleen (splenestomy) may be needed on drug-resistant cases, this is very expensive surgical process in many cases these countries have not theatres to carry out this procedure Department of Mathematics, www.math.ac.ug

21. Poverty trap • In some parts of Asia, a family in which there is a case of leishmaniasis is three times more likely to have sold its cow or rice field, than unaffected family; plunging it into a vicious circle of disease-poverty-malnutrition-disease! Department of Mathematics, www.math.ac.ug

22. Need for a cost-effective control exits • WHO report 2006: no well-defined cost-effective control exits. There is need to strengthen both active case detection and diagnostic capacity in rural health centres where most of the patients are usually treated • Cost of medication and cost of admission to hospitals as many of the drugs need intravenous admin • Unit costs of vector control and active case detection need to be synchronized • Costs associated with public training, surveillance etc • Mathematical model Department of Mathematics, www.math.ac.ug

23. Threat • Co-infection with other emerging infections rendering leishmaniasis a neglected disease of Africa Department of Mathematics, www.math.ac.ug

24. What are we doing? • Mathematical models • consider the dynamics of the disease between three different populations, -human host -animal reservoir and -vector population Department of Mathematics, www.math.ac.ug

25. Model Department of Mathematics, www.math.ac.ug

26. Basic reproduction number • numerical solution shows that human treatment is the key parameter in the disease control among human population, but is not sufficient to eliminate the disease, even if it is high and effective. • to eradicate the disease from the community high rate of human treatment should be followed by vector control strategies by either using treated bed-nets • or direct killing of sand flies, and reservoir control strategies either by killing all infective reservoirs • or by separating all reservoir from humans to a safe distance. Department of Mathematics, www.math.ac.ug

27. END.. THANK YOU and special thanks to DIMACS Department of Mathematics, www.math.ac.ug