Justifications:

Visceral leishmaniasis is now the first public health problem in Gadarif State for the following reasons:

1- The incidence of the disease is increasing and attaining epidemic levels (As in Tabarak Alla and Barber-elfugara areas). Previous reports indicated that at least 1,000 cases of V.L occur each year in Gadarif State and according to the current reports of Gadarif Ministry of Health, VL cases in endemic areas increased in 2014 to 2818 cases.

2- The disease is spreading to areas in which V.L was unknown previously.

3- Difficulty in effective control measures against V.L because of the high cost of prevention, management and insufficient epidemiological researches. Thus attempt to control the disease would be impossible without prior planning.

4- The disease affects the productive age groups and young children.

5- Increasing number of HIV and VL /HIV Co-infections is a problem in Gadarif state with increasing mortality.

6- Tuberculosis is a disease that spreading widely in Gadarif state, there is excess in positive cases estimated to be 1193 cases in 2014, which is regarded as one of the most important co-infections with VL.  

Literature review

Definition:-

Visceral leishmaniasis (VL), also called kala-azar, is a parasitic disease caused by members of the Leishmania donovani complex (L. donovani and L. infantum) and transmitted by the female phlebotomine sand flies of the genera Phlebotomus and Lutzomyia. It mainly affects areas in South Asia (India, Bangladesh, and Nepal) and Eastern Africa, where Sudan is the most affected country, followed by Ethiopia, Kenya, Somalia and Uganda. In Sudan, the causative agent is L. donovani, transmitted by the Phlebotomus orientalis.The is fatal if untreated.

Transmission:-

The sand flies feed on blood of animals and humans, which they need for developing their eggs. If blood containing leishmania parasites is drawn from an animal or human, the next person to receive a bite will then become infected and develop leishmaniasis. Months after this initial infection the disease can progress into a more severe form, called visceral leishmaniasis or kala azar.

Pathophysiology:-

The various forms of Leishmaniasis (cutaneous, visceral, mucocutaneous and post-kala-azar dermal) are caused by more than 20 different species of protozoa belonging to the genus Leishmania. Some who are infected remain asymptomatic while others progress to serious illness and death. At risk are those who are immunocompromised or malnourished. The promastigote (flagellated) form of the parasite multiplies in the gut of female sand flies after it has ingested the amastigote form an infected person (or animal). The promastigotes, which are injected into a human host while the sand fly is feeding, are phagocytised by macrophages where they return to an amastigote form. The amastigotes multiply within the macrophage’s phagolysosomes, protected from an immune response by the host. The incubation period in the human host can range from 10 days up to 2 years. In visceral leishmaniasis the parasite is able to multiply without suppression from the host’s immune system leading to complications affecting the spleen, liver, intestinal mucosa, bone marrow and lymph nodes. Hematopoiesis is depressed leading to pancytopenia, prothrombin becomes depleted (leading to bleeding complications when combined with thrombocytopenia), and decreased albumin predisposes the patient to edema. The host’s immune system becomes severely compromised as infection spreads and, if left untreated, most patients will die within 2-3 years often from intercurrent infections such as tuberculosis, pneumonia or dysentery.

Clinical finding:-

Many individuals infected by L. donovani have subclinical infection, while others develop clinical VL, a devastating illness that is usually fatal when left untreated. If the disease progresses, it attacks the immune system. In Sudan, clinical signs develop gradually 2 weeks to 1 year after infection (in most cases after 2 to 4 months). Typical features are persistent fever, splenomegaly, weight loss and lymphadenopathies [1]. Post-kala-azar dermal leishmaniasis (PKDL) is a skin rash appearing after VL treatment, affecting up to 50% of treated cases in Sudan [2]. PKDL usually appears within 6 months after apparent cure and can last for months or years. Leishmania parasites can be found in smears of the skin lesions, and PKDL lesions are suspected to be an important parasite reservoir for human-to-human transmission. In Sudan, most lesions heal spontaneously. If not, PKDL treatment is challenging [3].

Diagnosis:-

The most effective diagnostic tests for leishmaniasis are invasive and potentially dangerous, where tissue samples are taken from the spleen, lymph nodes, or bone marrow. These tests require lab facilities and specialists not readily available in resource-poor, endemic areas. The most common method of diagnosing kala azar is by dipstick testing. However, this method is highly problematic. In endemic areas, people can become infected with kala azar but it may not develop into the disease. Therefore, no treatment will be required. Unfortunately, dipstick testing only establishes whether a patient is immune to kala azar—so if the parasite is present it would appear that the patient has the disease. Because of this, dipstick testing can’t be used to see if the patient is cured, is re-infected, or has relapsed.

Treatment:-

There are different treatment options available for kala azar, with varying effectiveness and side effects. Pentavalent antimonials are usually the first line group of drugs, given as a 30 day course of intravenous injections. While antimonials are quite toxic and present a risk to patients receiving treatment, those who are cured for kala azar almost always develop immunity for life. Researchers hope to identify ways to simplify treatment regimes, improve their safety, and reduce the risk of drug resistance. Médecins Sans Frontières (MSF) has treated around 100,000 patients with kala azar. MSF is also campaigning for more research into suitable diagnostic techniques and affordable drugs to treat this neglected disease.

Visceral leishamaniasis in Sudan:-

Sudanese VL has been known since 1904 to be endemic along the Blue Nile where it lives Ethiopia and its tributaries[4]. The causative agent of VL in Sudan as in other regions of the Old World is L. donovani, and the main sandfly vector is Phlebotomus orientalis whose habitat is Acacia-Balanites woodland and black cotton soils[5,6] . Anthroponotic transmission is probably the main transmission cycle, especially during epidemics, because no animal species has yet been definitively identified as a reservoir[7]. Throughout the 20th century, VL has been reported in southern Sudan, and major outbreaks have followed population movement, flooding, food shortages, and conflict[8]. The worst recorded epidemic probably killed 100,000 people in the western Upper Nile area of southern Sudan from 1984–1994, a loss of one-third of the population of that area[9]. Médecins Sans Frontiéres–Holland has been running VL treatment centers since 1989, and 120,000 patients were treated by MSFH in southern Sudan between 1989 and February 2002[10].

Visceral leishamaniasis in Gadarif State:-

In January 2010, MSF, in collaboration with the Ministry of Health, opened a project in Al- Gadarif State in eastern Sudan to provide free treatment for kala azar, a parasitic disease caused by the bite of a sand fly. According to data from the Ministry of Health, the World Health Organization and MSF, Al- Gadarif State is the main endemic area of VL in Sudan. Passive detection figures from 1996 to 1999 have shown a mean yearly incidence between 6.6 and 8.4 VL cases per 1000 persons, with a large variation between villages (from 0 to 60 cases per 1000 persons per year) [1], [2]. Villages with high incidence are clustered along two rivers (Atbara and Rahad), in areas of low altitude and high rainfall. Leishmanin skin testing, a marker of past exposure to the disease, has been shown to be positive in 21.6% of the population of the Atbarah area [3].

Kala-azar- co-infections:-

HIV co-infection:-

Leishmaniasis is one of the opportunistic infections that attack HIV-infected individuals, most of the co-infection involves the visceral form of Leishmaniasis. Recently more notice has been taken of Leishmania/HIV co-infection. There is concern that Leishmania/HIV co-infection may increase the transmission of leishmaniasis, particularly the visceral form. The overlap in the geographical areas with high risk of both HIV and leishmaniasis is increasing, with the spread of leishmaniasis (typically a rural disease) into urban areas and the increased spread of HIV into rural areas. Leishmaniasis patients are highly susceptible to HIV infection and in HIV- infected patients, leishmaniasis accelerates the onset of AIDS by cumulative immuno-suppression and by stimulation of the replication of the virus. It also may change asymptomatic Leishmania infections into symptomatic ones. In addition, since visceral leishmaniasis can be spread intravenously, sharing of needles by intravenous drug users is a direct way of spreading leishmaniasis.(11)

TB co-infection:-

Co-infection of visceral leishmaniasis and pulmonary tuberculosis are increasing public health problem in eastern region of country. A large number of clinical cases of leishmaniasis – tuberculosis coinfection have been reported in Sudan. Such type of co-infections lead to decreased host's immune system. Although their etiology and transmission mechanism are different, they share several features. Tuberculosis is immunosuppressive condition that causes progression of latent leishmaniasis to clinical leishmaniasis, and visceral leishmaniasis can produce latent tuberculosis. Treatment of leishmaniasis depends on effective immune response which activates macrophages to produce nitric oxide for killing intracellular amastigotes.(12)  

Vision:-

As hopefully one of the unique centres in Sudan, East Africa and worldwide, the centre will be a nucleus for prevention & control, diagnosis, management, training and scientific researches in VL and VL co-infections.

Mission:-

The centre will be established to provide and implement strategies for prevention & control, diagnosis, scientific based management, training, researches in VL and VL co-infections and provision of other community services collaborating with national and international centres dealing with VL and VL co-infections.

Objectives: -

General objectives:-

1- To develop a nationally and internationally recognized centre of excellence in the field of research, training, prevention, diagnosis and management of VL and VL co-infections.

7- To provide an environment for the development and capacity building of health care cadre.

Specific Objectives-

1- To encourage researches in VL and other VL CO-infections in Gadarif state.

2- To train medical personnel in the field of prevention, diagnosis and management of VL and VL co-infections.

3- To train community volunteers in the field of prevention and vector control.

4- To provide medical services to the community.

5- To provide health services to the community.

6- To provide new protocols that help in proper management of VL and VL co-infections.

7- Delivery of scintific consultation concering VL to governmental and private health sectors dealing with VL.

8- Publishing and dcumentation of scientific recommendation of researches regarding VL.

9- Participation in scientific national aind international conferances.  

Strategy :-

To fulfil the above mentioned objectives the following strategies should be made <3>The centre administrative structures:-

a. Director general

b. Deputy

c. The heads of the centre units ( academic ,technical, field stations staff and statistic Unit) vd. Secretary

e. Financial Unit

Gadarif Kala-azar Research Centre administrative Council

The chief of administrative Council director general- Ministry of health gadarif state Health committee – Gadarif legislative representative. Preventive medicine director- Ministry of health gadarif state Treatment director- Ministry of health gadarif state Medical directors of Kala-azar Centres- gadarif state Zakat chamber director gadarif state Kala-core and MSF representatives Kala-azar coordinator- Ministry of health gadarif state Ahamed Mohammed Al hassan centre representative Pharmacy administration representative- Ministry of health gadarif state Other NGOs dealing with kala-azar management representatives  

Structures of the centre:-

A building containing the following:

a. Multipurpose Laboratory

b. Lecture room

c. Library

d. Offices

e. Statistic and information uint

f. Transportation vehicles.

Non funding partners:-

1- Federal ministry of health

2- Gadarif state ministry of health

3- Institute of endemic diseases U of K

4- El -Hassan centre for tropical diseases

Funding partners:-

1- Gadarif state

2- Gadarif university

3- Ministry of high education & researches

4- Kala Core

5- WHO and other NGOs

6- Zakat chamber Gadarif state.  

References

1. Elnaiem DE, Schorscher J, Bendall A, Obsomer V, Osman ME, et al. (2003) Risk mapping of visceral leishmaniasis: the role of local variation in rainfall and altitude on the presence and incidence of kala-azar in eastern Sudan. AmJTropMedHyg 68: 10–17 [PubMed]

2. Ritmeijer K, Davidson RN (2003) Royal Society of Tropical Medicine and Hygiene joint meeting with Medecins Sans Frontieres at Manson House, London, 20 March 2003: field research in humanitarian medical programmes. Medecins Sans Frontieres interventions against kala-azar in the Sudan, 19. TransRSocTropMedHyg 97: 609–613 [PubMed]

3. Elnaiem DE, Mukhawi AM, Hassan MM, Osman ME, Osman OF, et al. (2003) Factors affecting variations in exposure to infections by Leishmania donovani in eastern Sudan. East MediterrHealth J 9: 827–836 [PubMed]

4. De Beer P, el Harith A, Deng LL, Semiao-Santos SJ, Chantal B, van Grootheest MA. Killing disease epidemic among displaced Sudanese population identified as visceral leishmaniasis. Am J Trop Med Hyg 1991;44:283-289.

5. Schorscher JA, Goris M. Incrimination of Phlebotomus (Larroussius) orientalis as a vector of visceral leishmaniasis in western Upper Nile province, southern Sudan. Trans R Soc Trop Med Hyg 1992;86:622–623.

6. Seaman J, Mercer AJ, and Sondorp E. The epidemic of visceral leishmaniasis in western Upper Nile, southern Sudan: course and impact from 1984 to 1994. Int J Epidemiol 1996;25:862–871.

7. Zijlstra EE, El-Hassan AM. Leishmaniasis in Sudan. Trans R Soc Trop Med hyg 2001;95(Suppl 1):S1–76.

8. Seaman J, Ashford RW, Schorscher J, Dereure J. Visceral leishmaniasis in southern Sudan: status of healthy villagers in epidemic conditions. Ann Trop Med Parasitol 1992;86:481–486.

9. Seaman J, Mercer AJ, Sondorp HE and Herwaldt BL. Epidemic visceral leishmaniasis in Southern Sudan: Treatment of severely debilitated patients under wartime conditions and with limited reso7urces. Ann Intern Med 1996;664-772.

10. Collin S, Davidson R, Ritmeijer K, Keus K, Melaku Y, Kipngetich S, Davies C. Conflict and Kala Azar: Determinants of Adverse Outcomes of Kala-Azar among Patients in Southern Sudan. Clin Infect Dis 2004;38:612–619.

11- Desjeux P. and UNAIDS. Leishmania and HIV in gridlock, World Health Organization and UNAIDS, 1998,

12- El-Safi, S. H., N. Hamid, A. Omer, A. Abdel-Haleem, A. Hammad, H. G. Kareem, et al. 2004. Infection rates with Leishmania donovani and Mycobacterium tuberculosis in a village in eastern Sudan. Trop. Med. Int. Health 9:1305–1311.