Kala Azar: Neglected Disease, Forgotten People, Amudat, Uganda

If we pull out of Amudat tomorrow, nothing will remain there. All the Kala-Azar patients will die.

Souheil Reaiche, Head of Mission Uganda,
Medcins Sans Frontieres (MSF) Switzerland.

MSF, ---“Doctors without Borders”--- is an international humanitarian aid organization, which provides emergency medical assistance to populations in danger. In Amudat, northeastern Uganda, MSF Switzerland has been conducting a project to diagnose and treat patients suffering from visceral leishmaniasis, more commonly known as Kala-Azar, which only occurs in developing countries like Uganda. It is transmitted by a specific form of sand fly that lives mainly in the forest regions of the sub-tropics (A.D.A.M. 2005). Although it is virtually a forgotten illness by the western world, it still threatens around 350 million people worldwide.

For the last seven years, the program in Amudat has helped the nomadic Pokot population combat the fatal, but curable disease. One of the key problems with treating Kala-Azar is the treatment is extremely expensive. The cost of one patient afflicted with Leishmaniasis is currently greater than one year of generic ARV tritherapy for an AIDS patient (MSF 2003-04:8). Since most of the patients can’t pay for any kind of treatment, they represent literately no market and conveniently fall outside the scope of the drug industry’s R&D efforts (MSF 2001-02:10). Although MSF has been providing accessible treatment to Kala-Azar in Amudat for seven years, Amudat Hospital will have to take over the project at some point. When asked what happened to most MSF projects after MSF handed over the projects to the local governments, “…most of the time, after the projects were handed over to the local governments, the projects didn’t stay long,” Souheil says. There are many factors contributing to the collapse of the projects. The extremely high expense of the medicine is the main one.

Why can’t these Pokot people have the best treatment, because they are the minority? Instead of making money from these poor people, maybe the US, Europe should reduce the price to make it more available for these countries.
Reaiche 2005.

As the number of patients being treated at Amudat has risen each year since the project began, it’s essential for Amudat to have access to existing treatment. Although more than $ 100 billion is spent on health research globally every year, less than $ 3 billion is spent on neglected diseases (MSF 2005a). MSF has been fighting the pharmaceutical industry’s lack of interest in neglected diseases and exerting pressure on the industry to produce user-friendly and inexpensive drugs (MSF 2003-04:61). Besides that, MSF along with other pressure groups, have been urging WTO to ease the rules of importing and exporting generic drugs under patent. Since the price of generic drugs is cheaper than branded name drugs, it’s more accessible for people in developing countries.


What is Kala-Azar/ Leishmaniasis?

There are three forms of leishmaniasis, monocutaneous leishmaniasis, cutaneous leishmaniasis and visceral leishmaniasis, the latter of which is commonly known as Kala-Azar. Monocutaneous leishmaniasis can disfigure those afflicted by it. Cutaneous leishmaniasis is the mildest form and usually causes slight alteration to the skin. Whereas Kala-Azar/visceral leishmaniasis is the lethal form, a fatal parasitic disease of the viscera ---the internal organs, especially the liver, spleen, bone marrow and lymph nodes. Kala-Azar attacks the immune system and causes death in 90% of cases (MSF 2003-04:40).

The leishmaniases are caused by the bite a sandfly. Only the female sandfly transmits the Leishmania parasites (WHOa 2005). The sandfly mainly lives in the forest regions of sub-tropics. These tiny insects hatch in shady, humid and windless locations, such as anthills, rock piles, tree barks and termite mounds. They mainly bite at twilight (MSF 2003-04:40). Kala-Azar can be found in parts of Asia (primarily India), Africa (primarily Sudan) and South America (primarily Brazil). Although hundred cases are also found in Europe (primarily in the Mediterranean region) and a few in North America, 90% of Kala-Azar cases occur in Bangladesh, Brazil, India and Sudan. (See figure 2) Kala-Azar can be treated, but treatment must be given early during the disease (A.D.A.M.).

What are the symptoms of Kala-Azar/ Leishmaniasis?

Only 10% of those infected with Kala-Azar show symptoms. It can take three months to several months between the moment of infection and the outbreak of the disease. There are few but typical symptoms, fever, loss of weight, fatigue and enlargement of the liver and spleen, which is located under the left diaphragm in the upper abdomen. Spleen filters the blood, removes old blood cells and forms new ones (MSF 2003-04:40). “The Pokot know the illness very well. The name they’ve given to it, “Termesh”, means spleen in their language,” says Dr.Pentz, responsible doctor of the MSF project in Amudat. Since the parasite attacks the immune system, other infections can occur as well. 34 countries around the world have already reported cases of Leishmania/ HIV co-infections (WHOa 2005).

How is Kala-Azar/ Leishmaniasis diagnosed?

Blood is taken from the patient and tested to ensure that the disease can be clearly diagnosed. The testing procedure is a costly one, and a clear-cut diagnosis is not possible unless the test produces a definite positive or negative result. If the result shows neither, it is not clear whether that person is suffering from Kala-Azar or not. Consequently, a spleen puncture is carried out to substantiate the diagnosis. As the parasites can be detected microscopically, this procedure involves the removal by needle of a microscopic piece of the spleen (MSF 2003-04:41).

What treatments are available for Kala-Azar/ Leishmaniasis?

Amphotercine B
Amphotericin B (Fungizone, Sarabhai Chemicals) available as a dry powder, a toxic drug, could be given only under supervision of a trained doctor. The major drawback is that relapse rates were high following initial clearance of parasites MSF used it as the second-line drug when the production of Glucantime stopped in May 2003 (Leishmania 2005)

Ambisome
It is simple to use. Patients revive within hours of getting the first shot, which has no side effects. The drawback is that there is only one producer and current price offer is US$ 1,500-2,400 per treatment (AmBisome 2005).

Glucantime
Glucantime is administered by daily injection. Because allopurinol works synergistically with glucantime it is helpful to use in combination to reduce side-effects and duration of glucantime treatment. Dosage: 100 mg/kg/day s/c for 20-40 days (Leishmania 2005).

Milterfosine
It is the first oral drug to treat the disease, but has only been registered for use in India. Treatment takes four weeks and there are limitations to its use in women of childbearing age and children (WHOa 2005).

Paromomycin
This old antibiotic against Kala-Azar was discovered in the 1960s. However, the drug got stuck in the research pipeline owing to market reasons. In addition, it hasn’t been registered for use anywhere in the world (WHOa 2005).

Pentostam
Sodium stibogluconate, a first-line drug, is used in the treatment of leishmaniasis. This drug is given for at least 20 days by intravenous injection. Since April 2004, MSF has been using Pentostam for the Kala-Azar patients in Amudat (Electronic Medicines Compendium 2005).

Medcins Sans Frontieres/ Doctors without Borders

Medcins Sans Frontieres (MSF), an independent nongovernmental organization (NGO), has been setting up emergency medical aid missions in nearly 80 countries around the world since 1971 and was awarded Nobel peace Prize in 1999. MSF is funded through a variety of sources to be able to provide the most up-to-date yet free medical treatment to patients in developing countries, where people are heavily stricken by poverty.

In countries where health structures are insufficient or even non-existent, MSF collaborates with authorities such as the Ministry of Health to provide assistance. There are three situations in which MSF intervenes to assist vulnerable populations---chronic conflicts, emergencies, and in the complete absence of health care. When a Ministry of Health exists and has its own definition of primary health care, MSF provides temporary support for the infrastructure already in place. MSF’s main responsibility is to point out the problems to the authorities instead of making policies for them (MSF 2005b). One of the main reasons for doing so is to prevent the system from becoming dependent on outside support. Another main reason is neutrality. In order to prevent compromise or manipulation of MSF’s relief activities, MSF maintains neutrality and independence from individual governments.

…if we get involved with the system, we are no longer neutral. If we’re in the government, for example, in Gulu, the rebels will consider us as part of the government. One day, if there is a fight, the rebels might think that we are part of the government, we might get attacked. ICRC and MSF are the only two, which don’t use military escort. We are the emergency NGOs in conflict areas.
Reaiche, 2005

Besides providing primary health care, MSF also commits itself to witness and therefore to raise awareness in an international level for these populations and the situations they are in.

Why is it that money was given to this country, and still why the people don’t deserve the best drug? WTO put lots of pressure on India and South Africa not to produce generic drugs. If they cut the production of making generic drugs, these patients will not be able to afford the treatment anymore. And that’s why when I give a new drug to patients and that works, I make sure that Kampala knows when we have meetings with the other NGOs, as they need to take responsibilities in an international level. It’s important to fight for this neglected disease and to fight for this neglected population in the north.
Reaiche 2005


Pokot County and MSF’s Kala-Azar Project in Amudat

Pokot County, Nakapiripirit district, is located in the Northeast of Uganda bordering Kenya. The area in Kenya, adjacent to Pokot County, is called Kacheliba division. Although the division is divided by a formal border from Uganda, it should be seen as a single area in terms of specific climate features and ecology, which is probably the most important factor in the distribution of the disease---Kala-Azar (Karamoja Data Centre 2004). Around 60,000 members of the Pokot tribe live in the region around Amudat and across the border in Kenya. These people risk exposure to Kala-Azar because they live in close quarters with livestock and large populations of sandflies, the carrier the disease (MSF 2003-04:40). There were more than half of the patients from Kenya. In fact, between April and July 2005, there were 155 Kenya Kala-Azar patients and there are 82 Ugandan Kala-Azar patients. “The treatment there in Kenya costs 170 USD,” says David Lomongn, a human right activist from Kenya.

The vegetation types of Nakapiripirit district fall mainly into the following categories: High Altitude Forest, High Altitude Moorland and Heath, Thicket, Savanna and Bush land. Three main ethnic groups, the Pokot, the Karimojong Pian and the Karimojong live in Nakapiripirit (Karamoja Data Centre 2004). According to the results of the 2002 Population and Housing Census, Nakapiripirit district has a population of 153,862 persons. Pokot County is sparsely populated, with 63,000 inhabitants. The center of the county is Amudat which includes the administrative offices, a trading center, seven primary schools, one secondary school and a small hospital: Amudat Hospital (AH). The living conditions are harsh in Pokot County as there are only 41 boreholes and a dam, which are the main sources of water for the 63,000 people. In addition, there are only 4 KM² of subsistence farmland. Most of the people are traditional cattle herders living a semi-nomadic lifestyle. The district has about 955 km of community access roads with 244 km national gravel road. The rest of the community roads are all in poor condition (Karamoja Data Centre 2004). The ongoing war against insurgents, both the lord’s Resistance Army and the Allied Democratic Front in the north has created instability among the region and has negatively affected the district’s development.

In 1954, Amudat Hospital was started by the Church Missionary Society as a dispensary. It wasn’t until 1977; the Uganda doctors started working in the hospital through the support of the Uganda government. In 1985, the involvement from the government lessened. In 1987 the Uganda government withdrew the medical officers from Amudat Hospital and the hospital was reduced to a health center. In 1997, the Reformed Mission League terminated their financial support to the Health Center; the center was left with ten staff. In 1999 MSF did an assessment of Kala-Azar in Pokot County because of the steady increase of Kala-Azar patients in Amudat. In 2000, MSF started a Kala-Azar project, based on the three main criteria: neglected disease, the absence of the treatment and chronic conflict zone (MSF Date Unknown).

According to Mr. Reaiche, Head of Mission Uganda, MSF is the only NGO working on Kala-Azar in the field. Before MSF set up the program in Amudat, the Kala-Azar patients in Pokot County had to cross the border to Kenya, where treatment was available until 1995. At that time, it cost 300,000 Ugandan Shillings (150 $USD) to treat an infected patient. In the beginning of the operation in Amudat, Kala-Azar patients were getting treated for free. However, after the hospital changed hands to the Church of Uganda in 2003, patients were charged 15,000 shillings/per treatment as a condition to keep the project. This situation is unprecedented for MSF.

We never have charged anybody. We had to accept because that was the condition. That’s the way for them to get some money for service.
Reaiche 2005

More than 90% of the patients there had to sell their cows, which can be sold for 300,000-400,000 shillings each to pay for the treatment, transportation and food as the treatment is one month. Janet, who is from Kenya claims that “Only 5%-6% of patients can afford to come for treatment.” She brought her two sons from Kenya to Amudat for the Kala-Azar treatment.

When asked whether the cost excludes large amount of people from receiving treatment, Mr. Reaiche stated that:

We would have had to move from the hospital to create our own unit if we hadn’t accepted the condition, set by Amudat Hospital. Without the support and the sustainability of the district, if we start our own project, how long can we stay there? Before, it was 300,000 Shillings in Kenya, now its 15,000 Shillings. Sometimes we have to compromise to save lives, even though it excludes some people.
Reaiche 2005

The Kala-Azar Ward is a vertical program inside Amudat Hospital to take care of these particular disease patients. Patients from far away can stay in the ward, which is equipped with sixty beds. Sometimes the staff has to put mattresses under the bed to accommodate the patients and their relatives. Since more than 50% of Kala-Azar patients are children, so the children’s family has to come along and take care of them (Amudat Hospital 2005). In addition, patients have to receive a daily, weight-adjusted dose of drug over a one-month period. Kitchen and washing up places are also set up to suit their need. The injection, called Pentostam is given out the patients every morning. Pentostam is another first-line drug, which MSF has switched to since April 2004. Before that, MSF was forced to use Amphotericin B, a second-line treatment because the production of the previous first-line drug, Glucantime, was suspended. These drugs are not produced continuously because the market is very small. Between May 2003 and April 2004, 344 cases were diagnosed and treated. And between April and July 2005, 209 cases were diagnosed and treated. “The treatment is successful in 95% of cases,” says Dr. Pentz. Amudat has now become known as the only place in the area where Kala-Azar can be treated.


Access to Essential Medicine

“Existing drugs for neglected diseases, such as leishmaniasis/Kala-Azar, human African trypanosomiasis, and Chagas’ disease, among other infections that affect millions of people across Asia, Africa, and Latin America are too expensive, too toxic, or just do not exist,” says Bernard Pecoul, director of Medcins Sans Frontieres’ campaign for essential medicine. MSF put 6% of the funding into Advocacy and Campaign for Access to Essential Medicine in 2003 (MSF 2003-04:61) (See Figure 3). The costs of research and development (R&D) are mainly paid through the sales of drugs. As a result of that, the price of medicine and diagnostic tests is beyond poor people’s reach. Public health experts estimate that just 10% of worldwide funding of pharmaceutical research goes into infectious diseases that affect the world’s poor people. Of the 1.450 new drugs introduced in the global market since the 1970s, just 13 were specifically designed to treat neglected diseases (MSFa 2005). From figure 4, we can see clearly how little attention B (neglected diseases) and C (the most neglected diseases) groups get from the pharmaceutical industry. Besides, although starting in 2003, WTO allows generic drugs to be exported under strict conditions, the complicated procedure has put off generic manufacturers (Taipei Times 2005). The GDP per capita (Intl $, 2002) in Uganda is 1,038 (WHOb 2005). It’s obvious that none of the Kala-Azar patients can afford the treatment.

Another hindrance of accessing affordable drugs is the World Trade Organization (WTO) rules (See Box 1). Firstly, Uganda can never pay an “adequate compensation” to obtain a compulsory license without a certain level of international help. Second, Kala-Azar is unlike bird-flu, which has haunted South-east Asia since January last year and has only now made its way into Europe. Although, Asian countries have been affected by bird-flu for a long time, the demand to push the WTO to relax its patent rules has never been so fierce until now. Chuck Schumer, a member of the U.S. Senate from New York has threatened to pressure the Swiss pharmaceutical giant Roche to give up its right to protect the patent on Tami flu, which is considered to be the only drug for the H5N1 strain of the bird flu virus. “Roche is putting its own interest ahead of world health. They shouldn’t be slow-walking this process when we have a potential pandemic that could occur at any time,” Schumer was quoted as saying. Roche has agreed to give the license to manufacture Tamil flu to four U.S. generic drug manufacturers (Spero News 2005). It took six years for India to produce generic drug, Miltefosine, the first oral drug against Kala-Azar (WHOSEA 2005).


A generic drug is identical to a brand name drug in dosage form, safety, and strength, route of administration, quality, performance characteristics and intended use. Although generic drugs are chemically identical to their branded ones, they are sold at a lower price. (CDER 2005) Under WTO rules, generic drugs were totally limited to domestic use until August 2003. Now generic drugs can be exported under compulsory licenses with strict conditions attached. Countries can issue compulsory licenses to disregard paten rights but only after negotiating with the patent owners and paying them adequate compensation. Governments can skip the negotiation only when WTO declares a public health emergency (Taipei Times 2005).
A generic drug is identical to a brand name drug in dosage form, safety, and strength, route of administration, quality, performance characteristics and intended use. Although generic drugs are chemically identical to their branded ones, they are sold at a lower price. (CDER 2005) Under WTO rules, generic drugs were totally limited to domestic use until August 2003. Now generic drugs can be exported under compulsory licenses with strict conditions attached. Countries can issue compulsory licenses to disregard paten rights but only after negotiating with the patent owners and paying them adequate compensation. Governments can skip the negotiation only when WTO declares a public health emergency (Taipei Times 2005).


In addition, European authorities felt that bird-flu should be labeled as “global threat”. Patients in the developing world suffering from diseases, such as HIV/AIDS, malaria and tuberculosis (TB) are directly affected by pandemics and yet have limited access to expensive drugs produced by pharmaceutical companies for decades. Only last year AIDS killed over three million people with a majority of them in Africa (Spero News 2005). Wonder this situation will change if the sandfly migrates to developed countries, such as the US.