Clinical trial to find new treatment for kala-azar begins in eastern Africa

A clinical trial to evaluate new treatment and improved diagnostic tools for kala-azar, a condition categorised under neglected tropical diseases, has begun in Ethiopia, Kenya and Sudan. The trial is also expected to begin in Uganda soon.

According to a press release from the Drugs for Neglected Diseases Initiative (DNDi), a Kenyan-based organization, the trial is assessing the efficacy and safety of a combination treatment of miltefosine (MF) and paromomycin (PM) in treating kala-azar in eastern Africa.

If the clinical trial succeeds, this will be the first time in eastern Africa that an oral treatment is included in kala-azar treatment in combination with an injectable one.

The new treatment is expected to be safer, efficacious and more patient-friendly.

According to DNDi, although the current treatment, which is administered either through injection or intravenously, was shown to be effective, it remains sub-optimal. This is because patients may suffer from rare, but heavy side-effects, such as damage to the heart, liver and pancreas.

In addition, the treatment is difficult to administer since patients must endure two painful injections every day for 17 days.
Factfile

Kala-azar, also referred to as visceral leishmaniasis, is spread by the bite of an infected female sand-fly. Kala-azar is grouped under neglected tropical diseases, a group of communicable diseases that prevail in tropical and subtropical conditions in 149 countries.

According to the World Health Organisation, these diseases affect more than one billion people and cost developing economies billions of dollars every year. Populations living in poverty, without adequate sanitation and in close contact with infectious vectors and domestic animals and livestock are those worst affected.

Uganda is endemic to 12 of these diseases. They include trachoma, river blindness, jiggers, Buruli ulcers and intestinal worms. Others are elephantiasis, bilharzia, sleeping sickness, plague and rabies.

Information form DNDi shows that there are up to 90,000 new cases of the disease every year worldwide. Its highest burden is in eastern Africa (Eritrea, Ethiopia, Kenya, Somalia, South Sudan, Sudan and Uganda) where most people who are affected live in remote areas far from health facilities. 
 
In Uganda, the disease is endemic in the seven districts of Karamoja that is Amudat, Moroto, Kaabong and Abim. Others are Napak, Nakapiripirit and Kotido. According to information from the health ministry, there is a treatment centre for kala-azar in Amudat.

People of all ages in endemic areas are at risk of getting infected with kala-azar, however, teenager males have a higher risk because they go out to herd animals where they get exposed to the sandflies.

Symptoms

Symptoms of the condition usually start showing between two weeks and three months after a person has been bitten by an infected sand-fly and they are similar to those of malaria. They include fever, general body weakness and anaemia.

In addition, patients also present with a swollen abdomen, skin ulcers, recurrent nosebleeds and over bleeding in case of a cut. Patients are also prone to other infections such as those of the ears, lungs (pneumonia) and diarrhoea.

Treatment

The disease is treatable with a combination of drugs and good diet and patients are expected to make full recovery, but if left untreated, up to 90% of patients will die.

After recovery, patients develop enough immunity to fight of the disease the next time they are exposed to the parasites.

Its spread can be prevented by sleeping under an insecticide-treated bed net.

Need for new treatment

According to information from DNDi, if found to be efficacious, the introduction of the new treatment combination will reduce the difficulty in treatment administration and lengthy hospital stays for patients. The first oral treatment registered for kala-azar was in 2002 in India and it was also used in an elimination programme in 2005 in India, Bangladesh and Nepal.

In Uganda, at a meeting that sat in Kampala in 2015, it was disclosed that the health ministry had started the process of revising the treatment guidelines for kala-azar. It was disclosed that there was need to develop new treatment guidelines because the available treatment is toxic and patients are on it for a prolonged duration (usually 17 days).

Another issue was that the available drugs could only be administered in injection form, which makes it necessary for patients to be admitted until they finish the treatment. Therefore, delegates at the Kampala meeting highlighted the need to develop oral medication.

Diagnostics

The study also involves an assessment of innovative non-invasive diagnostic tools since countries in the region still use splenic aspirate for diagnosis. Splenic aspirate is an invasive diagnostic technique which involves removal of fluid from the spleen, often with the use of a fine-needle. This can be dangerous if performed incorrectly.

Trial

The clinical trial will be conducted under the umbrella of the new Afri-KA-DIA Consortium composed of 10 academic and research partners who have conducted innovative kala-azar clinical trials in eastern Africa over the past 12 years.

The study, which began in January 2018, will take place in eight sites in Ethiopia, Kenya, Uganda, and Sudan for a period of three years and is expected to enroll a total of 576 patients.

More than 20 patients have already been enrolled in the study from trial sites in Ethiopia, Kenya, and Sudan.