HIV/Aids complicates fight against kala azar

Tuesday October 21 2014
Kala azar

Gondar University Hospital and Leishmaniasis Treatment Centre. PHOTO | ANDUALEM S. GESSESSE

When Shiferaw Abegaz lost his wife last November, their second child was only three years old. Not long after, Shiferaw 39, also fell sick.

“I never thought I would be alive today,” he said, remembering the severity of the situation then.

At a local hospital, he was diagnosed with kala azar, also known as visceral leishmaniasis (VL), a fatal tropical disease caused by female sandfly bites. He contracted the disease while working as a daily labourer for commercial farms around Metema, northwest Ethiopia.

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During harvest season, as many as 300,000 daily labourers migrate from the highlands of Ethiopia to these lowland farms bordering Sudan such as Metema and Abdurafi to work on commercial cotton and sesame farms.

“We treat up to 60 patients suffering from kala azar every month,” said Dr Ermias Diro, principal site investigator at the University of Gondar.


Shiferaw’s blood was also found to contain HIV. He realised then that this was the cause of his wife’s death.

Yimer Abera is also a migrant worker on those farms and is infected by both kala azar and HIV/Aids. Yiber did not take long to visit the centre after he fell sick.

“It is because government-recruited health extension workers told us where to go when we experienced the symptoms, which are similar to malaria symptoms such as fever,” he said.

He weighed 40 kilogrammes when he came to the Gondar University Hospital and Leishmaniasis Treatment Centre for treatment last year. “After I was treated for about three months, my weight increased to 59kg,” he said.

One of the reasons for the high prevalence rate of kala azar among immigrant commercial farm labourers is that they sleep on the ground where the sand flies breed, according to Yimer. The trees where the workers take shelter are another breeding spot for the flies.

Initially, the parasite (leishmania) causes skin sores or ulcers at the site of the bite. If the disease progresses, it attacks the immune system. Kala-azar manifests after two to eight months with more generalised symptoms including prolonged fever and weakness.

There are different treatment options for kala azar, with varying effectiveness and side effects. Pentavalent antimonials are the first line group of drugs given as a 30-day course of intramuscular injections. While antimonials are quite toxic and risky to patients, those who are cured of 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.

With 300,000 new cases — over 90 per cent — every year, Bangladesh, Brazil, India, Ethiopia, Kenya, Nepal, and Sudan are the most affected countries by kala azar, according to the World Health Organisation.

After several years of clinical tests in Ethiopia and Sudan, two different injections to be taken by kala azar patients per day for 17 days are found to be 95 per cent effective.

“We have convincing evidence that we should continue using this new treatment. We have been testing it in 12 centres and will use it in our centres across the country,” said Dr Mousab Elhag, principal investigator at the Leishmaniasis East Africa Platform (Leap), formed 10 years ago to find better treatment for the disease in the East African region.

The combined treatment now awaits the approval of the drug administration authorities of the Leap member countries (Kenya, Ethiopia, Uganda and Sudan). Requests to register drugs in individual countries come from drug manufacturers.

Heran Gerba, deputy director of the Ethiopian Food, Medicine and Healthcare Administration and Control Authority, said they are likely to approve use of the drugs after the regulatory body verifies the appropriateness of the trial.

“The new treatment increases available hospital space by 40 per cent while reducing treatment duration from 30 to 17 days. I hope it will be taken up by all countries,” said Prof Asrat Hailu Mekuria, Leap principal investigator.

Kala azar with HIV

Like HIV/Aids, kala azar attacks the immune system. Co-existence of the two diseases in one person makes the treatment difficult. Of the patients treated at Gondar University’s Hospital and Leishmaniasis Treatment Centre, 15-20 per cent are co-infected.

“We remember the 2005 outbreak and the loss of more than 200 lives because of visceral type of leishmaniasis in Libokemkem district,” said Ayeligne Mulualem, head of Amhara Regional State Health Bureau, while speaking at the first scientific conference of Leap in Bahir Dar on September 29.

“Because of the magnitude of the problem we faced in kala azar, we opened five treatment centres and practised community surveillance,” he says.

When the two diseases occur together, treatment becomes more challenging. The risk of death from VL is nine times higher in patients who are co-infected with HIV. Kala-azar also accelerates the progression of HIV. Relapses of kala azar in patients co-infected with HIV are also common, affecting half of treated patients within a year of initial treatment.

An emerging global problem, VL-HIV cases are reported in 35 countries spread across Southern Europe, East Africa, the Indian subcontinent, and Latin America. One of the hardest hit areas in Africa is northwest Ethiopia, where 20 per cent to 40 per cent of patients with VL were found to be also infected with HIV.

“Treating patients who suffer both HIV and visceral leishmaniasis is a real battle for clinicians. Research suggests a balance between stronger and safer treatment,” said Koert Ritmeijer, health adviser at Médecins Sans Frontières, which has treated around 100,000 patients with kala azar since 1989.

Poverty and kala azar

Since kala azar affects the very poor who cannot afford drugs, medical companies tend not to invest in research on drugs for the disease. This has made it one of the 17 neglected diseases listed by the WHO.

“The neglect is a severe constraint that frustrates efforts to eliminate the disease,” Prof Asrat said.

Neglected tropical disease

Neglected tropical diseases affect more than 1 billion people, primarily poor populations living in tropical and subtropical climates. They are frequently clustered together geographically and individuals are often afflicted with more than one parasite or infection.

More than 70 per cent of countries and territories that report the presence of neglected tropical diseases are low-income or lower middle-income economies.

Out of the 1,556 new drugs approved between 1975 and 2004, only 21 (1.3 per cent) were specifically developed for tropical diseases and tuberculosis, even though these diseases account for 11.4 per cent of the global disease burden, according to WHO. It is estimated that some $2 billion is required by 2015 to deal with the 17 neglected tropical diseases.

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Infections are caused by unsafe water, poor housing conditions and poor sanitation. Children are the most vulnerable to these diseases, which kill, impair or permanently disable millions of people every year.

Best practices across the globe show that many of the neglected diseases can be controlled through community-based preventive actions that can be carried out by non-specialists such as schoolteachers, village heads and local volunteers. But the challenge remains as effectiveness of the treatment for HIV and kala azar co-infected patients remains at 50 per cent.

“Combining better initial cure treatments and preventing relapses will be a major step forward for our patients, who fear that the diseases, which can be managed when they occur separately, often become a death sentence when they occur together,” Dr Ermias said.

To improve the effectiveness of the treatment, AfriCoLeish, an international research and development consortium formed by six research organisations from East Africa and Europe, recently launched a clinical study. The study will be conducted on 132 patients in Gondar and Abdurafi towns, in northwest Ethiopia The clinical trialwill assess the efficacy and the safety of the two treatments: A combination treatment of AmBisome alone and AmBisome with miltefosine.

For now, they have succeeded in saving the life ofa kala azar-HIV patient. Their next phase of clinical trial aims to extend the life of the other patient like they did for Shiferaw and Yimer.

“After one and a half years, we will be in a better position to improve the cure rate and reduce the relapse rate,” said Fabiana Alves, clinical project manager of not-for-profit Drugs for Neglected Diseases initiative (DNDi).