Two medical conditions form major obstacles to India's kala azar elimination plan

Through most of July, August and September, 34-year-old Krishna Kumar* had been ill with fever. Kumar drives trailers in Haryana and is on the road almost all year, going home to Motihari district in Bihar for a few days every five or six months.

“I would keep going to doctors on the road but I could not get rid of the fever,” said Kumar.

On his last visit home, Kumar consulted a private doctor who diagnosed him with kala azar and sent him to the district hospital. Here, as guidelines set out in 2014 for all patients with kala azar, Kumar was tested for HIV and his results showed that he was HIV-positive.

Doctors at the Motihari district hospital sent Kumar to the Rajendra Memorial Research Institute of Medical Sciences, Patna. This institute, along with Médecins Sans Frontiers, has been conducting a clinical trial on the effectiveness of a treatment protocol with a higher dose of Liposomal Amphotericin B, the new drug that has vastly simplified treatment of kala azar.

Kala azar, or visceral leishmaniasis as is its scientific name, is caused by a leishmania parasite transmitted by the female sand fly. It is characterised by irregular bouts of fever, weight loss, enlargement of the spleen and liver that gives the patient a pot belly, and anaemia. If left untreated for more than two years, it is almost certainly fatal.

HIV-kala azar co-infection and post-dermal kala azar leishmaniasis, a skin presentation of kala azar often abbreviated to PKDL, are serious threats to the government’s ambitions of eliminating kala azar by 2017. Bihar has about 70% of the total kala azar cases in the country. The other states where the disease is significant are Jharkhand, West Bengal and Uttar Pradesh.

Consumptive co-infections

HIV and kala azar are mutually reinforcing infections, which means that HIV-infected people are vulnerable to kala azar, while kala azar advances an HIV infection.

“Both kala azar and HIV are immunosuppressants,” said Dr Ravinder Singh Rishi, the medical team leader for a kala azar-HIV co-infection treatment study with Médecins Sans Frontiers. “Treatment relapse rate [in case of an HIV co-infection] is almost 100-1,200 times higher than the treatment rate of kala azar without complications.”

Many patients with co-infections suffer from severe acute malnutrition due to which their immunity is already low. Kala azar is considered a consumptive disease that leads to wastage of the body and pulls immunity levels further down.

When Scroll.in visited the Patna institute on August 29, there were two kala azar patients with HIV and tuberculosis co-infections. Both suffered severe acute malnutrition, which is very low weight for height. Both were confined to an isolation room so that they would not spread tuberculosis to other low-immunity patients in the ward.

Difficult to detect

A Médecins Sans Frontières study conducted in Hajipur city’s district hospital in Bihar in 2014 showed that 5.6% of kala azar patients had HIV too. This number is much higher than the HIV prevalence of 0.37%, as recorded by the National Aids Control Organisation in their 2015-’16 report. Nearly 40% to 50% of patients with kala azar and HIV co-infection do not know their HIV status, which makes them very vulnerable to the disease since they would not not receive anti-HIV treatment.

Things get more complicated with kala azar being difficult to detect in HIV-positive people. Kala azar is normally diagnosed using the rk-39 dipstick test, which can detect the infection with a drop of blood obtained by pricking a finger and is 99% accurate. The same test is less effective in HIV co-infected kala azar patients, who instead need to undergo bone marrow aspiration to check for kala azar.

Despite the known risks of co-infection, antiretroviral therapy centres in Bihar often do not look for symptoms of kala azar. In addition, most government health establishments do not refer kala azar patients for HIV tests despite guidelines issued in 2014 to that effect. Kumar in Motihari was one of the few patients who was tested for HIV after being diagnosed with kala azar.

“It is like finding a needle in a haystick,” said Rishi. Médecins Sans Frontières plans to conduct an awareness campaign among laboratory technicians, district government hospitals, primary health care centres, private doctors and other facilitators to test for HIV among patients with kala azar.

In the next few months, the non-profit will start this campaign in seven Bihar districts where kala azar is endemic – Vaishali, Darbanga, Muzaffarpur, Samastipur, Siwan, Gopalganj and Motihari.

Difficult to treat

Unlike the single dose Liposomal Amphotericin B treatment given in a day for HIV-negative kala azar, HIV-positive patients are given eight doses over a period of 24 days. Treatment failure and relapse rates are very high with various treatment protocols. Most patients will, therefore, continue to be infectious.

So far, no treatment protocol has been effective on a large scale in treating people with kala azar-HIV co-infections.

Liposomal Amphotericin B is known to work in a small group of HIV patients in Bihar but with a higher risk of relapse and death. The study conducted by Médecins Sans Frontières found that antiretroviral treatment initiated after kala azar treatment is known to reduce risk of relapse and mortality. Yet, the risk of relapse and death remained a significant 25.9% and 29.7 %, respectively, after two and four years of treatment.

“The earlier study had given only 20-25 mg per/kg of Liposomal Amphotericin B,” explained Dr Gaurab Mitra, medical activity manager, Médecins Sans Frontières. “In the new one, we are giving 40 mg per kg of the drug in eight doses to the patients. We are also comparing this protocol to another one, with Liposomal Amphotericin B and miltefosene oral drugs.”

The new study hopes to have a better protocol for treatment of HIV-kala azar co-infection patients. “We do not have a good protocol yet for these patients,” he said.

The skin infection version

Another possible threat to the grand kala azar elimination plan is a condition called post kala azar dermal leishmaniasis, more commonly referred to as PKDL or cutaneous leishmaniasis.

PKDL patients have visible lesions or discolouration of the skin. The Kala Azar Elimination Programme considers PKDL a threat as patients are said to be reservoirs of the parasite leishmaniasis.

Some studies show that the nodular lesions are a blood meal for sandflies, which infect them when they bite. The sandflies, in turn, infect other humans. PKDL is reported in patients with a history of kala azar, where the rashes appear on the face and other parts of the body.

“Around 95% of PKDL cases have a history of kala azar,” said Dr Nupur Roy, additional director of the National Vector Borne Disease Control Programme. “These are parasites not cleared by antibiotics, as they may not reach under the skin. The skin has less supply of blood as compared to the rest of the body.”

Unlike HIV-kala azar co-infections, the challenge here is not to find the patients or treatment failures but a lack of incentive to patients to get treated. PKDL is non-fatal and causes little pain and discomfort. Doctors in the public health system, therefore, find it difficult to convince patients to spend time and money on treatment.

Why treatment?

Take the case of 10-year old Preeti Kumari, a resident of Bhagwatpur village in Samastipur distict in Bihar. Kumari was on her way to school when Mukesh Singh stopped her and asked her if she had been to the nearby public health centre in Sarairanjan block. Singh is the Samastipur district programme manager with New Concept, which is part of KalaCore – a consortium of organisations that is now on a mission to control and eliminate the disease by 2017.

In 2015, Kumari had suffered a bout of kala azar and had been treated for it. After treatment, she developed rashes on her face, hands and neck that looked like small discoloured spots. She was suspected to have been suffering from PKDL.

In June, after a communication programme in Kumari’s school, the New Concept team had identified possible PKDL carriers and asked them to get tested. “We went to the Sarairanjan Primary Health Centre mid-June,” Kumari’s mother Poonam Devi told Singh. “They told us that the kits are not available. We did not go after that.”

“Why did you not go after a few days?” Singh asked.

Devi, a single mother who takes care of the home and works in the fields to bring in money to feed her family, gave him a resigned look.

Kumari’s schoolmate, seven-year-old Sharda, also had spots on her body and was referred to the primary health centre. Her parents had made no effort to get a diagnosis.

The biggest barrier for treatment is the fact that only two facilities – the Rajendra Memorial Research Institute of Medical Sciences in Patna and the Kala Azar Research Institute in Muzaffarpur – give reliable diagnoses of PKDL. The treatment mostly lasts 12 weeks, often with the oral drug miltefosine, and sometimes a combination of other drugs. The patient has to visit the hospital every month.

The treatment has side effects. Twelve-year-old Shubham from Bajitpur village in Samastipur has spots on his face and body and was diagnosed with PKDL in August. He had to be taken to the Patna institute to get treatment, which takes more than two hours in a bus.

“His stomach hurts and he feels nauseous, giddy and vomits often,” said his mother Munni Devi. “He has been told not to be exposed to sunlight, but it is difficult to stop a child from playing.” Shubham had not gone to school in over a month.

Finally, PKDL gets attention

About 10% of people treated for kala azar cases in Bihar are now being detected with PKDL. This year, 361 cases of PKDL have been recorded in the state so far.

In the past, chronic PKDL cases in interepidemic periods have been implicated in the upsurge of visceral leishmaniasis epidemics in the Indian subcontinent and Sudan.

While the focus of the Kala Azar Elimination Programme is detection and treatment of kala azar cases, the government for the first time is also tracking PKDL. This year, the Bihar government too started recording cases of PKDL.

“PKDL was earlier not included in the elimination programme,” said Roy. “The patient would not be bothered to get treated, as the treatment is for a long duration. Even physicians felt that why should we be treating this disease at all.”

Though the numbers of both PKDL and HIV-kala azar patients are few, their treatment is important, feel experts.

Mitra said, “Since the government is on an elimination mode, it needs to take in all arms of the problem, including PKDL and HIV-kala azar co-infection, into consideration. Otherwise there will be no elimination.”

Public health problem

The only reason to send a person with a non-fatal condition that does not bother him for treatment that has uncomfortable side-effects is if the existence of the condition poses a real public health problem.

In 1980, Dr A Nandy and his associate from the Calcutta School of Tropical Medicine conducted a study too try and determine whether PKDL patients can infect sandflies, who in turn can infect other healthy people. Sandflies were allowed to bite four patients with PKDL. A significant number of sandflies were found with the parasite in their guts.

However, this evidence is being reassessed now by Dr Shyam Sunder from Benaras Hindu University, who has conducted some of the most important research on kala azar. “PKDL-sandfly infection studies are on,” he said in an email to Scroll.in. “Thus far, there is no evidence, or little evidence.”

Some research even shows that the most common form of PKDL among Indians is less likely to infect sandflies.

Recently, scientists from the Rajendra Memorial Research Institute of Medical Sciences in Patna conducted a study to test whether PKDL patients infect sandflies among 400 patients. “Most of our patients have a macular form of PKDL, not other mixed infections such as nodular or papular,” explained Dr Pradeep Das, the director of the insitute.

While macular PKDL is mostly characterised by discolouration of the skin, papular PKDL consists of an elevated lesion and and nodular PKDL is a small elevated mass of tissue. In the papular and nodular forms of PKDL, the parasite can be found in the skin, said Das.

“This is usually characterised by skin depigmentation,” said Das. “Among these patients, only 40% have the parasite under the skin, which makes it less likely that the sandfly becomes infected. The hypothesis that PKDL transmits the disease in a big way may not be correct.”

Should the programme be designed in a way that only nodular and papular PKDL patients be sent for treatment? Das felt that the government should not bother treating patients with macular PKDL. “We should not waste any drug [since patients do not need it] as it could create resistance in society,” he said.

*Names of HIV-positive people have been changed to protect their identity.

This reporting project has been made possible partly by funding from the New Venture Fund for Communications project, which receives support from the Bill & Melinda Gates Foundation.