India’s ambition to eliminate visceral leishmaniasisBMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g6671 (Published 07 November 2014) Cite this as: BMJ 2014;349:g6671
- Talha Burki, journalist, London
In 2005 India signed a memorandum of understanding with Nepal and Bangladesh, undertaking to eliminate visceral leishmaniasis, also known as kala azar, as a public health problem by 2015. Elimination was defined as an incidence of less than one case in 10 000 people at district level. This was an arbitrary figure, borrowed from the campaign against leprosy and epidemiologically meaningless. But it had political cachet, and while the previous Congress government that signed the memorandum seemed to lose interest in the disease, the Bharatiya Janata Party (BJP), which took over earlier this year, has reinvigorated efforts. The BJP renewed the international commitment, and at a high level meeting in Patna, Bihar, on 2 September 2014 the minister of health Harsh Vardhan unveiled a roadmap for tackling kala azar,1 including financial incentives for community health workers who identify patients with the disease. Accredited social health activists will be given 300 rupees (£3; €3.90; $4.90) for each patient identified with a rapid blood test. Patients treated in hospital will get 500 rupees a day as compensation for missed earnings.
A new drug
Crucially, India is finally ready to roll out liposomal amphotericin B (AmBisome), a safe and effective treatment that requires only one intravenous administration. The World Health Organization, through an agreement with the producers of AmBisome, Gilead Sciences, has committed to provide supplies to cover the predicted caseloads until the end of 2016, and subsequently as required until 2021. In 2010, WHO recommended AmBisome as the preferred treatment in India. But the country was slow to react, continuing to base its treatment policy on miltefosine (Impavido, Miltex), which is subject to suggestions of fading efficacy and requires contraception for women of child bearing age for up to three months after treatment.2 Compliance with the drug’s 28 day regimen is also a concern.
“Hopefully, within 8 to 10 months, all patients will be able to access high quality treatment for free,” said Sakib Burza, a regional coordinator for the KalaCORE consortium, which is a partnership including Médecins Sans Frontières and the Drugs for Neglected Diseases Initiative (DNDi), and is backed by a £27m grant from the UK government’s Department for International Development.
AmBisome’s use is not straightforward though. The drug requires a temperature controlled supply chain, and staff need to be trained to test patients for any kind of reaction and to administer the infusion. But it does seem likely that India’s downward trend in prevalence will continue. This year has seen about 6000 cases, and last year there were fewer than 14 000, Burza told The BMJ. But how much of this is down to control efforts is moot. Kala azar is cyclical, peaking every 10 to 15 years. “Nature is giving us a big hand in dropping down to the elimination target,” said Burza.
The non-profit Bill and Melinda Gates Foundation is backing vector control efforts, the mainstay of which are campaigns for indoor spraying using DDT, which almost eradicated the sandfly spread disease in the 1960s. Meanwhile, KalaCORE focuses on capacity building. “We have to encourage strategies that ensure sustainable elimination: outbreak monitoring, surveillance systems, and drug resistance monitoring,” said Burza.
Today, 60% of the global burden of visceral leishmaniasis falls upon the Indian subcontinent, predominantly in Bihar. Two studies found that official figures have underestimated Bihar’s true kala azar burden by 4 and 8 times, respectively.3 4
Extrapolating from these data, WHO estimated that in 2004-08 the annual caseload in India was between 146 700 and 282 800.5 Mortality rates are trickier, but it seems reasonable to suggest that 10-20% of these patients did not receive treatment and so eventually died (for those who did enter treatment, the newer therapies are associated with mortality of less than 5%). Under-reporting rates are now estimated to hover around 20%—India’s move to miltefosine, which can only be obtained in the public sector, meant that even patients who consult in the private sector are recorded as having contracted the disease so reporting is more accurate.
Falling sick with kala azar is expensive. On average it costs patients in Bihar US$127, but 40% of the population live on less than $1.25 a day. Patients are largely from underprivileged castes. They tend to live in conditions in which the sandfly proliferates, often in damp muddy shacks surrounded by vegetation, and their poor nutritional status increases the chances that a bite from an infected insect will lead to their falling sick. Damaged drug packets or testing kits in the public sector, where treatment for kala azar is theoretically freely available, often forces them to access care in the private sector. Antimonials, widely available in the private sector, have high rates of resistance and adverse events and require a painful series of intramuscular injections.
Crucial scientific questions remain unanswered, Jorge Alvar, former head of WHO’s leishmaniasis programme and now at DNDi, told The BMJ. Foremost of these is the role that post kala azar dermal leishmaniasis (PKDL) plays in transmission of kala azar. Some 5% to 10% of patients are thought to develop PKDL in the form of skin lesions within a year or so of treatment for kala azar. Just how infective these lesions are has yet to be established. But these patients could conceivably form a reservoir from which the disease could resurge.
“There is no clear position on how to treat PKDL—there have not been any proper clinical trials,” said Alvar. Moreover, the lesions often do not bother the patient, raising ethical questions over the necessity for treatment.
Coinfection with HIV is a small but growing problem; such patients are highly infectious for visceral leishmaniasis and particularly difficult to treat.
Finally, there are asymptomatic patients who harbour infection—estimated to be somewhere between 10% and 30% of the population in endemic regions. Just how infectious are these individuals? Were they the reservoirs of infection that caused the sharp resurgence of kala azar in the 1970s, after the campaigns of indoor residual spraying ended?
Despite these unknowns, the fact that experts such as Alvar are turning their attention to such questions is testament to the progress of the past decade or so, which has seen the World Health Assembly issue its first resolution on visceral leishmaniasis; enormous advances in treatment; and estimates of disease burden established.
India will attain its elimination target sometime in the foreseeable future—though probably not by the end of 2015—but for now at least a neglected tropical disease is receiving welcome attention.
A history of kala azar in India
Through the ages, there have been dozens of different terms for visceral leishmaniasis. Dum-dum fever and Burdwan fever were named after Indian localities in which the disease was endemic. Cachexial fever referenced its characteristic wasting symptoms, and non-malarial remittent fever hinted at the mystery that surrounded the sickness.
One name, however, has stuck—kala azar. It is commonly taken to mean “black fever” in Hindi, so called because some patients experience a darkening of the skin. But kala has another meaning—deadly—as the British Army medical officer Ronald Ross suggested in 1899.6
The nature of visceral leishmaniasis certainly justifies the appellation: without treatment, the mortality rate is nearly 100%, and treatment did not arrive until the 1920s. By that time, the parasite responsible for transmitting the disease in India had been identified (Leishmania donovani) and a consensus was emerging that the sandfly was the vector.
Cite this as: BMJ 2014;349:g6671
Competing interests: I have read and understood the BMJ policy on declaration of interests and have no relevant interests to declare.
Provenance and peer review: Commissioned; not externally peer reviewed.