Bangladesh beats a deadly scourge
By combining active case management and vector control strategies informed by TDR-supported research, the country is on track to eliminate visceral leishmaniasis by 2015.
In 2005, the governments of Bangladesh, India and Nepal signed a Memorandum of Understanding to reduce the burden of visceral leishmaniasis (VL) from about 300 cases per 100 000 to less than 10 in each of the three countries by 2015.
The world’s second biggest parasitic killer after malaria, VL is a worthy target. Also known as kala-azar, the disease occurs predominantly among the poorest of the poor, causing an estimated 59 000 deaths and 2.4 million disability-adjusted life years (DALYs) per year. Close to 70 percent of that global burden occurs on the Indian subcontinent, where more than 186 million people remain at risk of infection.
But it’s there too that VL’s epidemiological profile makes it amenable to elimination, says Dr Byron Arana, who worked for TDR and is now at the Drugs for Neglected Diseases initiative (DNDi). “On the Indian subcontinent, several drugs have been shown to be very effective, the only vector involved is susceptible to insecticides, and the only reservoir is humans.” That’s in stark contrast, he says, to the situation in Brazil, where VL is zoonotic—dogs are the main reservoirs—multiple vectors are involved, and the drugs are less effective.
WHO and TDR support for the 3 main elimination components
Bangladesh, in particular, has made large strides toward VL elimination, the result of a collaborative undertaking guided by TDR-generated research and made possible by technical and financial support from the WHO’s Department of Control of Neglected Tropical Diseases (WHO NTD). Working with those partners, the government of Bangladesh has reduced the incidence of VL to fewer than 1 900 cases per year, down from more than 9 000 less than a decade ago, and is on pace to eliminate VL a year ahead of the target date.
“Based on our study, the government of Bangladesh decided to adopt single-dose liposomal amphotericin B as a first line drug for VL.”
“The programme has three main components,” says Prof Be-Nazir Ahmed, Director of the Directorate General of Health Services in the Ministry of Health in Bangladesh. These cover diagnostics, treatment, and managing the sandfly vector.
“First, diagnosis can be done very easily with rK39,” a rapid diagnostic test (RDT) that has emerged as a reliable alternative to conventional methods. “Before, diagnosis was limited to the laboratory,” says Ahmed, “but the RDT can be performed in endemic areas at the sub-district and even the community level.”
Research establishes an easier medical treatment
Equally important, says Prof Be-Nazir Ahmed, is improved access to easier and less painful treatment regimens for patients with kala-azar and post kala-azar dermal leishmaniasis (PKDL). “For 60 years, the only treatment for VL in Bangladesh was sodium stibogluconate,” which requires 30 days of painful daily intramuscular injections and carries the risk of severe side effects. “The course was very long, compliance was poor, and 15% of patients died due to the drug itself,” says Ahmed.
When Bangladesh launched the National Kala-azar Elimination Program (NKEP) in 2005, liposomal amphotericin B, a safe and effective alternative sold by the American drug company Gilead, was prohibitively expensive for use in national control programmes. But in 2007, Gilead announced a price reduction of 90% for all low- and middle-income countries where VL is endemic, and WHO NTD proposed to the government of Bangladesh that it use the drug as a first-line treatment for VL, modifying its treatment policy in line with the recommendation of the WHO Expert Committee on the Control of VL for the Indian subcontinent.
The government of Bangladesh has reduced the incidence of VL to fewer than 1 900 cases per year, down from more than 9 000 less than a decade ago, and is on pace to eliminate VL a year ahead of the target date.”
Be-Nazir Ahmed, Director of the Directorate General of Health Services, Ministry of Health, Bangladesh
Four randomized controlled trials of this drug had demonstrated its high safety and efficacy profile for the treatment of VL in controlled conditions. But there was little evidence showing that the drug could be effectively distributed through the kind of primary health care centers where most VL patients seek care. “So we decided with the Ministry of Health to conduct a feasibility study in Bangladesh,” says Dr Jean Jannin, coordinator of innovative and intensified disease management at WHO’s Neglected Tropical Diseases department. “We provided the funding and drugs for the single-dose study, and we requested that TDR conduct it.”
That study, led by principal investigator Dr Dinesh Mondal, a senior scientist at the International Center for Diarrhoeal Disease Research, Bangladesh (icddr,b) and a TDR grantee, showed that treatment of VL with a single intravenous infusion of the liposomal amphotericin B could indeed be administered at the primary health-care level in a remote, rural part of the country. As Mondal and colleagues reported in The Lancet Global Health, the final cure rate at 6 months post treatment with 10 mg/kg liposomal amphotericin B was 97% with no serious side effects and no patients needing referral to the tertiary hospital.
“Based on our study, the government of Bangladesh decided to adopt single-dose liposomal amphotericin B as a first line drug for VL,” says Mondal. “And so far hundreds of patients have been treated with no cases of adverse events.” To support the country’s efforts, WHO has been donating drugs, and the United Kingdom’s Department for International Development (DFID) has provided support for training, distribution and active case detection.
Controlling the sandfly vector
In addition to new drugs and diagnostics, integrated vector management has also been key to Bangladesh’s success. A recent study conducted by Mondal and TDR consultants Axel Kroeger and Greg Matlashewski showed that a community-based intervention to impregnate existing bed nets with a slow-release insecticide significantly reduced VL incidence in VL-endemic areas of the country, leading to that intervention’s adoption by the Bangladeshi government. And according to Ahmed, “indoor residual spraying with deltamethrin has also been highly effective in reducing the concentration of sandflies per household.”
Together, he says, these three components, along with the commitment shown by everyone from the programme director on down to field-level workers, has resulted in a 90% reduction of kala-azar over the past three years. “They have really been working hard,” says Ahmed. “And because of this, we expect elimination by 2015.”
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