Update on the kala-azar elimination programme in Bangladesh
Visceral leishmaniasis, or kala-azar (KA), is a vector-borne disease, caused by the Leishmania species protozoan parasites that are transmitted by infected female phlebotomine sandflies. L. donovani is the Leishmania species commonly found in South Asia. KA is characterized by prolonged fever, wasting and enlargement of the spleen. If left untreated, KA is generally fatal. KA primarily affects the poor. It is estimated that 200 million people are at risk of infection and 200,000-400,000 new cases of KA occur worldwide each year.
Data collected between 2004 and 2008 showed that sixty percent of estimated cases worldwide occurred in Bangladesh, Nepal and India. Post-kala-azar dermal leishmaniasis (PKDL) is a complication of KA. After successful treatment of KA, 10% of patients may develop some dermal spots (Figure 3). These patients are the reservoir of KA. In 2008, the Government of Bangladesh initiated the National KA Elimination Programme (NKEP), with the goal of reducing the incidence of KA to less than one case per 10,000 population by 2015. NKEP focuses on hyper-endemic areas in the country (Figure 1) and on three elements: 1) early case detection, 2) effective treatment, and 3) vector control. From 2008 to 2012, the number of cases decreased steadily from 4,824 to 1,902 (Figure 1).
In the same time period, the number of hyper-endemic sub-districts (incidence rate more than 2.5 per 10,000 population) decreased from seven to three and the incidence in Mymensingh District, the district with the highest incidence, fell from 8.7 to 2.6 per 10,000 population. This report provides an update on the programme and identifies challenges to reducing the KA burden in Bangladesh.
One of the first steps that NKEP took was to introduce the rK39 rapid diagnostic test (RDT) to Bangladesh. This is a sensitive, specific, commercially available, and inexpensive (less than one USD/test) diagnostic test that is easy to perform. It requires only one drop of blood and detects antibodies for rK39, Leishmania antigen.
This test obviates the need for using the conventional microscopic method for diagnosing KA, which consists of obtaining an aspirate from the spleen, a procedure which requires trained professionals and poses risks to patients.
NKEP defined a KA case as an illness with fever for more than two weeks, an enlarged spleen and a positive rK39 test result. NKEP defined PKDL as an illness in a person with past history of KA that consists of maculo-papular or nodular skin lesions and a positive rK39 test result.
The sensitivity and specificity of the rK39 RDT can vary, but in an analysis of studies from different countries, the World Health Organization (WHO) reported 94% sensitivity and 91% specificity compared with microscopic examination of splenic aspirates, which is considered the gold standard for diagnosis. In 2008, NKEP distributed rK39 test kits to all upazilla health complexes (UHCs) in Bangladesh.
The second element of NKEP is effective treatment. In 2009, a new drug, miltefosine, was introduced as an alternative to sodium stiobogluconate (SSG), the drug that had been previously used but requires inpatient treatment for 28 days to receive intramuscular injections.
Miltefosine can be administered orally for 28 days on an outpatient basis. Several months after the introduction of miltefosine in Bangladesh, another drug, liposomal amphotericin, which can be administered as a single dose for the treatment of KA, was introduced in Bangladesh. Single-dose liposomal amphotericin B (sLAB) is very effective and has fewer side effects than miltefosine and SSG.
However, sLAB requires equipment to maintain a cold chain and more clinical monitoring than is needed for treatment with miltefosine or SSG. The WHO, in collaboration with the Government of Bangladesh, trained 96 doctors and 96 nurses in hyper-endemic areas (Figure 2) to administer sLAB for the treatment of KA.
The third element of the NKEP is vector control. Two things are important for transmission of leishmaniasis. One is the vector, sandflies, and the other is the reservoir, persons with leishmaniasis, and particularly those with the chronic form, or PKDL (if a sandfly bites a person with PKDL and then bites someone else, there is a risk of KA transmission). Beginning in 2011, NKEP focused on vector control to reduce the transmission of the parasite to humans.
Trials of indoor residual spraying in two areas in Mymensingh District and long-lasting insecticide treated bed nets in Rajshahi and Mymensingh District were conducted. These trials were successful and NKEP began to use these vector control methods in hyper-endemic subdistricts of Bangladesh (Figure 2).
Since NKEP was initiated in 2008, the number of KA cases has declined steadily. Although NKEP has been a successful programme, which can be attributed in large part to the introduction of a new diagnostic test and treatment and vector control, there are still several challenges.
First, the programme uses passive case detection, in which the government relies on the patients attendance at government hospitals. KA patients who go to private doctors or private facilities may be missed in addition to those who do not access healthcare. A study conducted in sub-districts of Mymensingh and Rajshahi districts found that 75% of deaths due to KA occurred at home and that none of these deaths were reported in Bangladeshs KA surveillance system . Implementation of active surveillance in areas endemic for KA, would capture more cases, enhance monitoring of the burden and mortality from KA and would likely increase access to effective treatment.
Second, though the rK39 RDT is a sensitive and specific test that is easy to perform and inexpensive, it has some limitations. For example, the test cannot distinguish between current and past KA infections because it detects antibodies against Leishmania spp., which can persist for years after infection with KA. Current KA infections need to be treated, whereas past infections do not, so physicians need to use judgment to determine the clinical implications of a positive RDT test result. A rapid test that specifically identifies a current infection, perhaps by detecting antigen to Leishmania, would be beneficial for appropriate clinical management of KA.
Third, although sLAB is an effective treatment regimen, it requires the maintenance of a cold chain until it is administered and it requires that patients temperature, blood pressure, and fluid status are closely monitored. However, the necessary resources and training are lacking in some UHC hospitals, particularly those in rural settings. A study conducted in Mymensingh District before mid 2013 reported that of five UHC hospitals, most lacked the necessary resources such as 5% Dextrose, distilled water, disposable infusion sets, disposable syringes, and gloves, needed to administer sLAB. Ensuring that there are adequate supplies and trained personnel to administer sLAB in UHCs will be necessary to further reduce KA.
Finally, vector control requires more attention. NKEPs use of indoor residual spray and long-lasting insecticide treated bed nets, has some limitations. Excessive use of insecticides can result in insecticide resistance in sandflies. Use of insecticides also has a negative impact on the environment. However, integrated vector control management is necessary to reach the NKEP goal of reducing KA incidence. It will be important to develop and pilot insecticides with limited deleterious environmental effects.
Treatment of persons with PKDL is also important for controlling transmission. Persons with PKDL are the reservoir for infection and might play a role in the re-emergence of KA several years later. Persons with PKDL are thought to have contributed to the resurgence of KA in South Asia in the 1990s. In the 1960s, government officials in South Asia initiated a programme to eradicate malaria by using insecticides to reduce the number of mosquitoes and interrupt transmission.
This was successful in reducing the number of mosquitoes and it also reduced the number of sandflies. Subsequently, both malaria and KA cases declined markedly. In the 1990s, KA again resurged, likely from transmission of the Leishmania parasite from persons with PKDL to sandflies and then onward to previously uninfected persons . As of 2012, 325 persons with PKDL had been treated.
Campaigns should be conducted to raise awareness about the role that persons with PKDL play in KA transmission and the individual and societal benefits that treatment will bring. Diagnosis of KA and PKDL can also be complex. KA can be mistaken for a variety of febrile illnesses and PKDL can be confused with,leprosy. Training providers to be able to detect and appropriately treat KA and PKDL will be very important.
The findings presented in this report indicate that progress is being made in reducing the number of KA cases in Bangladesh. However, efforts will be needed to improve case detection, treatment, and control of vectors and reservoirs.
Continued technical and financial assistance from national and international agencies will be essential for NKEP to achieve its goal to reduce the incidence of KA to less than one case per 10,000 population in every endemic sub-district by 2015.
Source : HSB; ICDDR,B
