At the time of our study, most PKDL patients in Bangladesh did not seek treatment, and those people who did encountered many barriers. These barriers included the cost of transportation, special diets, and sometimes, treatment drug, but perhaps most importantly, they included the many days of lost income resulting from the prolonged regimen. Despite this finding, most patients who started treatment had the persistence and hardiness to complete the full 120-injection course. Some barriers came from the healthcare system itself. Before 2007, Fulbaria Upazila Health Center physicians were able to prescribe PKDL treatment without further referral, but beginning in 2007, new guidelines required patients to obtain a recommendation for treatment from the district hospital (30 km from the Upazila Health Center). Despite the good intentions behind promoting a stricter requirement for PKDL diagnosis, this change seems to have discouraged many PKDL patients from seeking treatment.
Because PKDL patients are usually not systemically ill, why is PKDL treatment important? PKDL has been known to be infectious to sand flies since 1928.12
Patients with PKDL, particularly the nodular forms, are known to remain infectious for decades, and they are thought to provide a durable infection reservoir that allows transmission to be sustained when kala-azar incidence is driven to very low levels, which it was by widespread indoor residual spraying during the 1950s and 1960s.13,14
Because kala-azar patients are usually treated within a few months of symptom onset, their contribution to the overall infection reservoir may be less than that of PKDL patients who remain untreated for years. Untreated PKDL patients, therefore, threaten the basic feasibility of eliminating visceral leishmaniasis as a public health problem.
Visceral leishmaniasis has strong bidirectional links with poverty.9,15–22
In South Asia, endemic foci are concentrated in rural areas and poorer states, and highly affected communities seem to be poorer than other communities in the same district.16,19
Superimposed on this background, the disease itself further impoverishes affected families. For example, the median treatment cost for a kala-azar patient exceeded the median per capita annual income by 20% in the earlier Bangladesh study.9
In Nepal, expenditures for treatment of visceral leishmaniasis caused 20% of previously non-poor study households to fall below the national poverty line.16
Our study shows the even greater financial burden caused by PKDL in Bangladesh. We estimate that the median annual per capita income in the study site was approximately US$160 based on income data collected in the same population in 2004 adjusted for growth in the Gross Domestic Product (GDP) in Bangladesh between 2004 and 2009.11
This finding implies that the median per patient cost for PKDL treatment was greater than the annual per capita income of the study population.
Because most PKDL occurs in treated kala-azar patients, nearly every household affected by PKDL must bear more than one heavy financial burden within a few years—first for kala-azar and then for PKDL treatment. Successive needs for costly treatment in a relatively short time frame may be catastrophic to affected families, many of who already live in poverty. One mother lamented her inability to provide her son with any additional food at the time that he was undergoing treatment. She reported that four earlier cases of kala-azar in the family had exhausted all their cash reserves, and by the time that the boy developed PKDL, they no longer had any valuables that could be sold or rented. For families like hers, the only available source of funds is a loan with a high interest rate.
These observations are consistent with findings from low-income countries with limited formal health insurance coverage. In Asian countries like Bangladesh, China, India, Nepal, and Vietnam, families manage more than 60% of healthcare costs out of pocket.23
Large out of pocket health expenditures alone can exacerbate poverty.23
More importantly, strategies that families use to cope with an illness can deplete assets, cause long-term indebtedness, and have a catastrophic impact on household welfare.24–26
Economists define health spending as catastrophic when a household spends a large fraction of the household budget at the expense of its subsistence.27,28
In our study, when lost income and debt payments were taken into account, the total expenditure for 86% of treated patients exceeded the median per capita income. Thus, PKDL treatment is likely to lead to catastrophic health expenditure for the majority of affected households.
The current study also found that patients were less likely to seek care for PKDL if they lived far from the provider or were required to be evaluated first at the district hospital. In particular, after the new referral guideline was introduced in 2007, PKDL patients seem to have been discouraged from seeking further medical attention because of logistical and financial constraints. Adding to the economic burden of the prolonged treatment, these barriers to healthcare access affect the disease outcome of individual patients and may have lead to low treatment uptake in the study population. In the present study, nearly 60% of all PKDL went untreated, and these patients had PKDL symptoms (and therefore, might be hypothesized to be infectious to sand flies) for a median of 25 months when they were interviewed for this study. Data from the active surveillance project showed a sharp increase in PKDL incidence in 2007 and 2008, echoing the prior kala-azar epidemic that peaked in 2005.5
Given the lack of active PKDL surveillance and sensitive diagnostic testing, the low treatment uptake leading to an increasing cumulative burden of untreated PKDL translates to a persistent and growing parasite reservoir in the community. These barriers to care may, therefore, have the unintended consequence of increasing levels of leishmaniasis transmission in the community.
Our study had several limitations. First, we relied primarily on recall by patients and/or their family members for an illness that occurred as early as 2003. Although we obtained written records of treatment and associated costs whenever possible, inaccurate recall may have caused under- or overestimation of the strength of associations and expenditure estimates. However, the requirement of 120 injections and trips to a hospital is a major family event that is not easily forgotten. Indeed, many of our interviewees remembered and described their experiences and expenses in impressive detail. Second, the difficulty of achieving parasitological diagnosis of PKDL may have resulted in over- or underdiagnosis in the study population. Diagnosis of PKDL is currently largely clinical, because the available tests, such as microscopic or molecular examination of a slit skin sample or skin biopsy, require invasive sampling and have suboptimal sensitivity, especially in macular disease.6
Clinical diagnosis can be subjective, especially by physicians without PKDL experience and in mild disease. In the present study, those patients who reported that their lesions resolved after 120 injections were considered as having past PKDL, and we have no way of determining the validity of their diagnoses that were made at local health facilities. In addition, our clinical data were insufficiently quantified to determine how the severity of PKDL lesions and changes in severity may have affected care-seeking behavior and resulting treatment-related expenses. It is also possible that the questionnaire may not have captured all categories of treatment-related costs. Finally and most importantly, our data did not include household-level assessment of income and other socioeconomic indicators, which may have had an impact on the ability to pay for care.
Conditions that influence treatment costs and the likelihood of receiving treatment vary among visceral leishmaniasis-endemic areas within Bangladesh and across the region. Qualitative studies are necessary to better capture the social and economic implications of PKDL. Thus, the generalization of our results to other populations should be made with caution. Nevertheless, the present study underscores the extremely high cost of the prolonged PKDL treatment regimen in endemic communities. Consistent with previous studies of the economic impact of kala-azar in South Asia, we found the overall cost of treatment to be substantially greater when associated costs, such as informal payments to service providers, lost incomes, and debt payments, are taken into account.16,26,29
These findings clearly indicate that the treatment regimen of 120 SAG injections is neither practical nor affordable. When a family chooses to have a PKDL patient treated, the patient will experience prolonged morbidity, and the household may be plunged further into poverty. When a family chooses not to have a PKDL patient treated, other family members and neighbors are exposed to ongoing parasite transmission.
The regional initiative to eliminate visceral leishmaniasis in South Asia was launched in 2005 with a goal of reducing the annual kala-azar incidence to below 1 per 10,000 persons by 2015.2
However, without better treatment of PKDL, this ambitious goal is unlikely to be achieved in the near future. There is an urgent need for sensitive low-cost diagnostic tools to facilitate community-based PKDL case detection and more practical shorter-course treatment regimens. The development of such diagnostic tools and treatment regimens requires additional studies, including trials to assess the efficacy of existing and newer drugs of interest. One trial in India suggested that 12 weeks of miltefosine might provide an alternative, and liposomal amphotericin (30 mg/kg total dose administered over 3 weeks) is currently being used off-label to treat PKDL in Fulbaria.30,31
However, further clinical trials to assess long-term efficacy of these regimens are needed. National and regional visceral leishmaniasis elimination will only be possible with coordinated efforts among stakeholders to develop and implement these tools.