Immediate rollout of an effective
Immediate rollout of an effective and safe short-course treatment regimen is essential for the attack phase of the visceral leishmaniasis elimination programme, which aims to reduce the incidence to less than one case per 10 000 could at risk. A single-dose liposomal amphotericin B regimen, which is very effective, safe, and is likely to have fewer issues of poor compliance because of its lower side-effect profile, is in principle an ideal alternative to miltefosine. However, distribution of liposomal amphotericin B requires a cool chain, which might be an impediment to its implementation in remote regions where most of the visceral leishmaniasis patients seek care. Therefore, studies into the feasibility of the use of liposomal amphotericin B in rural public hospitals are needed.
Results We enrolled 300 participants between March 5 and Aug 14, 2012, and 6 month follow-up was completed by Feb 14, 2013 (figure, table 1). Notably, 232 (77%) of participants had primary visceral leishmaniasis and 68 (23%) were relapses. 46 (68%) of these patients with relapse had previously received miltefosine. In general, study patients were underweight and young (table 1). 175 (58%) patients had anaemia, defined as a haemoglobin concentration of less than 100 g/L. Table 2 shows initial cure rates in the intention-to-treat and per-protocol populations. One participant did not show any clinical improvement and was referred to the specialist centre, where a spleen aspiration confirmed the presence of leishmania parasites. The remaining 36 participants who were not regarded as initially cured according to the study protocol had not reached the necessary increase in haemoglobin concentrations by 10% compared with baseline value. However, these 36 participants had no clinical evidence of active diseases. In all these patients, spleen sizes had decreased in size and no recurrence of fever was noted. Nevertheless, we referred them to the hospital doctor. On the basis of hospital doctor\'s judgment, they were not referred to the specialist hospital, but were followed up closely and their haemoglobin concentration was assessed on day 60 or day 90. In all cases apart from one, the haemoglobin concentration increased to more than 100 g/L at day 60 or day 90, and therefore these patients were asked to return for final cure assessment. One patient was diagnosed with thalassaemia at the specialist centre (figure). No participants were lost during the follow-up period. Between day 30 and day 180 assessment, seven participants relapsed, resulting in a per-protocol final cure rate at 6 months of 98% and an intention-to-treat cure rate of 97% (table 2). Most patients tolerated single-dose liposomal amphotericin B (table 3). All drug-related adverse events were mild-to-moderate and all were managed with the resources available at the Mugtagasha upazila hospital. None of the participants required referral to tertiary hospital for complications. The most common adverse event during trial medication was fever, vomiting, and fever with rigor (table 3). Within 2 h of medication, the most common adverse event was fever with rigor followed by fever and hypotension (table 3), which responded well to oral rehydration therapy only. On the day after infusion, all patients were afebrile and all adverse events had resolved.
Discussion In view of present treatment options, WHO has recommended monotherapy with liposomal amphotericin B during the attack phase of visceral leishmaniasis elimination to rapidly reduce the burden of the disease. Therefore, our study provides an important assessment of the feasibility of administering single-dose liposomal amphotericin B close to endemic villages at a rural hospital primary health-care level (panel). Our study showed that treatment of visceral leishmaniasis was feasible in a rural hospital in Bangladesh with a single intravenous infusion of liposomal amphotericin B. Most patients were treated in the rural hospital only (91%), with a high acceptance (98%), cure rate (97% in the intention-to-treat analysis), and good safety profile. We noted no serious adverse events related to study drug and all adverse events were manageable in the hospital with straightforward procedures. Thus, we believe single-dose liposomal amphotericin B offers the best option in terms of efficacy and compliance during the attack phase of the visceral leishmaniasis elimination programme and community age strategy could be extended to Bangladesh, India, and Nepal.