Effectiveness Study of Paromomycin IM Injection (PMIM) for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh
Kazi M Jamil, Rashidul Haque, Ridwanur Rahman, M Abul Faiz, Abu Toha Md Rezwanul Haque Bhuiyan, Amresh Kumar, Syed Misbah Hassan, Heather Kelly, Pritu Dhalaria, Sonali Kochhar, Philippe Desjeux, Mohammad A A Bhuiyan, Mohammed M Khan, Raj Shankar Ghosh, Kazi M Jamil, Rashidul Haque, Ridwanur Rahman, M Abul Faiz, Abu Toha Md Rezwanul Haque Bhuiyan, Amresh Kumar, Syed Misbah Hassan, Heather Kelly, Pritu Dhalaria, Sonali Kochhar, Philippe Desjeux, Mohammad A A Bhuiyan, Mohammed M Khan, Raj Shankar Ghosh
Abstract
Background: This study was conducted in Bangladeshi patients in an outpatient setting to support registration of Paromomycin Intramuscular Injection (PMIM) as a low-cost treatment option in Bangladesh.
Methodology: This Phase IIIb, open-label, multi-center, single-arm trial assessed the efficacy and safety of PMIM administered at 11 mg/kg (paromomycin base) intramuscularly once daily for 21 consecutive days to children and adults with VL in a rural outpatient setting in Bangladesh. Patients ≥5 and ≤55 years were eligible if they had signs and symptoms of VL (intermittent fever, weight loss/decreased appetite, and enlarged spleen), positive rK39 test, and were living in VL-endemic areas. Compliance was the percentage of enrolled patients who received 21 daily injections over no more than 22 days. Efficacy was evaluated by initial clinical response, defined as resolution of fever and reduction of splenomegaly at end of treatment, and final clinical response, defined as the absence of new clinical signs and symptoms of VL 6 months after end of treatment. Safety was assessed by evaluation of adverse events.
Principal findings: A total of 120 subjects (49% pediatric) were enrolled. Treatment compliance was 98.3%. Initial clinical response in the Intent-to-Treat population was 98.3%, and final clinical response 6 months after end of treatment was 94.2%. Of the 119 subjects who received ≥1 dose of PMIM, 28.6% reported at least one adverse event. Injection site pain was the most commonly reported adverse event. Reversible renal impairment and/or hearing loss were reported in 2 subjects.
Conclusions/significance: PMIM was an effective and safe treatment for VL in Bangladesh. The short treatment duration and lower cost of PMIM compared with other treatment options may make this drug a preferred treatment to be investigated as part of a combination therapy regimen. This study supports the registration of PMIM for use in government health facilities in Bangladesh.
Trial registration: ClinicalTrials.gov identifier: NCT01328457.
Conflict of interest statement
The authors have declared that no competing interests exist.
Figures
References
- Joshi A, Narain JP, Prasittisuk C, Bhatia R, Hashim G, et al. (2008) Can visceral leishmaniasis be eliminated from Asia? J Vector Borne Dis 45: 105–111.
- Rahman KM, Islam N (1983) Resurgence of visceral leishmaniasis in Bangladesh. Bull World Health Organ 61: 113–116.
- World Health Organization. (2011) Bangladesh. .
- Sundar S, Jha TK, Thakur CP, et al. (2007) Injectable paromomycin for visceral leishmaniasis in India. N Engl J Med 356: 2571–2581.
- Sinha PK, Jha TK, Thakur CP, et al. (2011) Phase 4 pharmacovigilance trial of paromomycin injection for the treatment of visceral leishmaniasis in India. J Trop Med 2011: 645203 10.1155/2011/645203
- Musa A, Khalil E, Hailu A, et al. (2012) Sodium stibogluconate (SSG) & paromomycin combination compared to SSG for visceral leishmaniasis in East Africa: a randomized controlled trial. PLoS Negl Trop Dis. 6:e1674 10.1371/journal.pntd.0001674
- Gomes MF, Faiz MA, Gyapong JO, et al. (2009) Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial. Lancet 373: 557–566. 10.1016/S0140-6736(08)61734-1
- World Health Organization. (2010) Control of the leishmaniases. World Health Organ Tech Rep Ser. xii-xiii, 1–186.
Source: PubMed