Relationship of Serum Antileishmanial Antibody With Development of Visceral Leishmaniasis, Post-kala-azar Dermal Leishmaniasis and Visceral Leishmaniasis Relapse.

Dinesh Mondal,Piero Olliaro,Md Anik Ashfaq Khan,Daniel Argaw,Rupen Nath,Faria Hossain,Malcolm S Duthie,Axel Kroeger,Christine Halleux,Jose A Ruiz-Postigo,Rajashree Chowdhury,Greg Matlashewski,Prakash Ghosh,Abdul Alim

doi:10.3389/fmicb.2019.02268

Abstract

IntroductionTo sustain the achievement of kala-azar elimination program (KEP), early detection and treatment of the visceral leishmaniasis (VL) cases and associated modalities such as treatment failure (TF), relapse VL (RVL), and Post-kala-azar dermal leishmaniasis (PKDL) is the cornerstone. A predictive biomarker for VL development and related complications could also play a crucial role in curtailing disease incidence and transmission. Investigations to find a biomarker with prospective capabilities are, however, scarce. Using samples and known clinical outcomes generated within two previous longitudinal cohort studies, we aimed to determine if fluctuations in serum anti-rK39 antibody levels could provide such predictive value.Materials and MethodsSerum samples collected at four different time points (Baseline, 12, 18, and 24 months) from 16 patients who had developed VL within the monitoring period and 15 of their asymptomatic healthy controls counterparts were investigated. To investigate potential prediction of VL related complications, serum samples of 32 PKDL, 10 RVL, 07 TF, and 38 cured VL from a single dose AmBisome trial were analyzed. Of this second panel, all patients were monitored for 5 years and sera were collected at four time points (Baseline then 1, 6, and 12 months after treatment). The level of anti-rK39 antibodies in archived samples was measured by a semi-quantitative ELISA.ResultsThe mean antibody level was significantly higher in VL patients compared to their asymptomatic healthy counterparts at each time point. Likewise, we observed a trend toward elevations in antibody levels for PKDL, RVL, TF relative to the reducing levels observed in cured VL. Receiver operating characteristic (ROC) analysis found a promising predictive power of rK39 antibody levels to reveal progression from asymptomatic Leishmania donovani infection stage to VL, defined as 87.5% sensitive and 95% specific. Following treatment, rk39 antibody notably showed 100% sensitivity and 95% specificity in predicting TF.ConclusionOur data indicate that the relative quantity of serum anti-rK39 antibody has promise within either a predictive or prognostic algorithm for VL and VL-related modalities. These could enable VL control programs to implement more effective measures to eliminate the disease. Further research is, however, imperative to standardize the rK39 antibody ELISA between sites prior to broader use.

Highlights

To sustain the achievement of kala-azar elimination program (KEP), early detection and treatment of the visceral leishmaniasis (VL) cases and associated modalities such as treatment failure (TF), relapse VL (RVL), and Post-kala-azar dermal leishmaniasis (PKDL) is the cornerstone
A recent cohort study from Bangladesh established that 3–7% of initially cured VL patients may develop VL again, and this is collectively defined as VL relapse (VLR) (Mondal et al, 2019)
While VL patients are generally believed to be the engine of L. donovani transmission, we have demonstrated that VL, VLR, and PKDL cases can all transmit Leishmania donovani (LD) to sand flies (Addy and Nandy, 1992; Molina et al, 2017; Mondal et al, 2018)

Summary

Introduction

To sustain the achievement of kala-azar elimination program (KEP), early detection and treatment of the visceral leishmaniasis (VL) cases and associated modalities such as treatment failure (TF), relapse VL (RVL), and Post-kala-azar dermal leishmaniasis (PKDL) is the cornerstone. For VL case management, control and elimination, critical remaining questions are which individuals are at risk of becoming diseased and who can transmit the infection. 90% of infected individuals do not develop VL symptoms but rather remain asymptomatic (dos Santos et al, 2016), while about 10% go on to develop clinically overt disease with fever, enlarged spleen, anemia or pancytopenia (VL patient) (unpublished data). A recent cohort study from Bangladesh established that 3–7% of initially cured VL patients may develop VL again, and this is collectively defined as VL relapse (VLR) (Mondal et al, 2019). In Bangladesh, 10–20% of cured VL patients may develop Post-kala-azar dermal leishmaniasis (PKDL), a dermatological sequela of VL, usually within 3 years following treatment (Mondal et al, 2019). In Bangladesh approximately 10% of asymptomatic may develop PKDL without having had clinical VL (Rahman et al, 2010)

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