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. 2023 Sep 27:10:1260375.
doi: 10.3389/fmed.2023.1260375. eCollection 2023.

Field-friendly anti-PGL-I serosurvey in children to monitor Mycobacterium leprae transmission in Bihar, India

Louise Pierneef  1 , Paritosh Malaviya  2 , Anouk van Hooij  1 , Shyam Sundar  2 , Abhishek Kumar Singh  2 , Rajiv Kumar  3 , Danielle de Jong  4 , Maaike Meuldijk  1 , Awnish Kumar  3 , Zijie Zhou  1 , Kristien Cloots  5 , Paul Corstjens  4 , Epco Hasker  5 , Annemieke Geluk  1
Affiliations

Field-friendly anti-PGL-I serosurvey in children to monitor Mycobacterium leprae transmission in Bihar, India

Louise Pierneef et al. Front Med (Lausanne). .

Abstract

Background: It has been amply described that levels of IgM antibodies against Mycobacterium leprae (M. leprae) phenolic glycolipid I (PGL-I) correlate strongly with the bacterial load in an infected individual. These findings have generated the concept of using seropositivity for antibodies against M. leprae PGL-I as an indicator of the proportion of the population that has been infected. Although anti-PGL-I IgM levels provide information on whether an individual has ever been infected, their presence cannot discriminate between recent and past infections. Since infection in (young) children by definition indicates recent transmission, we piloted the feasibility of assessment of anti-PGL-I IgM seroprevalence among children in a leprosy endemic area in India as a proxy for recent M. leprae transmission.

Material and methods: A serosurvey for anti-PGL-I IgM antibodies among children in highly leprosy endemic villages in Bihar, India, was performed, applying the quantitative anti-PGL-I UCP-LFA cassette combined with low-invasive, small-volume fingerstick blood (FSB).

Results: Local staff obtained FSB of 1,857 children (age 3-11 years) living in 12 leprosy endemic villages in Bihar; of these, 215 children (11.58%) were seropositive for anti-PGL-I IgM.

Conclusion: The anti-PGL-I seroprevalence level of 11.58% among children corresponds with the seroprevalence levels described in studies in other leprosy endemic areas over the past decades where no prophylactic interventions have taken place. The anti-PGL-I UCP-LFA was found to be a low-complexity tool that could be practically combined with serosurveys and was well-accepted by both healthcare staff and the population. On route to leprosy elimination, quantitative anti-PGL-I serology in young children holds promise as a strategy to monitor recent M. leprae transmission in an area.

Keywords: anti-M. leprae PGL-I antibodies; children; diagnostics; infection; leprosy; serosurvey; transmission; upconversion.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Fully integrated anti-PGL-I UCP-LFA cassette and analysis. Left: FSB is collected with a minivette (20 μl). To initiate LF, a diluted FSB sample is added to the cassette onto the sample pad. Hydration of the anti-IgM UCP-conjugate will allow the binding of anti-PGL-I IgM antibodies from the sample to the conjugate and sequential binding to the T line with synthetic PGL-I. The FC line can bind UCP conjugate not bound to the T line. Color-coded T and FC lines visible by the eye disappear upon flow. Right: UCP signals are detected with a reader upon excitation with 980 IR light generating 540 nm emission. Results for positive and negative samples are shown. Results are calculated as R-value, with the T signal divided by the FC signal. This figure was created with BioRender.com. FC, flow control line; FSB, fingerstick blood; IgM, immunoglobulin M; IR, infrared excitation; PGL-I, phenolic glycolipid I; R, ratio value, result of the UCP-LFA; T, test line; UCP-LFA, upconverting reporter particle lateral flow assay.
Figure 2
Figure 2
Presence of anti-PGL-I IgM antibodies in FSB of 1,857 children 3–11 years old in Bihar, India. UCP-LFA cassettes were used to obtain a quantitative R-value (T/FC) indicating the presence of anti-PGL-I IgM antibodies using a UCP reader. (A) Histogram with a mode of 0.01 for R: the highest R-value detected was 0.84 (n = 1). The cutoff for positivity (R ≥ 0.12) for the UCP-LFA batch used in this study is indicated by the dotted line and was based on the median of a sextuple test performed in India of a standard control serum sample (+) plus its standard deviation (SD). (B) Histogram of log-transformed R-values. FC, flow control line; IgM, immunoglobulin M; PGL-I, phenolic glycolipid I; R, ratio value, result of the UCP-LFA; T, test line.
Figure 3
Figure 3
Presence of anti-PGL-I IgM antibodies in FSB of children in relation to age, gender, and place of residence. UCP-LFA cassettes were used to obtain a quantitative ratio (R) value (T/FC) indicating the presence of anti-PGL-I IgM using a UCP reader. Median values for each group are indicated by horizontal bars. The cutoff for positivity (R ≥ 0.12) for the UCP-LFA batch used in this study was based on the median of a sextuple test performed in India of a standard control serum sample (+) plus its standard deviation (SD). The numbers of individuals per group are given in parentheses. (A) Anti-PGL-I IgM R values per age group. Two children aged 3 years and one child aged 4 years were included in the 5-year-old age group and one child aged 11 years was included in the 9-year-old age group. (B) Venn diagrams displaying the proportion of children per age category for anti-PGL-I IgM-positive (+) and -negative (–) children. Colors indicate the age groups. (C) Anti-PGL-I IgM R values per gender. (D) Anti-PGL-I IgM R values per village. A: Singar Phulkahan, B: Madhopur Chhapra, C: Godai Phulkahan, D: Godai Jamal, E: Vishwanathpur, F: Raksha North, G: Raksha North Chauk, H: Raksha South West, I: Raksha South, J: Raksha Deah, K: Nariyar Nawada, L: Arizpur Kothi. FC, flow control line; IgM, immunoglobulin M; PGL-I, phenolic glycolipid I; R, ratio value, result of the UCP-LFA; T, test line.
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