Detection and Monitoring of Mycobacterium leprae Infection in Nine Banded Armadillos (Dasypus novemcinctus) Using a Quantitative Rapid Test

Zhou, Zhongqiang; Peña, María; Hooij, Anouk van; Pierneef, Louise; Jong, Daniëlle de; Stevenson, Roena; Walley, Rachel; Corstjens, Paul L. A. M.; Truman, Richard W.; Adams, Linda B.; Geluk, Annemieke

doi:10.3389/fmicb.2021.763289

Cited by 7 publications

(4 citation statements)

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“…We have previously shown that antibody levels for the M. leprae-specific PGL-1 correlate with bacterial load in armadillos (39)(40)(41). In order to determine the correlation between anti-PGL-1 antibody levels and impaired nerve conduction, we stratified 71 M. leprae-infected armadillos at different stages of leprosy disease into two groups according to serum anti-PGL-1 IgM antibody levels.…”

Section: Correlation Of Mnct With Disease Progression and Anti-pgl-1 ...mentioning

confidence: 99%

The Armadillo as a Model for Leprosy Nerve Function Impairment: Preventative and Therapeutic Interventions

Peña

Lahiri

Ebenezer³

et al. 2022

Front. Med.

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Mycobacterium leprae infection of peripheral nerves and the subsequent nerve function impairment (NFI), especially in response to reactional episodes, are hallmarks of leprosy. Improved treatments for M. leprae-induced nerve injury are needed, as most if not all of the disability and stigma associated with leprosy arises from the direct or indirect effects of NFI. Nine-banded armadillos (Dasypus novemcinctus), like humans, exhibit the full clinical spectrum of leprosy and extensive involvement of the peripheral nerves. In this study, state-of-the-art technology was used to compare nerve function between uninfected and M. leprae-infected armadillos. Motor nerve conduction velocity (MNCV) and compound muscle action potential (cMAP), which measure changes in the rate of impulse conduction velocity and amplitude, revealed a progression of impairment that was directly correlated with the duration of M. leprae infection and enabled development of an objective nerve impairment scoring system. Ultrasonography accompanied by color Doppler imaging detected enlargement of the M. leprae-infected nerves and increased vascularity, possibly due to inflammation. Assessment of epidermal nerve fiber density (ENFD), which shows a length-dependent innervation in armadillos that is similar to humans, identified small fiber degeneration early after M. leprae infection. Staining for neuromuscular junction (NMJ) integrity, which is an indicator of signal transduction efficiency into skeletal muscle, discerned a markedly lower number and structural integrity of NMJ in M. leprae-infected armadillo footpads. These tools for assessing nerve injury were used to monitor the effects of intervention therapy. Two potential neuro-protective drugs, ethoxyquin (EQ) and 4-aminopyridine (4-AP), were tested for their ability to ameliorate peripheral nerve injury in M. leprae-infected armadillos. 4-AP treatment improved MNCV, cMAP, and EFND compared to untreated animals, while EQ had less effect. These results support the armadillo as a model for M. leprae-induced peripheral nerve injury that can provide insights toward the understanding of NFI progression and contribute to the preclinical investigation of the safety and efficacy of neuro-preventive and neuro-therapeutic interventions for leprosy.

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Section: Correlation Of Mnct With Disease Progression and Anti-pgl-1 ...mentioning

confidence: 99%

The Armadillo as a Model for Leprosy Nerve Function Impairment: Preventative and Therapeutic Interventions

Peña

Lahiri

Ebenezer³

et al. 2022

Front. Med.

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“…Over the past years, we have developed a robust, user-friendly test that detects anti-PGL-I IgM antibodies using the unique upconverting reporter particle (UCP) technology in a low-cost lateral flow-based assay (LFA) format [( 18 , 22 – 26 ) and Pierneef et al ( manuscript in preparation )]. The anti-PGL-I UCP-LFA offers a sensitive, low-complexity rapid test to quantitatively determine anti-PGL-I IgM levels in capillary and venous blood ( 24 , 27 ).…”

Section: Introductionmentioning

confidence: 99%

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

Pierneef,

Malaviya,

van Hooij

et al. 2023

Front. Med.

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BackgroundIt 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 methodsA 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).ResultsLocal 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.ConclusionThe 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.

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“…Recent studies showed that zoonotic transmission is possible from a nine‐banded Armadillo ( Dasypus novemcinctus ) to healthy individuals 3 . Leprosy is not an inherited disorder, but genetics and the alteration in genes may increase susceptibility towards the disease.…”

Section: Introductionmentioning

confidence: 99%

Hyperfunction variant rs708035 of interleukin 1 receptor‐associated kinases 2 gene involved in the predisposition of leprosy infection

Saleem

Zia²,

Siddiqui

et al. 2023

The Journal of Gene Medicine

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Background Mycobacterium leprae (slow‐growing bacteria) is the etiological agent for leprosy infection, which is a chronic granulomatous disease. Symptoms initiate with the loss of sensation in the affected areas, which can lead to severe injuries, cuts and burns. IRAK2 (interleukin‐1 receptor‐associated kinases 2) is reported to function in the regulation of the NFκB pathway. The frequency of the IRAK2 polymorphism (rs708035) was unknown in the Pakistani population. Therefore, the study was designed to identify the role of the rs708035 SNP (single nucleotide polymorphism) in susceptibility to leprosy. Methodology The case–control study was designed, and participants were selected by Ridley–Jopling Classification. Blood samples from healthy individuals and patients were collected after ethical approval. Genomic DNA was extracted for the amplification of selected polymorphisms by tetra‐primer amplification refractory mutation system polymerase chain reaction. The desired products were observed via agarose gel (2.5%) electrophoresis followed by data analysis using bioinformatics tools (SNP Stats and SHEsis) and statistical tests (odds ratio, OR, and chi square). Results The study revealed that the mutant genotype (TT) was found to be frequent among cases (22.80%) in comparison with the controls (1.66%). The SNP rs708035 was significantly associated with the progression of leprosy (χ2 = 17.62, p < 0.0001). The targeted SNP significantly increases the risk of leprosy 2.3 times (OR = 2.3119, 95% CI 1.2729–4.1989, p < 0.01). The genetic model also confirms the significant association of the A/T genotype with leprosy in the over‐dominant model (OR = 2.83, 95% CI 1.16–6.89, p < 0.001). Conclusions The study revealed a significant association of the targeted SNP with leprosy and provided baseline data regarding the association of rs708035. The current research could be utilized for the preparation of biomarkers by considering a larger sample size. Highlights The patients suffering from leprosy faced various comorbidities, including hypertension and diabetes. The study reports for the first time a significant association of interleukin 1 receptor associated kinases 2 (IRAK2) single nucleotide polymorphism (SNP) rs708035 among the Pakistani population (Karachi). The current study provides baseline data to develop diagnostic biomarkers for early detection of leprosy.

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Detection and Monitoring of Mycobacterium leprae Infection in Nine Banded Armadillos (Dasypus novemcinctus) Using a Quantitative Rapid Test

Cited by 7 publications

References 54 publications

The Armadillo as a Model for Leprosy Nerve Function Impairment: Preventative and Therapeutic Interventions

The Armadillo as a Model for Leprosy Nerve Function Impairment: Preventative and Therapeutic Interventions

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

Hyperfunction variant rs708035 of interleukin 1 receptor‐associated kinases 2 gene involved in the predisposition of leprosy infection

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