A systematic review and meta-analysis of studies on the diagnostic accuracy and screening of tests to detect antimicrobial resistance in leprosy

Andrade, Elaine Silva Nascimento; Brandão, Jurema Guerrieri; Silva, Juliana Souza da; Kurizky, Patrícia Shu; Rosa, Patrícia Sammarco; Araújo, Wildo Navegantes de; Gomes, Ciro Martins

doi:10.1016/j.diagmicrobio.2021.115325

Cited by 10 publications

(11 citation statements)

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“…Leprosy is a chronic infectious disease caused by Mycobacterium leprae and Mycobacterium lepromatosis. [1] Affected patients may experience a variety of neurological and cutaneous symptoms because of the immunological response stimulated by the bacillus. [2] Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, an interaction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and M. leprae infection has been considered a possibility.…”

Section: Introductionmentioning

confidence: 99%

The influence of leprosy-related clinical and epidemiological variables in the occurrence and severity of COVID-19: A prospective real-world cohort study

et al. 2021

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Background Protective effects of Bacillus Calmette–Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19. Methodology/Principal findings We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93–13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04–4.06) were significant risk factors for COVID-19. Conclusions/Significance Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.

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Section: Introductionmentioning

confidence: 99%

The influence of leprosy-related clinical and epidemiological variables in the occurrence and severity of COVID-19: A prospective real-world cohort study

et al. 2021

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“…At first glance, this might be considered a contradictory result according to the quantification limit of less than 1 bacillus. However, sensitivity limitations are expected to exist in clinical practice because of several factors, including human-related limitations and biological factors such as the presence of DNA inhibitors ( Andrade et al, 2021 ). In line with our results, previous studies of leprosy reached a reduced summary sensitivity of approximately 75% for real-time PCR, proving that clinical conditions imply a variety of limiting factors in addition to those encountered under purely laboratory studies ( Gurung et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…In the sample size calculation, the following parameters were considered. First, we considered a sensitivity value of 78.5% (95% CI 61.9–89.2) and a specificity value of 89.3% (95% CI 61.4–97.8) for real-time PCR according to a previous meta-analysis ( Andrade et al, 2021 ). We consider an initial sensitivity and specificity of 60% (H0), compatible with the lower limit of both confidence intervals described in the cited review ( Andrade et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…First, we considered a sensitivity value of 78.5% (95% CI 61.9–89.2) and a specificity value of 89.3% (95% CI 61.4–97.8) for real-time PCR according to a previous meta-analysis ( Andrade et al, 2021 ). We consider an initial sensitivity and specificity of 60% (H0), compatible with the lower limit of both confidence intervals described in the cited review ( Andrade et al, 2021 ). The prevalence of patients diagnosed with leprosy within the service according to internal data is approximately 50%.…”

Section: Methodsmentioning

confidence: 99%

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Standardization of SYBR Green-Based Real-Time PCR Through the Evaluation of Different Thresholds for Different Skin Layers: An Accuracy Study and Track of the Transmission Potential of Multibacillary and Paucibacillary Leprosy Patients

2021

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The development of new molecular techniques is essential for the early diagnosis of leprosy. Studies in the field have failed to elucidate the performance of these tests in clinical practice. We aimed to design a new primer pair for the repetitive element (RLEP) target of Mycobacterium leprae and to test the accuracy of SYBR green-based real-time PCR through the evaluation of different thresholds for different skin layers. We also aimed to track the transmission potential of multibacillary and paucibacillary leprosy patients. The in vitro validation of our reaction resulted in a quantification limit of 0.03 bacilli. We then conducted a cross-sectional/cohort-based study of diagnostic accuracy. Patients were included, and skin samples were divided into four layers: epidermis, superior dermis, inferior dermis, and hypodermis. We also quantified M. leprae in nasal swabs of the included patients and compared the results to the number of household contacts also diagnosed with leprosy. One hundred patients with a clinical presentation compatible with leprosy were allocated to the leprosy or control group. Although the parasite load was greater in the superior and inferior dermis, M. leprae DNA was found in all skin layers. The best sensitivity was observed for the superior dermis using the presence of any quantifiable bacillus DNA as the threshold [sensitivity=59.26% (95% CI=45.97–71.32)]. In the epidermis, setting 1 quantifiable bacillus as the threshold resulted in 100% specificity (95% CI=92.29–100). The number of bacilli found in nasal swabs was not significantly related to the number of household contacts also diagnosed with leprosy. Paucibacillary patients tested positive only for bacillus fragments in nasal swabs but not for the entire bacilli. We can conclude that superficial biopsies might result in sensitivity loss, although different skin sample types will have little influence on the final accuracy. In contrast, threshold changes greatly influence these properties. Paucibacillary patients may not be a relevant source of disease transmission.

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“…Moreover, the low capacity to distinguish M. leprae from other mycobacteria by microscopy is an important concern due to the poor precision and sensitivity of these experiments (8). In the last twenty years, many experiments in clinical and molecular settings have been conducted which have advanced the area of leprosy diagnostics (9)(10)(11). However, a variety of diagnostics tests have been proposed based on the detection of pathogen's DNA, RNA, protein or host antibodies, cytokines and other host biomarkers such as gene expression profiles (12).…”

Section: Introductionmentioning

confidence: 99%

Advances in the Diagnosis of Leprosy

Sharma¹,

Singh²

2022

Front. Trop. Dis

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Leprosy is a public health issue, and early detection is critical to avert disability. Despite the global attempt to eradicate this disease as a public health problem, it remains an important cause of global neurological disability. India, Brazil and Indonesia share more than 70% of the cases. The reduction of new cases is a priority in the WHO global strategy 2021-2030 which aims to reduce disease transmission in the community by diagnosing cases and identifying subclinical infection. The clinical manifestations of leprosy range from a few to several lesions. The identification remains difficult due to the limited sensitivity of traditional approaches based on bacillary counts of skin smears and histology. To aid in the diagnosis of this disease, molecular biology, and biotechnological technologies have been applied, each with its own set of benefits and downsides despite providing an essential tool to validate the clinical diagnosis of leprosy. Because of this, it is strongly recognized that specific, inexpensive point of care technologies should be developed, particularly to identify asymptomatic M. leprae infections or leprosy nearer to the suspected cases seeking medical attention. Thus, this review will provide an overview of the advancements in leprosy diagnosis over the world. The purpose of this review is to improve our understanding of the outcomes of current tests and technologies used in leprosy diagnosis and to emphasize critical aspects concerning the detection of leprosy bacilli.

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A systematic review and meta-analysis of studies on the diagnostic accuracy and screening of tests to detect antimicrobial resistance in leprosy

Cited by 10 publications

References 32 publications

The influence of leprosy-related clinical and epidemiological variables in the occurrence and severity of COVID-19: A prospective real-world cohort study

The influence of leprosy-related clinical and epidemiological variables in the occurrence and severity of COVID-19: A prospective real-world cohort study

Standardization of SYBR Green-Based Real-Time PCR Through the Evaluation of Different Thresholds for Different Skin Layers: An Accuracy Study and Track of the Transmission Potential of Multibacillary and Paucibacillary Leprosy Patients

Advances in the Diagnosis of Leprosy

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