Primary cutaneous large B cell lymphoma masquerading as lupus vulgaris.

Primary cutaneous large B cell lymphoma, leg type is a rare and aggressive variant of cutaneous B cell lymphoma. It predominantly affects elderly women, with the lower limb being the most common site of presentation. The overall prognosis is poor, compared to other cutaneous B cell lymphomas. A 47-year-old man presented with a progressively enlarging nodule over the medial aspect of the left foot since 2 months. Clinical examination revealed a nodular plaque-like lesion with central ulceration that measured 7 × 7 cm, firm in consistency, and with ill-defined margins. The initial clinical diagnosis was lupus vulgaris. An incision biopsy was done, which on histopathology and immunohistochemistry revealed a rare diagnosis of primary cutaneous B cell lymphoma, leg type. The patient was started on chemotherapy; however, he succumbed to his illness about 1 year after the initial presentation. It is a rare type of cutaneous lymphoma, which may masquerade infectious disorders such as lupus vulgaris. A detailed histopathological and immunohistochemical analysis is essential for its correct diagnosis and management. Only a handful of cases of this rare condition are reported to date. This case has been reported in view of its rarity and unusual clinical presentation.

Trends of syphilis seroprevalence at a tertiary care center in New Delhi, India: A 10-year analysis.

Objectives: Syphilis has been called the great mimicker or the great imitator due to its myriad of clinical presentations. Despite strenuous concerted efforts toward the elimination of syphilis, it still remains a goal to be achieved. During recent years, many different trends of syphilis have been reported from around the globe. Methods: A retrospective observational clinico-investigative study was carried out to analyze the 10-year trends of syphilis at one of the largest public sector hospitals in India. Results and Conclusion: Both venereal disease research laboratory and Treponema pallidum Hemagglutination assay positivity rates showed a significant declining trend from 2007 to 2016, reflecting the success of the National Sexually Transmitted Infection Prevention and Control Program.

Revisiting the pathogenesis of dermatophytosis: A cross-sectional analytic study of serum levels of interleukins-2, 8, 10 and 17.

BACKGROUND: Given the current epidemic-like scenario of dermatophyte infections, it is prudent to revisit the immunopathogenesis of dermatophytosis. Comprehending the intricate interactions among interleukins can aid in understanding the recent trends in infection. There is a paucity of literature on the various cytokine levels observed in the serum of patients suffering from various dermatophytoses. AIM: To study serum cytokine levels of interleukins 2, 8, 10 and 17 in patients with dermatophytosis. METHODS: A cross-sectional analytic study was conducted on 64 cases of clinical dermatophyte infections (KOH confirmed) and 64 controls. The clinico-epidemiological profile of the cases was studied. By using a solid phase sandwich ELISA (enzyme-linked immunosorbent assay), the serum levels of interleukins 2, 8, 10 and 17 were measured and compared between cases and controls. Serum interleukin-2, 8, 10 and 17 levels were studied among cases based on mode of onset, duration of illness, treatment history, site of infection and multiple other morphological characteristics of the infection. RESULTS: The cases had statistically higher levels of interleukins-8, 10 and 17 in comparison with controls. The levels of interleukin-8 were significantly lower (p < .05) among those who had received oral antifungals. In cases where the lesion had scaling, the serum levels of interleukin-10 were significantly higher (p < .05). The lesional hyperpigmentation was significantly (p < .05) associated with low levels of interleukin-17. Also, interleukin-17 was significantly (p < .05) elevated in patients with lesions in the abdomen. CONCLUSION: It is the first time that serum interleukin levels are studied in dermatophytosis. There is an immunological dysfunction specific to dermatophytoses initiated by their infection. Key factor in this dysfunction is the elevation of IL-10, contributing to persistent infection. In turn, causing an increase in IL-17, promoting inflammation and tissue damage. This cycle of elevated IL-10 and IL-17 can further exacerbate the infection and lead to chronicity. The activity of IL-2 and the Th1 immune pathway is reduced by two opposing immune pathways: the Th17 and Th2 axes.

Patterns of human immunodeficiency virus drug resistance mutations in people living with human immunodeficiency virus in India: A scoping review.

The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic still exists as a major global public health burden, especially in the middle- and low-income countries. Antiretroviral therapy (ART) remains a sole option to reduce the mortality and morbidity associated with this disease as no approved vaccine candidates are available. About 67% of the people living with HIV (PLHIV) have received the ART in 2019 worldwide. As a consequence of increased ART regimes, the prevalence of drug resistance mutations (DRM) also has been escalating and it would become a significant barrier in achieving the United Nations Programme on HIV/AIDS goal of eliminating HIV by 2030. So far, nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), and protease inhibitor-(PI) associated DRM have been reported across the globe with a considerable escalation in the annual prevalence rate of pretreatment NNRTI DRM. Conversely, NRTI-associated DRM is still under 5%, with a few scattered reports of significant increase from few countries such as southern and eastern Africa. Likewise, in India, the propositions of NRTI and NNRTI-associated DRM have increased since the commencement of the nationwide ART program in 2004. In agreement to the global trend, M1841/V, a type of NNRTI, remains as a dominant DRM among PLHIV. In this review, we tried to collate various mechanisms of DRM in PLHIV. In addition, patterns of HIV DRM in India and their future challenges on drug-related mutations have been discussed.

Emerging and re-emerging sexually transmitted diseases: A review of epidemiological evidences.

Substantial increase in the outbreaks of sexually transmitted infections (STIs) and associated mortalities have raised international concerns. Concurrent with the escalation of established STIs, developing epidemics and outbreaks of newly emerging sexually transmissible pathogens pose serious problems for people and added burden and challenges for public health practitioners and researchers. Importantly, most of the emerging STIs are frequently found among vulnerable groups, such as men having sex with men and human immunodeficiency virus patients, which may result in large outbreaks in the near future. Furthermore, enhanced spread of antimicrobial resistance among these pathogens ever more limits treatment options for STIs. Thus, it is the optimal time to consider whether an infectious agent is sexually transmissible and develop treatment protocol for handling new STIs with pandemic potential. In this review, we explore emerging STIs, their current epidemiological status, and future perspective.

Etiology of cervicitis: Are there new agents in play?

Background: Considering the changing causative and resistance pattern of agents implicated in sexually transmitted infections (STIs), etiological diagnosis is imperative, especially in countries practicing syndromic management. This study was designed to identify etiological agents associated with cervicitis and to analyze their association with clinical and behavioral profile. Materials and Methods: Female STI clinic attendees presenting with cervico-vaginal discharge were examined for the presence of cervicitis. Endocervical swabs were collected for gram staining and real-time polymerase chain reaction was performed for various bacterial and viral STI agents in patients presenting with cervical discharge. A vaginal swab was also evaluated for bacterial vaginosis by Nugent's criteria. Results: Of 64 patients with vaginal discharge, 26.6% and 12.5% patients complained of genital itching and lower abdominal pain, respectively. Mean of 36.6 pus cells/hpf were observed, appreciably greater number in patients with Neisseria gonorrhoeae and Chlamydia trachomatis infections (P = 0.0063 and 0.0032, respectively). Pus cells were high (mean 68 pus cells/hpf) in patients with Ureaplasma urealyticum, though this may be attributed to coexisting N. gonorrhoeae. Agents isolated from endocervix were N. gonorrhoeae, 17 (26.6%), Trichomonas vaginalis, 4 (6.3%), HSV1 and C. trachomatis, 1 each (1.6%), HSV2, 9 (14.1%), U. urealyticum 5 (7.8%), Ureaplasma parvum 26 (40.6%), Mycoplasma genitalium (0%), and Mycoplasma hominis 11 (17.2%). Bacterial vaginosis was diagnosed in 14 (21.9%) patients. Multiple agents were isolated in 10 (two), 6 (three), 6 (four), and 1 (five) patients. Isolation of M. hominis and U. parvum was significantly associated with bacterial vaginosis (P = 0.04 and 0.003, respectively). Nonusage of condoms and mental stress predisposed to cervicitis. Conclusion: We concluded that there are changing etiological patterns of cervicitis. There is need to use tests that detect wider array of organisms, and can replace standard culture methods with molecular assays, to increase the ability to diagnose more number of organisms implicated in cervicitis.

Does performance and operational superiority of point-of-care test make it the investigation of choice in confirming syphilis?

Background: According to the World Health Organization, 6 million cases of syphilis occur every year. Serological tests for syphilis form the mainstay of diagnosis for syphilis. We evaluated the performance of point-of-care test (POCT) against other specific treponemal test for confirming the diagnosis of syphilis. Materials and Methods: Does performance and operational superiority of POCT make it the investigation of choice in confirming syphilis? Retrospectively, data were analyzed of 599 serum samples from Apex Regional sexually transmitted disease centre, Safdarjung Hospital, New Delhi, received for testing by syphilis treponemal assays (both nontreponemal reactive and nonreactive). These samples underwent treponemal testing for syphilis by the Treponema pallidum hemagglutination (TPHA), fluorescent treponemal antibody absorption test (FTA-ABS), and POCT. Performance characteristics (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], and diagnostic accuracy), and operational characteristics of POCT and TPHA were evaluated against the gold standard FTA-ABS. Results: A total of 599 samples were evaluated, of which 61.76% were positive by FTA-ABS. On analysis, the sensitivity was 91.08% and 91.89%, specificity was 89.08% and 87.34%, PPV was 93.09% and 92.14%, NPV was 86.08% and 86.96%, and diagnostic accuracy was 90.32% and 90.15% for POCT and TPHA, respectively. The lower cost, shorter turnaround time, lesser infrastructure and workforce need, and easy availability make the POCT operationally superior to TPHA. Conclusion: Owing to its operational superiority and higher specificity POCT can replace TPHA for confirming the diagnosis of Syphilis. POCT are affordable, equipment free, have room temperature storage, and yield result within 15 minutes, enabling same day testing and treatment. It can be used in a resource limited setting, for community setup or even self-testing.

Evaluation of reliability of self-collected vaginal swabs over physician-collected samples for diagnosis of bacterial vaginosis, candidiasis and trichomoniasis, in a resource-limited setting: a cross-sectional study in India.

OBJECTIVES: Self-collected vaginal swabs can facilitate diagnosis of vaginal discharge (VD) in resource-limited settings, provided reliability of the method is established. The aim of this study was to evaluate the concordance between self-collected and physician-collected vaginal swabs for aetiological diagnosis of VD and to determine the prevalence of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) and trichomonas vaginitis (TV). METHODS: A total of 550 females (median age: 32 years; range: 18-45 years) attending two sexually transmitted infection/reproductive tract infection (STI/RTI) clinics with VD from January 2015 to May 2016 were included in the study after obtaining written informed consent. Swabs were self-collected by patients after instructions and subsequently by a physician under speculum examination. Samples were processed for standard bedside tests, Gram staining, wet mount and culture (gold standard) according to the national guidelines. Concordance between the two methods was determined by the Cohen's kappa value. RESULTS: BV, VVC and TV were diagnosed in 79 (14.4%), 144 (26.2%) and 3 (0.5%) patients, respectively. VVC coexisted with BV in 58 (10.5%) patients. There was no coinfection of TV with BV or VVC. Candida albicans was isolated in 84 (58.3%) VVC cases. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-collected swabs for diagnosing BV was 91.1%, 100%, 100% and 98.5%, respectively, while for the C. albicans VVC and TV, sensitivity, specificity, PPV and NPV all were 100% as compared with physician-collected swabs. Highly concordant results were obtained between two methods by the Kappa values of 0.95 (BV), 0.99 (VVC) and 1.0 (TV). CONCLUSION: The comparative performance of self-collected and physician-collected vaginal swabs establishes self-collection of samples for BV, VVC and TV as a viable alternative tool in the management of STIs/RTIs, especially in peripheral and resource-constrained settings. This would be effective in implementing the diagnostic approaches for STIs/RTIs in community-based surveillance studies at national or regional level and therefore strengthening the National STI/RTI Control Programme.

Revisiting the role of the slit-skin smear in the diagnosis of Indian post-kala-azar dermal leishmaniasis.

BACKGROUND: Post kala azar dermal leishmaniasis (PKDL) is a neglected dermatosis that develops as a sequel to kala azar after apparent complete treatment. Being a non life threatening condition, patients often delay treatment thereby maintaining a reservoir of infection. The diagnosis of PKDL rests on the demonstration of the parasite in tissue smears, immune diagnosis by detection of parasite antigen or antibody in blood, or detection and quantitation of parasite DNA in tissue specimens. Sophisticated molecular tests are not only expensive but also need skilled hands and expensive equipment. To be useful, diagnostic methods must be accurate, simple and affordable for the population for which they are intended. AIMS: This study was designed to assess functionality and operational feasibility of slit-skin smear examination. METHODS: Sensitivity and specificity was evaluated by performing slit-skin smear and histo-pathological examination in 46 PKDL patients and the results were compared with the parasite load in both the slit aspirate and tissue biopsy specimens by performing quantitative Real-time PCR (Q-PCR). RESULTS: The slit-skin smear examination was more sensitive than tissue biopsy microscopy. The parasite loads significantly differed among various types of clinical lesions (P < 0.05). The threshold of parasite load for detection by SSS microscopy was 4 parasites/µl in slit aspirate and 60 parasites/µg tissue DNA in tissue biopsy while that for tissue microscopy was 63 parasites/µl and 502 parasites/µg tissue DNA respectively. As detection of Leishmania donovani bodies may be challenging in inexperienced hands, the microscopic structure of these has been detailed along with a comprehensive discussion of pre analytical, analytical and post analytical variables affecting its identification. To facilitate the diagnosis of PKDL, some scenarios have been suggested taking into consideration the clinical, epidemiological, immunological and microscopic aspects. CONCLUSION: Such evidence based medicine helps minimize intuition, systematize clinical experience and provides a diagnostic rationale as sufficient grounds for a clinical decision.

In vitro efficacy of 21 dual antimicrobial combinations comprising novel and currently recommended combinations for treatment of drug resistant gonorrhoea in future era.

BACKGROUND: Recent WHO guidelines recommend dual therapy with ceftriaxone or cefixime plus azithromycin for gonorrhea. Azithromycin in combination with gentamicin or spectinomycin has been recommended in treatment failure cases. Due to emergence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) Neisseria gonorrhoeae strains, it is important to look for efficacy of these combinations and also of others that might be used in future. Therefore, we aimed to evaluate in vitro synergy of 21 dual combinations including current and alternative WHO recommended treatment regimens and other dual combinations. METHODS AND FINDINGS: The potential utility of in-vitro interactions of 21 combinations was investigated against 95 N. gonorrhoeae strains including 79 MDR and one XDR strain collected during March 2013 to July 2017 and fractional inhibitory concentration index (FICI) was calculated. These 21 combinations comprised of two WHO currently recommended (cefixime+azithromycin, ceftriaxone+azithromycin); two WHO recommended in treatment failure cases (azithromycin+gentamicin, spectinomycin+azithromycin) and other 17 combinations. RESULTS: FICI of the four WHO recommended antimicrobial combinations were higher (>1.0) than the five novel combinationbreeds (FICI range 0.603-0.951) in the study i.e. gentamicin+ertapenem, moxifloxacin+ertapenem, spectinomycin+ertapenem, azithromycin+ moxifloxacin, cefixime+gentamicin. No antagonistic effect of the above four WHO recommended combinations except spectinomycin+azithromycin (FICI = 4.25) was observed for the XDR strain. Out of above five novel combinations, four combinations produced high synergistic effects in overall 95 strains and also for the XDR strain with FICI of 0.13 to 0.38. Antagonistic effects varying from 3.2 to 12.6% were observed for 10 out of 21 tested combinations (azithromycin in combination with gentamicin and spectinomycin; ceftriaxone with moxifloxacin, gentamicin, spectinomycin and ertapenem; spectinomycin with moxifloxacin and gentamicin; cefixime and gentamicin combination with moxifloxacin). CONCLUSION: WHO recommended cefixime+azithromycin, ceftriaxone+azithromycin combinations having no antagonism indicates their continuing clinical utility. Highest antagonism without any synergistic effect for the WHO recommended spectinomycin+azithromycin in treatment failure cases suggests that this combination should be evaluated further both in vitro and in vivo. Highest synergistic or additive effect without any antagonistic effect of the above five novel combinations suggests that these may be recommended for treatment in future.

In Vitro Synergy Testing of Gentamicin, an Old Drug Suggested as Future Treatment Option for Gonorrhoea, in Combination With Six Other Antimicrobials Against Multidrug-Resistant Neisseria gonorrhoeae Strains.

BACKGROUND: Emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Neisseria gonorrhoeae is a serious concern and combination therapy has been recommended to delay the onset of treatment failures. Gentamicin, an old and inexpensive antibiotic, is recommended in combination with azithromycin for treatment failures cases with the first-line regimen as per the latest Centers for Disease Control and Prevention sexually transmitted disease treatment guidelines. However, not much literature is available on in vitro and in vivo efficacy of this combination. Therefore, this study was carried out to evaluate the in vitro synergy of gentamicin in combination with azithromycin and 5 other antimicrobials. METHODS: In vitro synergy of gentamicin in combination with cefixime, ceftriaxone, spectinomycin, azithromycin, moxifloxacin, and ertapenem was determined by Etest for 75 N. gonorrhoeae strains, of which 65 were MDR and one was XDR. Fractional inhibitory concentration index (FICI) of ≤0.5 and >4.0 denoted synergy and antagonism respectively. RESULTS: Maximum efficacy of gentamicin was observed in combination with ertapenem (geometric mean FICI, 0.56) followed by cefixime (FICI, 0.87). There was no antagonism for both these combinations. However, antagonism was demonstrated in 5.3%, 8%, 8%, and 10.7% strains when gentamicin was paired with spectinomycin (FICI, 1.34), ceftriaxone (FICI, 1.13), azithromycin (FICI, 1.49), and moxifloxacin (FICI, 1.30), respectively. CONCLUSIONS: The findings suggest that gentamicin significantly enhances the in vitro therapeutic potency of ertapenem and cefixime which will be potentially effective to control the spread of MDR and XDR N. gonorrhoeae. The study warrants more in vitro studies and clinical trials for gentamicin + azithromycin and other 3 combinations because of considerable antagonism.

How Reliable Is Microscopy and Culture for the Diagnosis of Gonorrhea? An 11-Year Experience from INDIA.

Positivity of microscopy and culture was greater (P < 0.0001) in men with urethral discharge syndrome (65.8%) than in women with vaginal/cervical discharge (0.5%), indicating that basic diagnostic tests may not be cost-effective for diagnosis of vaginal/cervical discharge syndrome. Microscopy when compared with culture showed sensitivity, specificity, positive predictive value and negative predictive value of 95.4%, 77.6%, 84.6%, and 95.3%, in men, whereas in women, it was 77.8%, 99.9%, 92.1%, and 99.9%, respectively.

Gentamicin Susceptibility among a Sample of Multidrug-Resistant Neisseria gonorrhoeae Isolates in India.

Antimicrobial susceptibility testing of 258 Neisseria gonorrhoeae isolates by Etest determined that 60.1% were multidrug resistant (MDR), while 5% of the strains had decreased susceptibility to currently recommended extended-spectrum cephalosporins (ESCs). Among these, 84.5% of MDR strains and 76.9% of strains that had decreased susceptibility to ESCs were susceptible to gentamicin. No MDR isolate was resistant to gentamicin. These in vitro results suggest that gentamicin might be an effective treatment option for the MDR strains and in dual therapy for gonorrhea. However, further research regarding the clinical treatment outcomes is essential.

Gentamicin in vitro activity and tentative gentamicin interpretation criteria for the CLSI and calibrated dichotomous sensitivity disc diffusion methods for Neisseria gonorrhoeae.

OBJECTIVES: XDR Neisseria gonorrhoeae imposes the threat of untreatable gonorrhoea. Gentamicin is considered for future treatment; however, no interpretation criteria for the CLSI and calibrated dichotomous sensitivity (CDS) disc diffusion (DD) techniques are available for N. gonorrhoeae. We investigated the in vitro gentamicin activity by MIC and DD methods, proposed DD breakpoints and determined DD ranges for 10 international quality control (QC) strains. METHODS: Gentamicin susceptibility of 333 N. gonorrhoeae isolates, including 323 clinical isolates and 10 QC strains, was determined. MIC determination (Etest) and DD methods (CLSI and CDS) were performed. The relationship between MIC, inhibition zone diameter and annular radius was determined by linear regression analysis and the correlation coefficient (r) was calculated. RESULTS: Gentamicin MICs for the QC strains were within published ranges. Of the 323 clinical isolates, according to published breakpoints 75.9%, 23.5% and 0.6% were susceptible, intermediately susceptible and resistant, respectively. Based on error minimization with MICs of ≤4, 8-16 and ≥32 mg/L, breakpoints proposed are susceptible ≥16 mm, intermediately susceptible 13-15 mm and resistant ≤12 mm for the CLSI method and susceptible ≥6 mm, less susceptible 3-5 mm and resistant ≤2 mm for the CDS technique. CONCLUSIONS: Low resistance to gentamicin was identified and gentamicin might be a future treatment option for gonorrhoea. Tentative gentamicin zone breakpoints were defined for two DD methods and QC ranges for 10 international reference strains were established. Our findings suggest that in resource-poor settings where MIC testing is not a feasible option, the DD methods can be used to indicate gentamicin resistance.

Trends of resistance to antimicrobials recommended currently and in the past for management of gonorrhea in the Apex STD center in India and comparison of antimicrobial resistance profile between 2002-2006 and 2007-2012.

BACKGROUND: Antimicrobial resistance in Neisseria gonorrhoeae jeopardizes public health and continues to spread out to currently recommended and older antimicrobial agents. Antimicrobial resistance (AMR) surveillance provides essential clues toward the modification of treatment guidelines. The aim of the study was to determine gonococcal AMR profile and trends between 2007 and 2012 and to evaluate any change in AMR profile in comparison with published trends in 2002 to 2006. METHODS: Antimicrobial susceptibility testing of 261 N. gonorrhoeae isolates from consecutive patients between 2007 and 2012 was determined for penicillin, tetracycline, ciprofloxacin, spectinomycin, extended-spectrum cephalosporins (ceftriaxone, cefixime, cefpodoxime) and azithromycin by the disk diffusion technique and the Etest method. P value was determined using χ test for comparisons of trends between the 2 periods. RESULTS: In comparison of AMR trends between 2002-2006 and 2007-2012, penicillinase-producing N. gonorrhoeae, tetracycline-resistant N. gonorrhoeae, and ciprofloxacin-resistant strains increased significantly from 21.2% to 47.9% (P < 0.0001), 13.6% to 25.3% (P = 0.0002), and 78% to 89.7% (P = 0.0001), respectively. An insignificant increase from 2.4% to 4.2% (P > 0.05) in decreased susceptibility to ceftriaxone and 0.8% to 1.5% (P > 0.05) for azithromycin resistance was observed. All isolates were susceptible to spectinomycin over both the periods, except for one isolate in 2002. CONCLUSIONS: The study highlights that there is a continuous increase in resistance to previously recommended antibiotics despite their disuse for treatment. The increase in number of strains with decreased susceptibility to extended-spectrum cephalosporins and azithromycin resistance, currently recommended for management of gonorrhea, is of serious concern. These trends should be monitored continuously to change antibiotic policy.

Assessment of knowledge, attitude and practices among healthcare workers in a tertiary care hospital on needle stick injury.

PURPOSE: The study aims to assess healthcare workers' needle-stick injury (NSI) knowledge, attitudes and practices (KAP). DESIGN/METHODOLOGY/APPROACH: A cross-sectional study was conducted in a 600-bedded hospital throughout six months. The data were collected using an anonymous, self-reporting questionnaire. Participants were various healthcare workers (HCW) drawn through stratified random sampling and their knowledge, attitude and practice regarding NSI were assessed. FINDINGS: There is significant difference in the mean knowledge, attitude and practice scores among healthcare workers. Even though scores are better for doctors and nurses, practice scores were better for technical staff. Healthcare workers, who had better practice scores, had suffered fewer NSIs. Since this study is a cross-sectional, the population's NSI incidence could not be calculated. PRACTICAL IMPLICATIONS: This study emphasizes that applying knowledge to practice is required to prevent NSIs. Various recommendations to help prevent and deal with NSIs are made. ORIGINALITY/VALUE: This study analyses healthcare workers' NSI knowledge, attitude and practices, and also assesses their correlation with NSI incidence, which has not been done previously.