Comparative evaluation of antibody detection tests to facilitate the diagnosis of multibacillary leprosy.

Despite control efforts, leprosy persists as a significant health concern in many regions. Diagnosis is achieved by a combination of clinical, histopathological, and bacteriological examinations, each of which presents a barrier to expeditious diagnosis, particularly by non-experts. Immunological investigations in research laboratories have clearly indicated that antibody detection tests could aid the diagnosis of leprosy. In this study, we detected circulating antibodies with two rapid diagnostic tests (RDT) involving immunochromatographic lateral flow platforms and one rapid ELISA system. Leprosy patients were identified with a high degree of sensitivity in each assay (over 80% in all; over 90% among cases with bacterial indices >1+), although critical differences were observed in specificity. While the specificity of CTK OnSite Leprosy Ab Rapid Test and InBios Leprosy Detect™ fast ELISA were high (96.4 and 93.7% in the general population, respectively), there was a marked reduction in OrangeLife NDO-LID® RDT (only 25.0%). As anticipated, seropositivity rates were marginally higher in contacts of leprosy patients than in endemic controls. Although we observed a slight drop in test band intensity when blood, rather than serum, was used to develop OnSite Leprosy Ab Rapid Tests, the sensitivity and specificity of these tests was unaffected. When we contrasted test performance with clinical and bacteriological information, we found that RDT and ELISA results positively correlated with the bacteriological index. These data indicate that these assays could be a ready replacement of invasive, insensitive, and time consuming skin slit smear procedures that additionally require expert microscopic examinations. We propose that, due to their speed and point of care applicability, the RDT could be used as an initial entry point to the diagnostic protocols, with confirmation of results attained in a highly quantitative manner following serum transfer to a reference laboratory.

Need for, and acceptability of, rapid diagnostic tests that can facilitate the diagnosis of leprosy.

New cases of leprosy indicate that M. leprae transmission is continuing. In the first half of 2015 we sequentially diagnosed new leprosy patients attending Cebu Skin Clinic, a referral and leprosy treatment centre in Cebu City, Philippines. The great majority of patients were characterised as multibacillary (145 of 147; 98·6%), most of whom had bacterial indices 3þ (86; 58·5%) or more than 20 skin lesions (94; 63·9%). Importantly, 65·3% estimated that slightly over a year had elapsed between their initial symptoms and diagnosis, while 26·5% reported a lapse of greater than 3 years. Many patients (73·8%) and their household contacts (79·2%) reported that their lives had already been adversely affected. This indicates that improvements to expedite diagnosis are required, and rapid diagnostic tests (RDT) appear suited for this. Questionnaires were conducted among various groups to ascertain the acceptability and perception of RDT. All groups responded favourably, with 95·9% patients, 93·2% contacts and 81·4% of the general population responding that RDT would be beneficial for leprosy. The vast majority of patients (88·6%) indicated that they would 'definitely' submit to testing, followed by 69·4% of contacts and 72·2% of the general population. The majority of patients thought their household members should also be tested, while a subset indicated that RDT use should be extended to their respective communities. We propose that, due to their ease of use, point of care applicability and acceptability within target populations, RDT could be used as an entry point to inform the diagnostic process for leprosy.

Rapid quantitative serological test for detection of infection with Mycobacterium leprae, the causative agent of leprosy.

Leprosy remains an important health problem in a number of regions. Early detection of infection, followed by effective treatment, is critical to reduce disease progression. New sensitive and specific tools for early detection of infection will be a critical component of an effective leprosy elimination campaign. Diagnosis is made by recognizing clinical signs and symptoms, but few clinicians are able to confidently identify these. Simple tests to facilitate referral to leprosy experts are not widely available, and the correct diagnosis of leprosy is often delayed. In this report, we evaluate the performance of a new leprosy serological test (NDO-LID). As expected, the test readily detected clinically confirmed samples from patients with multibacillary (MB) leprosy, and the rate of positive results declined with bacterial burden. NDO-LID detected larger proportions of MB and paucibacillary (PB) leprosy than the alternative, the Standard Diagnostics leprosy test (87.0% versus 81.7% and 32.3% versus 6.5%, respectively), while also demonstrating improved specificity (97.4% versus 90.4%). Coupled with a new cell phone-based test reader platform (Smart Reader), the NDO-LID test provided consistent, objective test interpretation that could facilitate wider use in nonspecialized settings. In addition, results obtained from sera at the time of diagnosis, versus at the end of treatment, indicated that the quantifiable nature of this system can also be used to monitor treatment efficacy. Taken together, these data indicate that the NDO-LID/Smart Reader system can assist in the diagnosis and monitoring of MB leprosy and can detect a significant number of earlier-stage infections.

A retrospective study of the epidemiology of leprosy in Cebu: an eleven-year profile.

BACKGROUND: Cebu has been one of the most leprosy endemic areas in the Philippines. Despite the high coverage rates of multiple drug therapy (MDT) and high BCG-vaccine coverage in children, leprosy control authorities believe that leprosy transmission and incidence (as evidence by continuing new case detection in both adults and children) have not declined as expected, once leprosy had been eliminated. In response to the concerns communicated by the authorities regarding ongoing leprosy transmission in Cebu, this study aims to examine the evidence for the hypothesized ongoing transmission, both in children and adults. Furthermore, it will be assessed which groups and areas are experiencing a continuing risk of leprosy infection; this can form a starting point for more targeted approaches to leprosy control. METHODOLOGY & PRINCIPAL FINDINGS: Case records from 2000-2010 were retrospectively collected from the Leonard Wood Memorial Clinic archives, and all other clinics on the island where leprosy was treated. Between 2000 and 2010, 3288 leprosy cases were detected. The overall five year case notification rate (CNR) dropped significantly from 47.35 (2001-2005) to 29.21 cases (2006-2010) per 100.000 population. Smaller CNRs were reported for children; however the decline in child-CNR over the same period was minimal. Furthermore, no increase in median age of notification in children or adults was found between 2000 and 2010. Population-adjusted clustering of leprosy cases was mainly detected in urban and peri-urban areas. CONCLUSIONS & SIGNIFICANCE: Although the overall CNR declined significantly, CNR seems to be rather static in lower risk populations and areas. Cases are mainly found in urban areas, however CNRs in these areas decline at a much faster rate than in the lower endemic rural areas. A similar situation was found when comparing adults and children: CNRs observed in children were lower than in adults, but further decline (and elimination) of these childhood CNRs was found to be difficult. Moreover, the median age of notification in children has remained stable, suggesting transmission is still on-going. It is unclear why many years of good MDT-coverage and a gradual decline in CNR have not been accompanied by evidence of reduced transmission, especially beyond a certain threshold level of case notification. We believe that a new approach to leprosy control is required to tackle transmission more directly. The most promising approach may involve chemoprophylaxis and/or immunoprophylaxis interventions, targeted at high risk (urban) areas and groups such as household contacts, followed by a different approach once decline in CNR starts to level off. Identified clusters and trends can form the starting point for implementing this approach.

Transmission of dapsone-resistant leprosy detected by molecular epidemiological approaches.

Drug resistance surveillance identified six untreated leprosy patients in the Philippines with Mycobacterium leprae folP1 mutations which confer dapsone resistance. Five patients share a village of residence; four who carried the mutation, Thr53Val, were also linked by M. leprae variable-number tandem repeat (VNTR) strain types. In India, folP1 mutations were detected in two relapse patients with a history of dapsone treatment. Mutations were not found in the rifampin target gene rpoB. These findings indicate that dapsone resistance is being transmitted.