Testing for exclusion of avian notifiable disease: six-year review.

This focus article has been prepared by Scott Reid of the APHA's virology department with Sharon Brookes, Rowena Hansen, David Welchman, Richard Irvine and Ian Brown of the APHA.

Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009-15.

OBJECTIVES: Antimicrobial resistance (AMR) is a priority for surveillance in bacterial infections. For leprosy, AMR has not been assessed because Mycobacterium leprae does not grow in vitro. We aim to obtain AMR data using molecular detection of resistance genes and to conduct a prospective open survey of resistance to antileprosy drugs in countries where leprosy is endemic through a WHO surveillance network. METHODS: From 2009 to 2015, multi-bacillary leprosy cases at sentinel sites of 19 countries were studied for resistance to rifampicin, dapsone and ofloxacin by PCR sequencing of the drug-resistance-determining regions of the genes rpoB, folP1 and gyrA. RESULTS: Among 1932 (1143 relapse and 789 new) cases studied, 154 (8.0%) M. leprae strains were found with mutations conferring resistance showing 182 resistance traits (74 for rifampicin, 87 for dapsone and 21 for ofloxacin). Twenty cases showed rifampicin and dapsone resistance, four showed ofloxacin and dapsone resistance, but no cases were resistant to rifampicin and ofloxacin. Rifampicin resistance was observed among relapse (58/1143, 5.1%) and new (16/789, 2.0%) cases in 12 countries. India, Brazil and Colombia reported more than five rifampicin-resistant cases. CONCLUSIONS: This is the first study reporting global data on AMR in leprosy. Rifampicin resistance emerged, stressing the need for expansion of surveillance. This is also a call for vigilance on the global use of antimicrobial agents, because ofloxacin resistance probably developed in relation to the general intake of antibiotics for other infections as it is not part of the multidrug combination used to treat leprosy.

Unexpectedly high leprosy seroprevalence detected using a random surveillance strategy in midwestern Brazil: A comparison of ELISA and a rapid diagnostic test.

BACKGROUND: Leprosy diagnosis is mainly based on clinical evaluation, although this approach is difficult, especially for untrained physicians. We conducted a temporary campaign to detect previously unknown leprosy cases in midwestern Brazil and to compare the performance of different serological tests. METHODS: A mobile clinic was stationed at the main bus terminal in Brasília, Brazil. Volunteers were quizzed and given a clinical exam to allow categorization as either patients, known contacts of patients or non-contacts, and blood was collected to determine anti-PGL-I and anti-LID-1 antibody titers by ELISA and by the NDO-LID rapid test. New cases of leprosy and the impact of performing this broad random surveillance strategy were evaluated. Accuracy values and concordance between the test results were evaluated among all groups. RESULTS: Four hundred thirty-four individuals were evaluated, and 44 (10.1%) were diagnosed with leprosy. Borderline forms were the most frequent presentation. Both tests presented higher positivity in those individuals with multibacillary disease. Serological tests demonstrated specificities arround 70% for anti-PGL-1 and anti-LID ELISA; and arround 40% for NDO-LID. Sensitivities ranged from 48 to 62%. A substantial agreement between NDO-LID and ELISA with concomitant positive results was found within leprosy patients (Kappa index = 0.79 CI95% 0.36-1.22). CONCLUSIONS: The unexpectedly high leprosy prevalence in this population indicates ongoing community-based exposure to Mycobacterium leprae antigens and high rates of subclinical infection. All tests showed low specificity and sensitivity values and therefore cannot be considered for use as stand-alone diagnostics. Rather, considering their positivity among MB patients and non-patients, these tests can be considered effective tools for screening and identifying individuals at high risk who might benefit from regular monitoring.

Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country.

An active search for Mycobacterium leprae drug resistance was carried out, 243 multibacillary patients from endemic regions of Colombia were included from 2004 to 2013 in a surveillance program. This program was a World Health Organization initiative for drug resistance surveillance in leprosy, where Colombia is a sentinel country. M. leprae DNA from slit skin smear and/or skin biopsy samples was amplified and sequenced to identify mutations in the drug resistance determining region (DRDR) in rpoB, folP1, gyrA, and gyrB, the genes responsible for rifampicin, dapsone and ofloxacin drug-resistance, respectively. Three isolates exhibited mutations in the DRDR rpoB gene (Asp441Tyr, Ser456Leu, Ser458Met), two in the DRDR folP1 gene (Thr53Ala, Pro55Leu), and one isolate exhibited mutations in both DRDR rpoB (Ser456Met) and DRDR folP1 (Pro55Leu), suggesting multidrug resistance. One isolate had a double mutation in folP1 (Thr53Ala and Thr88Pro). Also, we detected mutations outside of DRDR that required in vivo evaluation of their association or not with drug resistance: rpoB Arg505Trp, folP1 Asp91His, Arg94Trp, and Thr88Pro, and gyrA Ala107Leu. Seventy percent of M. leprae mutations were related to drug resistance and were isolated from relapsed patients; the likelihood of relapse was significantly associated with the presence of confirmed resistance mutations (OR range 20.1-88.7, p < 0.05). Five of these relapsed patients received dapsone monotherapy as a primary treatment. In summary, the current study calls attention to M. leprae resistance in Colombia, especially the significant association between confirmed resistance mutations and relapse in leprosy patients. A high frequency of DRDR mutations for rifampicin was seen in a region where dapsone monotherapy was used extensively.

Does Leprosy Need a Stronger Surveillance System Now? A point of view article.

Multi Drug Therapy (MDT) for leprosy was introduced by WHO in 1982 and the programme has been implemented for more than 3 decades. The main presumption out of the PR based elimination was that with reduction of disease load below 1 per 10000 persons, the transmission of leprosy would be arrested resulting in disappearance of the disease. MDT made the disease description, definition and epidemiological indicators so different that it ceases to be like any other disease. To eliminate the leprosy totally from the country needs following activities: 1. Scaling up of some sentinel sites (SS) to surveillance units (SUs), 2. Source of information, 3. Authentication and standardisation, 4. Generation of own data, 5. Need for a skin smear laboratory, 6. Promoting referral of suspects for DST.

[Our role in sentinel surveillance for drug resistance in leprosy by global leprosy programme].

Sentinel surveillance for drug resistance in leprosy by global leprosy programme has launched in 2006. Possible contribution of Japanese researchers to global leprosy control in the future were discussed on the base of circumstances of the project and our assignment in the sueveillance.

Need and strategy for sentinel surveillance for drug resistance in leprosy in India.

In the fight against leprosy drug resistance poses a serious impediment at a stage when there is dramatic decline in prevalence due to intensive and concerted chemotherapy intervention. Drug resistance in leprosy has been reported since 1964 for dapsone, 1976 for rifampicin and 1996 for ofloxacin. Recent reports and publications have indicated few instances of rifampicin resistance in several endemic areas. In light of reporting drug resistance in leprosy, the National Leprosy Eradication Programme (NLEP) in India has started collecting information on relapse cases from peripheral institutions. The data show quite significant number of relapse cases (328 in year 2008-09) reported from few endemic states. Comprehensive data on the magnitude of drug resistance are crucial to evaluate the efficacy of MDT and to maintain the effectiveness of the current leprosy control strategy. It has become a necessity to develop a surveillance system to keep a close vigil on drug resistance. PCR based assays have convincingly demonstrated that detection of rifampicin resistance by this method is a feasible and practical alternative to the mouse foot pad (MFP) assay and has practical application in India. Surveillance of drug resistance in leprosy can be carried out based on a sentinel surveillance model. Certain district hospitals and tertiary institutions can be identified as sentinel sites in endemic states where tissue samples can be collected and transported to the identified reference laboratories. Based on the suspected and confirmed relapsed cases reported, 12 states have been identified for inclusion under the surveillance of drug resistance in leprosy. These are Andhra Pradesh, Bihar, Chhattisgarh, Karnataka, Madhya Pradesh, Maharashtra, Orissa, Rajasthan, Tamilnadu, Uttar Pradesh, West Bengal and Delhi. Four reference laboratories have already been identified, one each in the states of Uttar Pradesh, Andhra Pradesh, Tamilnadu and Delhi. Tissue samples from sentinel sites would be sent to designated laboratories for conducting the DNA sequencing tests to confirm rifampicin resistance.

Secular trends of new leprosy cases diagnosed in Brazil during 1987-2006.

OBJECTIVE: To analyze trends in occurrence of new leprosy cases in Brazil in the light of changes in public health policy during the period 1987-2006. MATERIAL AND METHODS: Study of secular trends in New case detection rate (NCDR), viz. for leprosy in Brazil between 1987 and 2006. A linear trend was used to analyze separately the detection rate during the two decades 1987-1996 and 1997-2006. The cut-off point was the year with the peak detection rate in 1997. To analyze the potential increase in accessibility to diagnosis and treatment, a comparison was made between the proportion of cases diagnosed within the health services and municipalities over a 20-year period, split into four 5-year intervals. RESULTS: The variation of the NCDR between 1987 and 2006 more than doubled between 1987 and 1997, decreased from 1997 to 2000, increased up to 2003 and then dropped considerably between 2004 and 2006. The number of facilities providing health services for the 5-year periods showed a marked increase-more than doubling between the second and third and between the third and fourth periods. The number and therapeutic services are indications that Brazil is perhaps making considerable progress towards eliminating leprosy as a public health problem.

Australia's notifiable diseases status, 2005: annual report of the National Notifiable Diseases Surveillance System.

In 2005, 60 diseases and conditions were nationally notifiable in Australia. States and territories reported a total of 125,461 cases of communicable diseases to the National Notifiable Diseases Surveillance System: an increase of 10% on the number of notifications in 2004. In 2005, the most frequently notified diseases were sexually transmissible infections (51,557 notifications, 41% of total notifications), gastrointestinal diseases (29,422 notifications, 23%) and bloodborne diseases (19,278 notifications, 15%). There were 17,753 notifications of vaccine preventable diseases; 4,935 notifications of vectorborne diseases; 1,826 notification of other bacterial infections (legionellosis, leprosy, meningococcal infections and tuberculosis) and 687 notifications of zoonotic diseases.

New case-detection trends in a multi-drug therapy programme: definite reduction in sight.

MDT has made a visible impact on leprosy in Andhra Pradesh as reflected by reduction of prevalence as well as in new case-detection, which is used as a proxy for incidence of the disease. Such reductions have also been seen in West Godavari district and the Damien Leprosy Centre at Vegavaram (an NGO project), where MDT is being implemented since 1988.

Trends in new case-detection leprosy in Bihar, India.

Multi-drug therapy (MDT) has been successfully implemented in all leprosy endemic countries. Prevalence of leprosy has declined remarkably after the introduction of MDT. Detection of new cases did not show expected decline in many endemic and low endemic situations. Bihar in India started implementing MDT in 1993. The Damien Foundation India Trust (DFIT) supported the leprosy control programme in Bihar by providing a district technical support team (DTST) for each district assigned to DFIT. Effective coverage was achieved in 1996-98. Data for the period 1996-2004 from 10 districts are presented in this paper. The total population in these districts was 29.4 million. Deformity among newly detected leprosy patients declined to 1% indicating effective early case-detection. Intensive new case-detection activities were in vogue contributing to high new case-detection rate (NCDR). The NCDR remained high during the 9-year period reported here and did not show any declining trend.

A review of trends in new case-detection in Subarnapur district of Orissa.

Trends in new case-detection are analysed by reviewing the demographic and leprosy epidemiological data and current indicators in Subarnapur district, Orissa State and India. Population-specific new case-detection rates were calculated for analysis. The trend of skin-smear positive cases over a period of 10 years was reviewed in respect of smear positive cases of 1991. During the years 2002 to 2004, a sudden fall was noticed in the new cases detected in both India and Orissa state, whereas the decline in Subarnapur district was more gradual. The fall in the female-specific new case-detection rates is found to be rapid from 11 to 2.5 over the last three years. This also indirectly indicated the health-seeking behaviour of women in accessing health services and hence required a changed strategy. A similar rapid decline was observed in child-specific new case-detection rates. On analysiS, the decline of highly bacilliferous cases from 1991 to 2001 was found to be statistically significant. The analysis also brought out the fact that cases with bacterial index of 1+, 2+ and 3+, though small in numbers, were detected during the last three years indicating continued presence of cases with low bacterial density in the community. The review indicates a definite decline in the occurrence of new cases in all groups. Caution needs to be exercised about continued presence of cases with low bacterial index though in small numbers. The rapid decrease of cases in all groups during the years 2004 and 2005 warrants meticulous surveillance. The surveillance activities could include monitoring of population-specific new case-detection rates and skin-smear positive cases at district and state levels in order to advise on leprosy eradication programme strategies.

Australia's notifiable diseases status, 2004, annual report of the National Notifiable Diseases Surveillance System.

In 2004, 60 diseases and conditions were nationally notifiable in Australia. States and Territories reported a total of 110,929 cases of communicable diseases to the National Notifiable Diseases Surveillance System (NNDSS): an increase of 4 per cent on the number of notifications in 2003. In 2004, the most frequently notified diseases were sexually transmissible infections (46,762 cases; 42% of total notifications), gastrointestinal diseases (25,247 cases; 23% of total notifications) and bloodborne diseases (19,191 cases; 17% of total notifications). There were 13,206 notifications of vaccine preventable diseases, 6,000 notifications of vectorborne diseases, 1,799 notifications of other bacterial infections (includes, legionellosis, leprosy, meningococcal infections and tuberculosis) and 877 notifications of zoonotic diseases.