International open trial of uniform multi-drug therapy regimen for 6 months for all types of leprosy patients: rationale, design and preliminary results.

OBJECTIVE: To describe the rationale, design and preliminary results of an open trial of 6 months uniform multi-drug therapy (U-MDT) for all types of leprosy patients assuming a cumulative relapse rate not exceeding 5% over 5 years of follow-up. METHODS: We intended to recruit 2500 patients each in multi-bacillary (MB) and pauci-bacillary (PB) groups from India (five centres) and China (two centres). Standardized clinical criteria were used to assess skin lesions in the field. RESULTS: A total of 2912 patients enrolled from November 2003 to May 2007 (India, 2746; China, 166). MB patients constituted 39% and 3% had grade 2 disability. During follow-up, 27 patients (0.9%) developed new lesions. Of these, 78% were on account of reactions. Six patients had clinically confirmed relapse. Clofazimine-related skin pigmentation was short-lived and was acceptable to patients. We analysed data for clinical status of skin lesions. About 2.9% of patients were lost to follow-up; 85.9% completed treatment, of whom 19% had inactive skin lesions. PB patients responded better than MB patients (27%vs. 6%; P < 0.001). At the end of the first (n = 2013) and second year (n = 807) of follow-up post-U-MDT, in 49% and 46% patients, lesions were inactive, respectively (59% and 57% in PB, 37% and 28% in MB; P < 0.001). CONCLUSION: U-MDT appears to be promising with respect to clinical status of skin lesions.

Detection of HIV type 1 env subtypes A, B, C, and E in Asia using dried blood spots: a new surveillance tool for molecular epidemiology.

Global surveillance of HIV-1 subtypes for genetic characterization is hampered by the biohazard of processing and the difficulties of shipping whole blood or cells from many developing country regions. We developed a technique for the direct automated sequencing of viral DNA from dried blood spot (DBS) specimens collected on absorbent paper, which can be mailed unrefrigerated in sturdy paper envelopes with low biohazard risk. DBS were collected nonrandomly from HIV-1-infected, mostly asymptomatic, patients in five Asian countries in 1991, and shipped via airmail or hand carried without refrigeration to Bangkok, and then transshipped to North America for processing. After more than 2 years of storage, including 6 months at ambient temperatures, proviral DNA in the DBS was amplified by nested PCR, and a 389-nucleotide segment of the C2-V3 env gene region was sequenced, from which 287 base pairs were aligned and subtyped by phylogenetic analysis with neighbor-joining and other methods. From southern India, there were 25 infections with subtype C and 2 with subtype A. From Myanmar (Burma), we identified the first subtype E infection, as well as six subtype BB, a distinct cluster within subtype B that was first discovered in Thailand and that has now appeared in China, Malaysia, and Japan. From southwest China, one BB was identified, while a "classical" B typical of North American and European strains was found in Indonesia. From Thailand, five DBS of ambiguous serotype were identified as three B, one BB, and one E. A blinded control serotype E specimen was correctly identified, but a serotype BB control was not tested. Most HIV-1 in southern India appears to be env subtype C, with rare A, as others have reported in western and northern India. The subtypes BB and E in Myanmar, and the BB in China, suggest epidemiological linkage with these subtypes in neighboring Thailand. DBS are a practical, economical technique for conducting large-scale molecular epidemiological surveillance to track the global distribution and spread of HIV-1 variants.

PIP: The global surveillance of HIV-1 subtypes for genetic characterization is frustrated by the danger of processing and the difficulties of shipping whole blood or cells from many developing country regions. The authors therefore developed a technique for the direct automated sequencing of viral DNA from dried blood spot (DBS) specimens collected on absorbent paper. Such specimens can be mailed unrefrigerated in paper envelopes with low biohazard risk. 51 DBS specimens were collected nonrandomly from HIV-1-infected, mostly asymptomatic individuals in India, Myanmar, China, Indonesia, and Thailand in 1991, then shipped via airmail or hand carried without refrigeration to Bangkok from where they were forwarded to North America for processing. After more than 2 years in storage, including 6 months at ambient temperatures, proviral DNA in 42 of the DBS was successfully amplified by nested polymerase chain reaction, and a 389-nucleotide segment of the C2-V3 env gene region was sequenced, from which 287 base pairs were aligned and subtyped by phylogenetic analysis with neighbor-joining and other methods. From southern India, there were 25 infections with subtype C and two with subtype A; the first subtype E infection was identified from Myanmar, as well as six subtype B(B); one B(B) was identified from southwest China; subtype B was identified from Indonesia; and five DBS of ambiguous serotype classified as three B, one B(B), and one E were identified from Thailand. DBS can be used as a practical, cost-effective way of tracking the global distribution and spread of HIV-1 variants.

Leprosy in Myanmar, epidemiological and operational changes, 1958-92.

The registered caseload and prevalence of leprosy have declined in Myanmar from a peak of 86.2 per 10,000 population (95% CI 85.43-86.97) in 1973-77 to 26.82 (95% CI 18.46-35.18) in 1988-92. The new case detection rates have also declined from 7.41 per 10,000 (95% CI 6.3- 8.52) in 1968-72 to 1.96 (95% CI 1.43-2.52) in 1988-92. The increase in the multibacillary proportion of new cases from 11.85% (95% CI 11.84-11.86) in 1968-72 to 40.54% (95% CI 37.2-43.88) in 1988-92 and the decline in proportion of new cases under 14 years of age from 26.81% (95% CI 26.8-26.82) in 1968-72 to 11.22% (95% CI 10.92-11.52), coupled with the finding of declining detection rates among school children and in mass village surveys could mean that the incidence of leprosy may be declining.

Comparison of saliva and serum for HIV surveillance in developing countries.

Saliva has been proposed as a non-invasive alternative to serum for HIV antibody testing. In a field study in Myanmar (formerly Burma), we evaluated such an alternative to identify the frequency of HIV infection in a surveillance programme of high-risk and low-risk sentinel groups. Duplicate vials of saliva and serum were collected from 479 high-risk and 1039 low-risk subjects. One vial of each pair was analysed blind in two laboratories, one in the USA and the other in Myanmar. The US laboratory followed WHO confirmatory strategy III with three different enzyme-linked immunosorbent assays (ELISAs), while the laboratory in Myanmar followed strategy I with one ELISA. Serum testing in the US was the gold standard. The Cambridge ELISA with saliva was a more effective surveillance tool (sensitivity 90.5%, specificity 99.5-100%) for describing the frequency of subjects with HIV antibodies than the serum ELISA supplied to Myanmar by WHO (95.9% and 98.3%, respectively). Saliva is recommended as a safe and effective alternative to serum for HIV antibody testing with ELISA in surveillance programmes in developing countries.

PIP: HIV infection is becoming increasingly prevalent in Myanmar. More widespread HIV testing is therefore needed to make people aware that HIV has reached their community and convince them that preventive measures must be taken. The expense of blood serum testing, however, generally makes such widespread testing nonviable for developing countries. Testing saliva for the presence of antibodies to HIV has been suggested as a noninvasive alternative to testing serum. In testing saliva, needlestick injuries would be avoided, highly trained personnel would not be needed, many subjects could be sampled simultaneously, subjects might prefer to give saliva samples instead of blood, and costs would be lower. 479 high-risk and 1039 low-risk subjects were recruited for the study from Myanmar. Their saliva and serum samples were then tested in both the US and Myanmar. 3 ELISA tests were used to test serum in the US in keeping with World Health Organization confirmatory strategy III. Only one ELISA was performed in the Myanmar laboratory. The Cambridge ELISA proved most effective in identifying the number of subjects with HIV antibodies. The authors recommend testing saliva instead of serum for HIV surveillance programs in developing countries. Given the Cambridge ELISA 10% false-negative rate in the Myanmar laboratory and the 5% false-negative rate in the US laboratory, saliva testing is, however, inadequate for diagnostic testing and should be used exclusively for surveillance purposes.

Risk factors among defaulters in the urban leprosy control centre of Thaketa Township in the city of Yangon, Myanmar, 1986.

A total of 884 registered cases from the city of Yangon were retrospectively analysed. The defaulter proportion among cases registered for treatment at the Thaketa Health Centre was 34.16%. It was established that patient sex and occupation are not a factor in defaulting. Paucibacillary cases and cases with no disability are more likely to default.

Estimation of leprosy prevalence in Bago and Kawa townships using two-stage probability proportionate to size sampling technique.

Two surveys to estimate leprosy prevalence using two-stage probability proportionate to size sampling technique were conducted in Bago and Kawa townships. A total of 3519 and 3739 individuals were examined in each township. The two surveys were finished within 25 (Bago) and 30 (Kawa) working days at a cost of Kyats 10,000 (US $1500) for each survey. The estimated leprosy prevalence obtained in Bago was 9.95 per 1000 population (95% confidence interval (CI): 7.11-12.78) and in Kawa it was 12.04 per 1000 population (95% CI: 8.85-15.22). A total of 30 (Bago) and 34 (Kawa) new leprosy cases were detected in the two surveys. Grade I disability was seen to be 20% in Bago and 18.78% in Kawa, whereas grade II disability was 17.14% in Bago and 15.56% in Kawa.

A comparative KAP study of leprosy patients and members of the community in Hlaing and Laung-Lon townships.

A KAP study was conducted in the peri-urban Hlaing and rural Laung-Lon Townships in Myanmar. It was found that both the leprosy patients as well as community members were still not sure about the cause of leprosy. Social stigma of leprosy encountered by patients needs to be addressed especially in peri-urban areas. It was also found that the patient's understanding of treatment regularity was still very unsatisfactory, for which health education measures needs to be introduced.