Clinical profiles of post-load glucose subgroups and their association with glycaemic traits over time: An IMI-DIRECT study.

AIM: To examine the hypothesis that, based on their glucose curves during a seven-point oral glucose tolerance test, people at elevated type 2 diabetes risk can be divided into subgroups with different clinical profiles at baseline and different degrees of subsequent glycaemic deterioration. METHODS: We included 2126 participants at elevated type 2 diabetes risk from the Diabetes Research on Patient Stratification (IMI-DIRECT) study. Latent class trajectory analysis was used to identify subgroups from a seven-point oral glucose tolerance test at baseline and follow-up. Linear models quantified the associations between the subgroups with glycaemic traits at baseline and 18 months. RESULTS: At baseline, we identified four glucose curve subgroups, labelled in order of increasing peak levels as 1-4. Participants in Subgroups 2-4, were more likely to have higher insulin resistance (homeostatic model assessment) and a lower Matsuda index, than those in Subgroup 1. Overall, participants in Subgroups 3 and 4, had higher glycaemic trait values, with the exception of the Matsuda and insulinogenic indices. At 18 months, change in homeostatic model assessment of insulin resistance was higher in Subgroup 4 (ß = 0.36, 95% CI 0.13-0.58), Subgroup 3 (ß = 0.30; 95% CI 0.10-0.50) and Subgroup 2 (ß = 0.18; 95% CI 0.04-0.32), compared to Subgroup 1. The same was observed for C-peptide and insulin. Five subgroups were identified at follow-up, and the majority of participants remained in the same subgroup or progressed to higher peak subgroups after 18 months. CONCLUSIONS: Using data from a frequently sampled oral glucose tolerance test, glucose curve patterns associated with different clinical characteristics and different rates of subsequent glycaemic deterioration can be identified.

Differential transcription of two highly divergent gut-expressed Bm86 antigen gene homologues in the tick Rhipicephalus appendiculatus (Acari: Ixodida).

The transcriptional control of gene expression is not well documented in the Arthropoda. We describe transcriptional analysis of two exceptionally divergent homologues (Ra86) of the Bm86 gut antigen from Rhipicephalus appendiculatus. Bm86 forms the basis of a commercial vaccine for the control of Rhipicephalus (Boophilus) microplus. The R. appendiculatus Ra86 proteins contain 654 and 693 amino acids, with only 80% amino acid sequence identity. Reverse-transcription PCR of gut cDNA showed transcription of only one genotype in individual female ticks. PCR amplification of 3' untranslated sequences from genomic DNA indicated that both variants could be encoded within a single genome. When both variants were present, one of the two Ra86 genotypes was transcriptionally dominant.

Identification of candidate sialome components expressed in ixodid tick salivary glands using secretion signal complementation in mammalian cells.

Ixodid ticks manipulate mammalian host pathways by secreting molecules from salivary glands. Novel cDNAs containing functional secretion signals were isolated from ixodid tick salivary glands using a signal sequence trap. Only 15/61 Rhipicephalus appendiculatus and 1/7 Amblyomma variegatum cDNAs had significant identity (< 1e-15) to previously identified sequences. Polypeptides that may interact with host pathways included a kinase inhibitor. Two proteins encoded homologues of the yolk protein vitellogenin and seventeen contained glycine-rich motifs. Four proteins without sequence matches had conserved structural folds, identified using a Threading algorithm. Predicted secretion signals were between fifteen and fifty-seven amino acids long. Four homologous polymorphic proteins contained conserved (26/27 residues) signal peptides. Ten functional tick secretion signals could not be unambiguously identified using predictive algorithms.

Case-control study of BCG vaccination as a risk factor for leprosy and tuberculosis in western Kenya.

A case-control study was carried out in western Kenya to measure the protection imparted by BCG against leprosy and tuberculosis. The study involved 69 newly diagnosed leprosy cases, 238 age-, sex- and neighborhood-matched controls, and 144 newly diagnosed, sputum-smear-positive tuberculosis cases along with 432 age-, sex- and neighborhood-matched controls. Information on BCG vaccination history was inferred from scars. Using matched analysis, the protection imparted by BCG against leprosy was estimated to be 81% [95% confidence interval (CI) = 67-90] with no apparent difference in protection against paucibacillary [vaccine efficacy (VE) = 83%, 95% CI = 58-92] and multibacillary leprosy (VE = 76%; 95% CI = 30-91). The effectiveness against tuberculosis was appreciably lower (VE = 22%) and was not statistically significant (95% CI = -20-51).

A case control study on human immunodeficiency virus-1 (HIV-1) infection as a risk factor for tuberculosis and leprosy in western Kenya.

A case control study was undertaken in Western Kenya from April 1989 to August 1990 to evaluate HIV-1 infection as a risk factor for tuberculosis and leprosy. The study involved 144 newly diagnosed sputum smear positive tuberculosis cases with 432 age, sex and neighbourhood-matched controls, and 132 diagnosed leprosy cases with 384 matched controls. Odds ratios obtained by conditional logistic regression (matched) analysis were 4.9 (95% CI 2.6, 6.8), and 1.8 (95% CI 0.9, 3.2), for the association between HIV-1 and tuberculosis and leprosy respectively. Approximately 31% of tuberculosis cases among males, and 11% of cases among females, were attributable to HIV infection.

PIP: Between April, 1989, and August 1990. in Busia, Siaya, Kisumu, and South Nyanza districts of Western Kenya, health workers recruited 144 sputum smear positive tuberculosis (TB) cases and 432 age, sex, and neighborhood matched controls. They also recruited 132 newly detected leprosy cases and 384 matched controls. Researchers wanted to determine the association between HIV-1 and TB and between HIV-1 and leprosy. TB cases were more likely to be HIV-1 seropositive than were their controls, regardless of age (odds ratio = 4.9). Less than 30-year-old female TB patients were less likely to be HIV-1 seropositive than were less than 30-year-old male TB patients (OR, 2.8 vs. 8.1), while the opposite was true for older TB patients (OR, 19.6 vs. 2.6). Though not statistically different, the OR was greater for certain TB cases than for possible TB cases (13.7 vs. 3.5) and for BCG negative cases than for BCG positive cases (16.5 vs. 3.1). Etiologic fractions indicated that HIV infection was responsible for 31% of TB cases among males and 11% of TB cases among females. Overall, leprosy cases and controls had lower HIV seropositivity rates than did their TB counterparts (OR, 1.8 vs. 4.9). Even though none of the ORs for the association between HIV infection and leprosy were statistically significant from unity, the fact that ORs were greater than unity in all (1.4-2.4) but 1 group (5-29 year old females, OR = 0.5) indicated a possible trend towards positive association. Though not statistically different, polar lepromatous type of leprosy and the leprosy category of histopathologically confirmed cases had the highest ORs (3.7 and 1.9, respectively). Multibacillary leprosy cases had a higher OR than did paucibacillary leprosy (2 vs. 1.6).

Occurrence of type 1 reactions in leprosy in West Kenya

Leprosy reactions are a major cause of leprosy deformities and disabilities. The risk factors that trigger off these reactions are ill understood and only associations with stressing conditions have been drawn. Type 1 reactions are known to occur in leprosy patients both before and after onset of chemotherapy. A total of 264 leprosy record cards belonging to patients treated at Alupe Leprosy and Skin Diseases Research Centre between March 1985 and February 1991 were reviewed to determine the differences between those who developed Type 1 reaction and those who did not. Disease classification; age; sex; treatment regimen and time of onset of the reactions were some of the variables examined. 39 of multibacillary leprosy cases compared to 61 of paucibacillary cased had Type 1 reactions. 49 of reactions in the two classes occurred during chemotherapy. Significant differences between sex; age and type of leprosy were found among those who had Type 1 reaction and those who did not

Multidrug therapy for treatment of paucibacillary leprosy in western Kenya--preliminary communications.

A prospective study is being undertaken in Western Kenya to evaluate the effectiveness and tolerability of WHO-MDT, while at the same time comparing it to a modified multidrug regimen, which is rifampicin 1500mg at the onset supervised, and repeated after 3 months and dapsone 100mg daily for 6 months. Preliminary analysis done on 127 cases admitted into the study are presented. The inactivity index observed between 0-12 weeks was 20% for WHO-MDT and 47% for modified-MDT (p less than 0.01). The inactivity index observed between 0-24 weeks was 63.3% for WHO-MDT and 82.3% for modified-MDT (p less than 0.05). The inactivity index observed between 0-32 weeks was 83% for WHO-MDT, and 88% for modified-MDT. Type 1 reaction was noted in 23.3% on those on WHO-MDT, and 20.3% on those cases on modified-MDT (p greater than 0.1). Compliance rate was 93.8% for those on WHO-MDT and 95.2% on those on modified MDT. All regimens were well tolerated. These preliminary results indicate that MDT is effective in treatment of paucibacillary leprosy, and also that clinical cure can be achieved in much shorter duration, particularly with higher dosage of rifampicin.