Physical distance, genetic relationship, age, and leprosy classification are independent risk factors for leprosy in contacts of patients with leprosy

BACKGROUND: Close contacts of patients with leprosy have a higher risk of developing leprosy. Several risk factors have been identified, including genetic relationship and physical distance. Their independent contributions to the risk of developing leprosy, however, have never been sufficiently quantified. METHODS: Logistic-regression analysis was performed on intake data from a prospective cohort study of 1037 patients newly diagnosed as having leprosy and their 21,870 contacts. RESULTS: Higher age showed an increased risk, with a bimodal distribution. Contacts of patients with paucibacillary (PB) leprosy with 2-5 lesions (PB2-5) and those with multibacillary (MB) leprosy had a higher risk than did contacts of patients with single-lesion PB leprosy. The core household group had a higher risk than other contacts living under the same roof and next-door neighbors, who again had a higher risk than neighbors of neighbors. A close genetic relationship indicated an increased risk when blood-related children, parents, and siblings were pooled together. CONCLUSIONS: Age of the contact, the disease classification of the index patient, and physical and genetic distance were independently associated with the risk of a contact acquiring leprosy. Contact surveys in leprosy should be not only focused on household contacts but also extended to neighbors and consanguineous relatives, especially when the patient has PB2-5 or MB leprosy.     

Host defence against disseminated Candida albicans infection and implications for antifungal immunotherapy

The different manifestations of Candida albicans infection are dictated by an underlying defect in the immune response of the host. Protective immunity to disseminated candidiasis, the manifestation of C. albicans infection discussed in this review, has traditionally been ascribed to innate immunity with emphasis on the role of granulocytes. Lately, however, immunological studies have learned that host defence against disseminated candidiasis is based on a complex interplay between innate and cell-mediated immunity. Despite the availability of new antifungal agents, mortality associated with disseminated C. albicans infection remains high. Immunotherapy that augments host defence is an important strategic option in the battle against disseminated candidiasis. Here, the authors review the chronological events in the pathogenesis of disseminated candidiasis that aid in predicting the impact of existing immunotherapy and the development of future immunomodulating strategies.     

Vacuolar invertase regulates elongation of Arabidopsis thaliana roots as revealed by QTL and mutant analysis

The possible role of the sucrose-splitting enzymes sucrose synthase and invertase in elongating roots and hypocotyls of Arabidopsis was tested by using a combination of histochemical methods and quantitative trait locus (QTL) analysis. Lengths of roots and hypocotyls correlated better with invertase activities than with sucrose synthase activities. The highest correlations were observed with activities in the elongating zones of roots. The genetic basis of these correlations was studied by using QTL analysis. Several loci, affecting invertase activity, colocated with loci that had an effect on root or hypocotyl length. Further fine mapping of a major locus for root length, but not for hypocotyl length (top chromosome 1), consistently showed colocation with the locus for invertase activity containing a gene coding for a vacuolar invertase. The analysis of a functional knockout line confirmed the role of this invertase in root elongation, whereas other invertase genes might play a role in hypocotyl elongation. Thus, we show the power of QTL analysis, combined for morphological and biochemical traits, followed by fine-mapping and mutant analysis, in unraveling the function of genes and their role in growth and development.     

Low lactase activity in a small-bowel biopsy specimen: should dietary lactose intake be restricted in children with small intestinal mucosal damage?

OBJECTIVE: Small intestinal mucosal damage can result in decreased lactase activity (LA). When LA is low in a small-bowel biopsy (SBB) specimen, a reduction of dietary lactose intake is usually advised. This is often done by reducing dietary dairy products, which also reduces the intake of calcium, protein and vitamins. Since intestinal damage can have a patchy character and LA varies along the horizontal axis of the small intestine, the relevance of SBB measurement for intestinal LA could be questioned. We compared LA in the SBB with the in vivo capacity to digest lactose using the Lactose Digestion Index (LDI). MATERIAL AND METHODS: LA was measured in 18 children aged 0.8-10.9 years (mean 3.9, SD 2.4) undergoing SBB for various indications. In all children the LDI was determined using the (13)C-lactose/(2)H-glucose test. RESULTS: In 9/18 biopsy specimens LA was low (<10 U/g protein). LDI was normal in 14/18 patients. In 8 out of 9 patients with normal lactase activity, LDI was also normal, while in 6 out of 9 patients LDI was normal despite low LA in the biopsy. In patients with normal LDI, histology was normal in 6/14, in 4/14 mild histological changes (Marsh II) were seen and in 4 patients histological damage was severe (grade III). CONCLUSIONS: In children with small-bowel mucosal damage, lactose digestive capacity can remain high despite low LA and histological changes in an SBB. Extrapolation of LA in SBB specimens to overall lactose digestive capacity may not be reliable. The advice concerning the restriction of intake of dairy products cannot be based on the data of the SBB only.     

Non-Invasive Detection of Low-Intestinal Lactase Activity in Children by Use of a Combined 13CO2/H2 Breath Test

Background: The aim of the study was to diagnose hypolactasia with a higher accuracy than with the traditional H₂ breath test. Methods: We used a combined ¹³C-lactose ¹³CO₂/H₂ breath test, which was performed in 33 patients in whom lactase activity was measured. Results: Lactase activity was reduced in 13 cases. The sensitivity and specificity of the H₂ test were 54% and 90%; those of the ¹³CO₂ test 69% and 70%. False-negative results did not always occur in the same patients. In five of six patients with both test results abnormal, lactase activity was low. In 13 of 15 patients with both test results normal, lactase activity was normal. In 6 of 12 cases with only 1 test abnormal, lactase activity was low. Conclusion: The combined H₂/¹³CO₂ breath test (sensitivity, 85%; specificity, 65%) is more adequate for diagnosis of hypolactasia than the H₂ breath test alone.     

Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls

Background

To evaluate co-administration of GlaxoSmithKline Biologicals’ human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB).

Methods

This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV (n = 247), HepB (n = 247) or HPV co-administered with HepB (HPV + HepB; n = 247) at Months 0, 1 and 6. Antibodies against hepatitis B surface antigen (HBs), HPV-16 and HPV-18 were measured, and reactogenicity and safety monitored. Co-primary objectives were to demonstrate non-inferiority of hepatitis B and HPV-16/18 immune responses at Month 7 for co-administered vaccines, compared with vaccines administered alone, in the according-to-protocol cohort.

Results

The pre-defined criteria for non-inferiority were met for all co-primary immunogenicity endpoints at Month 7. Anti-HBs seroprotection rates ≥10 mIU/mL were achieved by 97.9% and 100% of girls, respectively, following co-administration or HepB alone. Anti-HBs geometric mean titers (GMTs) (95% confidence interval) were 1280.9 (973.3-1685.7) and 3107.7 (2473.1-3905.1) milli-international units/mL, respectively. Anti-HPV-16 and -18 seroconversion rates were achieved by ≥99% of girls following co-administration or HPV alone. Anti-HPV-16 GMTs were 19819.8 (16856.9-23303.6) and 21712.6 (19460.2-24225.6) ELISA units (ELU)/mL, respectively. Anti-HPV-18 GMTs were 8835.1 (7636.3-10222.1) and 8838.6 (7948.5-9828.4) ELU/mL, respectively. Co-administration was generally well tolerated.

Conclusions

The study results support the co-administration of HPV-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine in adolescent girls aged 9-15 years.

Clinical trials registration

ClinicalTrials.gov registration number NCT00652938.