The Impact of Leprosy Control: Epidemiological and modelling studies

This thesis addresses the impact of leprosy control on the occurrence of leprosy and its associated impairments. Chapter 1 introduces leprosy, an infectious disease. Its manifestations vary widely: from mild self-healing forms to chronic and destructive disease. Knowledge regarding transmission of the leprosy bacterium Mycobacterium leprae is limited. For instance, it is unknown to what extent individuals incubating for disease contribute to transmission. Leprosy is a public health problem because it may cause nerve function impairment, leading to secondary complications of eyes, hands and feet. Disability, handicap and social stigma are ultimate consequences. Activities to prevent impairment and disability are very important. Early detection of patients followed by chemotherapy is the mainstay of leprosy control. The introduction of highly bactericidal multidrug therapy (MDT) in the 1980s was a strong impetus for control programmes. However, evidence for an impact of MDT on transmission and incidence is still lacking

The effect of chemical variability and weathering on Raman spectra of enargite and fahlore

Enargite (Cu3AsS4) and tennantite (Cu12As4S13) are typical As-bearing sulfides in intermediate-and high-sulfidation epithermal deposits. Trace and major element variations in enargite and tennantite and their substitution mechanisms are widely described. However, Raman spectra of the minerals with correlative quantitative chemical information are rarely documented, especially for enargite. Therefore, comparative electron and μ-Raman microprobe analyses were performed on enargite and fahlore grains. These spectra can be used in the industrial detection and subsequent removal of As-bearing sulfides prior to ore beneficiation in order to diminish the environmental impact of the metallurgical technologies. A simple Sb5+-As5+ substitution in enargite was confirmed by Raman analyses. Similarly, a complete solid solution series from tetrahedrite to tennantite (i.e., Sb3+-As3+ substitution) can be correlated with a gradual evolution in their Raman spectra. In turn, Te4+ occupies the As3+ and Sb3+ sites in fahlore by the coupled substitution Te4+gCu+g(As, Sb)3+g(Cu, Fe, Zn)2+. Accordingly, Raman bands of goldfieldite (Te-rich member) are strongly broadened compared with those of tetrahedrite and tennantite. A secondary phase with high porosity and a fibrous or wormlike texture was found in enargite in a weathered sample. The chemical composition, Raman spectrum, and X-ray diffraction signature of the secondary phase resemble tennantite. A gradual transformation of the primary enargite into this secondary phase was visualized by comparative electron and Raman microprobe mapping

Disappearance of leprosy from Norway: an exploration of critical factors using an epidemiological modelling approach

BACKGROUND: By the middle of the 19th century, leprosy was a serious public health problem in Norway. By 1920, new cases only rarely occurred. This study aims to explain the disappearance of leprosy from Norway. METHODS: Data from the National Leprosy Registry of Norway and population censuses were used. The patient data include year of birth, onset of disease, registration, hospital admission, death, and emigration. The Norwegian data were analysed using epidemiological models of disease transmission and control. RESULTS: The time trend in leprosy new case detection in Norway can be reproduced adequately. The shift in new case detection towards older ages which occurred over time is accounted for by assuming that infected individuals may have a very long incubation period. The decline cannot be explained fully by the Norwegian policy of isolation of patients: an autonomous decrease in transmission, reflecting improvements in for instance living conditions, must also be assumed. The estimated contribution of the isolation policy to the decline in new case detection very much depends on assumptions made on build-up of contagiousness during the incubation period and waning of transmission opportunities due to rapid transmission to close contacts. CONCLUSION: The impact of isolation on interruption of transmission remains uncertain. This uncertainty also applies to contemporary leprosy control that mainly relies on chemotherapy treatment. Further research is needed to establish the impact of leprosy interventions on transmission

Sensory testing in leprosy:Comparison of ballpoint pen and monofilaments

The 10 g monofilament has been replaced by the ballpoint pen in routine sensory testing of nerves in leprosy control in Ethiopia. Results of sensory testing between the ballpoint pen and different monofilaments on hands and feet were compared. Ballpoint pen underdiagnosis of loss of sensation was defined to occur when the pen was felt and the monofilament was not. Differences were evaluated both for individual test points (test point level) and for the test points of extremities collectively (extremity level). An extremity (either a hand or a foot) was defined as having sensory nerve function impairment (SNFI) if a supplying nerve had SNFI, which was the case when sensation was absent in two or more test points in the area supplied by that nerve. At test point level, the percentages with ballpoint pen underdiagnosis relative to the 2, 10, 20 and 50 g monofilaments were 40, 21, 9 and 7%, respectively, in the hands, and 47, 30, 15 and 7% in the feet. Ballpoint pen underdiagnosis percentages of SNFI at extremity level were 32, 18, 8 and 9% in the hands, and 37, 26, 14 and 6% in the feet. The risk of ballpoint pen underdiagnosis appears to be higher in extremities without visible damage. In conclusion, substantial levels of underdiagnosis of sensory loss with the ballpoint pen were observed. However, the consequences for the prognosis of treatment with corticosteroids in patients with the more subtle sensation loss noted here need to be established. Development and testing of guidelines is a prerequisite for the use of the ballpoint pen

Sensory testing in leprosy:Comparison of ballpoint pen and monofilaments

The 10 g monofilament has been replaced by the ballpoint pen in routine sensory testing of nerves in leprosy control in Ethiopia. Results of sensory testing between the ballpoint pen and different monofilaments on hands and feet were compared. Ballpoint pen underdiagnosis of loss of sensation was defined to occur when the pen was felt and the monofilament was not. Differences were evaluated both for individual test points (test point level) and for the test points of extremities collectively (extremity level). An extremity (either a hand or a foot) was defined as having sensory nerve function impairment (SNFI) if a supplying nerve had SNFI, which was the case when sensation was absent in two or more test points in the area supplied by that nerve. At test point level, the percentages with ballpoint pen underdiagnosis relative to the 2, 10, 20 and 50 g monofilaments were 40, 21, 9 and 7%, respectively, in the hands, and 47, 30, 15 and 7% in the feet. Ballpoint pen underdiagnosis percentages of SNFI at extremity level were 32, 18, 8 and 9% in the hands, and 37, 26, 14 and 6% in the feet. The risk of ballpoint pen underdiagnosis appears to be higher in extremities without visible damage. In conclusion, substantial levels of underdiagnosis of sensory loss with the ballpoint pen were observed. However, the consequences for the prognosis of treatment with corticosteroids in patients with the more subtle sensation loss noted here need to be established. Development and testing of guidelines is a prerequisite for the use of the ballpoint pen

Compositional and functional stability of aerobic methane consuming communities in drained and rewetted peat meadows

The restoration of peatlands is an important strategy to counteract subsidence and loss of biodiversity. However, responses of important microbial soil processes are poorly understood. We assessed functioning, diversity and spatial organization of methanotrophic communities in drained and rewetted peat meadows with different water table management and agricultural practice. Results show that the methanotrophic diversity was similar between drained and rewetted sites with a remarkable dominance of the genus Methylocystis. Enzyme kinetics depicted no major differences, indicating flexibility in the methane (CH4) concentrations that can be used by the methanotrophic community. Short-term flooding led to temporary elevated CH4 emission but to neither major changes in abundances of methane-oxidizing bacteria (MOB) nor major changes in CH4 consumption kinetics in drained agriculturally used peat meadows. Radiolabeling and autoradiographic imaging of intact soil cores revealed a markedly different spatial arrangement of the CH4 consuming zone in cores exposed to near-atmospheric and elevated CH4. The observed spatial patterns of CH4 consumption in drained peat meadows with and without short-term flooding highlighted the spatial complexity and responsiveness of the CH4 consuming zone upon environmental change. The methanotrophic microbial community is not generally altered and harbors MOB that can cover a large range of CH4 concentrations offered due to water-table fluctuations, effectively mitigating CH4 emission

The effect of chemical variability and weathering on Raman spectra of enargite and fahlore

Enargite (Cu3AsS4) and tennantite (Cu12As4S13) are typical As-bearing sulfides in intermediate- and high-sulfidation epithermal deposits. Trace and major element variations in enargite and tennantite and their substitution mechanisms are widely described. However, Raman spectra of the minerals with correlative quantitative chemical information are rarely documented, especially for enargite. Therefore, comparative electron and μ-Raman microprobe analyses were performed on enargite and fahlore grains. These spectra can be used in the industrial detection and subsequent removal of As-bearing sulfides prior to ore beneficiation in order to diminish the environmental impact of the metallurgical technologies. A simple Sb5+–As5+ substitution in enargite was confirmed by Raman analyses. Similarly, a complete solid solution series from tetrahedrite to tennantite (i.e., Sb3+–As3+ substitution) can be correlated with a gradual evolution in their Raman spectra. In turn, Te4+ occupies the As3+ and Sb3+ sites in fahlore by the coupled substitution Te4+ + Cu+ → (As, Sb)3+ + (Cu, Fe, Zn)2+. Accordingly, Raman bands of goldfieldite (Te-rich member) are strongly broadened compared with those of tetrahedrite and tennantite. A secondary phase with high porosity and a fibrous or wormlike texture was found in enargite in a weathered sample. The chemical composition, Raman spectrum, and X-ray diffraction signature of the secondary phase resemble tennantite. A gradual transformation of the primary enargite into this secondary phase was visualized by comparative electron and Raman microprobe mapping.</p

Insights into the mechanism of MCT8 oligomerization

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The bdbDC operon of Bacillus subtilis encodes thiol-disulfide oxidoreductases required for competence development

The development of genetic competence in the Gram-positive eubacterium Bacillus subtilis is a complex postexponential process. Here we describe a new bicistronic operon, bdbDC, required for competence development, which was identified by the B. subtilis Systematic Gene Function Analysis program. Inactivation of either the bdbC or bdbD genes of this operon results in the loss of transformability without affecting recombination or the synthesis of ComK, the competence transcription factor. BdbC and BdbD are orthologs of enzymes known to be involved in extracytoplasmic disulfide bond formation. Consistent with this, BdbC and BdbD are needed for the secretion of theEscherichia coli disulfide bond-containing alkaline phosphatase, PhoA, by B. subtilis. Similarly, the amount of the disulfide bond-containing competence protein ComGC is severely reduced in bdbC or bdbD mutants. In contrast, the amounts of the competence proteins ComGA and ComEA remain unaffected by bdbDC mutations. Taken together, these observations imply that in the absence of either BdbC or BdbD, ComGC is unstable and that BdbC and BdbD catalyze the formation of disulfide bonds that are essential for the DNA binding and uptake machinery