Antibiotic resistance of Escherichia coli isolated from uncomplicated UTI in general practice patients over a 10-year period.

Recommendations of first choice antibiotic therapy need to be based on actual antibiotic susceptibility data. We determined the antibiotic susceptibility of E. coli in uncomplicated UTI among women and compared the results with 2004 and 2009. In 30 sentinel general practitioner practices of Nivel Primary Care database, urine samples were collected from women with symptoms of uncomplicated UTI. Patient characteristics, E. coli susceptibility, and ESBL production were analyzed. Six hundred eighty-nine urine samples were collected; E. coli was the most isolated uropathogen (83%). Antibiotic susceptibility was stable over time except for ciprofloxacin (96% in 2004, 97% in 2009, and 94% in 2014; P < 0.05). The susceptibility to co-amoxiclav was 88%, 87%, and 92% in 2004, 2009, and 2014, respectively. The prevalence of ESBL-producing E. coli increased from 0.1% in 2004 to 2.2% in 2014 (P < 0.05). Regional differences in antibiotic susceptibility for co-trimoxazole were found being the highest in the west (88%) and the lowest in the north (72%, P = 0.021). Ciprofloxacin susceptibility was related to antibiotic use in the past 3 months (97% no use versus 90% use, P = 0.002) and age > 70 years (P = 0.005). In 2014, prescription of fosfomycin increased compared to 2009 (14.3% versus 5.6%) at the expense of co-amoxiclav, co-trimoxazole, and fluoroquinolones (P < 0.05). The susceptibility percentages to most antimicrobial agents tested were stable over 10 years' period although the prevalence of E. coli and ESBLs significantly increased. Performance of a survey with regular intervals is warranted.

Risk factors for the development of clinical leprosy among contacts, and their relevance for targeted interventions.

Existing knowledge on risk factors for the development of clinical leprosy among contacts of known leprosy patients is reviewed with the aim to identify factors associated with leprosy among contacts that have potential for developing effective targeted interventions in leprosy control. Different definitions of 'contact' have been used and most studies on this subject were among so-called household members. Yet several studies indicate that contacts found in other places than the household are also at risk of developing leprosy. The type of leprosy and the bacterial index are the main patient-related factors involved in transmission, but also contacts of PB patients have a higher risk of contracting leprosy as compared to the general population. The most important contact-related factors are the closeness and intensity of the contact and inherited susceptibility, while the role of age and sex of the contacts is not clear. The role of socio-economic factors is also vague. The significance of immunological and molecular markers in relation to risk of transmitting or developing leprosy is not yet fully understood, but there is an indication that contacts who are sero-positive for anti-PGL-I antibodies are at increased risk of developing clinical leprosy. The presence of a BCG scar is likely to be related to a lower risk. Analogies with tuberculosis suggest that the 'stone-in-the-pond' approach to control may be applicable to leprosy too. Sputum smear negative tuberculosis patients are known to spread the bacteria to others. This analogy strengthens the suggestion that the contacts of paucibacillary leprosy cases should also be included in contact tracing and examination. It is concluded that targeted interventions should be aimed at close contacts of both MB and PB patients inside and outside the household, particularly when genetically related.

Case detection, gender and disability in leprosy in Bangladesh: a trend analysis.

A trend analysis is presented of all newly detected leprosy cases over an 18-year period (1979-1996) in a highly leprosy endemic area of Bangladesh. A total of 23,678 new cases were registered, with an average of 860 new cases per year in the first 12 years, and increasing to around 3000 in 1996. The male:female (M:F) ratio decreased from 2.3 to 1.4. The proportions of newly detected cases with MB leprosy and of newly detected cases with any disability decreased over time. These reductions were more marked in the higher age groups of both sexes. The reduction in disability was primarily attributable to a decline in grade 2 disability. New case detection rates (NCDR) of all leprosy patients per 10,000 general population increased for males from 3 to 6; and for females from 1 to 4, while the NCDR of MB leprosy decreased in males from 1.4 to 0.6, and in females fluctuated around 0.45. The NCDRs of leprosy patients with disabilities showed an initial decrease in the first period, especially in males, but later showed an increase. The NCDR of males with disability was about twice as high as that of females. Finally, female NCDRs in the ages between 15 and 30 were low by comparison with the male NCDRs at the same time. This may be due to the sociocultural characteristics of the Bangladeshi society, with gender differences in exposure, health seeking behaviour and opportunities for case detection. Operational changes in the control programme have contributed to the changed profile of newly detected cases. This study shows that the application of general population statistics is essential for understanding the dynamics in leprosy control programmes under changing operational conditions. Combining case detection figures with such statistics helps to identify population groups that are possibly not benefiting sufficiently from the services provided, and to clarify the dynamics in control programmes and the future trends and programme requirements.

Dynamics of impairment during and after treatment: the AMFES cohort.

This study investigates the dynamics of impairment during and after multidrug therapy treatment for the patient cohort of the prospective ALERT MDT Field Evaluation Study (AMFES). The impairment status was compared at intake, at release from treatment (rft), and at the time of the latest survey between 24 and 48 months after release from treatment (follow-up). The eye-hand-foot impairment score (EHF score), which is the sum of the WHO impairment grades of the eyes, hands, and feet, was used as tool for comparison. In all, 433 out of the 592 patients (224 PB and 209 MB) completed treatment in time and were assessed at release from treatment. The risk of getting impaired was 4% for the 113 PB and 21% for the 91 MB patients who were initially free from impairment. Out of the 111 initially impaired PB patients, 41% recovered or improved and 13% worsened in EHF score. For the 118 initially impaired MB patients, these figures were: recovery or improvement 43% and worsening 13%. Three hundred and twenty-three out of the 433 patients (158 PB and 165 MB) had a follow-up examination in between the next 24-48 months after rft. The risks of impairment at follow-up were 6% for the 79 PB and 18% for the 77 MB patients without impairment at rft. Out of the 79 PB patients with impairment at rft, 35% recovered or improved and 28% worsened. For the 88 impaired MB patients, these figures were: recovery or improvement 26% and worsening 27%. Patients showed a tendency to compensate EHF score improvement before rft by worsening after rft and vice versa. The first main conclusion is that the impairment status at intake was by far the most important determinant for future impairment. The second one is that the dynamics of impairment were less favourable after rft than before. Little is known about the long-term fate of leprosy patients with irreversible nerve damage and the associated risk of developing severe secondary impairment. Especially in this era of the leprosy elimination goal, we should give this accumulating patient group due attention in research and health policy agendas.

The hand-foot impairment score as a tool for evaluating prevention of disability activities in leprosy: an exploration in patients treated with corticosteroids.

The hand-foot (HF) impairment score in leprosy patients is the sum of the WHO disability grades for hands and feet. This retrospective study explored the possibility of using the HF score for evaluation of the effectiveness of corticosteroid treatment programmes for nerve function impairment (NFI). Changes in the score were compared with changes in sensory testing (ST) and voluntary muscle testing (VMT) for 42 leprosy patients who received corticosteroid treatment. The WHO grade did not change in 30/60 (50%) of extremities gaining, and in 4/10 (40%) extremities losing sensation and/or muscle strength. However, 18/24 (75%) patients with a definite gain in function improved in HF score, while the HF score remained unchanged in 10/11 (91%) patients with no change in nerve function. Five patients with impairment in multiple extremities showed both gain and loss of sensation and/or muscle strength in the same or different extremities. Overall, improvement, deterioration and absence of change in NFI, as indicated by changes in ST and VMT were reflected correctly by the HF score in 28 (76%) of the remaining 37 patients. It was also shown that the HF score does not give appropriate information on the extent of the effect of corticosteroid treatment. This study illustrates that the HF score can not be used to support management of corticosteroid treatment of individual patients, but indicates this score to be a promising device for the evaluation of the effectiveness of corticosteroid treatment programmes. This study used the HF score because information on (changes in) eye impairment was not considered reliable. However, in principle, we consider the EHF score, which is the sum of the WHO disability grades for hands, feet and eyes, preferable for evaluation purposes. We strongly recommend further validation of the EHF score as a tool for evaluation of corticosteroid treatment programmes for patient groups with different distributions of NFI through prospective studies.

Factors associated with impairments in new leprosy patients: the AMFES cohort.

Data on the importance of the delay between onset of symptoms and registration as a risk factor for impairment are sparse. This study investigates the quantitative relationship between this delay, other risk factors and the impairment status in new leprosy patients. It reports on 592 new leprosy patients enrolled in 1988-1992 in the prospective ALERT MDT Field Evaluation Study in central Ethiopia (AMFES). The influence of the risk factors sex, age, delay, PB/MB classification in relation to BI, and prior dapsone treatment on the impairment status at intake is analysed. Estimates for the delay are based on patient recall. For the risk factors, odds ratios on impairment and on severity of impairment were calculated using both univariate and multivariate logistic regression. The registration delay was 2 years or more for 44% of new patients. The prevalence of impairment (WHO impairment grades 1 and 2 combined) increased continuously from 36% for new patients with a delay of 0-1 year to 81% for new patients with delays of 4 years or more. This prevalence also increased continuously with age; it rose from 26% in children to 80% for the age group 60 and over. In the multivariate regression, the odds ratios for new patients to be impaired were statistically significant for all delay categories (baseline 1-2 years) and age groups (baseline 15-29 years). No statistically significant differences in odds ratios were observed with respect to sex and PB/MB classification in relation to BI. Overall, 31% of new patients presented with WHO impairment grade 1 and 23% with grade 2. The risk on grade 2 also increased with the registration delay amongst the impaired new patients. Relatively few impaired males and relatively few impaired MB patients with a BI value of 3 or higher had grade 2 impairment. Registration delay and age are the main risk factors for presentation with impairment. Reduction of delay in central Ethiopia requires re-thinking of control methodologies. The search for ways to reduce delays in diagnosis and treatment should receive high priority in leprosy research and in leprosy control programmes.

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.

Trends in leprosy case detection rates.

BACKGROUND: A systematic review of the trends in leprosy incidence is lacking. The question of whether leprosy transmission has declined remains, therefore, unanswered. This study investigates trends in new case detection rates (NCDRs) in selected leprosy-endemic areas from different continents. METHODS: A literature search using specific inclusion criteria was performed. Average annual rates of change in NCDRs were obtained by exponential curve fitting. The variation in trends within individual areas was investigated using direct and indirect information on leprosy control activities. RESULTS: This review covers 16 areas in the Pacific, Asia, Africa and Latin America. For 10 out of the 16 areas, the trend was seen to be declining consistently over the last 10 years or longer. Near stabilization or stabilization after decline was observed for two areas. For three areas, interpretation of recent NCDRs was difficult due to changes in control, but two of them showed a decline over the study period. A consistently increasing trend was observed over the last 20 years in the one remaining area. The observed downward trends could not be attributed to reduced control activities or changed diagnostic criteria. A general acceleration of downward trends in the NCDR after the introduction of multidrug therapy (MDT) has not so far occurred. CONCLUSION: Our main conclusion is that despite many differences between the studies and study areas, the review demonstrates a considerable tendency of downward NCDR trends. Lack of information and changing control conditions necessitate caution in interpreting NCDR trends in individual areas. A general impact of MDT on NCDR trends is so far not visible. The coming years will be crucial for MDT-based control to prove its ability to reduce leprosy incidence.

SIMLEP: a simulation model for leprosy transmission and control.

SIMLEP is a computer program for modeling the transmission and control of leprosy which can be used to project epidemiologic trends over time, producing output on indicators such as prevalence, incidence and case-detection rates of leprosy. In SIMLEP, health states have been defined that represent immunologic conditions and stages of leprosy infection and disease. Three types of interventions are incorporated: vaccination, case detection and chemotherapy treatment. Uncertainties about leprosy have led to a flexible design in which the user chooses which of many aspects should be included in the model. These aspects include natural immunity, asymptomatic infection, type distribution of new cases, delay between onset of disease and start of chemotherapy, and mechanisms for leprosy transmission. An example run illustrates input and output of the program. The output produced by SIMLEP can be readily compared with observed data, which allows for validation studies. The support that SIMLEP can give to health policy research and actual decision making will depend upon the extent of validation that has been achieved. SIMLEP can be used to improve the understanding of observed leprosy trends, for example, in relation to early detection campaigns and the use of multidrug therapy, by exploring which combinations of assumptions can explain these trends. In addition, SIMLEP allows for scenario analysis in which the effects of control strategies combining different interventions can be simulated and evaluated.

Trabajos científicos y colaboraciones. Factores de riesgo para el desarrollo de lepra clínica entre contactos y su importancia como objetivos de intervención / No disponible

Se revisan los conocimiento actuales sobre factores de riesgo para contraer lepra entre contactos de casos confirmados para intentar identificar los factores asociados con la enfermedad que entre los contactos presentan potencial para ser objetivos de intervenciones en los programas de control de la lepra. Se han utilizado distintas definiciones para el termino “contacto” aunque la mayoría de estudios emplean el de conviviente. Sin embargo, hay estudios que indican que otro tipo de contacto distinto al conviviente también esta en peligro de contraer la enfermedad. El tipo de lepra y su carga bacilar son los dos factores mas implicados en la transmisión pero los contactos de pacientes PB presentan mayor riesgo de contraer la lepra que los individuos de la población general. Los factores de contacto más importantes son: la cercanía e intensidad de contacto y la susceptibilidad heredada mientras que el sexo y la edad de los contactos junto a los factores socio-económicos no están muy claros. Tampoco están definidos los conceptos de marcadores inmunológicos y moleculares en cuanto al riesgo de transmitir o desarrollar la enfermedad pero existen evidencia de que contactos PGL1 seropositivos están en mayor riesgo. La presencia de cicatriz BCG parece apuntar hacia un menor riesgo. Las analogías con tuberculosis parecen indicar la similitud del concepto de “ondas en el estanque” en las dos enfermedades. Se sabe que pacientes esputo negativos pueden transmitir la tuberculosis, por tanto se debe extender este concepto de riesgo a los contactos de pacientes PB. La conclusión es que los contactos de pacientes MB y PB, tanto convivientes como no, deben ser objeto de intervenciones dirigidas sobre todo cuando están relacionadas genéticamente

Existing knowledge on risk factors the development of clinical leprosy among contacts of know leprosy patients is reviewed with the aim to identify factors associated with leprosy among contacts that have potential or developing effective targeted interventions in leprosy control. Different definitions of “contact” have been used and most study on this subject were among so-called household members. Yet several studies indicate that contacts found in other places that the household are also at risk of developing leprosy. The type of leprosy and the bacterial index are the main patient-related factors involved in transmission, but also contacts of PB patients have a higher risk of contracting leprosy as compared to general population. The most important contact-related factors are the closeness and intensity of the contact and inherited susceptibility, while the role of age and sex of the contacts is not clear. The role of socio-economic factors is also vague. The significance of immunological and molecular markers in relation to risk of transmitting or developing leprosy is not yet fully understood, but there is an indication that contacts who are sero-positive for anti-PGL-I antibodies are at increased risk of developing clinical leprosy. The presence of BCG scar is likely to be related to a lower risk. Analogies with tuberculosis suggest that the “stone-in-the-pond” approach to control may be applicable to leprosy too. Sputum smear negative tuberculosis patients are known to spread the bacteria to other. This analogy strengthens the suggestion that the contacts of paucibacillary leprosy cases should also be included in contact tracing and examination. It is included that targeted interventions should be aimed at close contacts of both MB and PB patients inside and outside the household, particularly when genetically related