Spatial and temporal variations of malaria epidemic risk in Ethiopia: factors involved and implications.

The aim of this study was to describe spatial and temporal variations in malaria epidemic risk in Ethiopia and to examine factors involved in relation to their implications for early warning and interpretation of geographical risk models. Forty-eight epidemic episodes were identified in various areas between September 1986 and August 1993 and factors that might have led to the events investigated using health facility records and weather data. The study showed that epidemics in specific years were associated with specific geographical areas. A major epidemic in 1988 affected the highlands whereas epidemics in 1991 and 1992 affected highland-fringe areas on the escarpments of the Rift Valley and in southern and north-western parts of the country. Malaria epidemics were significantly more often preceded by a month of abnormally high minimum temperature in the preceding 3 months than based on random chance, whereas frequency of abnormally low minimum temperature prior to epidemics was significantly lower than expected. Abnormal increases of maximum temperature and rainfall had no positive association with the epidemics. A period of low incidence during previous transmission seasons might have aggravated the events, possibly due to low level of immunity in affected populations. Epidemic risk is a dynamic phenomenon with changing geographic pattern based on temporal variations in determinant factors including weather and other eco-epidemiological characteristics of areas at risk. Epidemic early warning systems should take account of non-uniform effects of these factors by space and time and thus temporal dimensions need to be considered in spatial models of epidemic risks

Forecasting malaria incidence from historical morbidity patterns in epidemic-prone areas of Ethiopia: a simple seasonal adjustment method performs best.

The aim of this study was to assess the accuracy of different methods of forecasting malaria incidence from historical morbidity patterns in areas with unstable transmission. We tested five methods using incidence data reported from health facilities in 20 areas in central and north-western Ethiopia. The accuracy of each method was determined by calculating errors resulting from the difference between observed incidence and corresponding forecasts obtained for prediction intervals of up to 12 months. Simple seasonal adjustment methods outperformed a statistically more advanced autoregressive integrated moving average method. In particular, a seasonal adjustment method that uses mean deviation of the last three observations from expected seasonal values consistently produced the best forecasts. Using 3 years' observation to generate forecasts with this method gave lower errors than shorter or longer periods. Incidence during the rainy months of June-August was the most predictable with this method. Forecasts for the normally dry months, particularly December-February, were less accurate. The study shows the limitations of forecasting incidence from historical morbidity patterns alone, and indicates the need for improved epidemic early warning by incorporating external predictors such as meteorological factors

Effects of meteorological factors on epidemic malaria in Ethiopia: a statistical modelling approach based on theoretical reasoning.

This study was conducted to quantify the association between meteorological variables and incidence of Plasmodium falciparum in areas with unstable malaria transmission in Ethiopia. We used morbidity data pertaining to microscopically confirmed cases reported from 35 sites throughout Ethiopia over a period of approximately 6-7 years. A model was developed reflecting biological relationships between meteorological and morbidity variables. A model that included rainfall 2 and 3 months earlier, mean minimum temperature of the previous month and P. falciparum case incidence during the previous month was fitted to morbidity data from the various areas. The model produced similar percentages of over-estimation (19.7% of predictions exceeded twice the observed values) and under-estimation (18.6%, were less than half the observed values). Inclusion of maximum temperature did not improve the model. The model performed better in areas with relatively high or low incidence (>85% of the total variance explained) than those with moderate incidence (55-85% of the total variance explained). The study indicated that a dynamic immunity mechanism is needed in a prediction model. The potential usefulness and drawbacks of the modelling approach in studying the weather-malaria relationship are discussed, including a need for mechanisms that can adequately handle temporal variations in immunity to malaria

Formulation of the Comfort Women Discourse in International Society

Cystic fibrosis (CF) causes a relatively high medical consumption. A large part of the treatment takes place at home. Because data regarding nonhospital care are lacking, we wished to determine the costs of care of patients with CF outside the hospital. A questionnaire was sent to 73 patients with CF from two Dutch hospitals (response rate 64%, 14 children and 33 adults). Average consumption and average costs per patient per year were calculated for children and adults for six categories: non-hospital medical care; domestic help; diet; travelling because of CF; medication; and devices and special facilities at home, work or school. The average non-hospital costs of care amounted to £4,641 per child per year (range £712-13,269) and £10,242 per adult (range £1,653-26,571). Nonhospital medical care for children and adults accounted for, respectively, 8 and 5% of these costs, domestic help for 15 and 9%, diet for 10 and 7%, travelling because of CF for 4 and 8%, medication for 63 and 67%, and devices and special facilities at home, work or school for 1 and 4%. Nonhospital costs of care of cystic fibrosis are very high and amount to 50% of the total (medical and nonmedical) lifetime costs of cystic fibrosis

Macrofilaricides and onchocerciasis control, mathematical modelling of the prospects for elimination

BACKGROUND: In most endemic parts of the world, onchocerciasis (river blindness) control relies, or will soon rely, exclusively on mass treatment with the microfilaricide ivermectin. Worldwide eradication of the parasite by means of this drug is unlikely. Macrofilaricidal drugs are currently being developed for human use. METHODS: We used ONCHOSIM, a microsimulation mathematical model of the dynamics of onchocerciasis transmission, to explore the potentials of a hypothetical macrofilaricidal drug for the elimination of onchocerciasis under different epidemiological conditions, as characterized by previous intervention strategies, vectorial capacity and levels of coverage. RESULTS: With a high vector biting rate and poor coverage, a very effective macrofilaricide would appear to have a substantially higher potential for achieving elimination of the parasite than does ivermectin. CONCLUSIONS: Macrofilaricides have a substantially higher potential for achieving onchocerciasis elimination than ivermectin, but high coverage levels are still key. When these drugs become available, onchocerciasis elimination strategies should be reconsidered. In view of the impact of control efforts preceding the introduction of macrofilaricides on the success of elimination, it is important to sustain current control efforts

Exploring the uncertainties of early detection results: model-based interpretation of mayo lung project

Background: The Mayo Lung Project (MLP), a randomized controlled clinical trial of lung cancer screening conducted between 1971 and 1986 among male smokers aged 45 or above, demonstrated an increase in lung cancer survival since the time of diagnosis, but no reduction in lung cancer mortality. Whether this result necessarily indicates a lack of mortality benefit for screening remains controversial. A number of hypotheses have been proposed to explain the observed outcome, including over-diagnosis, screening sensitivity, and population heterogeneity (initial difference in lung cancer risks between the two trial arms). This study is intended to provide model-based testing for some of these important arguments.Method: Using a micro-simulation model, the MISCAN-lung model, we explore the possible influence of screening sensitivity, systematic error, over-diagnosis and population heterogeneity.Results: Calibrating screening sensitivity, systematic error, or over-diagnosis does not noticeably improve the fit of the model, whereas calibrating population heterogeneity helps the model predict lung cancer incidence better.Conclusions: Our conclusion is that the hypothesized imperfection in screening sensitivity, systematic error, and over-diagnosis do not in themselves explain the observed trial results. Model fit improvement achieved by accounting for population heterogeneity suggests a higher risk of cancer incidence in the intervention group as compared with the control group

Field evaluation of a rapid immunochromatographic dipstick test for the diagnosis of cholera in a high-risk population

BACKGROUND: Early detection of cholera outbreaks is crucial for the implementation of the most appropriate control strategies. METHODS: The performance of an immunochromatographic dipstick test (Institute Pasteur, Paris, France) specific for Vibrio cholerae O1 was evaluated in a prospective study in Beira, Mozambique, during the 2004 cholera season (January-May). Fecal specimens were collected from 391 patients with acute watery nonbloody diarrhea and tested by dipstick and conventional culture. RESULTS: The overall sensitivity and specificity of the rapid test compared to culture were 95% (95% confidence interval [CI]: 91%–99%) and 89% (95% CI: 86%–93%), respectively. After stratification by type of sample (rectal swab/bulk stool) and severity of diarrhea, the sensitivity ranged between 85% and 98% and specificity between 77% and 97%. CONCLUSION: This one-step dipstick test performed well in the diagnosis of V. cholerae O1 in a setting with seasonal outbreaks where rapid tests are most urgently needed

Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis: a randomized placebo-controlled study

In a randomized, placebo-controlled trial in Ghana, 67 onchocerciasis patients received 200-mg/day doxycycline for 4–6 weeks, followed by ivermectin (IVM) after 6 months. After 6–27 months, efficacy was evaluated by onchocercoma histology, PCR and microfilariae determination. Administration of doxycycline resulted in endobacteria depletion and female worm sterilization. The 6-week treatment was macrofilaricidal, with >60% of the female worms found dead, despite the presence of new, Wolbachia-containing worms acquired after the administration of doxycycline. Doxycycline may be developed as second-line drug for onchocerciasis, to be administered in areas without transmission, in foci with IVM resistance and in areas with Loa co-infections

Mathematical modelling of lymphatic filariasis elimination programmes in India: Required duration of mass drug administration and post-treatment level of infection indicators

Background: India has made great progress towards the elimination of lymphatic filariasis. By 2015, most endemic districts had completed at least five annual rounds of mass drug administration (MDA). The next challenge is to determine when MDA can be stopped. We performed a simulation study with the individual-based model LYMFASIM to help clarify this. Methods: We used a model-variant for Indian settings. We considered different hypotheses on detectability of antigenaemia (Ag) in relation to underlying adult worm burden, choosing the most likely hypothesis by comparing the model predicted association between community-level microfilaraemia (Mf) and antigenaemia (Ag) prevalence levels to observed data (collated from literature). Next, we estimated how long MDA must be continued in order to achieve elimination in different transmission settings and what Mf and Ag prevalence may still remain 1 year after the last required MDA round. The robustness of key-outcomes was assessed in a sensitivity analysis. Results: Our model matched observed data qualitatively well when we assumed an Ag detection rate of 50 % for single worm infections, which increases with the number of adult worms (modelled by relating detection to the presence of female worms). The required duration of annual MDA increased with higher baseline endemicity and lower coverage (varying between 2 and 12 rounds), while the remaining residual infection 1 year after the last required treatment declined with transmission intensity. For low and high transmission settings, the median residual infection levels were 1.0 % and 0.4 % (Mf prevalence in the 5+ population), and 3.5 % and 2.0 % (Ag prevalence in 6-7 year-old children). Conclusion: To achieve elimination in high transmission settings, MDA must be continued longer and infection levels must be reduced to lower levels than in low-endemic communities. Although our simulations were for Indian settings, qualitatively similar patterns are also expected in other areas. This should be taken into account in decision algorithms to define whether MDA can be interrupted. Transmission assessment surveys should ideally be targeted to communities with the highest pre-control transmission levels, to minimize the risk of programme failure