Malaria transmission and vector behaviour in a forested malaria focus in central Vietnam and the implications for vector control

BACKGROUND: In Vietnam, malaria is becoming progressively restricted to specific foci where human and vector characteristics alter the known malaria epidemiology, urging for alternative or adapted control strategies. Long-lasting insecticidal hammocks (LLIH) were designed and introduced in Ninh Thuan province, south-central Vietnam, to control malaria in the specific context of forest malaria. An entomological study in this specific forested environment was conducted to assess the behavioural patterns of forest and village vectors and to assess the spatio-temporal risk factors of malaria transmission in the province. METHODS: Five entomological surveys were conducted in three villages in Ma Noi commune and in five villages in Phuoc Binh commune in Ninh Thuan Province, south-central Vietnam. Collections were made inside the village, at the plot near the slash-and-burn fields in the forest and on the way to the forest. All collected mosquito species were subjected to enzyme-linked immunosorbent assay (ELISA) to detect Plasmodium in the head-thoracic portion of individual mosquitoes after morphological identification. Collection data were analysed by use of correspondence and multivariate analyses. RESULTS: The mosquito density in the study area was low with on average 3.7 anopheline bites per man-night and 17.4 culicine bites per man-night. Plasmodium-infected mosquitoes were only found in the forest and on the way to the forest. Malaria transmission in the forested malaria foci was spread over the entire night, from dusk to dawn, but was most intense in the early evening as nine of the 13 Plasmodium positive bites occurred before 21H. The annual entomological inoculation rate of Plasmodium falciparum was 2.2 infective bites per person-year to which Anopheles dirus s.s. and Anopheles minimus s.s. contributed. The Plasmodium vivax annual entomological inoculation rate was 2.5 infective bites per person-year with Anopheles sawadwongporni, Anopheles dirus s.s. and Anopheles pampanai as vectors. CONCLUSION: The vector behaviour and spatio-temporal patterns of malaria transmission in Southeast Asia impose new challenges when changing objectives from control to elimination of malaria and make it necessary to focus not only on the known main vector species. Moreover, effective tools to prevent malaria transmission in the early evening and in the early morning, when the treated bed net cannot be used, need to be developed

Optimization of Immunoglobulin Substitution Therapy by a Stochastic Immune Response Model

Background: The immune system is a complex adaptive system of cells and molecules that are interwoven in a highly organized communication network. Primary immune deficiencies are disorders in which essential parts of the immune system are absent or do not function according to plan. X-linked agammaglobulinemia is a B-lymphocyte maturation disorder in which the production of immunoglobulin is prohibited by a genetic defect. Patients have to be put on life-long immunoglobulin substitution therapy in order to prevent recurrent and persistent opportunistic infections. Methodology: We formulate an immune response model in terms of stochastic differential equations and perform a systematic analysis of empirical therapy protocols that differ in the treatment frequency. The model accounts for the immunoglobulin reduction by natural degradation and by antigenic consumption, as well as for the periodic immunoglobulin replenishment that gives rise to an inhomogeneous distribution of immunoglobulin specificities in the shape space. Results are obtained from computer simulations and from analytical calculations within the framework of the Fokker-Planck formalism, which enables us to derive closed expressions for undetermined model parameters such as the infection clearance rate. Conclusions: We find that the critical value of the clearance rate, below which a chronic infection develops, is strongly dependent on the strength of fluctuations in the administered immunoglobulin dose per treatment and is an increasing function of the treatment frequency. The comparative analysis of therapy protocols with regard to the treatment frequency yields quantitative predictions of therapeutic relevance, where the choice of the optimal treatment frequency reveals a conflict of competing interests: In order to diminish immunomodulatory effects and to make good economic sense, therapeutic immunoglobulin levels should be kept close to physiological levels, implying high treatment frequencies. However, clearing infections without additional medication is more reliably achieved by substitution therapies with low treatment frequencies. Our immune response model predicts that the compromise solution of immunoglobulin substitution therapy has a treatment frequency in the range from one infusion per week to one infusion per two weeks

Optimal temperature control of a steady-state exothermic plug-flow reactor

Optimal heat exchanger temperature profiles of exothermic tubular reactors were determined under the assumption of steady-state and plug-flow characteristics. The minimum principle of Pontryagin (optimal control theory) was applied in a straightforward analytical sense. To enable a trade-off between process performance and heat loss, a combined cost criterion was defined. In the first approach of specifying only, terminal costs, the optimal control input was of the bang-bang type that keeps the heat exchanger temperature constant at its maximum or minimum value. Afterwards, the terminal cost criterion was extended with an integral part that accounts for the global heat loss during the process. This integral cost part induced a control of the bang-singular-bang type. The desired performance call be met by selecting appropriate weights for terminal and integral costs

Feedback stabilization of fed-batch bioreactors: Non-monotonic growth kinetics

This paper deals with the design of a feedback controller for fed-batch microbial conversion processes that forces the substrate concentration C-S to a desired setpoint C-S*, starting from an arbitrary (initial) substrate concentration when non-monotonic growth kinetics apply. This problem is representative for a lot of industrial fermentation processes, with the baker's yeast fermentation as a well-known example. It is assumed that the specific growth rate mu is function of the substrate concentration only. A first approach exploits the availability of on-line measurements of both the substrate and biomass concentration. A second approach is merely based on on-line measurements of the biomass concentration, which provide an estimate for the specific growth rate. After a reformulation of the substrate concentration setpoint into a specific growth rate setpoint, it is demonstrated that the fed-batch process can still be stabilized around any desired operating point along the non-monotonic kinetics

Optimal adaptive control of a bioprocess with yield-productivity conflict

This paper is concerned with the optimization of biological production processes. The process is characterized by a conflict between yield and productivity as revealed by the analysis of the model. The optimization problem is to find an operating mode that achieves the best trade off between yield and productivity. It is shown how this problem can be formulated as a parametric optimization involving parameters that have a clear engineering meaning. This parametric optimization leads to the definition of a control problem which requires a feedback implementation under the form of an adaptive regulator combined with a software sensor. A simple mechanistic model is considered as a benchmark example for this optimization study. (C) 1998 Elsevier Science B.V. All rights reserved

Extracting information on the evolution of living- and dead-cell fractions of Salmonella Typhimurium colonies in gelatin gels based on microscopic images and plate-count data

Aims: The aim of this study was to extract information on cell number and colony volume dynamics of Salmonella Typhimurium colonies. Methods and Results: Both cell number and colony volume of Salmonella Typhimurium in gelatin were monitored during the exponential and the stationary phase with varying pH and water activity, by plate counts and microscopic image analysis respectively. The exponential growth rates of cell numbers and colony volumes were correlated. The exponential growth rate of cell numbers was estimated based on this correlation and a secondary model that describes the effect of pH and water activity on the growth rate of the colony volumes. During the stationary phase, the cell number was constant, while colony volume increased, thus indicating the formation of a dead fraction. Models were developed to describe the living and dead population. Conclusions: By comparing colony volumes and cell numbers, the formation of dead fraction can be noticed from the beginning of the stationary phase, which indicates that the stationary phase is a dynamic - including both cell death and cell growth - rather than a static phase. Significance and Impact of the Study: This study was the first to investigate the proportion of living and dead bacteria within a stationary colony quantitatively