Helminth infections and type 2 diabetes: a cluster-randomized placebo controlled SUGARSPIN trial in Nangapanda, Flores, Indonesia.

BACKGROUND: Insulin resistance is a strong predictor of the development of type 2 diabetes mellitus. Chronic helminth infections might protect against insulin resistance via a caloric restriction state and indirectly via T-helper-2 polarization of the immune system. Therefore the elimination of helminths might remove this beneficial effect on insulin resistance. METHODS/DESIGN: To determine whether soil-transmitted helminth infections are associated with a better whole-body insulin sensitivity and whether this protection is reversible by anthelmintic treatment, a household-based cluster-randomized, double blind, placebo-controlled trial was conducted in the area of Nangapanda on Flores Island, Indonesia, an area endemic for soil-transmitted helminth infections. The trial incorporates three monthly treatment with albendazole or matching placebo for one year, whereby each treatment round consists of three consecutive days of supervised drug intake. The presence of soil-transmitted helminths will be evaluated in faeces using microscopy and/or PCR. The primary outcome of the study will be changes in insulin resistance as assessed by HOMA-IR, while the secondary outcomes will be changes in body mass index, waist circumference, fasting blood glucose, 2 h-glucose levels after oral glucose tolerance test, HbA1c, serum lipid levels, immunological parameters, and efficacy of anthelmintic treatment. DISCUSSION: The study will provide data on the effect of helminth infections on insulin resistance. It will assess the relationship between helminth infection status and immune responses as well as metabolic parameters, allowing the establishment of a link between inflammation and whole-body metabolic homeostasis. In addition, it will give information on anthelmintic treatment efficacy and effectiveness. TRIAL REGISTRATION: This study has been approved by the ethical committee of Faculty of Medicine Universitas Indonesia (ref: 549/H2.F1/ETIK/2013), and has been filed by the ethics committee of Leiden University Medical Center, clinical trial number: ISRCTN75636394. The study is reported in accordance with the CONSORT guidelines for cluster-randomised trials.

Assessing the Impact of Relapse, Reinfection and Recrudescence on Malaria Eradication Policy: A Bifurcation and Optimal Control Analysis.

In the present study, we propose and analyze an epidemic mathematical model for malaria dynamics, considering multiple recurrent phenomena: relapse, reinfection, and recrudescence. A limitation in hospital bed capacity, which can affect the treatment rate, is modeled using a saturated treatment function. The qualitative behavior of the model, covering the existence and stability criteria of the endemic equilibrium, is investigated rigorously. The concept of the basic reproduction number of the proposed model is obtained using the concept of the next-generation matrix. We find that the malaria-free equilibrium point is locally asymptotically stable if the basic reproduction number is less than one and unstable if it is larger than one. Our observation on the malaria-endemic equilibrium of the proposed model shows possible multiple endemic equilibria when the basic reproduction number is larger or smaller than one. Hence, we conclude that a condition of a basic reproduction number less than one is not sufficient to guarantee the extinction of malaria from the population. To test our model in a real-life situation, we fit our model parameters using the monthly incidence data from districts in Central Sumba, Indonesia called Wee Luri, which were collected from the Wee Luri Health Center. Using the first twenty months' data from Wee Luri district, we show that our model can fit the data with a confidence interval of 95%. Both analytical and numerical experiments show that a limitation in hospital bed capacity and reinfection can trigger a more substantial possibility of the appearance of backward bifurcation. On the other hand, we find that an increase in relapse can reduce the chance of the appearance of backward bifurcation. A non-trivial result appears in that a higher probability of recrudescence (treatment failure) does not always result in the appearance of backward bifurcation. From the global sensitivity analysis using a combination of Latin hypercube sampling and partial rank correlation coefficient, we found that the initial infection rate in humans and the mosquito infection rate are the most influential parameters in determining the increase in total new human infections. We expand our model as an optimal control problem by including three types of malaria interventions, namely the use of bed net, hospitalization, and fumigation as a time-dependent variable. Using the Pontryagin maximum principle, we characterize our optimal control problem. Results from our cost-effectiveness analysis suggest that hospitalization only is the most cost-effective strategy required to control malaria disease.

Optimal control of a discrete age-structured model for tuberculosis transmission.

In this present paper, a discrete age-structured model of tuberculosis (TB) transmission is formulated and analyzed. The existence and stability of the model equilibriums are discussed based on the basic reproduction ratio. A sensitivity analysis of the model parameters is determined. We then apply the optimal control strategy for controlling the transmission of TB in child and adult populations. The control variables are TB prevention, chemoprophylaxis of latent TB, and active TB treatment efforts. The optimal controls are then derived analytically using the Pontryagin Maximum Principle. Various intervention strategies are performed numerically to investigate the impact of the interventions. We used the incremental cost-effectiveness ratios (ICER) to assess the benefit of each one the control strategies.

An optimal control strategy to reduce the spread of malaria resistance.

This paper presents a mathematical model of malaria transmission considering the resistance of malaria parasites to the anti-malarial drugs. The model also incorporates mass treatment and insecticide as control strategies. We consider the sensitive and resistant strains of malaria parasites in human and mosquito populations. First, we investigated the existence and stability of equilibria of the model without control based on two basic reproduction ratios corresponding to the strains. Then, the Pontryagins Maximum Principle is applied to derive the necessary conditions for optimal control. Simulation results show the effectiveness of the optimal control to reduce the number of infected hosts and vectors.

A model for transmission of partial resistance to anti-malarial drugs.

Anti-malarial drug resistance has been identified in many regions for a long time. In this paper we formulate a mathematical model of the spread of anti-malarial drug resistance in the population. The model is suitable for malarial situations in developing countries. We consider the sensitive and resistant strains of malaria. There are two basic reproduction ratios corresponding to the strains. If the ratios corresponding to the infections of the sensitive and resistant strains are not equal and they are greater than one, then there exist two endemic non-coexistent equilibria. In the case where the two ratios are equal and they are greater than one, the coexistence of the sensitive and resistant strains exist in the population. It is shown here that the recovery rates of the infected host and the proportion of anti-malarial drug treatment play important roles in the spread of anti-malarial drug resistance. The interesting phenomena of ''long-time" coexistence, which may explain the real situation in the field, could occur for long period of time when those parameters satisfy certain conditions. In regards to control strategy in the field, these results could give a good understanding of means of slowing down the spread of anti-malarial drug resistance.