Stability and estimation problems related to a stage-structured epidemic model.

In this work, we consider a class of stage-structured Susceptible-Infectious (SI) epidemic models which includes, as special cases, a number of models already studied in the literature. This class allows for n different stages of infectious individuals, with all of them being able to infect susceptible individuals, and also allowing for different death rates for each stage-this helps to model disease induced mortality at all stages. Models in this class can be considered as a simplified modelling approach to chronic diseases with progressive severity, as is the case with AIDS for instance. In contradistinction to most studies in the literature, we consider not only the questions of local and global stability, but also the observability problem. For models in this class, we are able to construct two different state-estimators: the first one being the classical high-gain observer, and the second one being the extended Kalman filter. Numerical simulations indicate that both estimators converge exponentially fast, but the former can have large overshooting, which is not present in the latter. The Kalman observer turns out to be more robust to noise in measurable data.

Safety monitoring of artemisinin combination therapy through a national pharmacovigilance system in an endemic malaria setting.

BACKGROUND: The National Malaria Control Programme in Senegal, introduced since 2006, artemisinin-based combination therapy (ACT administration) for the treatment of uncomplicated malaria cases. In this framework, an anti-malarial pharmacovigilance plan was developed and implemented in all public health services. This study investigated the occurrence of Adverse Drug Events (ADEs) after ACT. METHODS: The study was conducted between January 2007 and December 2009. It was based on spontaneous reports of ADEs in public health facilities. Data on patient demographic characteristics, dispensing facility, adverse signs and symptoms and causality were collected from a total of 123 patients. RESULTS: The age range of these patients was six months to 93 years with a mean of 25.9 years. Of the reported symptoms, 46.7% were related to the abdomen and the digestive system. Symptoms related to the nervous system, skin and subcutaneous tissue, circulatory and respiratory systems and general symptoms and signs were 7%, 9.7%, 3.5% and 31.3%, respectively. Causality results linked 14.3% of symptoms to Falcimon® (Artesunate-Amodiaquine) with certainty. Effects were classified as mild and severe in 69.1% and 7.3% of cases respectively while 23.6% were serious. All patients with serious ADEs were hospitalized. One death was reported in a patient who had taken 24 pills at once. CONCLUSION: These results confirm the need to develop and implement pharmacovigilance systems in malaria endemic countries in order to monitor the safety of anti-malarial treatments.

Scale-up of home-based management of malaria based on rapid diagnostic tests and artemisinin-based combination therapy in a resource-poor country: results in Senegal.

BACKGROUND: Effective case management of malaria requires prompt diagnosis and treatment within 24 hours. Home-based management of malaria (HMM) improves access to treatment for populations with limited access to health facilities. In Senegal, an HMM pilot study in 2008 demonstrated the feasibility of integrated use of RDTs and ACT in remote villages by volunteer Home Care Providers (HCP). Scale-up of the strategy began in 2009, reaching 408 villages in 2009 and 861 villages in 2010. This paper reports the results of the scale-up in the targeted communities and the impact of the strategy on malaria in the formal health sector. METHODS: Data reported by the HCPs were used to assess their performance in 2009 and 2010, while routine malaria morbidity and mortality data were used to assess the impact of the HMM programme. Two high transmission regions where HMM was not implemented until 2010 were used as a comparison. RESULTS AND DISCUSSION: From July 2009 through May 2010, 12582 suspected cases were managed by HCPs, 93% (11672) of whom were tested with an RDT. Among those tested, 37% (4270) had a positive RDT, 97% (4126) of whom were reported treated and cured. Home care providers referred 6871 patients to health posts for management: 6486 with a negative RDT, 119 infants < 2 months, 105 pregnant women, and 161 severe cases. There were no deaths among these patients. In 2009 compared to 2008, incidence of suspected and confirmed malaria cases, all hospitalizations and malaria-related hospitalizations decreased in both intervention and comparison regions. Incidence of in-hospital deaths due to malaria decreased by 62.5% (95% CI 43.8-81.2) in the intervention regions, while the decrease in comparison regions was smaller and not statistically significant. CONCLUSION: Home-based management of malaria including diagnosis with RDT and treatment based on test results is a promising strategy to improve the access of remote populations to prompt and effective management of uncomplicated malaria and to decrease mortality due to malaria. When scaled-up to serve remote village communities in the regions of Senegal with the highest malaria prevalence, home care providers demonstrated excellent adherence to guidelines, potentially contributing to a decrease in hospital deaths attributed to malaria.