Browsing by Subject "Surveillance"

Dengue viruses (DENV) and other mosquito-borne flaviviruses are rapidly emerging human pathogens that threaten nearly half of the world’s population. There is currently no effective vaccine or antiviral therapeutics for the prophylaxis or treatment of DENV. While traditional drug development efforts have focused on inhibitors of viral enzymes, an alternative approach is to target host proteins that support virus replication. In an effort to identify novel human enzymes important for the DENV-2 life-cycle, we conducted a genome-wide RNAi screen and identified ERI3, a putative 3′-5′ exonuclease, as a novel DENV-2 host factor. Cell-free assays confirmed that purified ERI3 is capable of degrading single-stranded RNA in a 3′ to 5′ direction. We conducted a screen for compounds that inhibit ERI3 in vitro and identified small molecules that antagonized both exonuclease activity. In summary, we identified a host exonuclease that is important for DENV-2 replication and is a potential therapeutic target. Our approach illustrates the utility of identifying host enzymatic functions for development of anti-viral drugs.

Large-scale molecular epidemiologic studies of Plasmodium falciparum parasites have provided insights into parasite biology and transmission, can identify the spread of drug resistance, and are useful in assessing vaccine targets. The polyclonal nature infections in high transmission settings is problematic for traditional genotyping approaches. Next-generation sequencing approaches to parasite genotyping allow sensitive detection of minority variants, disaggregation of complex parasite mixtures, and scalable processing of large samples sets. Therefore, we designed, validated, and applied to field parasites a new approach that leverages sequencing of individually barcoded samples in a multiplex manner. We utilize variant barcodes, invariant linker sequences and modular template-specific primers to allow for the simultaneous generation of high-dimensional sequencing data of multiple gene targets. This modularity permits a cost-effective and reproducible way to query many genes at once. In mixtures of reference parasite genomes, we quantitatively detected unique haplotypes comprising as little as 2% of a polyclonal infection. We applied this genotyping approach to field-collected parasites collected in Western Kenya in order to simultaneously obtain parasites genotypes at three unlinked loci. In summary, we present a rapid, scalable, and flexible method for genotyping individual parasites that enables molecular epidemiologic studies of parasite evolution, population structure and transmission.

Background: Dengue is one of the most common vector transmitted diseases in the world and it has become a public health problem in many countries including Fiji. Efficient methods need to be taken for dengue prevention and control in Fiji. Disease surveillance is one of the most effective way for dengue prevention and idea of using weather parameters to estimate dengue cases as one part of dengue surveillance has been studied by different researchers worldwide. The study aimed to estimate the relationship between weather variables including rainfall, temperature and humidity and to identify problems existed in current surveillance system in Fiji. Methods: Both quantitative and qualitative methods were used in the study. In the quantitative study, disease data of dengue cases collected by Fiji National Notifiable Disease Surveillance System from Jan 2011 to Dec 2014 and weather data collected by meteorological station in Laucala Bay, Suva from Jan 2011 to Dec 2014 were provided by Fiji Ministry of Health. Disease data were divided into two parts, years with sporadic cases (Jan2011-Oct2013) and years with dengue outbreak (Nov2013-Dec2014), and negative binominal regression was conducted to estimate the association between weather variables including rainfall, maximum temperature, minimum temperature and relative humidity. In the qualitative study, in-depth interviews were conducted with health workers and dengue patients in Suva and evaluations of current surveillance system and problems being noticed in the surveillance system were discussed. Results: Statistically significant positive associations between weather variables including weekly cumulative rainfall and weekly average relative humidity and dengue cases were identified in years with sporadic cases. In years with dengue outbreak, weekly average maximum temperature and relative humidity were also found to be significantly positively associated with dengue cases. Average minimum temperature per week was found to be significantly negatively associated with dengue cases. Problems of timeliness, accuracy and completeness in dengue case report process were identified and inadequate public health awareness of health workers was also raised in the interviews. Conclusions: Weather variables including rainfall, temperature and humidity showed significant effects on variations of dengue cases. The significant associations between weather variables and dengue cases may establish the foundation of developing a climate-based early warning system for dengue in Fiji. Problems in the current surveillance system for dengue have been identified including lack of timeliness and compromised quality in the case reporting process. Web-based disease reporting system and standardized reporting procedures may be useful in improving the surveillance system. A more efficient disease surveillance system can be developed combining the effects of weather variations on the number of dengue cases and routine surveillance together.