Public health interventions for Aedes control in the time of Zikavirus- A metareview on effectiveness of vector control strategies

Background: There is renewed interest in effective control measures to control Zika and dengue vectors. A synthesis of published systematic reviews with a focus on grading of intervention evidence is warranted to determine the reliability of evidence for control strategies. Methodology: We conducted a meta-review (a systematic review of systematic reviews) assessing the effectiveness of any Aedes control measure. We searched Scopus and Medline for relevant reviews through to 11 May 2016. Titles, abstracts and full texts were assessed independently for inclusion by two authors. Data extraction was performed independently in duplicate using a standardised form and validity of the evidence in each review was assessed using GRADE criteria. Findings: 13 eligible systematic reviews that investigated the effect of community interventions on entomological parameters (such as vector density) or disease incidence were included. Quality of evidence was mostly low to very low due to poor reporting of study design, observational methodologies, heterogeneity, and indirect outcomes, hindering an evidence-based recommendation. Biological controls seem to achieve better reduction of entomological indices than chemical controls, while educational campaigns can reduce breeding habitats and interrupt disease transmission cycle. Integrated control strategies may not add efficiency to educational campaigns. Conclusions: Despite decades of Aedes mosquito abatement programmes, mosquito populations are widely established and abundant, and associated with a significant disease burden. The efficiency of any control programme is dependent on local settings and resources. More good quality primary studies for the control of Aedes transmitted diseases are still required

Broad-Spectrum Antiviral Activity of RNA Interference against Four Genotypes of Japanese Encephalitis Virus Based on Single MicroRNA Polycistrons

Japanese encephalitis virus (JEV), a neurotropic mosquito-borne flavivirus, causes acute viral encephalitis and neurologic disease with a high fatality rate in humans and a range of animals. Small interfering RNA (siRNA) is a powerful antiviral agent able to inhibit JEV replication. However, the high rate of genetic variability between JEV strains (of four confirmed genotypes, genotypes I, II, III and IV) hampers the broad-spectrum application of siRNAs, and mutations within the targeted sequences could facilitate JEV escape from RNA interference (RNAi)-mediated antiviral therapy. To improve the broad-spectrum application of siRNAs and prevent the generation of escape mutants, multiple siRNAs targeting conserved viral sequences need to be combined. In this study, using a siRNA expression vector based on the miR-155 backbone and promoted by RNA polymerase II, we initially identified nine siRNAs targeting highly conserved regions of seven JEV genes among strains of the four genotypes of JEV to effectively block the replication of the JEV vaccine strain SA14-14-2. Then, we constructed single microRNA-like polycistrons to simultaneously express these effective siRNAs under a single RNA polymerase II promoter. Finally, these single siRNAs or multiple siRNAs from the microRNA-like polycistrons showed effective anti-virus activity in genotype I and genotype III JEV wild type strains, which are the predominant genotypes of JEV in mainland China. The anti-JEV effect of these microRNA-like polycistrons was also predicted in other genotypes of JEV (genotypes II and IV), The inhibitory efficacy indicated that siRNAs×9 could theoretically inhibit the replication of JEV genotypes II and IV

Isolation and Genetic Characteristics of Human Genotype 1 Japanese Encephalitis Virus, China, 2009

BACKGROUND: Several studies have shown that the predominant genotype of Chinese Japanese encephalitis virus (JEV) is evolving from genotype 3 to genotype 1. However, in recent years, almost all genotype 1 isolates were from mosquitoes, and genotype 1 has been less associated with human disease than genotype 3. This study reports the isolation of human genotype 1 JEV and its genetic characteristics to provide additional insights into human JE pathogens that are currently circulating in China. METHODS AND RESULTS: In 2009, 31 cerebrospinal fluid samples were collected from patients living in Yunnan and Shanxi provinces and were used to inoculate Aedes albopictus C6/36 cells for virus isolation. The JEV strains were identified using immunofluorescent assays and the reverse transcription-polymerase chain reaction. Phylogenetic analyses based on the partial capsid/pre-membrane and full envelope (E) sequences were performed using Clustalx 1.8 software. Three JEV isolates were obtained from a 4-year-old girl and a 2-year-old boy living in Yunnan and an 82-year-old woman in Shanxi. The boy had been immunized with one dose of JE live attenuated vaccine. New isolates were grouped into genotype 1. Amino acid sequence for the viral E protein indicated 95% to 100% identity with each other and with other JEV strains. When compared with a consensus sequence of E protein, two amino acid substitutions were found: Ser(E-123)-Asn in the two Yunnan isolates and Lys(E-166)-Arg in the Shanxi isolate. CONCLUSIONS: Our findings indicate that the genotype 1 of JEV is causing human infections in China. Our observation of a previously vaccinated boy developing JE from genotype 1 virus infection also calls for more detailed studies, both in vitro and in vivo neutralization tests as well as active surveillance, to examine the possibility of a lack of complete protection conferred by the live attenuated JE vaccine against genotype 1 virus

Changing Patterns of Malaria Epidemiology between 2002 and 2010 in Western Kenya: The Fall and Rise of Malaria

The impact of insecticide treated nets (ITNs) on reducing malaria incidence is shown mainly through data collection from health facilities. Routine evaluation of long-term epidemiological and entomological dynamics is currently unavailable. In Kenya, new policies supporting the provision of free ITNs were implemented nationwide in June 2006. To evaluate the impacts of ITNs on malaria transmission, we conducted monthly surveys in three sentinel sites with different transmission intensities in western Kenya from 2002 to 2010.Longitudinal samplings of malaria parasite prevalence in asymptomatic school children and vector abundance in randomly selected houses were undertaken monthly from February 2002. ITN ownership and usage surveys were conducted annually from 2004 to 2010. Asymptomatic malaria parasite prevalence and vector abundances gradually decreased in all three sites from 2002 to 2006, and parasite prevalence reached its lowest level from late 2006 to early 2007. The abundance of the major malaria vectors, Anopheles funestus and An. gambiae, increased about 5-10 folds in all study sites after 2007. However, the resurgence of vectors was highly variable between sites and species. By 2010, asymptomatic parasite prevalence in Kombewa had resurged to levels recorded in 2004/2005, but the resurgence was smaller in magnitude in the other sites. Household ITN ownership was at 50-70% in 2009, but the functional and effective bed net coverage in the population was estimated at 40.3%, 49.4% and 28.2% in 2010 in Iguhu, Kombewa, and Marani, respectively.The resurgence in parasite prevalence and malaria vectors has been observed in two out of three sentinel sites in western Kenya despite a high ownership of ITNs. The likely factors contributing to malaria resurgence include reduced efficacy of ITNs, insecticide resistance in mosquitoes and lack of proper use of ITNs. These factors should be targeted to avoid further resurgence of malaria transmission

Cultural drivers and health-seeking behaviours that impact on the transmission of pig-associated zoonoses in Lao People's Democratic Republic

Pig rearing is an important income source in the Lao People’s Democratic Republic (PDR), with many smallholder farmers using traditional free-range pig production systems. Despite the potentially significant health risks posed by pig production regarding pig-associated zoonoses, information on the sociocultural drivers of these zoonoses is significantly lacking. This review summarises the existing sociocultural knowledge on eight pig-associated zoonoses suspected to be endemic in Southeast Asia: brucellosis, Q fever (Coxiella burnetii), trichinellosis, hepatitis E virus, leptospirosis, Japanese encephalitis, Streptococcus suis and Taenia solium taeniasis-cysticercosis. It summarises current knowledge on these diseases grouped according to their clinical manifestations in humans to highlight the propensity for underreporting. A literature search was conducted across multiple databases for publications from 1990 to the present day related to the eight pig-associated zoonoses and the risk and impact connected with them, with Lao PDR as a case study. Many of these pig-associated zoonoses have similar presentations and are often diagnosed as clinical syndromes. Misdiagnosis and underreporting are, therefore, substantial and emphasise the need for more robust diagnostics and appropriate surveillance systems. While some reports exist in other countries in the region, information is significantly lacking in Lao PDR with existing information coming mainly from the capital, Vientiane. The disease burden imposed by these zoonoses is not only characterised by morbidity and mortality, but directly impacts on livelihoods through income reduction and production losses, and indirectly through treatment costs and lost work opportunities. Other factors crucial to understanding and controlling these diseases are the influence of ethnicity and culture on food-consumption practices, pig rearing and slaughter practices, hygiene and sanitation, health-seeking behaviours and, therefore, risk factors for disease transmission. Published information on the knowledge, attitudes and beliefs of people regarding pig zoonoses and their risk factors is also extremely limited in Lao PDR and the broader Southeast Asian region. The need for more transdisciplinary research, using a One Health approach, in order to understand the underlining social determinants of health and their impacts on health-seeking behaviours, disease transmission and, ultimately, disease reporting, cannot be more emphasized