Seasonal Influenza Vaccination for Children in Thailand: A Cost-Effectiveness Analysis

Background

Seasonal influenza is a major cause of mortality worldwide. Routine immunization of children has the potential to reduce this mortality through both direct and indirect protection, but has not been adopted by any low- or middle-income countries. We developed a framework to evaluate the cost-effectiveness of influenza vaccination policies in developing countries and used it to consider annual vaccination of school- and preschool-aged children with either trivalent inactivated influenza vaccine (TIV) or trivalent live-attenuated influenza vaccine (LAIV) in Thailand. We also compared these approaches with a policy of expanding TIV coverage in the elderly.

Methods and Findings

We developed an age-structured model to evaluate the cost-effectiveness of eight vaccination policies parameterized using country-level data from Thailand. For policies using LAIV, we considered five different age groups of children to vaccinate. We adopted a Bayesian evidence-synthesis framework, expressing uncertainty in parameters through probability distributions derived by fitting the model to prospectively collected laboratory-confirmed influenza data from 2005-2009, by meta-analysis of clinical trial data, and by using prior probability distributions derived from literature review and elicitation of expert opinion. We performed sensitivity analyses using alternative assumptions about prior immunity, contact patterns between age groups, the proportion of infections that are symptomatic, cost per unit vaccine, and vaccine effectiveness. Vaccination of children with LAIV was found to be highly cost-effective, with incremental cost-effectiveness ratios between about 2,000 and 5,000 international dollars per disability-adjusted life year averted, and was consistently preferred to TIV-based policies. These findings were robust to extensive sensitivity analyses. The optimal age group to vaccinate with LAIV, however, was sensitive both to the willingness to pay for health benefits and to assumptions about contact patterns between age groups.

Conclusions

Vaccinating school-aged children with LAIV is likely to be cost-effective in Thailand in the short term, though the long-term consequences of such a policy cannot be reliably predicted given current knowledge of influenza epidemiology and immunology. Our work provides a coherent framework that can be used for similar analyses in other low- and middle-income countries.     

Autoimmune disease in mothers with the FMR1 premutation is associated with seizures in their children with fragile X syndrome

An increased prevalence of autoimmune diseases in family members of children with autism spectrum disorders (ASD) has been previously reported. ASD is also a common problem co-occurring in children with fragile X syndrome (FXS). Why ASD occurs in some individuals with FXS, but not all, is largely unknown. Furthermore, in premutation carrier mothers, there is an increased risk for autoimmune diseases. This study compared the rate of ASD and other neurodevelopmental/behavioral problems in 61 children with FXS born to 41 carrier mothers who had autoimmune disease and in 97 children with FXS of 78 carrier mothers who did not have autoimmune disease. There were no significant differences in the mean age (9.61 ± 5.59 vs. 9.41 ± 6.31, P = 0.836), cognitive and adaptive functioning in children of mothers with and without autoimmune disease. Among children whose mothers had autoimmune disease, the odds ratio (OR) for ASD was 1.27 (95% CI 0.62–2.61, P = 0.5115). Interestingly, the OR for seizures and tics was 3.81 (95% CI 1.13–12.86, P = 0.031) and 2.94 (95% CI 1.19–7.24, P = 0.019), respectively, in children of mothers with autoimmune disease compared to children of mothers without autoimmune disease. In conclusion, autoimmune disease in carrier mothers was not associated with the presence of ASD in their children. However, seizures and tics were significantly increased in children of mothers with autoimmune disease. This suggests a potential new mechanism of seizure and tic exacerbation in FXS related to an intergenerational influence from autoimmunity in the carrier mother.     

Increased prevalence of seizures in boys who were probands with the <Emphasis Type="Italic">FMR1</Emphasis> premutation and co-morbid autism spectrum disorder

Seizures are a common co-occurring condition in those with fragile X syndrome (FXS), and in those with idiopathic autism spectrum disorder (ASD). Seizures are also associated with ASD in those with FXS. However, little is known about the rate of seizures and how commonly these problems co-occur with ASD in boys with the FMR1 premutation. We, therefore, determined the prevalence of seizures and ASD in boys with the FMR1 premutation compared with their sibling counterparts and population prevalence estimates. Fifty premutation boys who presented as clinical probands (N = 25), or non-probands (identified by cascade testing after the proband was found) (N = 25), and 32 non-carrier controls were enrolled. History of seizures was documented and ASD was diagnosed by standardized measures followed by a team consensus of ASD diagnosis. Seizures (28%) and ASD (68%) were more prevalent in probands compared with non-probands (0 and 28%), controls (0 and 0%), and population estimates (1 and 1.7%). Seizures occurred more frequently in those with the premutation and co-morbid ASD particularly in probands compared with those with the premutation alone (25 vs. 3.85%, p = 0.045). Although cognitive and adaptive functioning in non-probands were similar to controls, non-probands were more likely to meet the diagnosis of ASD than controls (28 vs. 0%, p < 0.0001). In conclusion, seizures were relatively more common in premutation carriers who presented clinically as probands of the family and seizures were commonly associated with ASD in these boys. Therefore, boys with the premutation, particularly if they are probands should be assessed carefully for both ASD and seizures.     

Bio-control of Stem Rot in Jerusalem Artichoke (Helianthus tuberosus L.) in Field Conditions

Stem rot is a serious disease in Jerusalem artichoke (JA). To reduce the impact of this disease on yield and quality farmers often use fungicides, but this control method can be expensive and leave chemical residues. The objective of this study was to evaluate the efficacy of two biological control agents, Trichoderma harzianum T9 and Bacillus firmus BSR032 for control of Sclerotium rolfsii under field conditions. Four accessions of JA (HEL246, HEL65, JA47, and JA12) were treated or notreated with T. harzianum T9 and B. firmus BSR032 in a 4 × 2 × 2 factorial experiment in two fields (environments), one unfertilized and one fertilized. Plants were inoculated with S. rolfsii and disease was evaluated at 3-day intervals for 46 days. T. harzianum T9 and B. firmus BSR032 reduced disease incidence by 48% and 49%, respectively, whereas T. harzianum T9 + B. firmus BSR032 reduced disease incidence by 37%. The efficacy of T. harzianum T9 and B. firmus BSR032 for control of S. rolfsii was dependent on environments and genotypes. The expression of host plant resistance also depended on the environment. However, HEL246 showed consistently low disease incidence and severity index in both environments (fertilized and unfertilized). Individually, T. harzianum T9, B. firmus BSR032, or host plant resistance control stem rot caused by S. rolfsii in JA. However, no combination of these treatments provided more effective control than each alone.     

Health system resource gaps and associated mortality from pandemic influenza across six Asian territories

Background

Southeast Asia has been the focus of considerable investment in pandemic influenza preparedness. Given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations. We aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in Asia.

Methods and Findings

We collected health system resource data from Cambodia, Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam. We applied a mathematical transmission model to simulate a “mild-to-moderate” pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory. The results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as “avoidable” mortalities), particularly in poorer areas. Severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except Taiwan. Other resources (oseltamivir, hospital beds and human resources) are inequitably distributed within countries. Estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario. However, geographic patterns observed within and across territories remained similar for the range of parameter values explored.

Conclusions

The findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic. Effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths.     

Targeted disruption of a G protein α subunit gene results in reduced growth and pathogenicity in <Emphasis Type="Italic">Rhizoctonia solani</Emphasis>

Cloning and disruption of Rga1, the gene encoding the G protein α subunit in the rice sheath blight fungus Rhizoctonia solani, was investigated. The deduced primary structure of the Rga1-encoded protein showed high identity to those of Gα subunits from other filamentous fungi. Disruption of Rga1 led to decreased vegetative growth and pathogenicity. The Rga1 disruptant showed altered colony morphology. In addition, the sclerotia formation ability of the disruptant was completely lost. These results suggest that the Gα subunit encoded by Rga1 is involved in a signal transduction pathway in R. solani that controls growth, development and pathogenicity.