METHODS: We employ a dynamic Markov model of the effects of vector control on dengue in both vectors and humans over a 15-year period, in six countries: Brazil, Columbia, Malaysia, Mexico, the Philippines, and Thailand. We evaluate the cost (direct medical costs and control programme costs) and cost-effectiveness of sustained vector control, outbreak response and/or medical case management, in the presence of a (hypothetical) highly targeted and low cost immunization strategy using a (non-hypothetical) medium-efficacy vaccine.
RESULTS: Sustained vector control using existing technologies would cost little more than outbreak response, given the associated costs of medical case management. If sustained use of existing or upcoming technologies (of similar price) reduce vector populations by 70-90%, the cost per disability-adjusted life year averted is 2013 US$ 679-1331 (best estimates) relative to no intervention. Sustained vector control could be highly cost-effective even with less effective technologies (50-70% reduction in vector populations) and in the presence of a highly targeted and low cost immunization strategy using a medium-efficacy vaccine.
DISCUSSION: Economic evaluation of the first-ever dengue vaccine is ongoing. However, even under very optimistic assumptions about a highly targeted and low cost immunization strategy, our results suggest that sustained vector control will continue to play an important role in mitigating the impact of environmental change and urbanization on human health. If additional benefits for the control of other Aedes borne diseases, such as Chikungunya, yellow fever and Zika fever are taken into account, the investment case is even stronger. High-burden endemic countries should proceed to map populations to be covered by sustained vector control.
METHODOLOGY/PRINCIPAL FINDINGS: We characterized human immune sera collected during two independent outbreaks in Malaysia of the Asian genotype in 2006 and the ECSA genotype in 2008-2010. Neutralizing capacity was analyzed against representative clinical isolates as well as viruses rescued from infectious clones of ECSA and Asian CHIKV. Using whole virus antigen and recombinant E1 and E2 envelope glycoproteins, we further investigated antibody binding sites, epitopes, and antibody titers. Both ECSA and Asian sera demonstrated stronger neutralizing capacity against the ECSA genotype, which corresponded to strong epitope-antibody interaction. ECSA serum targeted conformational epitope sites in the E1-E2 glycoprotein, and E1-E211K, E2-I2T, E2-H5N, E2-G118S and E2-S194G are key amino acids that enhance cross-neutralizing efficacy. As for Asian serum, the antibodies targeting E2 glycoprotein correlated with neutralizing efficacy, and I2T, H5N, G118S and S194G altered and improved the neutralization profile. Rabbit polyclonal antibody against the N-terminal linear neutralizing epitope from the ECSA sequence has reduced binding capacity and neutralization efficacy against Asian CHIKV. These findings imply that the choice of vaccine strain may impact cross-protection against different genotypes.
CONCLUSION/SIGNIFICANCE: Immune serum from humans infected with CHIKV of either ECSA or Asian genotypes showed differences in binding and neutralization characteristics. These findings have implications for the continued outbreaks of co-circulating CHIKV genotypes and effective design of vaccines and diagnostic serological assays.
METHODOLOGY/PRINCIPAL FINDINGS: Photos of urine samples were taken in a customized photo booth, then processed using Adobe Photoshop to index urine colour into the red, green, and blue (RGB) colour space and assigned a unique RGB value. The RGB values were then correlated with patients' clinical and laboratory hydration indices using Pearson's correlation and multiple linear regression. There were strong correlations between urine osmolality and the RGB of urine colour, with r = -0.701 (red), r = -0.741 (green), and r = -0.761 (blue) (all p-value <0.05). There were strong correlations between urine specific gravity and the RGB of urine colour, with r = -0.759 (red), r = -0.785 (green), and r = -0.820 (blue) (all p-value <0.05). The blue component had the highest correlations with urine specific gravity and urine osmolality. There were moderate correlations between RGB components and serum urea, at r = -0.338 (red), -0.329 (green), -0.360 (blue). In terms of urine biochemical parameters linked to dehydration, multiple linear regression studies showed that the green colourimetry code was predictive of urine osmolality (β coefficient -0.082, p-value <0.001) while the blue colourimetry code was predictive of urine specific gravity (β coefficient -2,946.255, p-value 0.007).
CONCLUSIONS/SIGNIFICANCE: Urine colourimetry using mobile phones was highly correlated with the hydration status of dengue patients, making it a potentially useful hydration status tool.
METHODS/FINDINGS: A total of 550 children participated, comprising 520 (94.5%) school children aged 7 to 12 years old, 30 (5.5%) young children aged 1 to 6 years old, 254 (46.2%) boys and 296 (53.8%) girls. Of the 550 children, 26.2% were anaemic, 54.9% iron deficient and 16.9% had iron deficiency anaemia (IDA). The overall prevalence of helminths was 76.5% comprising Trichuris trichiura (71.5%), Ascaris lumbricoides (41.6%) and hookworm infection (13.5%). It was observed that iron deficiency was significantly higher in girls (p = 0.032) compared to boys. Univariate analysis demonstrated that low level of mother's education (OR = 2.52; 95% CI = 1.38-4.60; p = 0.002), non working parents (OR = 2.18; 95% CI = 2.06-2.31; p = 0.013), low household income (OR = 2.02; 95% CI = 1.14-3.59; p = 0.015), T. trichiura (OR = 2.15; 95% CI = 1.21-3.81; p = 0.008) and A. lumbricoides infections (OR = 1.63; 95% CI = 1.04-2.55; p = 0.032) were significantly associated with the high prevalence of IDA. Multivariate analysis confirmed that low level of mother's education (OR = 1.48; 95 CI% = 1.33-2.58; p<0.001) was a significant predictor for IDA in these children.
CONCLUSION: It is crucial that a comprehensive primary health care programme for these communities that includes periodic de-worming, nutrition supplement, improved household economy, education, sanitation status and personal hygiene are taken into consideration to improve the nutritional status of these children.
METHODS: A decision-analytic Markov model was developed to simulate the impact of S. suis infection and its major complications: death, meningitis and infective endocarditis among Thai people in 2019 with starting age of 51 years. Transition probabilities, and inputs pertaining to costs, utilities and productivity impairment associated with long-term complications were derived from published sources. A lifetime time horizon with follow-up until death or age 100 years was adopted. The simulation was repeated assuming that the cohort had not been infected with S.suis. The differences between the two set of model outputs in years of life, QALYs, and PALYs lived reflected the impact of S.suis infection. An annual discount rate of 3% was applied to both costs and outcomes. One-way sensitivity analyses and Monte Carlo simulation modeling technique using 10,000 iterations were performed to assess the impact of uncertainty in the model.
KEY RESULTS: This cohort incurred 769 (95% uncertainty interval [UI]: 695 to 841) years of life lost (14% of predicted years of life lived if infection had not occurred), 826 (95% UI: 588 to 1,098) QALYs lost (21%) and 793 (95%UI: 717 to 867) PALYs (15%) lost. These equated to an average of 2.46 years of life, 2.64 QALYs and 2.54 PALYs lost per person. The loss in PALYs was associated with a loss of 346 (95% UI: 240 to 461) million Thai baht (US$11.3 million) in GDP, which equated to 1.1 million Thai baht (US$ 36,033) lost per person.
CONCLUSIONS: S.suis infection imposes a significant economic burden both in terms of health and productivity. Further research to investigate the effectiveness of public health awareness programs and disease control interventions should be mandated to provide a clearer picture for decision making in public health strategies and resource allocations.
METHODS: We determined the ability of B. pseudomallei to invade and survive intracellularly in A549 human lung epithelial cells, and also investigated the early transcriptional responses using an Illumina HumanHT-12 v4 microarray platform, after three hours of exposure to live B. pseudomallei (BCMS) and its secreted proteins (CCMS).
RESULTS: We found that the ability of B. pseudomallei to invade and survive intracellularly correlated with increase of multiplicity of infection and duration of contact. Activation of host carbohydrate metabolism and apoptosis as well as suppression of amino acid metabolism and innate immune responses both by live bacteria and its secreted proteins were evident. These early events might be linked to initial activation of host genes directed towards bacterial dissemination from lungs to target organs (via proposed in vivo mechanisms) or to escape potential sensing by macrophages.
CONCLUSION: Understanding the early responses of A549 cells toward B. pseudomallei infection provide preliminary insights into the likely pathogenesis mechanisms underlying melioidosis, and could contribute to development of novel intervention strategies to combat B. pseudomallei infections.