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 conducted comprehensive surveys in three areas where P. knowlesi transmission is reported: Limbuak, Pulau Banggi and Matunggung, Kudat, Sabah, Malaysia and Bacungan, Palawan, the Philippines. Infection prevalence was low with parasites detected by PCR in only 0.2% (4/2503) of the population. P. knowlesi PkSERA3 ag1 antibody responses were detected in 7.1% (95% CI: 6.2-8.2%) of the population, compared with 16.1% (14.6-17.7%) and 12.6% (11.2-14.1%) for P. falciparum and P. vivax. Sero-prevalence was low in individuals <10 years old for P. falciparum and P. vivax consistent with decreased transmission of non-zoonotic malaria species. Results indicated marked heterogeneity in transmission intensity between sites and P. knowlesi exposure was associated with agricultural work (OR 1.63; 95% CI 1.07-2.48) and higher levels of forest cover (OR 2.40; 95% CI 1.29-4.46) and clearing (OR 2.14; 95% CI 1.35-3.40) around houses. Spatial patterns of P. knowlesi exposure differed from exposure to non-zoonotic malaria and P. knowlesi exposed individuals were younger on average than individuals exposed to non-zoonotic malaria.
CONCLUSIONS/SIGNIFICANCE: This is the first study to describe serological exposure to P. knowlesi and associated risk factors within endemic communities. Results indicate community-level patterns of infection and exposure differ markedly from demographics of reported cases, with higher levels of exposure among women and children. Further work is needed to understand these variations in risk across a wider population and spatial scale.
METHODOLOGY/PRINCIPAL FINDINGS: We assessed oral susceptibility of Malaysian Ae. aegypti and Ae. albopictus by real-time PCR to an Australian RRV strain SW2089. Replication kinetics in midgut, head and saliva were determined at 3 and 10 days post-infection (dpi). With a 3 log10 PFU/ml blood meal, infection rate was higher in Ae. albopictus (60%) than Ae. aegypti (15%; p<0.05). Despite similar infection rates at 5 and 7 log10 PFU/ml blood meals, Ae. albopictus had significantly higher viral loads and required a significantly lower median oral infectious dose (2.7 log10 PFU/ml) than Ae. aegypti (4.2 log10 PFU/ml). Ae. albopictus showed higher vector competence, with higher viral loads in heads and saliva, and higher transmission rate (RRV present in saliva) of 100% at 10 dpi, than Ae. aegypti (41%). Ae. aegypti demonstrated greater barriers at either midgut escape or salivary gland infection, and salivary gland escape. We then assessed seropositivity against RRV among 240 Kuala Lumpur inpatients using plaque reduction neutralization, and found a low rate of 0.8%.
CONCLUSIONS/SIGNIFICANCE: Both Ae. aegypti and Ae. albopictus are susceptible to RRV, but Ae. albopictus displays greater vector competence. Extensive travel links with Australia, abundant Aedes vectors, and low population immunity places Kuala Lumpur, Malaysia at risk of an imported RRV outbreak. Surveillance and increased diagnostic awareness and capacity are imperative to prevent establishment of new arboviruses in Malaysia.
METHODS: Relevant studies published between January 2000 and December 2020 were identified by systematic online search on PubMed, Web of Science, Embase and Scopus databases without language restriction. Pooled prevalence was estimated using a random-effects model. Heterogeneity of studies were assessed using Cochrane Q test and I2 test, while publication bias was evaluated using Egger's test.
RESULTS: Of the 1,645 articles identified through our searches, 46 cross-sectional studies matched our inclusion criteria, reported data from 29,968 school children of Africa. The pooled prevalence of intestinal protozoan parasites amongst African school children was 25.8% (95% CI: 21.2%-30.3%) with E. histolytica/ dispar (13.3%; 95% CI: 10.9%-15.9%) and Giardia spp. (12%; 95% CI: 9.8%-14.3%) were the most predominant pathogenic parasites amongst the study participants. While E. coli was the most common non-pathogenic protozoa (17.1%; 95% CI: 10.9%-23.2%).
CONCLUSIONS: This study revealed a relatively high prevalence of IPPs in school children, especially in northern and western Africa. Thus, poverty reduction, improvement of sanitation and hygiene and attention to preventive control measures will be the key to reducing protozoan parasite transmission.
METHODOLOGY/PRINCIPAL FINDINGS: Using in silico tools, we designed and expressed four novel P. knowlesi protein products to address the distinct lack of suitable serosurveillance tools: PkSERA3 antigens 1 and 2, PkSSP2/TRAP and PkTSERA2 antigen 1. Antibody prevalence to these antigens was determined by ELISA for three time-points post-treatment from a hospital-based clinical treatment trial in Sabah, East Malaysia (n = 97 individuals; 241 total samples for all time points). Higher responses were observed for the PkSERA3 antigen 2 (67%, 65/97) across all time-points (day 0: 36.9% 34/92; day 7: 63.8% 46/72; day 28: 58.4% 45/77) with significant differences between the clinical cases and controls (n = 55, mean plus 3 SD) (day 0 p<0.0001; day 7 p<0.0001; day 28 p<0.0001). Using boosted regression trees, we developed models to classify P. knowlesi exposure (cross-validated AUC 88.9%; IQR 86.1-91.3%) and identified the most predictive antibody responses.
CONCLUSIONS/SIGNIFICANCE: The PkSERA3 antigen 2 had the highest relative variable importance in all models. Further validation of these antigens is underway to determine the specificity of these tools in the context of multi-species infections at the population level.
METHODS: The data were based on a cross-sectional study collected from the Bangladesh Demographic and Health Survey (BDHS), 2011. The women participants numbered 16,025 from seven divisions of Bangladesh - Rajshahi, Dhaka, Chittagong, Barisal, Khulna, Rangpur and Sylhet. The 𝟀2 test and logistic regression model were applied to determine the prevalence and factors associated with child deaths in Bangladesh.
RESULTS: In 2011, the prevalence of child deaths in Bangladesh for boys and girls was 13.0% and 11.6%, respectively. The results showed that birth interval and birth order were the most important factors associated with child death risks; mothers' education and socioeconomic status were also significant (males and females). The results also indicated that a higher birth order (7 & more) of child (OR=21.421 & 95%CI=16.879-27.186) with a short birth interval ≤ 2 years was more risky for child mortality, and lower birth order with longer birth interval >2 were significantly associated with child deaths. Other risk factors that affected child deaths in Bangladesh included young mothers of less than 25 years (mothers' median age (26-36 years): OR=0.670, 95%CI=0.551-0.815), women without education compared to those with secondary and higher education (OR =0 .711 & .628, 95%CI=0.606-0.833 & 0.437-0.903), mothers who perceived their child body size to be larger than average and small size (OR= 1.525 & 1.068, 95%CI=1.221-1.905 & 0.913-1.249), and mothers who delivered their child by non-caesarean (OR= 1.687, 95%CI=1.253-2.272).
CONCLUSION: Community-based educational programs or awareness programs are required to reduce the child death in Bangladesh, especially for younger women should be increase the birth interval and decrease the birth order. The government should apply the strategies to enhance the socioeconomic conditions, especially in rural areas, increase the awareness program through media and expand schooling, particularly for girls.
METHODS: A retrospective study of 246 culture-confirmed melioidosis cases in Queen Elizabeth Hospital, Sabah, Malaysia was performed between 2016 and 2018. The epidemiological data and clinical and laboratory findings were extracted and analysed.
RESULTS: The annual incidence of culture-confirmed melioidosis cases was estimated to be 4.97 per 100,000 people. The mean age of the patients was 50±15 years. Males and members of the Kadazan-Dusun ethnic group accounted for the majority of the melioidosis cases. The odds ratio analysis indicated that bacteraemic melioidosis in this region was significantly associated with fever (76%), and patients having at least one underlying illness (43%), including diabetes mellitus (32%). Sixty-eight patients (28%) succumbed to melioidosis. Contrary to what is known regarding factors that promote bacteraemic melioidosis, neither patients with fever nor patients with at least one comorbid disease, including diabetes mellitus, were significantly associated with death from melioidosis. There was no statistically significant difference between patients without comorbidities (24, 27%) and those with at least one comorbid disease (26, 25%), including diabetes mellitus (18, 23%). The odds ratios indicate that melioidosis mortality in this region is related to patients showing respiratory organ-associated symptoms (29%), bacteraemia (30%), and septic shock (47%). Burkholderia pseudomallei isolates in this study were highly susceptible to ceftazidime (100%), imipenem (100%), and trimethoprim-sulfamethoxazole (98%).
CONCLUSIONS: Information obtained from this study can be used by clinicians to recognise individuals with the highest risk of acquiring melioidosis, estimate an accurate prognosis, and provide effective treatment for melioidosis patients to reduce death from melioidosis.
METHODOLOGY: We conducted a retrospective data retrieval from the medical records of 254 paediatric patients who had been diagnosed with confirmed cases of dengue fever. The clinical characteristics were compared between severe and non-severe dengue. Multiple logistic regression analysis was utilised to elucidate the variables that exhibited associations with severe dengue.
RESULTS: A total of 254 paediatric patients were included, among whom 15.4% (n = 39) were diagnosed with severe dengue. Multiple logistic regression analysis identified lethargy, systolic blood pressure (SBP) below 90 mmHg, capillary refilled time (CRT) longer than 2 seconds, ascites, and hepatomegaly were independently associated with severe dengue.
CONCLUSION: In paediatric patients, severe dengue is associated with specific clinical indicators, including lethargy, low systolic blood pressure, prolonged capillary refill time (CRT), and the presence of ascites and hepatomegaly. Identifying these clinical features early is crucial for primary care physicians, as it enables accurate diagnosis and timely intervention to manage severe dengue effectively.
METHODS: A multi-host, multi-site transmission model was developed, taking into account the three areas (forest, farm, and village) where transmission is thought to occur. Latin hypercube sampling of model parameters was used to identify parameter sets consistent with possible prevalence in macaques and humans inferred from observed data. We then explore the consequences of increasing human-macaque contact in the farm, the likely impact of rapid treatment, and the use of long-lasting insecticide-treated nets (LLINs) in preventing wider spread of this emerging infection.
RESULTS: Identified model parameters were consistent with transmission being sustained by the macaques with spill over infections into the human population and with high overall basic reproduction numbers (up to 2267). The extent to which macaques forage in the farms had a non-linear relationship with human infection prevalence, the highest prevalence occurring when macaques forage in the farms but return frequently to the forest where they experience higher contact with vectors and hence sustain transmission. Only one of 1,046 parameter sets was consistent with sustained human-to-human transmission in the absence of macaques, although with a low human reproduction number (R(0H) = 1.04). Simulations showed LLINs and rapid treatment provide personal protection to humans with maximal estimated reductions in human prevalence of 42% and 95%, respectively.
CONCLUSION: This model simulates conditions where P. knowlesi transmission may occur and the potential impact of control measures. Predictions suggest that conventional control measures are sufficient at reducing the risk of infection in humans, but they must be actively implemented if P. knowlesi is to be controlled.
METHODOLOGY/PRINCIPAL FINDINGS: Monthly data on serologically confirmed JE cases were acquired from Sibu Hospital in Sarawak from 1997 to 2006. JE vaccine coverage (non-vaccine years vs. vaccine years) and meteorological predictor variables, including temperature, rainfall and the Southern Oscillation index (SOI) were tested for their association with JE cases using Poisson time series analysis and controlling for seasonality and long-term trend. Over the 10-years surveillance period, 133 confirmed JE cases were identified. There was an estimated 61% reduction in JE risk after the introduction of vaccination, when no account is taken of the effects of climate. This reduction is only approximately 45% when the effects of inter-annual variability in climate are controlled for in the model. The Poisson model indicated that rainfall (lag 1-month), minimum temperature (lag 6-months) and SOI (lag 6-months) were positively associated with JE cases.
CONCLUSIONS/SIGNIFICANCE: This study provides the first improved estimate of JE reduction through vaccination by taking account of climate inter-annual variability. Our analysis confirms that vaccination has substantially reduced JE risk in Sarawak but this benefit may be overestimated if climate effects are ignored.
METHODS AND FINDINGS: We recruited 280 adults from 27 post-outbreak villages in the state of Terengganu, east coast of Malaysia. Measures of health promotion and educational intervention activities and types of communication during outbreak, level of dengue knowledge, level and strength of self-efficacy and dengue preventive behaviour were obtained via face-to-face interviews and questionnaires. A structural equation model was tested and fitted the data well (χ(2) = 71.659, df = 40, p = 0.002, RMSEA = 0.053, CFI = 0.973, TLI = 0.963). Mass media, local contact and direct information-giving sessions significantly predicted level of knowledge of dengue. Level and strength of self-efficacy fully mediated the relationship between knowledge of dengue and dengue preventive behaviours. Strength of self-efficacy acted as partial mediator in the relationship between knowledge of dengue and dengue preventive behaviours.
CONCLUSIONS: To control and prevent dengue outbreaks by behavioural measures, health promotion and educational interventions during outbreaks should now focus on those approaches that are most likely to increase the level and strength of self-efficacy.
METHODOLOGY/PRINCIPAL FINDINGS: Genome-wide microarray-based transcription analysis was carried out to detect the genes associated with metabolic resistance in these populations. Comparisons of the susceptible New Orleans strain to three non-exposed multiple insecticide resistant field strains; Penang, Kuala Lumpur and Kota Bharu detected 2605, 1480 and 425 differentially expressed transcripts respectively (fold-change>2 and p-value ≤ 0.05). 204 genes were commonly over-expressed with monooxygenase P450 genes (CYP9J27, CYP6CB1, CYP9J26 and CYP9M4) consistently the most up-regulated detoxification genes in all populations, indicating that they possibly play an important role in the resistance. In addition, glutathione S-transferases, carboxylesterases and other gene families commonly associated with insecticide resistance were also over-expressed. Gene Ontology (GO) enrichment analysis indicated an over-representation of GO terms linked to resistance such as monooxygenases, carboxylesterases, glutathione S-transferases and heme-binding. Polymorphism analysis of CYP9J27 sequences revealed a high level of polymorphism (except in Joho Bharu), suggesting a limited directional selection on this gene. In silico analysis of CYP9J27 activity through modelling and docking simulations suggested that this gene is involved in the multiple resistance in Malaysian populations as it is predicted to metabolise pyrethroids, DDT and bendiocarb.
CONCLUSION/SIGNIFICANCE: The predominant over-expression of cytochrome P450s suggests that synergist-based (PBO) control tools could be utilised to improve control of this major dengue vector across Malaysia.