The diagnosis of dengue in patients presenting with acute febrile illness using supervised machine learning and impact of seasonality

Background: Symptomatic dengue infection can result in a life-threatening shock syndrome and timely diagnosis is essential. Point-of-care tests for non-structural protein 1 and IgM are used widely but performance can be limited. We developed a supervised machine learning model to predict whether patients with acute febrile illnesses had a diagnosis of dengue or other febrile illnesses (OFI). The impact of seasonality on model performance over time was examined. Methods: We analysed data from a prospective observational clinical study in Vietnam. Enrolled patients presented with an acute febrile illness of 90%). Conclusion: Supervised machine learning models are able to discriminate between dengue and OFI diagnoses in patients presenting with an early undifferentiated febrile illness. These models could be of clinical utility in supporting healthcare decision-making and provide passive surveillance across dengue endemic regions. Effects of seasonality and changing disease prevalence must however be taken into account—this is of significant importance given unpredictable effects of human-induced climate change and the impact on health

Three phylogenetic groups have driven the recent population expansion of Cryptococcus neoformans.

Cryptococcus neoformans (C. neoformans var. grubii) is an environmentally acquired pathogen causing 181,000 HIV-associated deaths each year. We sequenced 699 isolates, primarily C. neoformans from HIV-infected patients, from 5 countries in Asia and Africa. The phylogeny of C. neoformans reveals a recent exponential population expansion, consistent with the increase in the number of susceptible hosts. In our study population, this expansion has been driven by three sub-clades of the C. neoformans VNIa lineage; VNIa-4, VNIa-5 and VNIa-93. These three sub-clades account for 91% of clinical isolates sequenced in our study. Combining the genome data with clinical information, we find that the VNIa-93 sub-clade, the most common sub-clade in Uganda and Malawi, was associated with better outcomes than VNIa-4 and VNIa-5, which predominate in Southeast Asia. This study lays the foundation for further work investigating the dominance of VNIa-4, VNIa-5 and VNIa-93 and the association between lineage and clinical phenotype

Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes

Background: Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of 10 biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD). Methods: We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included. Results: On days 1–3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults. Conclusions: Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients. Funding: This study was supported by the EU's Seventh Framework Programme (FP7-281803 IDAMS), the WHO, and the Bill and Melinda Gates Foundation

Enterovirus D68 in Viet Nam (2009-2015)

Background: Since 1962, enterovirus D68 (EV-D68) has been implicated in multiple outbreaks and sporadic cases of respiratory infection worldwide, especially in the USA and Europe with an increasing frequency between 2010 and 2014. We describe the detection, associated clinical features and molecular characterization of EV-D68 in central and southern Viet Nam between 2009 and 2015. Methods: Enterovirus/rhinovirus PCR positive respiratory or CSF samples taken from children and adults with respiratory/central nervous system infections in Viet Nam were tested by an EV-D68 specific PCR. The included samples were derived from 3 different observational studies conducted at referral hospitals across central and southern Viet Nam 2009 2015. Whole-genome sequencing was carried out using a MiSeq based approach. Phylogenetic reconstruction and estimation of evolutionary rate and recombination were carried out in BEAST and Recombination Detection Program, respectively. Results: EV-D68 was detected in 21/625 (3.4%) enterovirus/rhinovirus PCR positive respiratory samples but in none of the 15 CSF. All the EV-D68 patients were young children (age range: 11.8 – 24.5 months) and had moderate respiratory infections. Phylogenetic analysis suggested that the Vietnamese sequences clustered with those from Asian countries, of which 9 fell in the B1 clade, and the remaining sequence was identified within the A2 clade. One intra sub-clade recombination event was detected, representing the second reported recombination within EV-D68. The evolutionary rate of EV-D68 was estimated to be 5.12E -3 substitutions/site/year. Phylogenetic analysis indicated that the virus was imported into Viet Nam in 2008. Conclusions: We have demonstrated for the first time EV-D68 has been circulating at low levels in Viet Nam since 2008, associated with moderate acute respiratory infection in children. EV-D68 in Viet Nam is most closely related to Asian viruses, and clusters separately from recent US and European viruses that were suggested to be associated with acute flaccid paralysis

Agricultural systems research and global food security in the 21st century: An overview and roadmap for future opportunities

This article presents a brief history and overview of some key intersections between Agricultural systems research and the literature on global food security. It also serves to contextualize the submissions for this special issue, which comprise selected relevant research presented at the 2nd International Conference on Global Food Security, held at Cornell University in October 2015

CURRENT CONCEPTS Dengue

Dengue is a self-limited, systemic viral infection transmitted between humans by mosquitoes. The rapidly expanding global footprint of dengue is a public health challenge with an economic burden that is currently unmet by licensed vaccines, specific therapeutic agents, or efficient vectorcontrol strategies. This review highlights our current understanding of dengue, including its clinical manifestations, pathogenesis, tests that are used to diagnose it, and its management and prevention. </p

The control of Typhoid fever in Vietnam

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a diminishing public health problem in Vietnam, and this process may represent a prototype for typhoid elimination in Asia. Here, we review typhoid epidemiology in Vietnam over 20 years and assess the potential drivers associated with typhoid reduction. In the 1990s, multidrug resistant S. Typhi were highly prevalent in a sentinel hospital in southern Vietnam. A national typhoid incidence rate of 14.7/100,000 population per year was estimated around the new millennium. The Vietnamese government recognized the public health issue of typhoid in the 1990s and initiated vaccine campaigns to protect the most vulnerable members of the population. At their peak, these campaigns immunized approximately 1,200,000 children in 35 provinces. Concurrently, Vietnam experienced unprecedented economic development from 1998 to 2014, with the gross national income per capita increasing from $360 to$1,890 over this period. More recent typhoid incidence data are not available, but surveillance suggests that the current disease burden is negligible. This trajectory can be considered a major public health success. However, a paucity of systematic data makes it difficult to disaggregate the roles of immunization and water, sanitation, and hygiene (WASH) interventions in typhoid reduction in Vietnam. Given the limitations of typhoid vaccines, we surmise the practical elimination of typhoid was largely driven by economic development and improvement in general population living standards. Better designed WASH intervention studies with clinical endpoints and systematic incidence data are essential to glean a greater understanding of contextual factors that impact typhoid incidence reduction

The control of Typhoid fever in Vietnam

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a diminishing public health problem in Vietnam, and this process may represent a prototype for typhoid elimination in Asia. Here, we review typhoid epidemiology in Vietnam over 20 years and assess the potential drivers associated with typhoid reduction. In the 1990s, multidrug resistant S. Typhi were highly prevalent in a sentinel hospital in southern Vietnam. A national typhoid incidence rate of 14.7/100,000 population per year was estimated around the new millennium. The Vietnamese government recognized the public health issue of typhoid in the 1990s and initiated vaccine campaigns to protect the most vulnerable members of the population. At their peak, these campaigns immunized approximately 1,200,000 children in 35 provinces. Concurrently, Vietnam experienced unprecedented economic development from 1998 to 2014, with the gross national income per capita increasing from $360 to$1,890 over this period. More recent typhoid incidence data are not available, but surveillance suggests that the current disease burden is negligible. This trajectory can be considered a major public health success. However, a paucity of systematic data makes it difficult to disaggregate the roles of immunization and water, sanitation, and hygiene (WASH) interventions in typhoid reduction in Vietnam. Given the limitations of typhoid vaccines, we surmise the practical elimination of typhoid was largely driven by economic development and improvement in general population living standards. Better designed WASH intervention studies with clinical endpoints and systematic incidence data are essential to glean a greater understanding of contextual factors that impact typhoid incidence reduction