G. Dennis Shanks

Bio: G. Dennis Shanks is an academic researcher from University of Queensland. The author has contributed to research in topics: Malaria & Pandemic. The author has an hindex of 32, co-authored 105 publications receiving 4235 citations. Previous affiliations of G. Dennis Shanks include United States Department of the Army & Walter Reed Army Medical Center.

Deaths from bacterial pneumonia during 1918-19 influenza pandemic.

Abstract: Deaths during the 1918–19 influenza pandemic have been attributed to a hypervirulent influenza strain. Hence, preparations for the next pandemic focus almost exclusively on vaccine prevention and antiviral treatment for infections with a novel influenza strain. However, we hypothesize that infections with the pandemic strain generally caused self-limited (rarely fatal) illnesses that enabled colonizing strains of bacteria to produce highly lethal pneumonias. This sequential-infection hypothesis is consistent with characteristics of the 1918–19 pandemic, contemporaneous expert opinion, and current knowledge regarding the pathophysiologic effects of influenza viruses and their interactions with respiratory bacteria. This hypothesis suggests opportunities for prevention and treatment during the next pandemic (e.g., with bacterial vaccines and antimicrobial drugs), particularly if a pandemic strain–specific vaccine is unavailable or inaccessible to isolated, crowded, or medically underserved populations.

A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting

Abstract: Many countries are scaling up malaria interventions towards elimination. This transition changes demands on malaria diagnostics from diagnosing ill patients to detecting parasites in all carriers including asymptomatic infections and infections with low parasite densities. Detection methods suitable to local malaria epidemiology must be selected prior to transitioning a malaria control programme to elimination. A baseline malaria survey conducted in Temotu Province, Solomon Islands in late 2008, as the first step in a provincial malaria elimination programme, provided malaria epidemiology data and an opportunity to assess how well different diagnostic methods performed in this setting. During the survey, 9,491 blood samples were collected and examined by microscopy for Plasmodium species and density, with a subset also examined by polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs). The performances of these diagnostic methods were compared. A total of 256 samples were positive by microscopy, giving a point prevalence of 2.7%. The species distribution was 17.5% Plasmodium falciparum and 82.4% Plasmodium vivax. In this low transmission setting, only 17.8% of the P. falciparum and 2.9% of P. vivax infected subjects were febrile (≥38°C) at the time of the survey. A significant proportion of infections detected by microscopy, 40% and 65.6% for P. falciparum and P. vivax respectively, had parasite density below 100/μL. There was an age correlation for the proportion of parasite density below 100/μL for P. vivax infections, but not for P. falciparum infections. PCR detected substantially more infections than microscopy (point prevalence of 8.71%), indicating a large number of subjects had sub-microscopic parasitemia. The concordance between PCR and microscopy in detecting single species was greater for P. vivax (135/162) compared to P. falciparum (36/118). The malaria RDT detected the 12 microscopy and PCR positive P. falciparum, but failed to detect 12/13 microscopy and PCR positive P. vivax infections. Asymptomatic malaria infections and infections with low and sub-microscopic parasite densities are highly prevalent in Temotu province where malaria transmission is low. This presents a challenge for elimination since the large proportion of the parasite reservoir will not be detected by standard active and passive case detection. Therefore effective mass screening and treatment campaigns will most likely need more sensitive assays such as a field deployable molecular based assay.

Malaria Blood Stage Parasites Activate Human Plasmacytoid Dendritic Cells and Murine Dendritic Cells through a Toll-Like Receptor 9-Dependent Pathway

Abstract: A common feature of severe Plasmodium falciparum infection is the increased systemic release of proinflammatory cytokines that contributes to the pathogenesis of malaria Using human blood, we found that blood stage schizonts or soluble schizont extracts activated plasmacytoid dendritic cells (PDCs) to up-regulate CD86 expression and produce IFN-α IFN-α production was also detected in malaria-infected patients, but the levels of circulating PDCs were markedly reduced, possibly because of schizont-stimulated up-regulation of CCR7, which is critical for PDC migration The schizont-stimulated PDCs elicited a poor T cell response, but promoted γδ T cell proliferation and IFN-γ production The schizont immune stimulatory effects could be reproduced using murine DCs and required the Toll-like receptor 9 (TLR9)-MyD88 signaling pathway Although the only known TLR9 ligand is CpG motifs in pathogen DNA, the activity of the soluble schizont extract was far greater than that of schizont DNA, and it was heat labile and precipitable with ammonium sulfate, unlike the activity of bacterial DNA These results demonstrate that schizont extracts contain a novel and previously unknown ligand for TLR9 and suggest that the stimulatory effects of this ligand on PDCs may play a key role in immunoregulation and immunopathogenesis of human falciparum malaria

Geographical variation in Plasmodium vivax relapse

Abstract: Plasmodium vivax has the widest geographic distribution of the human malaria parasites and nearly 2.5 billion people live at risk of infection. The control of P. vivax in individuals and populations is complicated by its ability to relapse weeks to months after initial infection. Strains of P. vivax from different geographical areas are thought to exhibit varied relapse timings. In tropical regions strains relapse quickly (three to six weeks), whereas those in temperate regions do so more slowly (six to twelve months), but no comprehensive assessment of evidence has been conducted. Here observed patterns of relapse periodicity are used to generate predictions of relapse incidence within geographic regions representative of varying parasite transmission. A global review of reports of P. vivax relapse in patients not treated with a radical cure was conducted. Records of time to first P. vivax relapse were positioned by geographic origin relative to expert opinion regions of relapse behaviour and epidemiological zones. Mixed-effects meta-analysis was conducted to determine which geographic classification best described the data, such that a description of the pattern of relapse periodicity within each region could be described. Model outputs of incidence and mean time to relapse were mapped to illustrate the global variation in relapse. Differences in relapse periodicity were best described by a historical geographic classification system used to describe malaria transmission zones based on areas sharing zoological and ecological features. Maps of incidence and time to relapse showed high relapse frequency to be predominant in tropical regions and prolonged relapse in temperate areas. The results indicate that relapse periodicity varies systematically by geographic region and are categorized by nine global regions characterized by similar malaria transmission dynamics. This indicates that relapse may be an adaptation evolved to exploit seasonal changes in vector survival and therefore optimize transmission. Geographic patterns in P. vivax relapse are important to clinicians treating individual infections, epidemiologists trying to infer P. vivax burden, and public health officials trying to control and eliminate the disease in human populations.

Acute Eosinophilic Pneumonia Among US Military Personnel Deployed in or Near Iraq

Abstract: ContextAcute eosinophilic pneumonia (AEP) is a rare disease of unknown etiology characterized by respiratory failure, radiographic infiltrates, and eosinophilic infiltration of the lung.ObjectivesTo describe a case series of AEP, illustrate the clinical features of this syndrome, and report the results of an epidemiologic investigation.Design, Setting, and ParticipantsEpidemiologic investigation of cases of AEP identified both retrospectively and prospectively from March 2003 through March 2004 among US military personnel deployed in or near Iraq. Survivors were offered a follow-up evaluation.Main Outcome MeasureMorbidity and mortality related to AEP.ResultsThere were 18 cases of AEP identified among 183 000 military personnel deployed in or near Iraq during the study period, yielding an AEP incidence of 9.1 per 100 000 person-years (95% confidence interval, 4.3-13.3). The majority of patients (89%) were men and the median age was 22 (range, 19-47) years. All patients used tobacco, with 78% recently beginning to smoke. All but 1 reported significant exposure to fine airborne sand or dust. Known causes of pulmonary eosinophilia (eg, drug exposures or parasitic disease) were not identified. Epidemiologic investigation revealed no evidence of a common source exposure, temporal or geographic clustering, person-to-person transmission, or an association with recent vaccination. Six patients underwent bronchoalveolar lavage (median eosinophilia of 40.5%). All patients developed peripheral eosinophilia (range, 8%-42%). Mechanical ventilation was required in 67% for a median of 7 (range, 2-16) days. Two soldiers died; the remainder responded to corticosteroids and/or supportive care. Twelve individuals were reevaluated a median of 3 months after diagnosis. At that point, 3 patients reported mild dyspnea and 1 reported wheezing. All patients had finished treatment and had either normal or nearly normal spirometry results. None had recurrent eosinophilia.ConclusionsAEP occurred at an increased rate among this deployed military population and resulted in 2 deaths. Failure to consider AEP in the differential diagnosis of respiratory failure in military personnel can result in missing this syndrome and possibly death. The etiology of AEP remains unclear, but the association with new-onset smoking suggests a possible link.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Climate change and water.

Abstract: The Intergovernmental Panel on Climate Change (IPCC) Technical Paper Climate Change and Water draws together and evaluates the information in IPCC Assessment and Special Reports concerning the impacts of climate change on hydrological processes and regimes, and on freshwater resources – their availability, quality, use and management. It takes into account current and projected regional key vulnerabilities, prospects for adaptation, and the relationships between climate change mitigation and water. Its objectives are:

Impact of regional climate change on human health

Abstract: The World Health Organisation estimates that the warming and precipitation trends due to anthropogenic climate change of the past 30 years already claim over 150,000 lives annually. Many prevalent human diseases are linked to climate fluctuations, from cardiovascular mortality and respiratory illnesses due to heatwaves, to altered transmission of infectious diseases and malnutrition from crop failures. Uncertainty remains in attributing the expansion or resurgence of diseases to climate change, owing to lack of long-term, high-quality data sets as well as the large influence of socio-economic factors and changes in immunity and drug resistance. Here we review the growing evidence that climate-health relationships pose increasing health risks under future projections of climate change and that the warming trend over recent decades has already contributed to increased morbidity and mortality in many regions of the world. Potentially vulnerable regions include the temperate latitudes, which are projected to warm disproportionately, the regions around the Pacific and Indian oceans that are currently subjected to large rainfall variability due to the El Nino/Southern Oscillation sub-Saharan Africa and sprawling cities where the urban heat island effect could intensify extreme climatic events.