High sensitivity detection of Plasmodium species reveals positive correlations between infections of different species, shifts in age distribution and reduced local variation in Papua New Guinea

BACKGROUND: When diagnosed by standard light microscopy (LM), malaria prevalence can vary significantly between sites, even at local scale, and mixed species infections are consistently less common than expect in areas co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium malariae. The development of a high-throughput molecular species diagnostic assay now enables routine PCR-based surveillance of malaria infections in large field and intervention studies, and improves resolution of species distribution within and between communities. METHODS: This study reports differences in the prevalence of infections with all four human malarial species and of mixed infections as diagnosed by LM and post-PCR ligase detection reaction-fluorescent microsphere (LDR-FMA) assay in 15 villages in the central Sepik area of Papua New Guinea. RESULTS: Significantly higher rates of infection by P. falciparum, P. vivax, P. malariae and Plasmodium ovale were observed in LDR-FMA compared to LM diagnosis (p > 0.001). Increases were particularly pronounced for P. malariae (3.9% vs 13.4%) and P. ovale (0.0% vs 4.8%). In contrast to LM diagnosis, which suggested a significant deficit of mixed species infections, a significant excess of mixed infections over expectation was detected by LDR-FMA (p > 0.001). Age of peak prevalence shifted to older age groups in LDR-FMA diagnosed infections for P. falciparum (LM: 7-9 yrs 47.5%, LDR-FMA: 10-19 yrs 74.2%) and P. vivax (LM: 4-6 yrs 24.2%, LDR-FMA: 7-9 yrs 50.9%) but not P. malariae infections (10-19 yrs, LM: 7.7% LDR-FMA: 21.6%). Significant geographical variation in prevalence was found for all species (except for LM-diagnosed P. falciparum), with the extent of this variation greater in LDR-FMA than LM diagnosed infections (overall, 84.4% vs. 37.6%). Insecticide-treated bednet (ITN) coverage was also the dominant factor linked to geographical differences in Plasmodium species infection prevalence explaining between 60.6% - 74.5% of this variation for LDR-FMA and 81.8% - 90.0% for LM (except P. falciparum), respectively. CONCLUSION: The present study demonstrates that application of molecular diagnosis reveals patterns of malaria risk that are significantly different from those obtained by standard LM. Results provide insight relevant to design of malaria control and eradication strategie

Symptoms of Anxiety and Cardiac Hospitalizations at 12 Months in Patients with Heart Failure

OBJECTIVE: Heart failure (HF) is a leading cause of hospitalization. Clinical and socio-demographic factors have been associated with cardiac admissions, but little is known about the role of anxiety. We examined whether symptoms of anxiety were associated with cardiac hospitalizations at 12 months in HF patients. METHODS: HF outpatients (N=237) completed the Hospital Anxiety and Depression Scale (HADS) at baseline (i.e., inclusion into the study). A cutoff ≥8 was used to indicate probable clinical levels of anxiety and depression. At 12 months, a medical chart abstraction was performed to obtain information on cardiac hospitalizations. RESULTS: The prevalence of symptoms of anxiety was 24.9 % (59/237), and 27.0 % (64/237) of patients were admitted for cardiac reasons at least once during the 12-month follow-up period. Symptoms of anxiety were neither significantly associated with cardiac hospitalizations in univariable logistic analysis [OR=1.13, 95% CI (0.59–2.17), p=0.72] nor in multivariable analysi

Malaria in Africa: Vector Species' Niche Models and Relative Risk Maps

A central theoretical goal of epidemiology is the construction of spatial models of disease prevalence and risk, including maps for the potential spread of infectious disease. We provide three continent-wide maps representing the relative risk of malaria in Africa based on ecological niche models of vector species and risk analysis at a spatial resolution of 1 arc-minute (9 185 275 cells of approximately 4 sq km). Using a maximum entropy method we construct niche models for 10 malaria vector species based on species occurrence records since 1980, 19 climatic variables, altitude, and land cover data (in 14 classes). For seven vectors (Anopheles coustani, A. funestus, A. melas, A. merus, A. moucheti, A. nili, and A. paludis) these are the first published niche models. We predict that Central Africa has poor habitat for both A. arabiensis and A. gambiae, and that A. quadriannulatus and A. arabiensis have restricted habitats in Southern Africa as claimed by field experts in criticism of previous models. The results of the niche models are incorporated into three relative risk models which assume different ecological interactions between vector species. The “additive” model assumes no interaction; the “minimax” model assumes maximum relative risk due to any vector in a cell; and the “competitive exclusion” model assumes the relative risk that arises from the most suitable vector for a cell. All models include variable anthrophilicity of vectors and spatial variation in human population density. Relative risk maps are produced from these models. All models predict that human population density is the critical factor determining malaria risk. Our method of constructing relative risk maps is equally general. We discuss the limits of the relative risk maps reported here, and the additional data that are required for their improvement. The protocol developed here can be used for any other vector-borne disease

Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol

Invasive pneumococcal disease: epidemiology in children and adults prior to implementation of the conjugate vaccine in the Oxfordshire region, England.

A 10-year invasive pneumococcal disease (IPD) enhanced surveillance project in the Oxfordshire region of the UK between 1996 and 2005 identified a total of 2691 Streptococcus pneumoniae isolates from all ages that provided a comprehensive description of pneumococcal epidemiology. All isolates were serotyped and those from children under 5 years of age were genotyped and a matched case-control study using adults hospitalized between 1995 and 2000 was performed to estimate the effectiveness of the pneumococcal polysaccharide vaccine in the local population. Fifty-one serotypes were isolated, with different age distributions. The overall incidence of IPD was 9.2 cases per 100 000 population per annum [95 % confidence interval (CI), 8.6-9.9] and that of meningitis was 0.7 per 100 000 population per annum (95 % CI 0.5-0.9). After adjusting for age, serotype 1 was found to be less likely to be associated with meningitis versus other IPD, compared with the most common serotype 14, whereas serotype 12F was more likely to cause meningitis than other IPD. There were significant temporal changes in IPD incidence of four serotypes, with decreases in serotypes 1, 12F and 14 and increases in serotype 8. A possible novel variant (from serotype 6A to 6B) was found using multilocus sequence typing analysis. From the matched case-control study of adults, the pneumococcal polysaccharide vaccine effectiveness was estimated to be 43 % (2-68 %), which did not change significantly after adjustment for pre-existing co-morbidities. The data provide a baseline against which the impact of the pneumococcal conjugate vaccine introduced in the UK in 2006 could be measured