Scrub typhus (ST) and murine typhus (MT) are common but poorly understood causes of fever in Laos. We examined the spatial and temporal distribution of ST and MT, with the intent of informing ...interventions to prevent and control both diseases.
This study included samples submitted from 2003 to 2017 to Mahosot Hospital, Vientiane, for ST and MT investigation. Serum samples were tested using IgM rapid diagnostic tests. Patient demographic data along with meteorological and environmental data from Laos were analysed. Approximately 17% of patients were positive for either ST (1,337/8,150 patients tested) or MT (1,283/7,552 patients tested). While both diseases occurred in inhabitants from Vientiane Capital, from the univariable analysis MT was positively and ST negatively associated with residence in Vientiane Capital. ST was highly seasonal, with cases two times more likely to occur during the wet season months of July-September compared to the dry season whilst MT peaked in the dry season. Multivariable regression analysis linked ST incidence to fluctuations in relative humidity whereas MT was linked to variation in temperature. Patients with ST infection were more likely to come from villages with higher levels of surface flooding and vegetation in the 16 days leading up to diagnosis.
The data suggest that as cities expand, high risk areas for MT will also expand. With global heating and risks of attendant higher precipitation, these data suggest that the incidence and spatial distribution of both MT and ST will increase.
Burkholderia pseudomallei is the cause of melioidosis, a serious and difficult to treat infection that is endemic throughout the tropics. Melioidosis incidence is highly seasonal. We aimed to ...identify the climatic drivers of infection and to shed light on modes of transmission and potential preventive strategies.
We examined the records of patients diagnosed with melioidosis at the Microbiology Laboratory of Mahosot Hospital in Vientiane, Laos, between October, 1999, and August, 2015, and all patients with culture-confirmed melioidosis presenting to the Angkor Hospital for Children in Siem Reap, Cambodia, between February, 2009, and December, 2013. We also examined local temperature, humidity, precipitation, visibility, and wind data for the corresponding time periods. We estimated the B pseudomallei incubation period by examining profile likelihoods for hypothetical exposure-to-presentation delays.
870 patients were diagnosed with melioidosis in Laos and 173 patients were diagnosed with melioidosis in Cambodia during the study periods. Melioidosis cases were significantly associated with humidity (p<0·0001), low visibility (p<0·0001), and maximum wind speeds (p<0·0001) in Laos, and humidity (p=0·010), rainy days (p=0·015), and maximum wind speed (p=0·0070) in Cambodia. Compared with adults, children were at significantly higher odds of infection during highly humid months (odds ratio 2·79, 95% CI 1·83–4·26). Lung and disseminated infections were more common during windy months. The maximum likelihood estimate of the incubation period was 1 week (95% CI 0–2).
The results of this study demonstrate a significant seasonal burden of melioidosis among adults and children in Laos and Cambodia. Our findings highlight the risks of infection during highly humid and windy conditions, and suggest a need for increased awareness among at-risk individuals, such as children.
Wellcome Trust.
•Four nucleic acid amplification tests for SARS-CoV-2 RNA demonstrated comparable performance using clinical specimens.•A limited number of discrepancies were observed in specimens with low viral ...loads.•The isothermal amplification assay was slightly less sensitive but was one hour faster than the other methods.•Assay selection requires consideration of test performance, instrument/reagent availability, turnaround and throughput.
Numerous nucleic acid amplification tests, including real-time, reverse transcription PCR (rRT-PCR) and isothermal amplification methods, have been developed to detect SARS-CoV-2 RNA, including many that have received emergency use authorization (EUA). There is a need to assess their test performance relative to one another.
The aim of this study was to compare the test performance of a high complexity laboratory-developed rRT-PCR EUA from Stanford Health Care (SHC) targeting the SARS-CoV-2 envelope (E) gene with other tests: the Atila isothermal amplification assay targeting the nucleocapsid (N) gene and open reading frame 1ab (ORF1ab), the Altona E and spike (S) multiplex, real-time RT-PCR, and the US Centers for Disease Control and Prevention (CDC) N1 and N2 rRT-PCRs.
A diagnostic comparison study was performed by testing nasopharyngeal samples from persons under investigation for coronavirus disease 2019 (COVID-19). Assay performance was assessed by percent agreement and Cohen’s kappa coefficient.
Positive percent agreement with the SHC EUA reference assay was 82.8 % (95 % confidence interval (CI) 65.0 to 92.9) for Atila, 86.7 % (95 % CI 69.7 to 95.3) for the Altona E and S targets, and 86.7 % (95 % CI 69.7 to 95.3) and 90.0 % (95 % CI 73.6 to 97.3), for the CDC N1 and N2 targets, respectively. All assays demonstrated 100 % negative percent agreement. Kappa coefficients ranged from 0.86 to 0.92, indicating excellent agreement.
Performance was comparable among the SARS-CoV-2 nucleic acid amplification methods tested, with a limited number of discrepancies observed in specimens with low viral loads.
•Both cellular and humoral immune responses to SARS-CoV-2 vaccination wane over time.•The rate of vaccine response decline is comparable between immunosuppressed patients and healthy populations.•S1P ...receptor modulators and mycophenolate are associated with lower cellular and humoral immune response.•Anti-CD20 therapy is associated with lower humoral immune response only.•35% of patients with poor humoral response after primary vaccination had a significantly increased humoral response after receiving the booster.
: Humoral and cellular immune responses to SARS-CoV-2 vaccination among immunosuppressed patients remain poorly defined, as well as variables associated with poor response.
: We performed a retrospective observational cohort study at a large Northern California healthcare system of infection-naïve individuals fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) with clinical SARS-CoV-2 interferon gamma release assay (IGRA) ordered between January through November 2021. Humoral and cellular immune responses were measured by anti-SARS-CoV-2 S1 IgG ELISA (anti-S1 IgG) and IGRA, respectively, following primary and/or booster vaccination.
: 496 immunosuppressed patients (54% female; median age 50 years) were included. 62% (261/419) of patients had positive anti-S1 IgG and 71% (277/389) had positive IGRA after primary vaccination, with 20% of patients having a positive IGRA only. Following booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Factors associated with low humoral response rates after primary vaccination included anti-CD20 monoclonal antibodies (P < 0.001), sphingosine 1-phsophate (S1P) receptor modulators (P < 0.001), mycophenolate (P = 0.002), and B cell lymphoma (P = 0.004); those associated with low cellular response rates included S1P receptor modulators (P < 0.001) and mycophenolate (P < 0.001). Of patients who had poor humoral response to primary vaccination, 35% (18/52) developed a significantly higher response after the booster. Only 5% (2/42) of patients developed a significantly higher cellular response to the booster dose compared to primary vaccination.
: Humoral and cellular response rates to primary and booster SARS-CoV-2 vaccination differ among immunosuppressed patient groups. Clinical testing of cellular immunity is important in monitoring vaccine response in vulnerable populations.
Dengue and COVID-19 cocirculation presents a diagnostic conundrum for physicians evaluating patients with acute febrile illnesses, both in endemic regions and among returning travelers. We present a ...case of a returning traveler from Pakistan who, following repeated negative SARS-CoV-2 tests, was found to have a Dengue virus serotype 2 infection.
Burkholderia pseudomallei (Bp) is an environmental organism that inhabits the rhizosphere, a rich and diverse zone of soil supported by a network of plant roots. In the rhizosphere, Bp faces intense ...competition with other bacterial species and fungi, as well as predation by protozoa, nematodes, and insects. Our hypothesis is that Bp virulence determinants that promote disease in mammals arose to defend against environmental predators. In this context, infections of humans and animals are likely to be incidental occurrences. We speculate that most Bp virulence determinants that are critical for intracellular survival could have relevant roles for interactions with ecological species, including the Bsa type III secretion system (T3SSBsa), BimA-mediated actin polymerization and type VI secretion (T6SS-5) in promoting intracellular survival and cell-cell spread in nematodes, grazing insects and social amoebae. Bp possesses two more T3SSs and numerous polyketide/non-ribosomal peptide synthetases (PKS/NRPS) that resemble systems in phytopathogenic bacteria, hinting at its ability to interact with plants or fungi. Bp is capable of adopting a lifestyle of obligate parasitism, as shown by the divergence of the equine host-restricted B. mallei. Some environmental species that prey on Bp may double as host organisms, and although not proven, it is conceivable that Bp may use them as a survival niche. Understanding the lifestyle of Bp in an ecological context will shed light on the mechanisms that promote human infections, and may potentially help explain the broad differentials in virulence and the genetic diversity that is a hallmark of the species.
Display omitted
•The Burkholderia pseudomallei (Bp) complex includes pathogenic and non-pathogenic species.•With the exception of Burkholderia mallei, which is adapted to survival in equine hosts, Bp-complex species are environmental microbes.•Virulence traits include type III and type VI secretion systems (T3SSBsa, T6SS-5), and actin-based motility.•We hypothesize that ecological interactions with eukaryotic predators provide selection for virulence traits that promote human infections.•Understanding the ecology of the Bp complex should provide insight into the origin of virulence mechanisms in these and other pathogens.
Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) cause the often-lethal infectious diseases melioidosis and glanders, respectively. Curiously, closely related species within the Bp complex share a nearly identical arsenal of virulence traits, yet are harmless to humans. Clues to the origin of virulence in this group can be found in their genetics and ecology. As a resident of the rhizosphere, Bp faces competition for nutrients and predation by other organisms. Adaptation over millennia has enabled Bp to accumulate mechanisms that overlap in their ability to promote fitness in the environment and virulence in mammals. Here, we review the ecology of Bp and its range of virulence attributes, and offer hypotheses on the evolution of virulence in the Bp complex which are relevant to other environmental pathogens.
Abstract
Background
Laboratory-based methods for SARS-CoV-2 antibody detection vary widely in performance. However, there are limited prospectively-collected data on assay performance, and minimal ...clinical information to guide interpretation of discrepant results.
Methods
Over a 2-week period, 1080 consecutive plasma samples submitted for clinical SARS-CoV-2 IgG testing were tested in parallel for anti-nucleocapsid IgG (anti-N, Abbott) and anti-spike IgG (anti-S1, EUROIMMUN). Chart review was conducted for samples testing positive or borderline on either assay, and for an age/sex-matched cohort of samples negative by both assays. CDC surveillance case definitions were used to determine clinical sensitivity/specificity and conduct receiver operating characteristics curve analysis.
Results
There were 52 samples positive by both methods, 2 positive for anti-N only, 34 positive for anti-S1 only, and 27 borderline for anti-S1. Of the 34 individuals positive for anti-S1 alone, 8 (24%) had confirmed COVID-19. No anti-S1 borderline cases were positive for anti-N or had confirmed/probable COVID-19. The anti-N assay was less sensitive (84.2% 95% CI 72.1-92.5% vs 94.7% 95% CI 85.4-98.9%) but more specific (99.2% 95% CI 95.5-100% vs 86.9% 95% CI 79.6-92.3%) than anti-S1. Abbott anti-N sensitivity could be improved to 96.5% with minimal effect on specificity if the index threshold was lowered from 1.4 to 0.6.
Conclusion
Real-world concordance between different serologic assays may be lower than previously described in retrospective studies. These findings have implications for the interpretation of SARS-CoV-2 IgG results, especially with the advent of spike antigen-targeted vaccination, as a subset of patients with true infection are anti-N negative and anti-S1 positive.
PDF
