Growing evidence suggests that the origins of the panzootic amphibian pathogens Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal) are in Asia. In Taiwan, an island ...hotspot of high amphibian diversity, no amphibian mass mortality events linked to Bd or Bsal have been reported. We conducted a multi-year study across this subtropical island, sampling 2517 individuals from 30 species at 34 field sites, between 2010 and 2017, and including 171 museum samples collected between 1981 and 2009. We analyzed the skin microbiome of 153 samples (6 species) from 2017 in order to assess any association between the amphibian skin microbiome and the probability of infection amongst different host species. We did not detect Bsal in our samples, but found widespread infection by Bd across central and northern Taiwan, both taxonomically and spatially. Museum samples show that Bd has been present in Taiwan since at least 1990. Host species, geography (elevation), climatic conditions and microbial richness were all associated with the prevalence of infection. Host life-history traits, skin microbiome composition and phylogeny were associated with lower prevalence of infection for high altitude species. Overall, we observed low prevalence and burden of infection in host populations, suggesting that Bd is enzootic in Taiwan where it causes subclinical infections. While amphibian species in Taiwan are currently threatened by habitat loss, our study indicates that Bd is in an endemic equilibrium with the populations and species we investigated. However, ongoing surveillance of the infection is warranted, as changing environmental conditions may disturb the currently stable equilibrium.
Introduction
Emerging infectious diseases are increasingly recognized as a global threat to wildlife. Pandemics in amphibians, caused by the fungal pathogen
Batrachochytrium dendrobatidis
(
Bd
), ...have resulted in biodiversity loss at a global scale. Genomic data suggest a complex evolutionary history of
Bd
lineages that vary in pathogenicity. Africa harbors a significant proportion of global amphibian biodiversity, and multiple
Bd
lineages are known to occur there; yet, despite the decline of many host species, there are currently no described
Bd
-epizootics. Here, we describe the historical and recent biogeographical spread of
Bd
and assess its risk to amphibians across the continent of Africa.
Methods
We provide a 165-year view of host-pathogen interactions by (i) employing a
Bd
assay to test 4,623 specimens (collected 1908–2013); (ii) compiling 12,297 published
Bd
records (collected 1852–2017); (iii) comparing the frequency of
Bd
-infected amphibians through time by both country and region; (iv) genotyping
Bd
lineages; (v) histologically identifying evidence of chytridiomycosis, and (vi) using a habitat suitability model to assess future
Bd
risk.
Results
We found a pattern of
Bd
emergence beginning largely at the turn of the century. From 1852–1999, we found low
Bd
prevalence (3.2% overall) and limited geographic spread, but after 2000 we documented a sharp increase in prevalence (18.7% overall), wider geographic spread, and multiple
Bd
lineages that may be responsible for emergence in different regions. We found that
Bd
risk to amphibians was highest in much of eastern, central, and western Africa.
Discussion
Our study documents a largely overlooked yet significant increase in a fungal pathogen that could pose a threat to amphibians across an entire continent. We emphasize the need to bridge historical and contemporary datasets to better describe and predict host-pathogen dynamics over larger temporal scales.
The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.
To evaluate clinical characteristics, outcomes, and treatment response to ...vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial.
Analysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020.
Vericiguat titrated to 10 mg daily vs placebo.
The primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH.
Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms.
Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF.
ClinicalTrials.gov Identifier: NCT02861534.
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