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Henipaviruses at the Interface Between Bats, Livestock and Human Population in Africa

Mbu'u CM, Mbacham WF, Gontao P, Sado Kamdem SL, Nlôga AMN, Groschup MH, et al.

Vector Borne Zoonotic Dis, 2019 07;19(7):455-465.
PMID: 30985268 DOI: 10.1089/vbz.2018.2365

Nipah virus (NiV) and Hendra virus (HeV) are closely related members within the genus Henipavirus, family Paramyxoviridae, for which fruit bats serve as the reservoir. The initial emergence of NiV infections in pigs and humans in Malaysia, and HeV infections in horses and humans in Australia, posed severe impacts on human and animal health, and continues threatening lives of humans and livestock within Southeast Asia and Australia. Recently, henipavirus-specific antibodies have also been detected in fruit bats in a number of sub-Saharan African countries and in Brazil, thereby considerably increasing the known geographic distribution of henipaviruses. Africa is progressively being recognized as a new high prevalence zone for henipaviruses, as deduced from serological and molecular evidence of past infections in Madagascar, Ghana, Republic of Congo, Gulf of Guinea, Zambia, Tanzania, Cameroon, and Nigeria lately. Serological data suggest henipavirus spillover from bats to livestock and human populations in Africa without reported clinical disease in any of these species. All virus isolation attempts have been abortive, highlighting the need for further investigations. The genome of the Ghanaian bat henipavirus designated Ghana virus (GhV), which was detected in a pteropid Eidolon helvum bat, is the only African henipavirus that has been completely sequenced limiting our current knowledge on the genetic diversity and pathogenesis of African henipaviruses. In this review, we summarize the available data on the circulation of henipaviruses in Africa, discuss potential sources for virus spillover, and highlight existing research gaps.
Fulltext Indirect ELISA based on Hendra and Nipah virus proteins for the detection of henipavirus specific antibodies in pigs

Fischer K, Diederich S, Smith G, Reiche S, Pinho Dos Reis V, Stroh E, et al.

PLoS One, 2018;13(4):e0194385.
PMID: 29708971 DOI: 10.1371/journal.pone.0194385

Hendra virus (HeV) and Nipah virus (NiV) belong to the genus Henipavirus in the family Paramyxoviridae. Henipavirus infections were first reported in the 1990's causing severe and often fatal outbreaks in domestic animals and humans in Southeast Asia and Australia. NiV infections were observed in humans in Bangladesh, India and in the first outbreak in Malaysia, where pigs were also infected. HeV infections occurred in horses in the North-Eastern regions of Australia, with singular transmission events to humans. Bats of the genus Pteropus have been identified as the reservoir hosts for henipaviruses. Molecular and serological indications for the presence of henipa-like viruses in African fruit bats, pigs and humans have been published recently. In our study, truncated forms of HeV and NiV attachment (G) proteins as well as the full-length NiV nucleocapsid (N) protein were expressed using different expression systems. Based on these recombinant proteins, Enzyme-linked Immunosorbent Assays (ELISA) were developed for the detection of HeV or NiV specific antibodies in porcine serum samples. We used the NiV N ELISA for initial serum screening considering the general reactivity against henipaviruses. The G protein based ELISAs enabled the differentiation between HeV and NiV infections, since as expected, the sera displayed higher reactivity with the respective homologous antigens. In the future, these assays will present valuable tools for serosurveillance of swine and possibly other livestock or wildlife species in affected areas. Such studies will help assessing the potential risk for human and animal health worldwide by elucidating the distribution of henipaviruses.
Fulltext Interleukin 6 and Development of Heart Failure With Preserved Ejection Fraction in the General Population

Chia YC, Kieneker LM, van Hassel G, Binnenmars SH, Nolte IM, van Zanden JJ, et al.

J Am Heart Assoc, 2021 06;10(11):e018549.
PMID: 33998283 DOI: 10.1161/JAHA.120.018549

Background The cause of heart failure with preserved ejection fraction (HFpEF) is poorly understood, and specific therapies are lacking. Previous studies suggested that inflammation plays a role in the development of HFpEF. Herein, we aimed to investigate in community-dwelling individuals whether a higher plasma interleukin 6 (IL-6) level is associated with an increased risk of developing new-onset heart failure (HF) over time, and specifically HFpEF. Methods and Results We performed a case-cohort study based on the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study, a prospective general population-based cohort study. We included 961 participants, comprising 200 participants who developed HF and a random group of 761 controls. HF with reduced ejection fraction or HFpEF was defined on the basis of the left ventricular ejection fraction of ≤40% or >40%, respectively. In Cox proportional hazard regression analyses, IL-6 levels were statistically significantly associated with the development of HF (hazard ratio [HR], 1.28; 95% CI, 1.02-1.61; P=0.03) after adjustment for key risk factors. Specifically, IL-6 levels were significantly associated with the development of HFpEF (HR, 1.59; 95% CI, 1.16-2.19; P=0.004), whereas the association with HF with reduced ejection fraction was nonsignificant (HR, 1.05; 95% CI, 0.75-1.47; P=0.77). In sensitivity analyses, defining HFpEF as left ventricular ejection fraction ≥50%, IL-6 levels were also significantly associated with the development of HFpEF (HR, 1.47; 95% CI, 1.04-2.06; P=0.03) after adjustment for key risk factors. Conclusions IL-6 is associated with new-onset HFpEF in community-dwelling individuals, independent of potential confounders. Our findings warrant further research to investigate whether IL-6 might be a novel treatment target to prevent HFpEF.
Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 and hepatitis B coinfection (ALLIANCE): a double-blind, multicentre, randomised controlled, phase 3 non-inferiority trial

Avihingsanon A, Lu H, Leong CL, Hung CC, Koenig E, Kiertiburanakul S, et al.

Lancet HIV, 2023 Oct;10(10):e640-e652.
PMID: 37494942 DOI: 10.1016/S2352-3018(23)00151-0

BACKGROUND: For most adults with HIV-1 and hepatitis B virus (HBV) coinfection, initial recommended treatment is a tenofovir-containing antiretroviral regimen, but no randomised studies have compared tenofovir disoproxil fumarate with tenofovir alafenamide. We aimed to investigate whether bictegravir, emtricitabine, and tenofovir alafenamide is non-inferior to dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for viral suppression in individuals with HIV-1 and HBV coinfection at 48 and 96 weeks.
METHODS: We did this randomised, double-blind, active-controlled, phase 3, non-inferiority trial at 46 outpatient centres in China, Dominican Republic, Hong Kong, Japan, Malaysia, South Korea, Spain, Taiwan, Thailand, Turkey, and the USA. Eligible participants were treatment-naive adults (aged ≥18 years) with plasma HIV-1 RNA of at least 500 copies per mL and plasma HBV DNA of at least 2000 IU/mL. Participants were randomly assigned (1:1) to receive daily oral bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, or dolutegravir 50 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg, each with corresponding matching placebo. Randomisation was stratified by hepatitis B e antigen (HBeAg) status (positive vs negative), HBV DNA (<8 vs ≥8 log10 IU/mL), and CD4 count (<50 vs ≥50 cells per μL) at screening. All investigators, participants, and staff providing treatment, assessing outcomes, and collecting data were masked to study treatment for 96 weeks. Coprimary endpoints were the proportion of participants with plasma HIV-1 RNA less than 50 copies per mL (defined by the US Food and Drug Administration snapshot algorithm) and plasma HBV DNA less than 29 IU/mL (using the missing-equals-failure approach) at week 48, with a prespecified non-inferiority margin of -12%. Coprimary endpoints were assessed in the full analysis set, which included all randomly assigned participants who received at least one dose of study drug and had at least one post-baseline HIV-1 RNA or HBV DNA result while on study drug. Safety endpoints were assessed in all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03547908.
FINDINGS: Between May 30, 2018 and March 16, 2021, 381 participants were screened, of whom 243 initiated treatment (121 in the receive bictegravir, emtricitabine, and tenofovir alafenamide group; 122 in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group). At week 48, both endpoints met the criteria for non-inferiority: 113 (95%) of 119 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group and 111 (91%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group had HIV-1 RNA less than 50 copies per mL (difference 4·1, 95% CI -2·5 to 10·8; p=0·21), and 75 (63%) of 119 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group versus 53 (43%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group had HBV DNA suppression (difference 16·6, 5·9 to 27·3; nominal p=0·0023). Drug-related adverse events up to week 96 occurred in 35 (29%) of 121 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group and 34 (28%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group. One (1%) of 121 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group reported a serious adverse event (cryptococcal meningitis attributed to immune reconstitution inflammatory syndrome) that was deemed to be treatment-related.
INTERPRETATION: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is an effective therapy for adults with HIV-1 and HBV coinfection starting antiviral therapy.
FUNDING: Gilead Sciences.
Fulltext The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Hudson LN, Newbold T, Contu S, Hill SL, Lysenko I, De Palma A, et al.

Ecol Evol, 2014 Dec;4(24):4701-35.
PMID: 25558364 DOI: 10.1002/ece3.1303

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - http://www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
Fulltext The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

Hudson LN, Newbold T, Contu S, Hill SL, Lysenko I, De Palma A, et al.

Ecol Evol, 2017 Jan;7(1):145-188.
PMID: 28070282 DOI: 10.1002/ece3.2579

The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.