Subregional origins of emerging SARS-CoV-2 variants during the second pandemic wave in Côte d'Ivoire.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility, virulence and immune escape abilities have heavily altered the COVID-19 pandemic's course. Deciphering local and global transmission patterns of those variants is thus key in building a profound understanding of the virus' spread around the globe. In the present study, we investigate SARS-CoV-2 variant epidemiology in Côte d'Ivoire, Western sub-Saharan Africa. We therefore generated 234 full SARS-CoV-2 genomes stemming from Central and Northern Côte d'Ivoire. Covering the first and second pandemic wave the country had been facing, we identified 20 viral lineages and showed that in Côte d'Ivoire the second pandemic wave in 2021 was driven by the spread of the Alpha (B.1.1.7) and Eta (B.1.525) variant. Our analyses are consistent with a limited number of international introductions of Alpha and Eta into Côte d'Ivoire, and those introduction events mostly stemmed from within the West African subregion. This suggests that subregional travel to Côte d'Ivoire had more impact on local pandemic waves than direct intercontinental travel.

Zoonotic origin of the human malaria parasite Plasmodium malariae from African apes.

The human parasite Plasmodium malariae has relatives infecting African apes (Plasmodium rodhaini) and New World monkeys (Plasmodium brasilianum), but its origins remain unknown. Using a novel approach to characterise P. malariae-related sequences in wild and captive African apes, we found that this group comprises three distinct lineages, one of which represents a previously unknown, highly divergent species infecting chimpanzees, bonobos and gorillas across central Africa. A second ape-derived lineage is much more closely related to the third, human-infective lineage P. malariae, but exhibits little evidence of genetic exchange with it, and so likely represents a separate species. Moreover, the levels and nature of genetic polymorphisms in P. malariae indicate that it resulted from the zoonotic transmission of an African ape parasite, reminiscent of the origin of P. falciparum. In contrast, P. brasilianum falls within the radiation of human P. malariae, and thus reflects a recent anthroponosis.

Yaws Disease Caused by Treponema pallidum subspecies pertenue in Wild Chimpanzee, Guinea, 2019.

Yaws-like lesions are widely reported in wild African great apes, yet the causative agent has not been confirmed in affected animals. We describe yaws-like lesions in a wild chimpanzee in Guinea for which we demonstrate infection with Treponema pallidum subsp. pertenue. Assessing the conservation implications of this pathogen requires further research.

Monkeypox virus emergence in wild chimpanzees reveals distinct clinical outcomes and viral diversity.

Monkeypox is a viral zoonotic disease on the rise across endemic habitats. Despite the growing importance of monkeypox virus, our knowledge on its host spectrum and sylvatic maintenance is limited. Here, we describe the recent repeated emergence of monkeypox virus in a wild, human-habituated western chimpanzee (Pan troglodytes verus, hereafter chimpanzee) population from Taï National Park, Ivory Coast. Through daily monitoring, we show that further to causing its typical exanthematous syndrome, monkeypox can present itself as a severe respiratory disease without a diffuse rash. By analysing 949 non-invasively collected samples, we identify the circulation of at least two distinct monkeypox virus lineages and document the shedding of infectious particles in faeces and flies, suggesting that they could mediate indirect transmission. We also show that the carnivorous component of the Taï chimpanzees' diet, mainly consisting of the sympatric monkeys they regularly hunt, did not change nor shift towards rodent consumption (the presumed reservoir) before the outbreaks, suggesting that the sudden emergence of monkeypox virus in this population is probably due to changes in the ecology of the virus itself. Using long-term mortality surveillance data from Taï National Park, we provide evidence of little to no prior viral activity over at least two decades. We conclude that great ape sentinel systems devoted to the longitudinal collection of behavioural and health data can help clarify the epidemiology and clinical presentation of zoonotic pathogens.

Tropical rainforest flies carrying pathogens form stable associations with social nonhuman primates.

Living in groups provides benefits but also incurs costs such as attracting disease vectors. For example, synanthropic flies associate with human settlements, and higher fly densities increase pathogen transmission. We investigated whether such associations also exist in highly mobile nonhuman primate (NHP) Groups. We studied flies in a group of wild sooty mangabeys (Cercocebus atys atys) and three communities of wild chimpanzees (Pan troglodytes verus) in Taï National Park, Côte d'Ivoire. We observed markedly higher fly densities within both mangabey and chimpanzee groups. Using a mark-recapture experiment, we showed that flies stayed with the sooty mangabey group for up to 12 days and for up to 1.3 km. We also tested mangabey-associated flies for pathogens infecting mangabeys in this ecosystem, Bacillus cereus biovar anthracis (Bcbva), causing sylvatic anthrax, and Treponema pallidum pertenue, causing yaws. Flies contained treponemal (6/103) and Bcbva (7/103) DNA. We cultured Bcbva from all PCR-positive flies, confirming bacterial viability and suggesting that this bacterium might be transmitted and disseminated by flies. Whole genome sequences of Bcbva isolates revealed a diversity of Bcbva, probably derived from several sources. We conclude that flies actively track mangabeys and carry infectious bacterial pathogens; these associations represent an understudied cost of sociality and potentially expose many social animals to a diversity of pathogens.

Laboratory Findings, Compassionate Use of Favipiravir, and Outcome in Patients With Ebola Virus Disease, Guinea, 2015-A Retrospective Observational Study.

BACKGROUND: In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus-specific reverse transcription-polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis. METHODS: To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome. RESULTS: The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors. CONCLUSIONS: Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

Evolutionary history of human Plasmodium vivax revealed by genome-wide analyses of related ape parasites.

Wild-living African apes are endemically infected with parasites that are closely related to human Plasmodium vivax, a leading cause of malaria outside Africa. This finding suggests that the origin of P. vivax was in Africa, even though the parasite is now rare in humans there. To elucidate the emergence of human P. vivax and its relationship to the ape parasites, we analyzed genome sequence data of P. vivax strains infecting six chimpanzees and one gorilla from Cameroon, Gabon, and Côte d'Ivoire. We found that ape and human parasites share nearly identical core genomes, differing by only 2% of coding sequences. However, compared with the ape parasites, human strains of P. vivax exhibit about 10-fold less diversity and have a relative excess of nonsynonymous nucleotide polymorphisms, with site-frequency spectra suggesting they are subject to greatly relaxed purifying selection. These data suggest that human P. vivax has undergone an extreme bottleneck, followed by rapid population expansion. Investigating potential host-specificity determinants, we found that ape P. vivax parasites encode intact orthologs of three reticulocyte-binding protein genes (rbp2d, rbp2e, and rbp3), which are pseudogenes in all human P. vivax strains. However, binding studies of recombinant RBP2e and RBP3 proteins to human, chimpanzee, and gorilla erythrocytes revealed no evidence of host-specific barriers to red blood cell invasion. These data suggest that, from an ancient stock of P. vivax parasites capable of infecting both humans and apes, a severely bottlenecked lineage emerged out of Africa and underwent rapid population growth as it spread globally.

Blow flies as urban wildlife sensors.

Wildlife detection in urban areas is very challenging. Conventional monitoring techniques such as direct observation are faced with the limitation that urban wildlife is extremely elusive. It was recently shown that invertebrate-derived DNA (iDNA) can be used to assess wildlife diversity in tropical rainforests. Flies, which are ubiquitous and very abundant in most cities, may also be used to detect wildlife in urban areas. In urban ecosystems, however, overwhelming quantities of domestic mammal DNA could completely mask the presence of wild mammal DNA. To test whether urban wild mammals can be detected using fly iDNA, we performed DNA metabarcoding of pools of flies captured in Berlin, Germany, using three combinations of blocking primers. Our results show that domestic animal sequences are, as expected, very dominant in urban environments. Nevertheless, wild mammal sequences can often be retrieved, although they usually only represent a minor fraction of the sequence reads. Fly iDNA metabarcoding is therefore a viable approach for quick scans of urban wildlife diversity. Interestingly, our study also shows that blocking primers can interact with each other in ways that affect the outcome of metabarcoding. We conclude that the use of complex combinations of blocking primers, although potentially powerful, should be carefully planned when designing experiments.

Seasonal and inter-annual variation of malaria parasite detection in wild chimpanzees.

BACKGROUND: Cross-sectional surveys of chimpanzee (Pan troglodytes) communities across sub-Saharan Africa show large geographical variation in malaria parasite (Plasmodium spp.) prevalence. The drivers leading to this apparent spatial heterogeneity may also be temporally dynamic but data on prevalence variation over time are missing for wild great apes. This study aims to fill this fundamental gap. METHODS: Some 681 faecal samples were collected from 48 individuals of a group of habituated chimpanzees (Taï National Park, Côte d'Ivoire) across four non-consecutive sampling periods between 2005 and 2015. RESULTS: Overall, 89 samples (13%) were PCR-positive for malaria parasite DNA. The proportion of positive samples ranged from 0 to 43% per month and 4 to 27% per sampling period. Generalized Linear Mixed Models detected significant seasonal and inter-annual variation, with seasonal increases during the wet seasons and apparently stochastic inter-annual variation. Younger individuals were also significantly more likely to test positive. CONCLUSIONS: These results highlight strong temporal fluctuations of malaria parasite detection rates in wild chimpanzees. They suggest that the identification of other drivers of malaria parasite prevalence will require longitudinal approaches and caution against purely cross-sectional studies, which may oversimplify the dynamics of this host-parasite system.

Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest.

Anthrax is a globally important animal disease and zoonosis. Despite this, our current knowledge of anthrax ecology is largely limited to arid ecosystems, where outbreaks are most commonly reported. Here we show that the dynamics of an anthrax-causing agent, Bacillus cereus biovar anthracis, in a tropical rainforest have severe consequences for local wildlife communities. Using data and samples collected over three decades, we show that rainforest anthrax is a persistent and widespread cause of death for a broad range of mammalian hosts. We predict that this pathogen will accelerate the decline and possibly result in the extirpation of local chimpanzee (Pan troglodytes verus) populations. We present the epidemiology of a cryptic pathogen and show that its presence has important implications for conservation.

Unique human immune signature of Ebola virus disease in Guinea.

Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.

Investigating the zoonotic origin of the West African Ebola epidemic.

The severe Ebola virus disease epidemic occurring in West Africa stems from a single zoonotic transmission event to a 2-year-old boy in Meliandou, Guinea. We investigated the zoonotic origins of the epidemic using wildlife surveys, interviews, and molecular analyses of bat and environmental samples. We found no evidence for a concurrent outbreak in larger wildlife. Exposure to fruit bats is common in the region, but the index case may have been infected by playing in a hollow tree housing a colony of insectivorous free-tailed bats (Mops condylurus). Bats in this family have previously been discussed as potential sources for Ebola virus outbreaks, and experimental data have shown that this species can survive experimental infection. These analyses expand the range of possible Ebola virus sources to include insectivorous bats and reiterate the importance of broader sampling efforts for understanding Ebola virus ecology.