Nature Microbiology

The ongoing evolution of SARS-CoV-2, particularly through the emergence of new variants, continues to challenge our understanding of immune protection. While antibody levels correlate with protection against earlier variants like Alpha and Delta, their relationship with Omicron sub-variants remains unclear. To investigate the role of antibody levels and neutralizing activity in preventing breakthrough infections, we analyzed longitudinal SARS-CoV-2 humoral responses and neutralizing activity aga...

SARS-CoV-2 is spread through exhaled breath of infected individuals. A fundamental question in understanding transmission of SARS-CoV-2 is how much virus an individual is exhaling into the environment while they breathe, over the course of their infection. Research on viral load dynamics during COVID-19 infection has focused on internal swab specimens, which provide a measure of viral loads inside the respiratory tract, but not on breath. Therefore, the dynamics of viral shedding on exhaled brea...

BackgroundHow human-associated microbial communities resist and respond to perturbations remains incompletely understood. Viral challenge provides one opportunity to test how human microbiota respond to disturbance. MethodsUsing an experimental human rhinovirus infection challenge model, we explored how viral infection may alter microbiota of the upper respiratory tract (URT). Healthy human volunteers were inoculated with HRV serotype 39. Samples were collected by lavage before and after inocul...

The primary risk factor for infection with members of the Klebsiella pneumoniae species complex is prior gut colonization, and infection is often caused by the colonizing strain. Despite the importance of the gut as a reservoir for infectious Klebsiella, little is known about the association between the gut microbiome and infection. To explore this relationship, we undertook a case-control study comparing the gut community structure of Klebsiella-colonized intensive care and hematology/oncology ...

BackgroundClassified by the WHO as one of the 19 most dangerous fungal pathogens, Pneumocystis jirovecii has been associated with increasing outbreaks of Pneumocystis pneumonia (PCP) among solid organ transplant (SOT) recipients worldwide. Mycophenolic acid (MPA), an inosine monophosphate dehydrogenase (IMPDH) inhibitor commonly used as an immunosuppressant to prevent organ rejection, is a risk factor for PCP. However, MPA also displays antifungal activity, potentially protecting against PCP, de...

There is widespread interest in the capacity for SARS-CoV-2 evolution in the face of selective pressures from host immunity, either naturally acquired post-exposure or from vaccine acquired immunity. Allied to this is the potential for long perm persistent infections within immune compromised individuals to allow a broader range of viral evolution in the face of sub-optimal immune driven selective pressure. Here we report on an immunocompromised individual who is hypogammaglobulinaemic and was p...

Genomic pathogen surveillance is a powerful tool for public health and research, but is costly and unachievable in low-resource settings. Most sub-genomic typing methods sacrifice resolution whilst remaining costly. We developed "Phylo-Plex", a novel approach that identifies information-rich genomic regions to maximise phylogenetic information whilst minimising the number of regions. Applied to Treponema pallidum and Neisseria gonorrhoeae, we designed a high-resolution multiplex PCR sequencing s...

BackgroundThe continuing increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We conducted a multi-center, observational study to explore Treponema pallidum subsp. pallidum (TPA) molecular epidemiology essential for vaccine research by analyzing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data. MethodsWe enrolled patients with primary (PS), secondary (SS) or early latent (ELS)...

In early 2022, a cluster of Monkeypox (now termed MPOX) virus (MPXV) cases were identified within the UK with no prior travel history to MPXV-endemic regions, suggesting localised transmission of MPXV within the UK. Subsequently, cases were identified in several other non-endemic countries and currently exceed 80,000 worldwide, primarily affecting gay, bisexual, and other men who have sex with men. Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individual...

In Brazil, Leishmania braziliensis is the main causative agent of the neglected tropical disease, cutaneous leishmaniasis (CL). CL presents on a spectrum of disease severity with a high rate of treatment failure. Yet the parasite factors that contribute to disease presentation and treatment outcome are not well understood, in part because successfully isolating and culturing parasites from patient lesions remains a major technical challenge. Here we describe the development of selective whole ge...

The latest SARS-CoV-2 variant of concern Omicron, with its immune escape from therapeutic anti-Spike monoclonal antibodies and WA-1 vaccine-elicited sera, demonstrates the continued relevance of COVID- 19 convalescent plasma (CCP) therapies. Lessons learnt from previous usage of CCP suggests focusing on early outpatients and immunocompromised recipients, with high neutralizing antibody (nAb) titer units. In this analysis we systematically reviewed Omicron-neutralizing plasma activity data, and f...

Plasmodium vivax transmission occurs throughout the tropics and is an emerging threat in areas of Plasmodium falciparum decline, causing relapse infections that complicate treatment and control. Targeted sequencing for P. falciparum has been widely deployed to detect population structure and the geographic spread of antimalarial and diagnostic resistance. However, there are fewer such tools for P. vivax. Leveraging global variation data, we designed four molecular inversion probe (MIP) genotypin...

The Omicron era of the COVID-19 pandemic commenced at the beginning of 2022 and whilst it started with primarily BA.1, it was latter dominated by BA.2 and related sub-lineages. Over the course of 2022, we monitored the potency and breadth of antibody neutralization responses to many emerging variants at two levels: (i) we tracked over 420,000 U.S. plasma donors over time through various vaccine booster roll outs and Omicron waves using sequentially collected IgG pools; (ii) we mapped the antibod...

Nasally inoculated influenza cases reported milder symptoms and shed lower viral RNA load in exhaled breath aerosols (EBA) than people with classic influenza-like illness including fever, in a previous study. Whether nasally inoculated influenza is representative of mild natural influenza infection, the majority of natural infections, is unknown. Here, we extend our previous analyses to include a broader range of community-acquired influenza cases. Previously, we reported on two groups: (A) volu...

BackgroundThe rapid worldwide spread of the mildly pathogenic SARS-CoV-2 Omicron variant has led to the suggestion that it will induce levels of collective immunity that will help putting an end to the COVID19 pandemics. MethodsConvalescent serums from non-hospitalized individuals previously infected with Alpha, Delta or Omicron BA.1 SARS-CoV-2 or subjected to a full mRNA vaccine regimen were evaluated for their ability to neutralize a broad panel of SARS-CoV-2 variants. FindingsPrior vaccinat...

The recent discovery that mutations in the Plasmodium falciparum genome are overrepresented in infections of sickle haemoglobin (HbS)-carriers has highlighted new questions about the underlying biological and evolutionary interaction, yet the full extent of this association is unknown. By meta-analysing host and parasite data from N=6,289 infections, including 831 newly sequenced samples from The Gambia, we implicate several new parasite genome regions in the interaction, including within the CL...

BackgroundGut microbiota (GM) composition has been associated with acute Graft-versus-Host Disease (aGvHD), however, current knowledge is insufficient to target the GM. MethodsA relevant series of microbiome data sets were combined and reanalyzed, with resolution of species level changes in the GM. ResultsGM composition was found strongly correlated with aGvHD status after one month post stem cell infusion (R2=0.51). The predicted average biological safety level, indicative of antibiotic resis...

Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re-infection. Using sequential serum samples collected up to 94 days post onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversi...

Plasmodium vivax infections are characterised by recurrent bouts of blood-stage parasitaemia. Understanding the genetic relatedness of recurrences can help distinguish whether these are caused by relapse, reinfection, or recrudescence, which is critical to understand treatment efficacy and transmission dynamics. We developed PvAmpseq, an amplicon sequencing assay targeting 11 SNP-rich regions of the P. vivax genome. PvAmpSeq was applied to field isolates from a clinical trial in the Solomon Isla...

Hematologic side effects are associated with prolonged antibiotic exposure in up to 34% of patients. Neutropenia, reported in 10-15% of patients, increases the risk of sepsis and death. Murine studies have established a link between the intestinal microbiota and normal hematopoiesis. We sought to identify predisposing factors, presence of microbiota-derived metabolites, and changes in intestinal microbiota composition in otherwise healthy pediatric patients who developed neutropenia after prolon...