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[Correspondence] Implementation of cholera RDTs: bridging laboratory precision and field reality

The comprehensive study by Javier Perez-Saez and colleagues, published in The Lancet Microbe, demonstrates a remarkable performance of cholera rapid diagnostic tests (RDTs) in Bangladesh, revealing 93·5% sensitivity and 97·3% specificity through rigorous Bayesian latent class analysis.1 The methodological advancement in accounting for imperfect reference standards represents a key contribution of the study, particularly considering the global rollout of 1·2 million RDTs across 14 high-risk countries initiated in 2024 under the Gavi diagnostic support programme.

[Correspondence] Revisiting quantitative PCR positivity thresholds to inform the development of shorter benznidazole regimens

We read with great interest the Article by James A Watson and colleagues published in The Lancet Microbe,1 who applied a hierarchical Bayesian model to individual patient data from the E1224 and BENDITA trials. This innovative pooled analysis showed that 4-week daily benznidazole regimens achieved cure rates approaching those of the 8-week standard—an important observation with implications for optimising future treatment strategies. However, the interpretation of the observation depends crucially on how quantitative PCR (qPCR) positivity is defined.

[Correspondence] Therapeutic potential of targeting ORF6 in persistent SARS-CoV-2 infections

In their study published in The Lancet Microbe, Mahan Ghafari and colleagues1 provide compelling evidence to suggest that ORF6 is under strong purifying selection during persistent SARS-CoV-2 infections, showing the lowest non-synonymous diversity and evolutionary rate among all viral genes. This remarkable conservation suggests that ORF6 could be an ideal target for novel antiviral therapies.

[Comment] Bridging microbial physiology and diagnostic interpretation in cholera surveillance

The Article by Javier Perez-Saez and colleagues,1 published in The Lancet Microbe provides a field-based reanalysis of cholera diagnostics performance based on the latent-class Bayesian model. The authors discovered that the CholKit rapid diagnostic test (RDT) possesses high sensitivity (93·5%) and specificity (97·3%). Conventional culture fails in comparison (73·7%), which is a substantial breakthrough in the assessment of diagnostics in endemic conditions. The study reported that younger age, previous exposure to antibiotics, and sampling delays significantly diminish culture sensitivity but do not affect the accuracy of RDTs, which also correlates with the multifaceted nature of host, microbial, and methodological influences on diagnostic outcomes.

[Comment] Genomics to function: integrating rapid metagenomics with quorum-sensing biosensing for precision infectious disease management

Microbial disease detection is central to addressing the global problem of antimicrobial resistance. We still depend on the gold standard microbial culturing technique to detect infection-causing pathogens. Rapid detection of pathogens helps to guide patient care with appropriate antibiotics and thereby minimises the risk of resistance development. In this regard, several techniques have been proposed for the effective detection of pathogens. The most recent addition is the technique proposed by Adela Alcolea-Medina and colleagues,1 published in 2025 in The Lancet Microbe, which emphasises the tremendous potential of rapid pan-microbial metagenomics for identifying broad-spectrum infections in the intensive care unit (ICU).

[Comment] Polio outbreaks due to vaccine-derived viruses demand a re-definition of vaccine safety

Vaccine safety is regarded as the absence of any serious adverse event following immunisation (sAEFI) in the vaccinated individual. The live oral poliovirus vaccine (OPV) causes an sAEFI—vaccine-associated paralytic polio (VAPP)—at a sufficiently low frequency (1 per 100 000 to 750 000 infants vaccinated with one or more doses), resulting in WHO declaring OPV to be safe for wide use.1,2 Thus, WHO, in effect, modified the standard definition of vaccine safety to be the absence of any sAEFI at an unacceptable frequency, thus introducing a subjective, arbitrary, element into the definition.

[Comment] Addressing methodological bias in phageome research to clarify bacteriophage diversity

Bacteriophages are the most abundant biological entities on Earth; however, their ecological and clinical relevance remains incompletely understood. The Article by Rachel M Wheatley and colleagues in The Lancet Microbe makes a crucial contribution to this field by evaluating whether changes in virome α or β diversity are associated with dysbiosis across multiple publicly available datasets.1 Their work advances the integration of viral ecology into studies of microbiome health and disease, offering valuable insights into how phageome diversity might serve as an indicator of microbial imbalance.

[Editorial] Action on infection needs grounding in the social sciences

In a Personal View, Claas Kirchhelle and colleagues argue for stronger involvement of social sciences in global frameworks for addressing the antimicrobial resistance (AMR) crisis. While not novel, it is a timely proposition, not only in the context of AMR, given the upcoming update of the WHO Global Action Plan (GAP) on AMR, but also as a reminder of the contributions social sciences can make in infectious disease control more broadly.

[Personal View] Whom tuberculosis tests detect and why it matters: implications for diagnostic algorithms

Tuberculosis encompasses a spectrum of characteristics—including bacillary burden, clinical severity, and access to care—that are relevant to clinical and epidemiological outcomes and the performance of diagnostic assays. The value of diagnostic assays depends not only on their numerical accuracy, which can vary substantially between populations, but also on which individuals with and without tuberculosis the assays identify. Moreover, detectable features of tuberculosis, such as pathogen burden or host responses, are often correlated, making it difficult to predict the accuracy and impact of diagnostic algorithms from the accuracies of individual component tests.

[Personal View] Fluorescent acid-fast stains for diagnosing mycobacteria and beyond: back to the future?

Acid-fast stains (AFS) remain indispensable in modern diagnostic microbiology; they are used for detecting mycobacteria (including Mycobacterium tuberculosis and Mycobacterium leprae), acid-fast parasites, and some acid-variable bacteria as well as in histopathology. Fluorescent AFS surpass brightfield AFS (Ziehl–Neelsen) in sensitivity, particularly when pathogen loads are low. However, latest evidence suggests that these stains target nucleic acids, whereas lipid-rich, intact cell walls merely prevent decolourisation; this evidence corrects the long-held assumption that AFS bind to mycolic acids.

[Articles] Fast-acting single-dose vesicular stomatitis virus-Sudan virus vaccine: a challenge study in macaques

We showed that a single dose of VSV-SUDV protected NHPs from lethal SUDV infection within 1 week. The fast-acting nature highlights VSV-SUDV as an ideal countermeasure for ring vaccination during outbreaks of Sudan virus disease pending further preclinical and clinical assessment. In contrast, VSV-EBOV provided no relevant protection against SUDV infection in NHPs, highlighting the need for species-specific filovirus vaccines.

[Articles] HIV drug resistance during antiretroviral therapy scale-up in Uganda, 2012–19: a population-based, longitudinal study

Despite rising NNRTI resistance among pretreatment people with HIV, overall population prevalence of pretreatment HIV drug-resistant viraemia decreased due to increasing ART uptake and viral suppression. This finding underscores the crucial role of achieving and maintaining high ART coverage in reducing transmission of drug-resistant HIV. The high prevalence of mutations conferring resistance to components of first-line ART regimens among viraemic people with HIV is potentially concerning.

[Articles] Evaluation of bacteriophages as a signature of microbiome health: a systematic review and meta-analysis

Overall, although specific viral signatures of dysbiosis are likely to be highly disease-specific and condition-specific, we show that existing ecological theory shows promise in predicting the relationship between bacterial and phage diversity and in providing broad signatures of dysbiosis across disease systems. Our observation that the relationship between bacterial and phage diversity breaks down under disturbance suggests that this feature could be a useful signature of dysbiosis and that future studies incorporating the virome could provide opportunity to diagnose, treat, and better understand the causes of microbiome disturbance.

[Articles] Evaluating 12 automated, whole-genome sequencing analysis pipelines for Mycobacterium tuberculosis complex: a comparative study

Numerous automated analysis pipelines capable of enhancing equity in M tuberculosis WGS are available. Given the overall similarities between the pipelines evaluated in this study in terms of gDST performance, lineage classification, and genomic relatedness inference, non-functional attributes such as availability, accessibility, scalability, and privacy could represent the point of difference for prospective users in LMICs with a high burden of tuberculosis.

[Articles] Effect of decreasing the frequency of screening for Neisseria gonorrhoeae and Chlamydia trachomatis on the incidence of these infections and antimicrobial use among men who have sex with men using HIV PrEP in Belgium: a retrospective cohort study

The incidence of symptomatic N gonorrhoeae and C trachomatis infections did not increase over time despite less frequent screening and antimicrobial prescriptions decreased. Our findings contribute to the evidence supporting the potential of reducing the frequency of screening as an antimicrobial stewardship intervention among MSM using PrEP. Future studies are needed to confirm our findings.