Presence of phage-plasmids in multiple serovars of Salmonella enterica.

Evidence is accumulating in the literature that the horizontal spread of antimicrobial resistance (AMR) genes mediated by bacteriophages and bacteriophage-like plasmid (phage-plasmid) elements is much more common than previously envisioned. For instance, we recently identified and characterized a circular P1-like phage-plasmid harbouring a bla CTX-M-15 gene conferring extended-spectrum beta-lactamase (ESBL) resistance in Salmonella enterica serovar Typhi. As the prevalence and epidemiological relevance of such mechanisms has never been systematically assessed in Enterobacterales, in this study we carried out a follow-up retrospective analysis of UK Salmonella isolates previously sequenced as part of routine surveillance protocols between 2016 and 2021. Using a high-throughput bioinformatics pipeline we screened 47 784 isolates for the presence of the P1 lytic replication gene repL, identifying 226 positive isolates from 25 serovars and demonstrating that phage-plasmid elements are more frequent than previously thought. The affinity for phage-plasmids appears highly serovar-dependent, with several serovars being more likely hosts than others; most of the positive isolates (170/226) belonged to S. Typhimurium ST34 and ST19. The phage-plasmids ranged between 85.8 and 98.2 kb in size, with an average length of 92.1 kb; detailed analysis indicated a high amount of diversity in gene content and genomic architecture. In total, 132 phage-plasmids had the p0111 plasmid replication type, and 94 the IncY type; phylogenetic analysis indicated that both horizontal and vertical gene transmission mechanisms are likely to be involved in phage-plasmid propagation. Finally, phage-plasmids were present in isolates that were resistant and non-resistant to antimicrobials. In addition to providing a first comprehensive view of the presence of phage-plasmids in Salmonella, our work highlights the need for a better surveillance and understanding of phage-plasmids as AMR carriers, especially through their characterization with long-read sequencing.

Identification of benzothiazole derived monosaccharides as potent, selective, and orally bioavailable inhibitors of human and mouse galectin-3; a rare example of using a S···O binding interaction for drug design.

As a result of our continued efforts to pursue Gal-3 inhibitors that could be used to fully evaluate the potential of Gal-3 as a therapeutic target, two novel series of benzothiazole derived monosaccharides as potent (against both human and mouse Gal-3) and orally bioavailable Gal-3 inhibitors, represented by 4 and 5, respectively, were identified. These discoveries were made based on proposals that the benzothiazole sulfur atom could interact with the carbonyl oxygen of G182/G196 in h/mGal-3, and that the anomeric triazole moiety could be modified into an N-methyl carboxamide functionality. The interaction between the benzothiazole sulfur and the carbonyl oxygen of G196 in mGal-3 was confirmed by an X-ray co-crystal structure of early lead 9, providing a rare example of using a S···O binding interaction for drug design. It was found that for both the series, methylation of 3-OH in the monosaccharides caused no loss in h & mGal-3 potencies but significantly improved permeability of the molecules.

A report of a prospective randomized trial of extended-release tacrolimus versus immediate release tacrolimus after liver transplantation with anti-thymocyte induction in a steroid free protocol.

PURPOSE: Our study hypothesis was that once daily dosing of extended-release tacrolimus (XRT) would be a safe and effective immunosuppression (IS) with the potential to decrease adverse events (AEs) associated with immediate release tacrolimus (IRT) after liver transplantation (LT). METHODS: All patients receiving LT at our center received rabbit anti-thymocyte globulin (RATG) induction therapy. Eligible patients were randomized in a 1:1 fashion to receive either XRT or IRT. Antimicrobial prophylaxis was the same between arms, and both groups received an antimetabolite for the first 6 months following LT. Patients were then followed at pre-determined study intervals for the following year after LT. We administered the RAND-36SF survey to assess patient's health-related quality of life at pre-determined intervals. All analysis was performed with an intention to treat basis. RESULTS: We screened 194 consecutive patients and enrolled 110. Our control and study arms were well matched. Transplant characteristics were similar between groups. At all timepoints, both arms had similar serum creatinine and estimated glomerular filtration rate (eGFR), calculated by MDRD6 equation, with post-transplant GFRs between 60 and 70 mL/min/1.73 m2 . Tacrolimus trough levels were similar between arms. The XRT arm had fewer AEs (166) and fewer serious AEs (70) compared to IRT (201 and 99, respectively). AEs most commonly were renal, infectious, or gastrointestinal in nature. While not statistically significant, XRT was held temporarily (25 vs. 35 cases) or discontinued (3 vs. 11 cases) less frequently than IRT and had fewer instances of rejection (7 vs. 12 cases). CONCLUSION: This analysis showed that XRT is safe and effective as de novo maintenance IS in a steroid-free protocol with RATG.

Environmental Surveillance for Salmonella Typhi and its Association With Typhoid Fever Incidence in India and Malawi.

BACKGROUND: Environmental surveillance (ES) for Salmonella Typhi potentially offers a low-cost tool to identify communities with a high burden of typhoid fever. METHODS: We developed standardized protocols for typhoid ES, including sampling site selection, validation, characterization; grab or trap sample collection, concentration; and quantitative PCR targeting Salmonella genes (ttr, staG, and tviB) and a marker of human fecal contamination (HF183). ES was implemented over 12 months in a historically high typhoid fever incidence setting (Vellore, India) and a lower incidence setting (Blantyre, Malawi) during 2021-2022. RESULTS: S. Typhi prevalence in ES samples was higher in Vellore compared with Blantyre; 39/520 (7.5%; 95% confidence interval [CI], 4.4%-12.4%) vs 11/533 (2.1%; 95% CI, 1.1%-4.0%) in grab and 79/517 (15.3%; 95% CI, 9.8%-23.0%) vs 23/594 (3.9%; 95% CI, 1.9%-7.9%) in trap samples. Detection was clustered by ES site and correlated with site catchment population in Vellore but not Blantyre. Incidence of culture-confirmed typhoid in local hospitals was low during the study and zero some months in Vellore despite S. Typhi detection in ES. CONCLUSIONS: ES describes the prevalence and distribution of S. Typhi even in the absence of typhoid cases and could inform vaccine introduction. Expanded implementation and comparison with clinical and serological surveillance will further establish its public health utility.

Surveillance of antimicrobial resistant Shiga toxin-producing E. coli O157:H7 in England, 2016-2020.

OBJECTIVES: Shiga toxin-producing Escherichia coli (STEC) O157:H7 are zoonotic pathogens and transmission to humans occurs via contaminated food or contact with infected animals. The aim of this study was to describe the frequency, and distribution across the phylogeny, of antimicrobial resistance (AMR) determinants in STEC O157:H7 isolated from human cases in England. METHODS: Short-read whole-genome sequencing data from 1473 isolates of STEC O157:H7 from all seven sub-lineages (Ia-Ic, IIa-IIc and I/II) were mapped to genes known to confer phenotypic resistance to 10 different classes of antibiotic. Long-read sequencing was used to determine the location and genomic architecture of the AMR determinants within phylogenetic clusters exhibiting multidrug resistance. RESULTS: Overall, 216/1473 (14.7%) isolates had at least one AMR determinant, although the proportion of isolates exhibiting AMR varied by sub-lineage. The highest proportion of AMR determinants were detected in sub-lineages Ib (28/64, 43.7%), I/II (18/51, 35.3%) and IIc (122/440, 27.7%). In all sub-lineages, the most commonly detected AMR determinants conferred resistance to the aminoglycosides, tetracyclines and sulphonamides, while AMR determinants conferring resistance to fluroquinolones, macrolides and third-generation cephalosporins were rarely detected. Long-read sequencing analysis showed that the AMR determinants were co-located on the chromosome in sub-lineages Ib and lineage I/II, whereas those associated with sub-lineage IIc were encoded on the chromosome and/or large plasmids. CONCLUSIONS: AMR genes were unevenly distributed across the different sub-lineages of STEC O157:H7 and between different clades within the same sub-lineage. Long-read sequencing facilitates tracking the transmission of AMR at the pathogen and mobile genetic element level.

A global genomic analysis of Salmonella Concord reveals lineages with high antimicrobial resistance in Ethiopia.

Antimicrobial resistant Salmonella enterica serovar Concord (S. Concord) is known to cause severe gastrointestinal and bloodstream infections in patients from Ethiopia and Ethiopian adoptees, and occasional records exist of S. Concord linked to other countries. The evolution and geographical distribution of S. Concord remained unclear. Here, we provide a genomic overview of the population structure and antimicrobial resistance (AMR) of S. Concord by analysing genomes from 284 historical and contemporary isolates obtained between 1944 and 2022 across the globe. We demonstrate that S. Concord is a polyphyletic serovar distributed among three Salmonella super-lineages. Super-lineage A is composed of eight S. Concord lineages, of which four are associated with multiple countries and low levels of AMR. Other lineages are restricted to Ethiopia and horizontally acquired resistance to most antimicrobials used for treating invasive Salmonella infections in low- and middle-income countries. By reconstructing complete genomes for 10 representative strains, we demonstrate the presence of AMR markers integrated in structurally diverse IncHI2 and IncA/C2 plasmids, and/or the chromosome. Molecular surveillance of pathogens such as S. Concord supports the understanding of AMR and the multi-sector response to the global AMR threat. This study provides a comprehensive baseline data set essential for future molecular surveillance.

Ceftriaxone resistant Salmonella enterica serovar Paratyphi A identified in a case of enteric fever: first case report from Pakistan.

BACKGROUND: Enteric fever is an acute systemic infectious disease associated with substantial morbidity and mortality in low- and middle-income countries (LMIC), with a global burden of 14.3 million cases. Cases of enteric fever or paratyphoid fever, caused by Salmonella enterica serovar Paratyphi A (S. Para A) have been found to rise in many endemic and non-endemic countries. Drug resistance is relatively uncommon in S. Para A. Here we report a case of paratyphoid fever caused by ceftriaxone resistant S. Para A from Pakistan. CASE PRESENTATION: A 29-year-old female presented with a history of fever, headache, and shivering. Her blood culture revealed a S. Para A isolate (S7), which was resistant to ceftriaxone, cefixime, ampicillin and ciprofloxacin. She was prescribed oral Azithromycin for 10 days, which resulted in resolution of her symptoms. Two other isolates of S. Para A (S1 and S4), resistant to fluoroquinolone were also selected for comparison. DST and whole genome sequencing was performed for all three isolates. Sequence analysis was performed for identification of drug resistance and phylogeny. Whole Genome Sequencing (WGS) of S7 revealed the presence of plasmids, IncX4 and IncFIB(K). blaCTX-M-15 and qnrS1 genes were found on IncFIB(K). The gyrA S83F mutation conferring fluoroquinolone resistance was also found present. Multi-locus sequence typing (MLST) showed the S7 isolate to belong to ST129. S1 and S4 had the gyrA S83Y and S83F mutations respectively. CONCLUSIONS: We highlight the occurrence of plasmid-mediated ceftriaxone resistant strain of S. Para A. This is of significance as ceftriaxone is commonly used to treat paratyphoid fever and resistance in S. Para A is not known. Continuous epidemiological surveillance is required to monitor the transmission and spread of antimicrobial resistance (AMR) among Typhoidal Salmonellae. This will guide treatment options and preventive measures including the need for vaccination against S. Para A in the region.

Longitudinal comparisons of mental health, burnout and well-being in patient-facing, non-patient-facing healthcare professionals and non-healthcare professionals during the COVID-19 pandemic: findings from the CoPE-HCP study.

BACKGROUND: The COVID-19 pandemic may disproportionately affect the mental health of healthcare professionals (HCPs), especially patient-facing HCPs. AIMS: To longitudinally examine mental health in HCPs versus non-HCPs, and patient-facing HCPs versus non-patient-facing HCPs. METHOD: Online surveys were distributed to a cohort at three phases (baseline, July to September 2020; phase 2, 6 weeks post-baseline; phase 3, 4 months post-baseline). Each survey contained validated assessments for depression, anxiety, insomnia, burnout and well-being. For each outcome, we conducted mixed-effects logistic regression models (adjusted for a priori confounders) comparing the risk in different groups at each phase. RESULTS: A total of 1574 HCPs and 147 non-HCPs completed the baseline survey. Although there were generally higher rates of various probable mental health issues among HCPs versus non-HCPs at each phase, there was no significant difference, except that HCPs had 2.5-fold increased risk of burnout at phase 2 (emotional exhaustion: odds ratio 2.50, 95% CI 1.15-5.46, P = 0.021), which increased at phase 3 (emotional exhaustion: odds ratio 3.32, 95% CI 1.40-7.87, P = 0.006; depersonalisation: odds ratio 3.29, 95% CI 1.12-9.71, P = 0.031). At baseline, patient-facing HCPs (versus non-patient-facing HCPs) had a five-fold increased risk of depersonalisation (odds ratio 5.02, 95% CI 1.65-15.26, P = 0.004), with no significant difference in the risk for other outcomes. The difference in depersonalisation reduced over time, but patient-facing HCPs still had a 2.7-fold increased risk of emotional exhaustion (odds ratio 2.74, 95% CI 1.28-5.85, P = 0.009) by phase 3. CONCLUSIONS: The COVID-19 pandemic had a huge impact on the mental health and well-being of both HCPs and non-HCPs, but there is disproportionately higher burnout among HCPs, particularly patient-facing HCPs.

Identification of Monosaccharide Derivatives as Potent, Selective, and Orally Bioavailable Inhibitors of Human and Mouse Galectin-3.

Galectin-3 (Gal-3), a member of the ß-galactoside-binding protein family, is implicated in a wide variety of human diseases. Identification of Gal-3 inhibitors with the right combination of potency (against both human and mouse Gal-3) and pharmacokinetic properties to fully evaluate the potential of Gal-3 for therapeutic intervention has been a major challenge due to the characteristics of its binding pocket: high hydrophilicity and key structural differences between human Gal-3 and the mouse ortholog. We report the discovery of a novel series of monosaccharide-based, highly potent, and orally bioavailable inhibitors of human and mouse Gal-3. The novel monosaccharide derivatives proved to be selective for Gal-3, the only member of the chimeric type of galectins, over Gal-1 and Gal-9, representative of the prototype and tandem-repeat type of galectins, respectively. The proposed binding mode for the newly identified ligands was confirmed by an X-ray cocrystal structure of a representative analogue bound to Gal-3 protein.

Liver Outcome in Renal Transplant Recipients Who Acquired Hepatitis C Infection From an Infected Graft: Study Based on Liver Biopsy Findings.

Long-term liver outcome in hepatitis C virus (HCV)-negative kidney recipients who acquired HCV infection from viremic donors is of intense interest in the transplant community. We evaluated the incidence of fibrosis in liver biopsy specimens of recipients who were transplanted with HCV-infected grafts. Methods: Patients were evaluated in the hepatology clinic, and 29 patients agreed to undergo liver biopsy. The liver histology was scored by the meta-analysis of histological data in viral hepatitis scoring system and was assessed by hepatopathologists. The fibrosis score was compared between patients who initiated direct-acting antiviral (DAA) within 6 wk (n = 6) and after 6 wk (n = 29). Results: Eighty-nine aviremic patients were transplanted with HCV-infected grafts between March 2018 and October 2019. All patients developed HCV infection and were treated with DAA treatment after kidney transplantation (median, 70 d; interquartile range, 55-85 d). All patients (n = 89) achieved sustained virologic response with DAA. The median follow-up time from kidney transplant to liver biopsy was 28 mo (interquartile range, 26-30 mo). Twenty-five patients (86%) had F0, and 4 patients (14%) had F1 fibrosis. No patient had advanced fibrosis (F3-F4). Grade 1 inflammation was present in 6 (21%) patients, whereas 26 (90%) patients had iron accumulation in the hepatocytes and reticuloendothelial cells. There was no difference in the fibrosis score between patients who received treatment within 6 wk versus after 6 wk (P = 0.55). Conclusions: Kidney transplantation of HCV-infected graft to HCV-negative recipients is safe and has no long-term liver-related complications with successful eradication of HCV. In our cohort, delayed treatment did not affect sustained virologic response or liver histology.

Phenotypic and molecular characterization of blaCTX-M-3 and blaCTX-M-55-producing monophasic Salmonella enterica serovar Typhimurium in Greece.

OBJECTIVES: To characterize three Salmonella enterica serovar Typhimurium strains using whole genome sequencing (WGS) and conventional methods. The isolates were recovered from three pediatric patients in Greece as part of the hospital's epidemiological surveillance system during 2016 to 2018. METHODS: Bacterial identification and antimicrobial susceptibility testing was performed using the VITEK 2 automated system, disc diffusion test, and MIC gradient test while serotyping by the slide agglutination method. Detection of resistance genes, eBurst groups (eBG), assignment to sequence types, single nucleotide polymorphism (SNP) typing, location and characterization of drug resistance regions, and in silico plasmid detection were carried out using WGS. RESULTS: All strains were identified as S. Typhimurium-monophasic, ST34, eBG1 with antigenic formula 1,4, [5], 12:i:-. They were phenotypically resistant to most antibiotics tested except piperacillin/tazobactam, imipenem, and co-trimoxazole. WGS revealed the chromosomally located genes encoding the ASSuT (ampicillin, streptomycin, sulfonamides, and tetracycline) resistant pattern in all three strains. WGS revealed extended spectrum ß-lactamase (ESBL) production in all three strains, the presence of blaCTX-M-3 on an IncI1 plasmid in two strains isolated in 2018, and the chromosomally encoded blaCTX-M-55 plus qnrS1 (resistance to ciprofloxacin) in the strain isolated in 2016. The two strains from 2018 were isolated from the same hospital ward and were genetically related. CONCLUSIONS: The emergence of ESBL among S. 1,4,[5], 12:i:- is worrisome due to its increasing antimicrobial resistance phenotype, making clinical treatment difficult. WGS provides an alternative to traditional methods of identification and genomic characterisation of strains, and serves to better understand their epidemiological dynamics and bacterial pathogenesis.

Use of Nanopore Sequencing to Characterise the Genomic Architecture of Mobile Genetic Elements Encoding bla CTX-M-15 in Escherichia coli Causing Travellers' Diarrhoea.

Increasing levels of antimicrobial resistance (AMR) have been documented in Escherichia coli causing travellers' diarrhoea, particularly to the third-generation cephalosporins. Diarrhoeagenic E. coli (DEC) can act as a reservoir for the exchange of AMR genes between bacteria residing in the human gut, enabling them to survive and flourish through the selective pressures of antibiotic treatments. Using Oxford Nanopore Technology (ONT), we sequenced eight isolates of DEC from four patients' specimens who had all recently returned to the United Kingdome from Pakistan. Sequencing yielded two DEC harbouring bla CTX-M-15 per patient, all with different sequence types (ST) and belonging to five different pathotypes. The study aimed to determine whether bla CTX-M-15 was located on the chromosome or plasmid and to characterise the drug-resistant regions to better understand the mechanisms of onward transmission of AMR determinants. Patients A and C both had one isolate where bla CTX-M-15 was located on the plasmid (899037 & 623213, respectively) and one chromosomally encoded (899091 & 623214, respectively). In patient B, bla CTX-M-15 was plasmid-encoded in both DEC isolates (786605 & 7883090), whereas in patient D, bla CTX-M-15 was located on the chromosome in both DEC isolates (542093 & 542099). The two bla CTX-M-15-encoding plasmids associated with patient B were different although the bla CTX-M-15-encoding plasmid isolated from 788309 (IncFIB) exhibited high nucleotide similarity to the bla CTX-M-15-encoding plasmid isolated from 899037 (patient A). In the four isolates where bla CTX-M-15 was chromosomally encoded, two isolates (899091 & 542099) shared the same insertion site. The bla CTX-M-15 insertion site in isolate 623214 was described previously, whereas that of isolate 542093 was unique to this study. Analysis of Nanopore sequencing data enables us to characterise the genomic architecture of mobile genetic elements encoding AMR determinants. These data may contribute to a better understanding of persistence and onward transmission of AMR determinants in multidrug-resistant (MDR) E. coli causing gastrointestinal and extra-intestinal infections.

Optimized methods for detecting Salmonella Typhi in the environment using validated field sampling, culture and confirmatory molecular approaches.

AIMS: This study evaluated detection methods for Salmonella Typhi (S. Typhi) in the environment, to establish a novel pathway from field sampling to isolation of viable organisms and molecular confirmation from complex environmental samples, thus enabling environmental surveillance of typhoid. METHODS AND RESULTS: Multiple media were assessed using clinical isolates from the Public Health England's (PHE) Culture collection. The culture pathway selected consisted of a primary 2% bile broth and secondary Selenite F broth, followed by modified Chromogenic Agar for Salmonella Esterase (mCASE). A qPCR assay was adapted from a validated S. Typhi PCR panel for confirmation of isolates, with comparison to biochemical and serological tests showing good specificity. Sampling locations in Blantyre, Malawi were used to compare sampling methods. Viable S. Typhi were isolated from a mixture of trap and grab river water samples on six occasions. CONCLUSIONS: Culture of viable S. Typhi from environmental samples was possible using effective capture and culture techniques. SIGNIFICANCE AND IMPACT OF STUDY: Whilst several studies have attempted to detect S. Typhi from the environment, this is the first successful attempt to isolate the organism from river water since the 1980s. Supplementing clinical data with environmental screening offers the potential for enhanced surveillance, which might inform interventions and assess vaccination programmes.

Characterization of a P1-bacteriophage-like plasmid (phage-plasmid) harbouring bla CTX-M-15 in Salmonella enterica serovar Typhi.

Antimicrobial-resistance (AMR) genes can be transferred between microbial cells via horizontal gene transfer (HGT), which involves mobile and integrative elements such as plasmids, bacteriophages, transposons, integrons and pathogenicity islands. Bacteriophages are found in abundance in the microbial world, but their role in virulence and AMR has not fully been elucidated in the Enterobacterales. With short-read sequencing paving the way to systematic high-throughput AMR gene detection, long-read sequencing technologies now enable us to establish how such genes are structurally connected into meaningful genomic units, raising questions about how they might cooperate to achieve their biological function. Here, we describe a novel ~98 kbp circular P1-bacteriophage-like plasmid termed ph681355 isolated from a clinical Salmonella enterica serovar Typhi isolate. It carries bla CTX-M-15, an IncY plasmid replicon (repY gene) and the ISEcP1 mobile element and is, to our knowledge, the first reported P1-bacteriophage-like plasmid (phage-plasmid) in S. enterica Typhi. We compared ph681355 to two previously described phage-plasmids, pSJ46 from S. enterica serovar Indiana and pMCR-1-P3 from Escherichia coli, and found high nucleotide similarity across the backbone. However, we saw low ph681355 backbone similarity to plasmid p60006 associated with the extensively drug-resistant S. enterica Typhi outbreak isolate in Pakistan, providing evidence of an alternative route for bla CTX-M-15 transmission. Our discovery highlights the importance of utilizing long-read sequencing in interrogating bacterial genomic architecture to fully understand AMR mechanisms and their clinical relevance. It also raises questions regarding how widespread bacteriophage-mediated HGT might be, suggesting that the resulting genomic plasticity might be higher than previously thought.

Phylogenomics and antimicrobial resistance of Salmonella Typhi and Paratyphi A, B and C in England, 2016-2019.

The emergence of antimicrobial resistance (AMR) to first- and second-line treatment regimens of enteric fever is a global public-health problem, and routine genomic surveillance to inform clinical and public-health management guidance is essential. Here, we present the prospective analysis of genomic data to monitor trends in incidence, AMR and travel, and assess hierarchical clustering (HierCC) methodology of 1742 isolates of typhoidal salmonellae. Trend analysis of Salmonella Typhi and S. Paratyphi A cases per year increased 48 and 17.3%, respectively, between 2016 and 2019 in England, mainly associated with travel to South Asia. S. Paratyphi B cases have remained stable and are mainly associated with travel to the Middle East and South America. There has been an increase in the number of S. Typhi exhibiting a multidrug-resistant (MDR) profile and the emergence of extensively drug resistant (XDR) profiles. HierCC was a robust method to categorize clonal groups into clades and clusters associated with travel and AMR profiles. The majority of cases that had XDR S. Typhi reported recent travel to Pakistan (94 %) and belonged to a subpopulation of the 4.3.1 (H58) clone (HC5_1452). The phenotypic and genotypic AMR results showed high concordance for S. Typhi and S. Paratyphi A, B and C, with 99.99 % concordance and only three (0.01 %) discordant results out of a possible 23 178 isolate/antibiotic combinations. Genomic surveillance of enteric fever has shown the recent emergence and increase of MDR and XDR S. Typhi strains, resulting in a review of clinical guidelines to improve management of imported infections.

Acute Hepatitis A Causing Severe Hemolysis and Renal Failure in Undiagnosed Glucose-6-Phosphate Dehydrogenase Deficient Patient: A Case Report and Review of the Literature.

Infection with hepatitis A virus is usually a self-limited illness that rarely results in fulminant liver failure. Severe hemolysis is an uncommon complication but has been reported in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Here, we report a case with undiagnosed G6PD deficiency who presented with hyperbilirubinemia, severe hemolysis, and acute renal failure precipitated by acute hepatitis A infection.