A Rare Modality of Concurrent Cryptococcal and Tubercular Meningitis in a Patient Living With HIV.

Patients with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) and a low CD4 count have decreased humoral and cellular immunity, predisposing them to opportunistic infections. Opportunistic infections are one of the main causes of morbidity and mortality in immunocompromised individuals due to impaired immune systems, particularly in persons living with HIV/AIDS. Common opportunistic infections in patients living with HIV include bacterial infections such as Mycobacterium tuberculosis and Mycobacterium avium complex (MAC); viral infections such as cytomegalovirus (CMV) and herpes simplex virus 1 (HSV-1); fungal infections such as Pneumocystis carinii pneumonia (PCP) and cryptococcal meningitis; and parasitic infections such as cryptosporidiosis and toxoplasmosis. Concurrent infection with cryptococcal and tubercular meningitis in patients with HIV is very rare. Here, we present the case of a 48-year-old male living with HIV who presented with complaints of breathlessness, fever, and weight loss and was evaluated and put on antitubercular medications for pulmonary tuberculosis. However, the presence of a continuous headache led us to investigate further. Upon brain imaging and cerebrospinal fluid evaluation, it was determined to be meningitis due to co-infection with Mycobacterium tuberculosis and Cryptococcus neoformans. The patient was treated with antitubercular therapy along with antifungal therapy. He is under regular follow-up without any further events.

Effectiveness of a serogroup B meningococcal vaccine against gonorrhea: A retrospective study.

BACKGROUND: Outer membrane vesicle (OMV) meningococcal serogroup B (MenB) vaccines might be protective against gonorrhea. We evaluated the effectiveness of MenB-4C, an OMV MenB vaccine, against gonorrhea. METHODS: We identified gonococcal mono-infections, chlamydial mono-infections, and gonococcal/chlamydial co-infections among persons aged 15-30 years in the electronic health records of Kaiser Permanente Northern California during 2016-2021. We determined MenB-4C vaccination status (vaccinated [≥1 MenB-4C vaccine dose] or unvaccinated [MenB-4C vaccine naïve]) at each infection. We used log-binomial regression with generalized estimating equations to calculate adjusted prevalence ratios (APR) and 95 % confidence intervals (CI) to determine if MenB-4C vaccination was protective against gonococcal mono-infections compared to chlamydial mono-infection. We also evaluated if MenB-4C vaccination was protective against gonococcal/chlamydial co-infections. Because of concerns with small sample size of vaccinated persons, we estimated effects using a limited model (adjusting for race/ethnicity only) and an expanded model (adjusting for additional potential confounders). RESULTS: Of 68,454 persons, we identified 558 (0.8 %) MenB-4C vaccinated persons and 85,393 infections (13,000 gonococcal mono-infections, 68,008 chlamydial mono-infections, and 4385 gonococcal/chlamydial co-infections). After adjusting for race/ethnicity, MenB-4C vaccination was 23 % protective against gonococcal mono-infection compared to chlamydial mono-infection (APR = 0.77, 95 % CI = 0.64-0.99) in the limited model but not in the expanded model. CONCLUSION: MenB-4C vaccination was protective against gonococcal mono-infection, independent of race/ethnicity. This protective effect was not observed when other potential confounders were included in the analysis. Protection against gonococcal/chlamydial co-infection was not observed. Efficacy data from clinical trials are needed.

Intragenomic diversity of the small subunit rDNA gene shows limited impact on the pathogenicity of Blastocystis infection in clinical patients.

The clinical significance of Blastocystis sp. remains to be fully elucidated. This study assesses whether Blastocystis subtype diversity can affect the outcome of the infection and the occurrence of clinical manifestations in infected individuals. Stool samples from 219 Blastocystis-positive patients by PCR targeting the ssu rDNA gene were fully genotyped by Sanger sequencing analyses. Co-infections by other parasitic, viral, and bacterial enteropathogens were identified by molecular and culture methods. Sequence analyses revealed the presence of six Blastocystis subtypes including ST1 (21.5%), ST2 (17.8%), ST3 (29.7%), ST4 (22.8%), ST6 (5.5%), and ST7 (2.3%), with a single sample harbouring a ST1+ST3 co-infection (0.5%). Multivariate risk factor analyses using logistic regression models indicated that neither Blastocystis subtypes nor patient-associated variables including sex, country of origin, travelling history, and presence of nonspecific symptoms were positively associated with a higher likelihood of developing gastrointestinal symptoms (abdominal pain and diarrhoea). However, being of a young age (p-value: 0.003) and experiencing skin pruritus (p-value < 0.001) and eosinophilia (p-value: 0.016) were found to increase the odds of presenting gastrointestinal symptoms. Blastocystis subtypes based on variability within the ssu rDNA gene do not seem to be the main drivers of clinical manifestations in the surveyed clinical population.

The evolution of envelope function during coinfection with phylogenetically distinct human immunodeficiency virus.

BACKGROUND: Coinfection with two phylogenetically distinct Human Immunodeficiency Virus-1 (HIV-1) variants might provide an opportunity for rapid viral expansion and the emergence of fit variants that drive disease progression. However, autologous neutralising immune responses are known to drive Envelope (Env) diversity which can either enhance replicative capacity, have no effect, or reduce viral fitness. This study investigated whether in vivo outgrowth of coinfecting variants was linked to pseudovirus and infectious molecular clones' infectivity to determine whether diversification resulted in more fit virus with the potential to increase disease progression. RESULTS: For most participants, emergent recombinants displaced the co-transmitted variants and comprised the major population at 52 weeks postinfection with significantly higher entry efficiency than other co-circulating viruses. Our findings suggest that recombination within gp41 might have enhanced Env fusogenicity which contributed to the increase in pseudovirus entry efficiency. Finally, there was a significant correlation between pseudovirus entry efficiency and CD4 + T cell count, suggesting that the enhanced replicative capacity of recombinant variants could result in more virulent viruses. CONCLUSION: Coinfection provides variants with the opportunity to undergo rapid recombination that results in more infectious virus. This highlights the importance of monitoring the replicative fitness of emergent viruses.

Co-infections and secondary infections amid COVID-19 outbreaks in Vietnam.

BACKGROUND: The mortality risk of co-infections/secondary infections (CoI/ScI) is under-reported in patients with non-critical COVID-19, leading to the under-management of CoI/ScI and publication bias in the medical literature. We aimed to investigate the association between CoI/ScI and mortality in patients hospitalised with mild-to-severe COVID-19. METHODS: We conducted a retrospective cohort study at a COVID-19 treatment hospital in Vietnam and collected all eligible medical records, with CoI/ScI status as the exposure (non-CoI/ScI and CoI/ScI, with the latter including nature of pathogen [bacterial, fungal, or bacterial + fungal] and multidrug-resistance pathogen [no MDRp or ≥ 1 MDRp]). The outcome was all-cause mortality, defined as in-hospital death by all causes or being discharged under critical illness. We used time-dependent analysis to report rates of mortality with 95% confidence intervals (95% CI, Poisson regression) and hazard ratios (HR) with 95% CI (Cox proportional hazards regression with Holm's method for multiplicity control). RESULTS: We followed 1466 patients (median age 61, 56.4% being female) for a median of 9 days. We recorded 387 (26.4%) deaths (95/144 [66.0%] in the CoI/ScI group and 292/1322 [22.1%] in the non-CoI/ScI group). Adjusted mortality rates (per 100 person-days) of the CoI/ScI (6.4, 95% CI 5.3 to 7.8), including bacterial (8.0, 95% CI 7.2 to 8.9), no MDRp (5.9, 95% CI 4.8 to 7.4), and ≥ 1 MDRp (9.0, 95% CI 8.2 to 10.0) groups were higher than that of the non-CoI/ScI group (2.0, 95% CI 1.8 to 2.2). These corresponded to higher risks of mortality in the overall CoI/ScI (HR 3.27, 95% CI 2.58 to 4.13, adjusted p < 0.001), bacterial CoI/ScI (HR 3.79, 95% CI 2.97 to 4.83, adjusted p < 0.001), no MDRp CoI/ScI (HR 3.13, 95% CI 2.42 to 4.05, adjusted p < 0.001), and ≥ 1 MDRp CoI/ScI group (HR 3.89, 95% CI 2.44 to 6.21, adjusted p < 0.001). We could not attain reliable estimates for fungal and bacterial + fungal CoI/ScI. CONCLUSION: Compared with the non-CoI/ScI group, patients with CoI/ScI had a significantly higher risk of all-cause mortality, regardless of resistance status. More evidence is needed to confirm the mortality risks in patients with fungal or bacterial + fungal CoI/ScI.

Impact of swine influenza A virus on porcine reproductive and respiratory syndrome virus infection in alveolar macrophages.

Porcine respiratory disease complex represents a major challenge for the swine industry, with swine influenza A virus (swIAV) and porcine reproductive and respiratory syndrome virus (PRRSV) being major contributors. Epidemiological studies have confirmed the co-circulation of these viruses in pig herds, making swIAV-PRRSV co-infections expected. A couple of in vivo co-infection studies have reported replication interferences between these two viruses. Herein, using a reductionist in vitro model, we investigated the potential mechanisms of these in vivo interferences. We first examined the impact of swIAV on porcine alveolar macrophages (AMs) and its effects on AMs co-infection by PRRSV. This was done either in monoculture or in co-culture with respiratory tracheal epithelial cells to represent the complexity of the interactions between the viruses and their respective target cells (epithelial cells for swIAV and AMs for PRRSV). AMs were obtained either from conventional or specific pathogen-free (SPF) pigs. SwIAV replication was abortive in AMs, inducing cell death at high multiplicity of infections. In AMs from three out of four conventional animals, swIAV showed no impact on PRRSV replication. However, inhibition of PRRSV multiplication was observed in AMs from one animal, accompanied by an early increase in the expression of interferon (IFN)-I and IFN-stimulated genes. In AMs from six SPF pigs, swIAV inhibited PRRSV replication in all animals, with an early induction of antiviral genes. Co-culture experiments involving tracheal epithelial cells and AMs from either SPF or conventional pigs all showed swIAV-induced inhibition of PRRSV replication, together with early induction of antiviral genes. These findings highlight the complex interactions between swIAV and PRRSV in porcine AMs, and would suggest a role of host factors, such as sanitary status, in modulating viral propagation. Our co-culture experiments demonstrated that swIAV inhibits PRRSV replication more effectively in the presence of respiratory tracheal epithelial cells, suggesting a synergistic antiviral response between AMs and epithelial cells, consistent with in vivo experiments.

Necrotizing pneumonia secondary to Influenza A (H1N1) coinfection with Staphylococcus aureus: A case report.

Objective: This study aims to enhance understanding of necrotizing pneumonia and toxic shock syndrome by analyzing an adult case of community-acquired necrotizing pneumonia caused by co-infection of Influenza A (H1N1) and Staphylococcus aureus with LukS-PV and LukF-PV virulence factor genes. Method: The clinical data of one patient admitted to the intensive care unit (ICU) with co-infection of Influenza A (H1N1) and Staphylococcus aureus was retrospectively analyzed. Results: The patient exhibited typical clinical manifestations of viral and Staphylococcus aureus co-infection, including necrotizing pneumonia and toxic shock syndrome. The presence of LukS-PV and LukF-PV virulence factor genes of Staphylococcus aureus was detected in the patient's bronchoalveolar lavage fluid. Unfortunately，although antiviral agents (oseltamivir) and antibiotics (linezolid, imipenem-cilastatin) were timely administrated, as well as corticosteroids for anti-inflammatory purposes, the patient's condition was progressively deteriorated and eventually led to death. Conclusion: Clinical practitioners should be vigilant about the co-infection of Influenza virus and Staphylococcus aureus, particularly when the latter carries virulence factors. The presence of virulence factor genes of Staphylococcus aureus can lead to necrotizing pneumonia with a poor prognosis. This is a particular concern because both infections can be life threatening in young adults.

A Case of Severe Adenovirus Infection with SARS-CoV-2 Co-infection.

A 34-year-old man with no medical history presented to our hospital with a sore throat and difficult oral intake for two days before admission. He had various symptoms, including red eyes, ocular discharge, a fever, and intraoral ulcers, and he was admitted immediately. The polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was positive, as was the adenovirus antigen test of the pharyngeal swab fluid, suggesting overlapping adenovirus and SARS-CoV-2 infections. The patient's condition improved with conservative treatment. This case of severe and varied symptoms caused by co-infection with adenovirus and SARS-CoV-2 has been previously reported.

Identification of concurrent infection with Jaagsiekte sheep retrovirus and maedi-visna virus in China.

IMPORTANCE: Ovine pulmonary adenomatosis (OPA) and maedi-visna disease (MVD) are chronic and progressive infectious diseases in sheep caused by Jaagsiekte sheep retrovirus (JSRV) and maedi-visna virus (MVV), respectively. OBJECTIVE: To investigate the pathological changes and conduct viral gene analysis of OPA and MVD co-occurrence in Inner Mongolia, China. METHODS: Using gross pathology, histopathology, immunohistochemistry, ultrastructural pathology, PCR, and sequence analysis, we investigated the concurrent infection of JSRV and MVV in 319 Dorper rams slaughtered in a private slaughterhouse in Inner Mongolia, in 2022. RESULTS: Of the 319 rams included, 3 showed concurrent JSRV and MVV infection. Gross lung pathology showed diffuse enlargement, consolidation, and greyish-white miliary nodules on the lung surface; the trachea was filled with a white foamy fluid; hilar and mediastinal lymph nodes were significantly enlarged. Histopathology results revealed typical OPA and MVD lesions in the lung tissue. Immunohistochemical results were positive for JSRV envelope protein (Env) in the tumor cells and MVV CA in alveolar macrophages. Transmission electron microscopy showed several virions and autophagosomes in the lung tissue, severely damaged mitochondria, and the induced mitophagy. Nucleotide sequences obtained for JSRV env and MVV gag showed the highest homology with the Inner Mongolian strains of JSRV env (JQ837489) and MVV gag (MW248464). CONCLUSIONS AND RELEVANCE: Our study confirmed that OPA and MVD co-occurrence and identified the pathological changes in Inner Mongolia, China, thereby providing references for the identification of concurrent JSRV and MVV infections.

Prevalence of co-infections with Ehrlichia spp. or Theileria spp. in dogs naturally infected with babesiosis in the Eastern Cape province.

BACKGROUND: Canine babesiosis and ehrlichiosis are tick-borne infections of great significance in South Africa. Theileriosis in dogs in South Africa is still poorly understood. Co-infection with multiple tick-borne diseases has been documented and is perceived as a common occurrence in South Africa. OBJECTIVES: The main objective of this study was to determine the prevalence of co-infections with Ehrlichia canis or Theileria equi in dogs with babesiosis in the Eastern Cape province. There is a lack of data on canine tick-borne disease distribution in this region. Possible associations of population characteristics and haematological and biochemistry measures with a co-infection of E. canis or T. equi in these dogs were also investigated. METHOD: The study population included 150 dogs naturally infected with babesiosis that presented to the Mdantsane State Veterinary Clinic between January 2021 and November 2021. Quantitative polymerase chain reaction was used to confirm the Babesia spp. that the dogs were infected with and to identify co-infections. Association with co-infection for the following parameters were evaluated: sex, breed, age, duration of illness, leukocyte count, band neutrophil count, monocyte count, platelet count, ARC, and serum globulin concentration. Positive and negative predictive values of monocytosis, leukopenia, band neutrophilia, thrombocytopenia, and non-regenerative absolute reticulocyte count for co-infection were also calculated. RESULTS: Babesia rossi was identified in 149/150 samples and B. vogeli in only 1/150 samples. A co-infection prevalence of 2.0% (3/149; 95% CI: 0.4-5.7) with B. rossi and E. canis was found. No other co-infections were reported. No investigated variables showed significant associations with co-infections. Monocytosis, in particular, was not associated with co-infection. CONCLUSION: Co-infection with other tick-borne diseases in dogs with babesiosis is uncommon in the Eastern Cape province. These findings raise the possibility that B. rossi may have a protective effect against other tick-borne diseases.

Clinical and pathogen features of COVID-19-associated infections during an Omicron strain outbreak in Guangzhou, China.

Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens. IMPORTANCE: Our study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.

Co-Infection with Nocardia Terpene and Pneumocystis Jirovecii in a Patient with Anti-Synthetase Syndrome: A Case Report.

Background: Pulmonary infection is a common clinical complication associated with glucocorticoid. There have been no reported cases of mixed infections involving Nocardia and Pneumocystis jirovecii combined with anti-synthetase syndrome (ASS) activity. Methods: This study conducted a retrospective analysis of the clinical data from a patient with active ASS, treated for a pulmonary coinfection. Results: The patient exhibited fever, asthma, and cough as initial symptoms. Chest CT scan revealed multiple infiltration shadows, consolidation shadows, nodules, mass shadows, and internal cavities in both lungs. BALF mNGS detected Nocardia terpene and Pneumocystis jiroveci. Treatment with sulfamethoxazole/trimethoprim and corticosteroids led to an improvement. However, the patient experienced recurrent fever and a new rash with the reduction of the glucocorticoid dosage. Further investigation identified positive anti-Jo-1 and anti-Ro-52 antibodies and myogenic lesions on electromyography, which confirmed the diagnosis of ASS. Following treatment with immunoglobulin, methylprednisolone, and cyclosporine, the patient's condition significantly improved. Conclusion: Immunodeficiency patients are susceptible to opportunistic infections. mNGS is valuable for diagnosis and treatment. Although the image of Nocardia terpene and Pneumocystis jiroveci infections lack specificity, they exhibit distinctive features. Should fever and skin lesions reoccur post-effective anti-infective therapy, it is imperative to explore non-infectious causes and expedite autoantibody testing.

Clinical Picture and Risk Factors for Severity of SARS-CoV-2 and Dengue Coinfection in Children: Experience From a Tertiary Hospital in Vietnam.

Introduction Dengue is an infectious disease that is a burden in Asia-Pacific and Latin America. The COVID-19 pandemic in dengue-endemic areas has caused a "double burden" because of the possibility of coinfection, especially in children who are vulnerable to both COVID-19 and dengue. This study aimed to describe the characteristics and identify risk factors for the severity of the coinfection in Vietnamese children. Methods This was a retrospective cohort study, undertaken at Children's Hospital 1 (Ho Chi Minh City, Vietnam) during the fourth wave of the COVID-19 pandemic. All children under 16 years old who were admitted to the hospital from April 27, 2021 to June 30, 2022, and diagnosed with SARS-CoV-2 and dengue coinfection were included. Results From April 2021 to June 2022, a total of 31 patients with the coinfection were included, with 19 of them being male (61.3%). The median age was 10.8 years old (IQR, 5.1-14.1). Fourteen children (45.2%) had preexisting comorbidities, with the most common comorbidity being overweight/obesity (ten children). Nearly two-thirds of the children were diagnosed with dengue without/with warning signs (61.3%) and were classified as having mild COVID-19 (83.9%). The most frequently observed clinical characteristics were fever (n=29, 93.6%), followed by abdominal pain, vomiting, and petechiae. All patients had high serum ferritin, and 83.9% presented with thrombocytopenia. None of the cases died. Overweight/obesity, abdominal pain, and petechiae were factors independently associated with severe disease. Conclusion Most of the children had mild COVID-19 and disease progression similar to patients with dengue alone. However, some children may have severe COVID-19 and dengue coinfection. Obesity, abdominal pain, and petechiae were identified as independent risk factors for disease severity in pediatric cases. Further studies with multicenters and a larger sample size are needed to assess the coinfection more thoroughly.

Prevalence of Co-infection of Culture-Proven Bacterial Pathogens in Microbiologically Confirmed Pulmonary Tuberculosis Patients From a Tertiary Care Center.

Tuberculosis (TB) is a chronic condition that weakens the immune system, causes structural changes in the lungs, and can lead to infections by other bacterial pathogens. Very few studies have been done to understand the magnitude of co-infection with other bacterial pathogens, so this study was conducted to understand the co-infection pattern and burden. A total of 174 microbiologically confirmed pulmonary TB patients' samples, identified by cartridge-based nucleic acid amplification test, were further tested for other bacterial pathogens by culture over a period of five months from May 2023 to September 2023. The isolates' identification and drug susceptibility were performed using the VITEK 2 system (bioMérieux, Marcy-l'Étoile, France). Of the 174 pulmonary samples tested, 19 samples grew a significant amount of other bacterial pathogens, making the prevalence 10.91% (19/174). Among the pulmonary samples tested, 54.59% were sputum, 38.5% were bronchoalveolar lavage, and 6.89% were endotracheal aspirate. Additionally, 70.11% of the patients tested were in the age group of 19-60 years. Of the patients who had co-infection, 94.73% (18/19) were male. The most common bacterial infection was caused by Pseudomonas aeruginosa, which was identified in 36.84% of the co-infection cases (7/19). This was followed by Acinetobacter baumannii in 31.57% (6/19), Klebsiella pneumoniae in 26.31% (5/19), and Stenotrophomonas maltophilia in 5.28% (1/19). Acinetobacter baumannii and Klebsiella pneumoniae showed high drug resistance, ranging from 60% to 100% against various groups of drugs tested. None of the patient samples with co-infection showed rifampicin resistance. Among all the samples with co-infection, the majority (42.10%, or 8/19) had a high load of Mycobacterium tuberculosis complex detected by CBNAAT Ultra (Cepheid, Sunnyvale, California). Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae are unusual pathogens causing infection in community patients and are known to cause illness in hospitalized patients. These organisms' resistance was also similar to the resistance shown by hospital-acquired infections. This indicates that bacterial co-infection in pulmonary TB patients will be similar to the pattern of hospital-acquired infections. The high prevalence of bacterial co-infections (10.91%) in patients with pulmonary TB poses a significant challenge as these bacterial pathogens are not susceptible to anti-tubercular drugs. Therefore, comprehensive screening for other bacterial infections in all pulmonary TB patients is crucial for effective treatment and outcomes.

Is the local environment more important than within-host interactions in determining coinfection?

Host populations often vary in the magnitude of coinfection they experience across environmental gradients. Furthermore, coinfection often occurs sequentially, with a second parasite infecting the host after the first has established a primary infection. Because the local environment and interactions between coinfecting parasites can both drive patterns of coinfection, it is important to disentangle the relative contributions of environmental factors and within-host interactions to patterns of coinfection. Here, we develop a conceptual framework and present an empirical case study to disentangle these facets of coinfection. Across multiple lakes, we surveyed populations of five damselfly (host) species and quantified primary parasitism by aquatic, ectoparasitic water mites and secondary parasitism by terrestrial, endoparasitic gregarines. We first asked if coinfection is predicted by abiotic and biotic factors within the local environment, finding that the probability of coinfection decreased for all host species as pH increased. We then asked if primary infection by aquatic water mites mediated the relationship between pH and secondary infection by terrestrial gregarines. Contrary to our expectations, we found no evidence for a water mite-mediated relationship between pH and gregarines. Instead, the intensity of gregarine infection correlated solely with the local environment, with the magnitude and direction of these relationships varying among environmental predictors. Our findings emphasize the role of the local environment in shaping infection dynamics that set the stage for coinfection. Although we did not detect within-host interactions, the approach herein can be applied to other systems to elucidate the nature of interactions between hosts and coinfecting parasites within complex ecological communities.

Identification of a novel recombinant polerovirus and other emergent viruses and tombusvirus-like associated RNA species associated with carrot motley dwarf disease in the United States.

Carrot motley dwarf (CMD) is a viral disease complex caused by co-infection of the polerovirus carrot red leaf virus with the umbraviruses carrot mottle virus or carrot mottle mimic virus, and/or a tombusvirus like associated RNA (tlaRNA), which depend on co-infection with a helper polerovirus to gain aphid transmissibility. In 2020 and 2021 carrot samples from Washington, United States (U.S.), and parsley and cilantro samples from California, U.S., exhibiting typical symptoms of CMD were submitted for diagnosis. Initial RT-PCR diagnostic assays identified the typical CMD viruses in the carrot samples, however only the umbraviruses and tlaRNAs were detected in the parsley and cilantro samples; as such, these samples were retested with another RT-PCR assay for generic polerovirus detection. Unexpectedly, the poleroviruses Torilis crimson leaf virus (TorCLV) and fennel motley virus were identified. Subsequent RNA sequencing analysis was conducted to confirm these results and look for other emergent viruses. In addition to confirming the diagnostic results, the recently described polerovirus Foeniculum vulgare polerovirus, the umbraviruses Pastinaca umbravirus 1 and wild carrot mottle virus, and the tlaRNA Arracacha latent virus E associated RNA were identified, making this the first report of these viruses and tlaRNA in the U.S. Using phylogenetic and pairwise identity comparisons and RDP4 recombination analyses, we also identified a putative novel polerovirus, for which we propose the name parsley polerovirus, that appears to be a recombinant between carrot polerovirus 1, sharing 92% amino acid (aa) identity with the RNA dependent RNA polymerase in the 5' gene block, and TorCLV, sharing >98% aa identity with the capsid protein in the 3 gene block. This work adds to the growing list of polerovirus species exhibiting recombination between the 5' and 3' gene blocks, and highlights the unique, variable, and dynamic associations that can occur in polerovirus, umbravirus, and tlaRNA disease complexes.

No increased risk of tuberculosis-related immune reconstitution inflammatory syndrome with integrase inhibitor-based antiretroviral therapy in people with HIV with profound immunosuppression.

INTRODUCTION: The issue of whether integrase inhibitors (INSTIs) may confer a higher risk of paradoxical tuberculosis-related immune reconstitution inflammatory syndrome (TB-IRIS) compared with other classes of antiretroviral in people with HIV with a profound level of immunosuppression remains insufficiently explored. We aimed to assess whether such a higher risk exists by examining a cohort of patients with TB-HIV initiating antiretroviral therapy (ART) in Hong Kong. METHODS: This was a retrospective review of 133 patients registered in the TB-HIV Registry of the Department of Health during the period 2014-2021. RESULTS: Sixteen of 70 patients (22.9%; 95% confidence interval [CI] 13.0-32.7) and 14 of 63 patients (22.2%; 95% CI 12.0-32.5) from the INSTI and non-INSTI groups experienced TB-IRIS (p = 0.920). The median intervals between ART initiation and IRIS among patients from the two groups were similar (3 weeks [interquartile range IQR 2.0-7.8] vs. 4 weeks [IQR 2.0-5.1], p = 0.620). The proportion of patients requiring steroid therapy were similar, as were the hospitalization rates. There was no IRIS-related death in either group. The risk of TB-IRIS with INSTI versus non-INSTI was also similar in a stratified analysis in a subgroup of patients with a baseline CD4 count of <50 µL (10/33 [30.3%; 95% CI 14.6-46.0] vs. 10/22 [45.5%; 95% CI 24.7-66.3], p = 0.252) and another subgroup of patients with ART initiated within 4 weeks of anti-TB treatment (10/26 [38.5%; 95% CI 19.8-57.2] vs. 10/23 [43.5%; 95% CI 23.2-63.7], p = 0.721). CONCLUSION: Our cohort study did not offer support for an increased risk of TB-IRIS with INSTIs compared with non-INSTIs, even in severely immunocompromised people with HIV.

Burden of drug-resistant tuberculosis by the GeneXpert MTB/RIF assay and its clinico-epidemiological aspects at a tertiary care hospital in West Bengal.

Multidrug -resistant tuberculosis (MDRTB) is a serious threat to mankind. India has the highest number of MDRTB cases, although majority remain undiagnosed due to inadequate diagnostic infrastructure, leading to increased community transmission and mortality. This one-year observational retrospective study highlighted the effectiveness of the National Tuberculosis Elimination Program (NTEP) for prompt detection of drug-resistant TB by GeneXpert MTB/RIF assay and revealed its associated clinico-epidemiological factors. The overall detection rates of MTB and RRTB were 20.70 % and 20.86 % respectively. The pediatric population had 7.69 % rifampicin resistance, and HIV was strongly associated with the development of TB and RRTB (P < 0.01).

Concurrent Ascaris infection modulates host immunity resulting in impaired control of Salmonella infection in pigs.

Ascaris is one of the most widespread helminth infections, leading to chronic morbidity in humans and considerable economic losses in pig farming. In addition, pigs are an important reservoir for the zoonotic salmonellosis, where pigs can serve as asymptomatic carriers. Here, we investigated the impact of an ongoing Ascaris infection on the immune response to Salmonella in pigs. We observed higher bacterial burdens in experimentally coinfected pigs compared to pigs infected with Salmonella alone. The impaired control of Salmonella in the coinfected pigs was associated with repressed interferon gamma responses in the small intestine and with the alternative activation of gut macrophages evident in elevated CD206 expression. Ascaris single and coinfection were associated with a rise of CD4-CD8α+FoxP3+ Treg in the lymph nodes draining the small intestine and liver. In addition, macrophages from coinfected pigs showed enhanced susceptibility to Salmonella infection in vitro and the Salmonella-induced monocytosis and tumor necrosis factor alpha production by myeloid cells was repressed in pigs coinfected with Ascaris. Hence, our data indicate that acute Ascaris infection modulates different immune effector functions with important consequences for the control of tissue-invasive coinfecting pathogens.IMPORTANCEIn experimentally infected pigs, we show that an ongoing infection with the parasitic worm Ascaris suum modulates host immunity, and coinfected pigs have higher Salmonella burdens compared to pigs infected with Salmonella alone. Both infections are widespread in pig production and the prevalence of Salmonella is high in endemic regions of human Ascariasis, indicating that this is a clinically meaningful coinfection. We observed the type 2/regulatory immune response to be induced during an Ascaris infection correlates with increased susceptibility of pigs to the concurrent bacterial infection.

Humans seropositive for Trypanosoma cruzi co-infected with intestinal helminths have higher infectiousness, parasitaemia and Th2-type response in the Argentine Chaco.

BACKGROUND: The Gran Chaco ecoregion is a well-known hotspot of several neglected tropical diseases (NTDs) including Chagas disease, soil-transmitted helminthiasis and multiparasitic infections. Interspecific interactions between parasite species can modify host susceptibility, pathogenesis and transmissibility through immunomodulation. Our objective was to test the association between human co-infection with intestinal parasites and host parasitaemia, infectiousness to the vector and immunological profiles in Trypanosoma cruzi-seropositive individuals residing in an endemic region of the Argentine Chaco. METHODS: We conducted a cross-sectional serological survey for T. cruzi infection along with an intestinal parasite survey in two adjacent rural villages. Each participant was tested for T. cruzi and Strongyloides stercoralis infection by serodiagnosis, and by coprological tests for intestinal parasite detection. Trypanosoma cruzi bloodstream parasite load was determined by quantitative PCR (qPCR), host infectiousness by artificial xenodiagnosis and serum human cytokine levels by flow cytometry. RESULTS: The seroprevalence for T. cruzi was 16.1% and for S. stercoralis 11.5% (n = 87). We found 25.3% of patients with Enterobius vermicularis. The most frequent protozoan parasites were Blastocystis spp. (39.1%), Giardia lamblia (6.9%) and Cryptosporidium spp. (3.4%). Multiparasitism occurred in 36.8% of the examined patients. Co-infection ranged from 6.9% to 8.1% for T. cruzi-seropositive humans simultaneously infected with at least one protozoan or helminth species, respectively. The relative odds of being positive by qPCR or xenodiagnosis (i.e. infectious) of 28 T. cruzi-seropositive patients was eight times higher in people co-infected with at least one helminth species than in patients with no such co-infection. Trypanosoma cruzi parasite load and host infectiousness were positively associated with helminth co-infection in a multiple regression analysis. Interferon-gamma (IFN-γ) response, measured in relation to interleukin (IL)-4 among humans infected with T. cruzi only, was 1.5-fold higher than for T. cruzi-seropositive patients co-infected with helminths. The median concentration of IL-4 was significantly higher in T. cruzi-seropositive patients with a positive qPCR test than in qPCR-negative patients. CONCLUSIONS: Our results show a high level of multiparasitism and suggest that co-infection with intestinal helminths increased T. cruzi parasitaemia and upregulated the Th2-type response in the study patients.