Clinical usefulness of metagenomic next-generation sequencing for the diagnosis of central nervous system infection in people living with HIV

Zhang, Renfang; Liu, Li; Qi, Tangkai; Wang, Zhenyan; Song, Wei; Tang, Yang; Sun, Jianjun; Liu, Danping; Lin, Yixiao; Xu, Shuibao; Yang, Junyang; Shen, Yinzhong; Lu, Hongzhou

doi:10.1016/j.ijid.2021.04.057

Cited by 16 publications

(24 citation statements)

References 31 publications

(33 reference statements)

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“…The culture method is often regarded as the gold standard of fungal infection, but most fungi should be cultured a relative long time, some of them even need a culture time as long as one month. The histopathological diagnosis is an invasive examination, whose sensitivity and specificity largely depend on the experience of pathologists, and there often exists a certain misdiagnosis rate[ 19 , 20 ]. This study showed that the positive rate of the fungal CNS infection detected by mNGS was 17/27(62.96%), while that of the conventional methods was only 12/17(44.4%).…”

Section: Discussionmentioning

confidence: 99%

Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases of the central nervous system after empirical treatment

Chen¹,

Guo²,

Xue³

et al. 2022

WJCC

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BACKGROUND The diagnostic value of metagenomic next-generation sequencing (mNGS) in central nervous system (CNS) infectious diseases after empirical treatment has not been reported. AIM To investigate the diagnostic value of mNGS of cerebrospinal fluid (CSF) in the empirically treated CNS infectious diseases. METHODS A total of 262 CSF samples from patients with suspected CNS infections were collected between August 2020 and December 2021. Both mNGS and conventional methods were used for testing. The conventional methods included microbial culture, smear, polymerase chain reaction, etc. RESULTS Among 262 suspected cases, 183 cases (69.84%) were diagnosed as CNS infection, including 86 cases of virus infection (47.00%), 70 cases of bacterial infection (38.25%) and 27 cases of fungal infection (14.76%). The sensitivity and specificity of mNGS were 65.6% (95%CI: 58.2%-72.3%) and 89.6% (95%CI: 79.1%-95.3%), respectively. The PPV of mNGS was 94.5% (95%CI: 88.6%-97.6%), and the NPV was 48.8% (95%CI: 39.7%–57.9%). The pathogen detective sensitivity and accuracy of mNGS were higher than those of conventional methods (Sensitivity: 65.6% vs 37.2%; P < 0.001; Accuracy: 72.0% vs 50%, P < 0.001). The results showed that compared with conventional methods, mNGS technology was a more sensitive method for the diagnosis of CNS infection after empirical treatment. CONCLUSION mNGS can be a better method applied in the diagnosis of CNS infection after empirical treatment.

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Section: Discussionmentioning

confidence: 99%

Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases of the central nervous system after empirical treatment

Chen¹,

Guo²,

Xue³

et al. 2022

WJCC

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“…Previous study showed that multiple pathogens were identified by NGS in CSF from more than 15.9% (14/88) of HIV-infected patients who were suspected to have CNS infection with negative result by conventional tests. This indicated that multipathogenic CNS infections are not uncommon in people living with HIV and NGS is capable to identify multiple pathogens in a single test in an unbiased manner (1). Although there is one previous report about the application of NGS in the identification of streptococcus suis septicemia in a patient whose blood bacterial cultures results were negative (14), its application in diagnosing streptococcus suis meningitis in HIV-infected patients with cryptococcal meningitis history has never been addressed until now.…”

Section: Discussionmentioning

confidence: 99%

“…Compared to patients with monomicrobial meningitis, patients infected with multiple types of meningitis are more difficult to be diagnosed (1). However, a fast and accurate diagnosis of the pathogens causing the meningitis is challenging because of the limitations of current conventional tests (2).…”

Section: Introductionmentioning

confidence: 99%

Case Report: Streptococcus Suis Meningitis Diagnosed in a HIV-Infected Patient With Cryptococcal Meningitis Using Next-Generation Sequencing

et al. 2021

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Background: Streptococcus suis has been recognized as a zoonotic pathogen that may cause infections in humans. Although rarely described, it is not surprising that both cryptococcal and streptococcus suis meningitis infections can co-exist in a HIV-infected patient with a low CD4 count. However, a fast and accurate diagnose of meningitis of multipathogenic infections is challenging. In this report, we describe such a case of a HIV-infected patient with meningitis of multipathogenic infections.Case Presentation: The patient was a 34-year-old Chinese male who was diagnosed with cryptococcal meningitis and HIV at the same time about 1 year ago. During the same time period, he had received (with good compliance) fluconazole and tenofovir-lamivudine- dolutegravir based antiretroviral therapy (ART). However, symptom of progressively worsening occipital headache appeared after he was exposed to a truck which was used for transporting pigs. Initial workup indicated an increase of the cerebrospinal fluid (CSF) opening pressure (OP) and an increase in the number of lymphocytes and proteins in CSF. A magnetic resonance imaging (MRI) scan revealed that partial cerebellar surface enhancement. The cryptococcus capsular antigen test of CSF was positive. The results of the India Ink microscopy for cryptococcus, nucleic acid of CMV and EBV and mycobacterium tuberculosis (MTB) tests of CSF were negative. The results of the bacteria and fungi smear and culture of CSF were also negative. Eventually, streptococcus suis was detected using next-generation sequencing (NGS) in CSF. The diagnosis of Streptococcus suis meningitis was made based on the patient's contact history with carrier pigs and the clinical findings addressed above. The treatment of 2 weeks of intravenous ceftriaxone and 1 week of oral moxifloxacin resulted in improvement of the condition of CSF. The anti-fungal treatment using fluconazole continued until the CFS OP went down to a normal level and the cryptococcus capsular antigen test of CSF was negative 6 months later.Conclusion: This case highlights that NGS might be beneficial to HIV-infected patients who have meningitis with negative CSF culture results. Multiple etiologies for such condition in the immunocompromised patients must be taken into consideration and early stage NGS is recommended.

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“…149 Sensitivity of mNGS has been compromised in few studies, compared to amplification-based assay due to the low viral loads in the specimen which is a common problem. 143,150 A recent study was conducted to counter this problem by enhanced the laboratory technique using hybrid capture (HC) of viral nucleic acids and methylated DNA depletion (MDD) to improve the sequencing analytical sensitivity. As the results, HC able to increase the viral read recovery in almost universally.…”

Section: Next Generation Sequencingmentioning

confidence: 99%

An Overview of Laboratory Diagnosis of Central Nervous System Viral Infections

Hussin¹,

Chua²,

Al-Talib³

et al. 2022

J. Pure Appl. Microbiol.

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Central nervous system (CNS) infection is a serious illness that can lead to death. CNS infections include meningitis, encephalitis, brain abscesses and myelitis. These diseases are caused by causative agents like bacteria, fungi, parasites, and protozoa, but most commonly by viral infections. To combat this issue, accurate diagnosis of etiological agents at an early stage is crucial for appropriate treatment, control of the disease and prevent from becoming life-threatening to the patients. This review paper summarises the main laboratory diagnostic methods for CNS infections caused by viruses ranging from conventional to molecular methods. Conventional isolation methods are considered the ‘gold standard’ as they provide accurate evidence, but require highly skilled personnel, are time-consuming, critical in cell type selection and are useless for non-cultivable viruses. Electron microscopy allows recognition of viral morphology and ultrastructural details as the principle of virus identification through negative staining or thin section technique (suitable for tissue or cell specimens). However, it offers low sensitivity and requires at least 106 virions per millilitre or milligram in the specimen to be detectable by microscopy. Immunological-based methods have been extensively applied for viral diagnosis by detecting the antiviral antibodies or viral antigens in clinical samples. While these methods provided high sensitivity and specificity, the incubation and window period of an infection may give false-negative results. Lastly, molecular detections have many advantages such as high sensitivity, specificity, rapid, require a small amount of sample, simultaneous detection of multiple different viruses, and produce both qualitative and quantitative results.

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Clinical usefulness of metagenomic next-generation sequencing for the diagnosis of central nervous system infection in people living with HIV

Cited by 16 publications

References 31 publications

Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases of the central nervous system after empirical treatment

Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases of the central nervous system after empirical treatment

Case Report: Streptococcus Suis Meningitis Diagnosed in a HIV-Infected Patient With Cryptococcal Meningitis Using Next-Generation Sequencing

An Overview of Laboratory Diagnosis of Central Nervous System Viral Infections

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