A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections.

RHOH, an atypical small GTPase predominantly expressed in hematopoietic cells, plays a vital role in immune function. A deficiency in RHOH has been linked to epidermodysplasia verruciformis, lung disease, Burkitt lymphoma and T cell defects. Here, we report a novel germline homozygous RHOH c.245G > A (p.Cys82Tyr) variant in a 21-year-old male suffering from recurrent, invasive, opportunistic infections affecting the lungs, eyes, and brain. His sister also succumbed to a lung infection during early adulthood. The patient exhibited a persistent decrease in CD4+ T, B, and NK cell counts, and hypoimmunoglobulinemia. The patient's T cell showed impaired activation upon in vitro TCR stimulation. In Jurkat T cells transduced with RHOHC82Y, a similar reduction in activation marker CD69 up-regulation was observed. Furthermore, the C82Y variant showed reduced RHOH protein expression and impaired interaction with the TCR signaling molecule ZAP70. Together, these data suggest that the newly identified autosomal-recessive RHOH variant is associated with T cell dysfunction and recurrent opportunistic infections, functioning as a hypomorph by disrupting ZAP70-mediated TCR signaling.

Disseminated coccidioidomycosis in immunocompetent patients in non-endemic areas: a case series and literature review.

Coccidioidomycosis is caused by the dimorphic fungi Coccidioides species which is endemic in the Western hemisphere. Reports on the characteristics of travel-related disseminated coccidioidomycosis in immunocompetent patients are rare, especially in non-endemic regions. The multifaceted symptoms of this condition present a diagnostic challenge to clinicians. This study aimed to review immunocompetent patients diagnosed with disseminated coccidioidomycosis in a tertiary hospital in Eastern China and other non-endemic areas, and to emphasize the importance of combining travel history with clinical manifestations and proper diagnostic examinations. This study retrospectively reviewed a case series of disseminated coccidioidomycosis diagnosed in an academic hospital in Eastern China. We conducted a global literature review of disseminated coccidioidomycosis in immunocompetent patients with travel history. We identified six patients in our case series and reviewed 42 cases in the literature. Travel history included Mexico, Arizona, California, and regions of low endemicity. Extrapulmonary sites of infection, which presented with diverse signs and symptoms, involved the skin and soft tissue, musculoskeletal system, lymph nodes, and central nervous system. Misdiagnoses and diagnostic delays were common. Next-generation sequencing substantially promoted precise diagnosis in our series. The overall prognosis for immunocompetent individuals was positive, mainly benefited from long-term azole therapies. The patients that succumbed had either central nervous system involvement or multiorgan dissemination. Progressive pneumonia with varied symptoms and travel history should alert healthcare professionals in non-endemic areas to consider the possibility of Coccidioides species infection. We recommend detailed history-taking and hypothesis-free detection of pathogens for cases with diagnostic delay.

Gene expression pattern analysis using dual-color RT-MLPA and integrative genome-wide association studies of eQTL for tuberculosis suscepitibility.

BACKGROUND: When infected with Mycobacterium tuberculosis, only a small proportion of the population will develop active TB, and the role of host genetic factors in different TB infection status was not fully understood. METHODS: Forty-three patients with active tuberculosis and 49 with latent tuberculosis were enrolled in the prospective cohort. Expressing levels of 27 candidate mRNAs, which were previously demonstrated to differentially expressed in latent and active TB, were measured by dual color reverse transcription multiplex ligation dependent probe amplification assay (dcRT-MLPA). Using expression levels of these mRNAs as quantitative traits, associations between expression abundance and genome-wild single nucleotide polymorphisms (SNPs) were calculated. Finally, identified candidate SNPs were further assessed for their associations with TB infection status in a validation cohort with 313 Chinese Han cases. RESULTS: We identified 9 differentially expressed mRNAs including il7r, il4, il8, tnfrsf1b, pgm5, ccl19, il2ra, marco and fpr1 in the prospective cohort. Through expression quantitative trait loci mapping, we screened out 8 SNPs associated with these mRNAs. Then, CG genotype of the SNP rs62292160 was finally verified to be significantly associated with higher transcription levels of IL4 in LTBI than in TB patients. CONCLUSION: We reported that the SNP rs62292160 in Chinese Han population may link to higher expression of il4 in latent tuberculosis. Our findings provided a new genetic variation locus for further exploration of the mechanisms of TB and a possible target for TB genetic susceptibility studies, which might aid the clinical decision to precision treatment of TB.

Fatal hemorrhagic varicella in a patient with abdominal pain: a case report.

BACKGROUND: Varicella is normally a self-limited childhood disease caused by varicella-zoster virus infection. However, it sometimes causes severe diseases, especially in immunocompromised individuals. We report a case of severe varicella in a young woman. CASE PRESENTATION: A 19-year-old woman presented to the emergency department with abdominal pain and a rash after taking methylprednisolone for 2 weeks for systemic lupus erythematosis. The laboratory data showed leukocytosis, thrombocytopenia, an elevated level of the liver transaminases and disseminated intravascular coagulation. Computed tomography of the abdomen revealed multiple air-fluid levels in the intestines. Hemorrhagic varicella was considered and antiviral therapy as well as immunoglobin were applied. Her condition deteriorated and she eventually died due to multi-organ failure and refractory shock. Next-generation sequencing performed on fluid from an unroofed vesicle confirmed the diagnosis of varicella. CONCLUSION: In its severe form, VZV infection can be fatal, especially in immunocompromised patients. Hemorrhagic varicella can be misdiagnosed by clinicians because of unfamiliar with the disease, although it is associated with a high mortality rate. In patients with suspected hemorrhagic varicella infection, antiviral therapies along with supportive treatment need to be initiated as soon as possible in order to minimize the case fatality rate.

Differential expression and predictive value of monocyte scavenger receptor CD163 in populations with different tuberculosis infection statuses.

BACKGROUND: Monocytes are the predominant innate immune cells at the early stage of Mycobacterium tuberculosis (M. tb) infection as the host defense against intracellular pathogens. Understanding the profile of different monocyte subpopulations and the dynamics of monocyte-related biomarkers may be useful for the diagnosis and prognosis of tuberculosis. METHODS: We enrolled 129 individuals comprising patients with pulmonary tuberculosis (PTB) (n = 39), tuberculous pleurisy (TBP) (n = 28), malignant pleural effusion (MPE) (n = 21), latent tuberculosis infection (LTBI) (n = 20), and healthy controls (HC) (n = 21). Surface expression of CD14, CD16, and CD163 on monocytes was detected using flow cytometry. In addition, soluble CD163 (sCD163) was determined by enzyme linked immunosorbent assay. RESULTS: Higher frequency of CD14+CD16+ (15.7% vs 7.8%, P < 0.0001) and CD14-CD16+ (5.3% vs 2.5%, P = 0.0011) monocytes and a decreased percentage of CD14+CD16- (51.0% vs 70.4%, P = 0.0110) cells was observed in PTB patients than in HCs. Moreover, PTB patients displayed a higher frequency of CD163+ cells in CD16+ monocytes than those in the HC group (40.4% vs 11.3%, P < 0.0001). The level of sCD163 was elevated in TBP patients and was higher in pleural effusion than in plasma (2116.0 ng/ml vs 1236.0 ng/ml, P < 0.0001). sCD163 levels in pleural effusion and plasma could be used to distinguish TBP from MPE patients (cut-off values: 1950.0 and 934.7 ng/ml, respectively; AUCs: 0.8418 and 0.8136, respectively). Importantly, plasma sCD163 levels in TBP patients decreased significantly after anti-TB treatment. CONCLUSIONS: Higher expression of membrane and soluble CD163 in active tuberculosis patients might provide insights regarding the pathogenesis of tuberculosis, and sCD163 may be a novel biomarker to distinguish TBP from MPE and to predict disease severity.

Human African Trypanosomiasis in Emigrant Returning to China from Gabon, 2017.

Human African trypanosomiasis is endemic to parts of sub-Saharan Africa and should be considered in the differential diagnosis of patients who have visited or lived in Africa. We report a 2017 case of stage 2 Trypanosoma brucei gambiense disease in an emigrant who returned to China from Gabon.

Isolation of Mycobacterium arupense from pleural effusion: culprit or not?

BACKGROUND: Mycobacterium arupense, first identified in 2006, is a slow-growing nontuberculous mycobacterium (NTM) and an emerging cause of tenosynovitis, potentially associated with immunosuppression. However, unlike the diagnostic value of its isolation from osteoarticular specimens, the significance of detecting M. arupense in respiratory specimens is not yet clear. CASE PRESENTATION: To our knowledge, we, for the first time, described the identification of M. arupense from the pleural effusion of an immunocompetent patient, who presented with fever and chylothorax. The symptoms resolved with doxycycline treatment for 45 days and a low-fat, high-protein diet. Follow-up at 14 months showed no relapse. CONCLUSIONS: Because the patient fully recovered without combined anti-NTM treatment, we did not consider M. arupense the etiological cause in this case. This indicates that M. arupense detected in pleural effusion is not necessarily a causative agent and careful interpretation is needed in terms of its clinical relevance.

Disseminated cryptococcosis with recurrent multiple abscesses in an immunocompetent patient: a case report and literature review.

BACKGROUND: Cryptococcus neoformans is frequently present as an opportunistic pathogen mainly affecting immunocompromised populations. Disseminated C. neoformans infection in immunocompetent population is rare and usually involves lung and central nerve system. Cryptococcus from biologic samples can easily grow on routine fungal and bacterial culture media. Besides, cryptococcal latex agglutination test has been established as a reliable diagnostic tool with overall sensitivities of 93-100%. CASE PRESENTATION: We report a rare disseminated cryptococcosis case which presented with chronic recurrent multiple abscess in an immunocompetent male involving skin, lung, spine and iliac fossa without evidence of central nerve system involving. The results of serum cryptococcal latex agglutination tests and standard microbial cultures were negative. The patient underwent empirical anti-bacterial and anti-tuberculosis therapy which turned out to be effectless. Finally, bedside inoculation of the pus was carried out and revealed Cryptococcus neoformans, which was confirmed by polymerase chain reaction. After the administration of anti-fungal drugs including liposomal amphotericin B, the patient recovered from fever and paraplegia. CONCLUSIONS: This case reveals an uncommon pattern of disseminated C. neoformans infection in immunocompetent population presented with chronic multiple abscess and without central nerve system involving. Negative routine microbial cultures may not necessarily rule out cryptococcosis, especially in early stage. Besides, cryptococcal latex agglutination test does have a chance of false negative, which might be related with "capsule-deficiency". Moreover, this phenomenon could be related with low-grade virulence and relative long illness duration.

Linezolid manifests a rapid and dramatic therapeutic effect for patients with life-threatening tuberculous meningitis.

We conducted a retrospective cohort study of patients with MRC grade II/III tuberculous meningitis (TBM) who accepted a background antitubercular regimen (BR) with or without linezolid (LZD). At the 4th week, the LZD-BR group achieved a faster and higher percentage of Glasgow coma scale recovery and temperature recovery, a higher cerebrospinal fluid (CSF)/blood glucose ratio, and lower CSF white blood cell counts than did the BR group. Short-term linezolid supplementation may be a more effective treatment for life-threatening TBM.

Transcriptional profiling of human peripheral blood mononuclear cells in household contacts of pulmonary tuberculosis patients provides insights into mechanisms of Mycobacterium tuberculosis control and elimination.

Household contacts (HHCs) of patients with active tuberculosis (ATB) are at higher risk of Mycobacterium tuberculosis (M. tuberculosis) infection. However, the immune factors responsible for different defense responses in HHCs are unknown. Hence, we aimed to evaluate transcriptome signatures in human peripheral blood mononuclear cells (PBMCs) of HHCs to aid risk stratification. We recruited 112 HHCs of ATB patients and followed them for 6 years. Among the HHCs, only 2 developed ATB, while the remaining HHCs were classified into three groups: (1) HHC-1 group (n = 23): HHCs with consistently positive T-SPOT.TB test, negative chest radiograph, and no clinical symptoms or evidence of ATB during the 6-year follow-up period; (2) HHC-2 group (n = 15): HHCs with an initial positive T-SPOT result that later became negative without evidence of ATB; (3) HHC-3 group (n = 14): HHCs with a consistently negative T-SPOT.TB test and no clinical or radiological evidence of ATB. HHC-2 and HHC-3 were combined as HHC-23 group for analysis. RNA sequencing (RNA-seq) in PBMCs, with and without purified protein derivative (PPD) stimulation, identified significant differences in gene signatures between HHC-1 and HHC-23. Gene ontology analysis revealed functions related to bacterial pathogens, leukocyte chemotaxis, and inflammatory and cytokine responses. Modules associated with clinical features in the HHC-23 group were linked to the IL-17 signaling pathway, ferroptosis, complement and coagulation cascades, and the TNF signaling pathway. Validation using real-time PCR confirmed key genes like ATG-7, CXCL-3, and TNFRSF1B associated with infection outcomes in HHCs. Our research enhances understanding of disease mechanisms in HHCs. HHCs with persistent latent tuberculosis infection (HHC-1) showed significantly different gene expression compared to HHCs with no M. tuberculosis infection (HHC-23). These findings can help identify HHCs at risk of developing ATB and guide targeted public health interventions.

The hsa_circ_0002371/hsa-miR-502-5p/ATG16L1 axis modulates the survival of intracellular Mycobacterium tuberculosis and autophagy in macrophages.

Circular RNAs (circRNAs) play a critical role in pathological mechanisms of Mycobacterium tuberculosis (Mtb) and can be used as a new biomarker for active tuberculosis (ATB) diagnosis. Therefore, we identified significantly dysregulated circRNAs in ATB patients and healthy controls (HC) and explored their molecular mechanism. We found that hsa_circ_0002371 was significantly up-regulated in PBMCs of ATB patients and Mycobacterium tuberculosis H37Rv- or Mycobacterium bovis bacillus Calmette Guerin (BCG)-infected THP-1 cells. Functional experiments demonstrated that hsa_circ_0002371 inhibited autophagy in BCG-infected THP-1 cells and promoted intracellular BCG survival rate. In terms of mechanism, hsa_circ_0002371 facilitated the expression of hsa-miR-502-5p, as shown by bioinformatics and dual-luciferase reporter gene analysis, respectively. Notably, hsa-miR-502-5p inhibited autophagy via suppressing autophagy related 16 like 1 (ATG16L1) in BCG-infected macrophages and thus promoting intracellular BCG growth. In summation, hsa_circ_0002371 increased the suppression of hsa-miR-502-5p on ATG16L1 and inhibited autophagy to promote Mtb growth in macrophages. In Conclusion, our data suggested that hsa_circ_0002371 was significantly up-regulated in the PBMCs of ATB patients compared with HC. The hsa_circ_0002371/hsa-miR-502-5p/ATG16L1 axis promoted the survival of intracellular Mtb and inhibited autophagy in macrophages. Our findings suggested hsa_circ_0002371 could act as a potential diagnostic biomarker and therapeutic target.

A rare missense p.C125Y mutation in the TNFRSF1A gene identified in a Chinese family with tumor necrosis factor receptor-associated periodic fever syndrome.

Background: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autosomal dominant disorder with a low incidence in Asia. The most frequent clinical manifestations include fever, rash, myalgia, joint pain and abdominal pain. Misdiagnosis rates are high because of the clinical and genetic variability of the disease. The pathogenesis of TRAPS is complex and yet to be fully defined. Early genetic diagnosis is the key to precise treatment. Methods: In this study, a Chinese family with suspected TRAPS were analyzed by genome-wide SNP genotyping, linkage analysis and targeted sequencing for identification of mutations in causative genes. To study the pathogenicity of the identified gene mutation, we performed a conservation analysis of the mutation site and protein structure analysis. Flow cytometry was used to detect TNFRSF1A shedding and quantitative real-time PCR were used to assess the activation of unfolded protein response (UPR) in the mutation carriers and healthy individuals. Results: A typical TRAPS family history, with a pattern of autosomal dominant inheritance, led to the identification of a rare mutation in the TNFRSF1A gene (c.G374A [p.Cys125Tyr]) with unknown significance. The patient responded well to corticosteroids, and long-term therapy with colchicine effectively reduced the inflammatory attacks. No amyloid complications occurred during the 6-year follow-up. In silico protein analysis showed that the mutation site is highly conversed and the mutation prevents the formation of intrachain disulfide bonds in the protein. Despite a normal shedding of the TNFRSF1A protein from stimulated monocytes in the TRAPS patients with p.C125Y mutation, the expression of CHOP and the splicing of XBP1 was significantly higher than healthy controls, suggesting the presence of an activation UPR. Conclusion: This is the first report of a Chinese family with the rare p.C125Y mutation in TNFRSF1A. The p.C125Y mutation does not result in aberrant receptor shedding, but instead is associated with an activated UPR in these TRAPS patients, which may provide new insights into the pathogenesis of this rare mutation in TRAPS.

Cerebral Infarction and Evan's Ratio on MRI Affect the Severity and Prognosis of Tuberculosis Meningitis Patients.

Background: Magnetic resonance imaging (MRI) is widely used in the diagnosis of tuberculous meningitis (TBM) and its complications. We aimed to explore the relationship between MRI features and neurological deficits and TBM patients' prognosis. Methods: patients diagnosed with TBM were subjected to a neurological evaluation on admission and divided into groups based on the Medical Research Council (MRC) scale. After several years of follow-up, the patients were further divided into groups according to the Modified Rankin Score (MRS). Their MR images were analyzed for meningeal enhancement, tuberculomas, infarction, hydrocephalus, and abscess, including the location and size of the lesion. Any changes in MRI features during the follow-up were recorded. MRI features between groups were compared, and the relationship between dynamic changes in images and Rankin grading was explored. Results: We found significant differences in acute cerebral infarction (ACI) and old cerebral infarctions (OCI) between the MRC groups, and the ORs of ACI and OCI were 21.818 (95% CI: 2.440−195.075) and 6.788 (95% CI: 1.516−30.392), respectively. There were significant differences in ACI, OCI, and Evan's ratio between the MRS groups (p < 0.05), and the ORs of ACI, OCI, and hydrocephalus were 6.375 (95% CI: 1.501−27.080), 5.556 (95% CI: 1.332−23.177), and 9.139 (95% CI: 2.052−40.700), respectively. The changes of Evan's ratio were related to the MRS grading (r = 0.335, p = 0.040). Conclusions: For patients with TBM, the presence of ACI or OCI is associated with neurological deficits, and ACI, OCI, and hydrocephalus can be regarded as poor prognostic predictors. Changes in Evan's ratio will affect the outcome.

Comparison of QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold-Plus in the Diagnosis of Mycobacterium tuberculosis Infections in Immunocompromised Patients: a Real-World Study.

QuantiFERON-TB Gold Plus (QFT-Plus) is an emerging QuantiFERON test after QuantiFERON-TB Gold In-Tube (QFT-GIT) for tuberculosis infection detection; it is an IFN-γ release assay. We compared QFTPlus, which has an additional TB antigen 2 (TB2) tube to induce cell-mediated (CD8+ T cell) immune responses, with QFT-GIT. We conducted this study to assess the agreement of the QFT-GIT and QFT-Plus assays in immunocompromised patients in a clinical setting. A total of 278 immunocompromised patients and 175 immunocompetent patients from different departments were continuously enrolled from August 2020 to March 2021, and each patient underwent both tests. Correlations between QFT-GIT and QFT-Plus assays showed good agreement (κ value = 0.859). Patients receiving long-term immunosuppressant therapy had the lowest concordance between QFT-GIT and QFT-Plus assays; 9 out of 11 positive latent tuberculosis infection (LTBI) cases were diagnosed by the QFT-Plus assay, implying that QFT-Plus may detect more LTBI than QFT-GIT does in these patients. Indeterminate results were associated with lower lymphocyte, CD4+ T cell, and CD8+ T cell absolute counts, and with lower CD4/CD8 ratios. In conclusion, we found that the QFT-GIT and QFT-Plus assays had high agreement not only in immunocompetent patients but also in immunocompromised patients. QFT-Plus may detect more LTBI than QFT-GIT in patients receiving long-term immunosuppressant therapy. Thresholds were established for lymphocyte absolute counts of >1.15 × 109 cells, and for CD4+ T cell absolute counts of >467.7 × 106 to 478.5 × 106 cells, which may lessen the incidence of indeterminate results. IMPORTANCE This study evaluated the performance of QFT-GIT and QFT-Plus in the diagnosis of M. tuberculosis infection in immunocompromised patients and found that QFT-Plus may detect more LTBI than QFT-GIT does in patients receiving long-term immunosuppressant therapy. We believe that our study makes a significant contribution to the literature because it highlights the different diagnostic accuracies of QFT-GIT and QFT-Plus in different subpopulations of immunocompromised and immunocompetent patients. Selecting a test with better performance, particularly in patients with a high risk of developing active TB, may assist the health sector in better managing TB. Furthermore, we believe that this study will be of significance to the diagnosis of LTBI.

Mycobacterium tuberculosis Infection among 1,659 Silicosis Patients in Zhejiang Province, China.

Silicosis is a well-established risk factor for Mycobacterium tuberculosis infection. This study aimed to estimate the burden and risk factors of M. tuberculosis infection. Silicosis patients from Zhejiang Province were screened for M. tuberculosis by sputum culture, chest radiographs, whole-blood gamma interferon (IFN-γ) release assay (QuantiFERON-TB Gold In-Tube [QFT-GIT]), and tuberculin skin test (TST). Potential risk factors for M. tuberculosis were identified. Data for 1,659 patients were obtained from 1,684 participants. Of these, 1,656 (99.8%) were men, and the average age was 58 (54 to 63) years. The prevalence of active tuberculosis (ATB) was 6,340/100,000 (6.34%) people; the proportion of patients with latent tuberculosis infection (LTBI) was 50.6%. Age (odds ratio [OR] = 1.059, 95% confidence interval [CI] = 1.020 to 1.099, P = 0.003), being underweight (OR = 2.320, 95% CI = 1.057 to 5.089, P = 0.036), and having a history of exposure to TB patients (OR = 4.329, 95% CI = 1.992 to 9.434, P < 0.001) were associated with ATB; BCG vaccination could reduce ATB risk in silicosis patients (OR = 0.541, 95% CI = 0.307 to 0.954, P = 0.034). Among patients without ATB, the QFT-GIT positivity rate was 40.5%, which was affected by silicosis severity, while that of TST was 57.2%. BCG vaccination was an independent factor for LTBI risk reduction (OR = 0.612, 95% CI = 0.468 to 0.801, P < 0.001). The quantitative results of QFT-GIT decreased with silicosis stage (H = 6.037; P = 0.048). In conclusion, M. tuberculosis prevalence was high in silicosis patients. BCG vaccination reduced the risk of both ATB and LTBI in silicosis patients. IMPORTANCE This study evaluated the prevalence of Mycobacterium tuberculosis infection in silicosis patients in mainland China and identified the potential risk factors for both active tuberculosis (ATB) and latent tuberculosis infection (LTBI). We believe that our study makes a significant contribution to the literature because we demonstrated that M. tuberculosis prevalence was high among silicosis patients. BCG vaccination was an independent factor that reduced the risk of M. tuberculosis infection in patients with silicosis. Furthermore, we show that the prevalence of LTBI in patients with silicosis may have been underestimated by immunological detection methods. This study can help to identify targeted subgroups prioritized for M. tuberculosis control and to reduce the risk of disease development.

B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection.

Latent tuberculosis infection (LTBI) treatment is known to accelerate the decline in TB incidence, especially in high-risk populations. Mycobacterium tuberculosis (M. tb) expression profiles differ at different growth periods, and vaccines protective and therapeutic effects may increase when they include antigenic compositions from different periods. To develop a post-exposure vaccine that targets LTBI, we constructed four therapeutic DNA vaccines (A39, B37, B31, and B21) using different combinations of antigens from the proliferation phase (Ag85A, Ag85B), PE/PPE family (Rv3425), and latent phase (Rv2029c, Rv1813c, Rv1738). We compared the immunogenicity of the four DNA vaccines in C57BL/6j mice. The B21 vaccine stimulated the strongest cellular immune responses, namely Th1/Th17 and CD8+ cytotoxic T lymphocyte responses. It also induced the generation of strengthened effector memory and central memory T cells. In latently infected mice, the B21 vaccine significantly reduced bacterial loads in the spleens and lungs and decreased lung pathology. In conclusion, the B21 DNA vaccine can enhance T cell responses and control the reactivation of LTBI.

Recurrent pulmonary tuberculosis after treatment success: a population-based retrospective study in China.

OBJECTIVES: Post-treatment recurrence remains a challenge for the global control of tuberculosis (TB). This study investigated longitudinal data on pulmonary TB recurrence rates and risk factors for recurrence among successfully treated smear-positive tuberculosis cases in China. METHODS: Between 1st January 2009 and 31st December 2016 we evaluated 33 441 treatment-naïve patients diagnosed with sputum-smear-positive, non-multidrug-resistant TB in Hangzhou, China. We included the data of 9828 patients with TB who were treated successfully. RESULTS: A total of 4.9% of the cases were recurrent (479/9828), identified within a median observation period lasting 1565 days. Altogether, 51.1% (245/479) of the recurrences occurred within 1 year. The cumulative 2- and 5-year recurrence rates were 3.90% (95% confidence interval (CI) 3.3-4.5%) and 5.4% (95%CI 4.8-6.0%), respectively. Prolonged treatment (over 7 months) occurred in 64.7% (6363/9828), with a median treatment duration of 242 days (interquartile range 195-348 days). Male sex (adjusted hazard ratio (aHR) (95%CI) 1.61 (1.30-2.00), p < 0.001), age 60 years old or older (aHR (95%CI) 2.03 (1.70-2.44), p < 0.001), pulmonary cavity (aHR (95%CI) 1.51 (1.25-1.82), p < 0.001) and sputum positivity at 2 months (aHR (95%CI) 1.39 (1.05-1.81), p 0.02) all increased the risk of TB recurrence. Prolonged treatment was associated with reduced TB recurrence (aHR (95%CI) 0.73 (0.61-0.88), p 0.001). CONCLUSIONS: Recurrence remains a problem for successfully treated patients with sputum-smear-positive pulmonary TB, especially those with independent risk factors. Further analysis of prolonged treatment is required.