Cervical and oropharyngeal human papillomavirus infection in women living with human immunodeficiency virus (HIV) and matched HIV-negative controls in Brazil

2020 ◽  
Author(s):  
Tamy Taianne Suehiro ◽  
Gabrielle Marconi Zago Ferreira Damke ◽  
Edilson Damke ◽  
Paloma Luana Rodrigues de Azevedo Ramos ◽  
Marcela de Andrade Pereira Silva ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Papillomavirus ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Hpv Infection ◽  
Hpv Dna ◽  
Oropharyngeal Infection ◽  
Immunodeficiency Virus ◽  
Hiv Women ◽  
Hiv Negative

Abstract Background: Despite the demonstrated role of human Papillomavirus (HPV) in the etiology of cervical cancer and the strong evidence suggesting the importance of HPV in the development of oropharyngeal cancer, several aspects concerning the interrelationship between HPV infections in both body sites remain unknown, specifically in human immunodeficiency virus (HIV)-positive (HIV+) female patients. We aimed to assess the prevalence, distribution, and concordance of cervical and oropharyngeal HPV in HIV+ women and matched HIV-negative (HIV-) controls in Brazil. Material and methods: Cervical and endocervical samples for cytological screening and HPV detection and oropharyngeal samples were collected from 115 HIV+ women using highly active antiretroviral therapy (HAART) and 139 HIV-matched controls (HIV-) in Maringá City, Brazil. Risk factors were assessed using a standardized questionnaire, and the data regarding HIV infection were obtained from the patients’ medical records. Detection and typing of HPV were performed using the Kit Multiplex XGEN Multi HPV Chip HS12. Results: HIV infection was well controlled in this cohort, but women who exhibited 1–100.000 viral copies/mL were significantly associated with HPV-positive status (P = 0.03). HIV+ women had significantly more abnormal cytological findings (P = 0.04) than HIV- women. Of the 115 HIV+ women, 48.7% were positive for cervical and/or oropharyngeal HPV DNA; of the 139 HIV- women, 41% were positive for cervical and/or oropharyngeal HPV (P = 0.25). Both HIV+ and HIV- women had a statistically higher prevalence of cervical HPV infection than oropharyngeal infection. The concurrent HPV infection in two anatomical sites was similar in HIV+ and HIV- women, however HPV type concordance was not observed. HPV type distribution was different between the anatomical sites in both groups, and HIV+ women presented types less common, mainly in oropharyngeal mucosa. Conclusion: Our data support the importance of HPV infection in HIV+ women, even when the HIV infection is well controlled. Prospective studies are required to better understand the natural history of HPV infection in both anatomical sites, specifically in HIV+ women.

scholarly journals Cervical and oral human papillomavirus infection in women living with human immunodeficiency virus (HIV) and matched HIV-negative controls in Brazil

2020 ◽  
Author(s):  
Tamy Taianne Suehiro ◽  
Gabrielle Marconi Zago Ferreira Damke ◽  
Edilson Damke ◽  
Paloma Luana Rodrigues de Azevedo Ramos ◽  
Marcela de Andrade Pereira Silva ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Papillomavirus ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Hpv Infection ◽  
Hpv Dna ◽  
Immunodeficiency Virus ◽  
Oral Hpv ◽  
Hiv Women ◽  
Hiv Negative

Abstract Background: Despite the demonstrated role of human Papillomavirus (HPV) in the etiology of cervical cancer and the strong evidence suggesting the importance of HPV in the development of oropharyngeal cancer, several aspects concerning the interrelationship between HPV infection in both body sites remain unknown, specifically in human immunodeficiency virus (HIV)-positive (HIV+) female patients. We aimed to assess the prevalence, distribution, and concordance of cervical and oral HPV in HIV+ women and matched HIV-negative (HIV-) controls in Brazil. Material and methods: Cervical and endocervical samples for cytological screening and HPV detection and oral samples were collected from 115 HIV+ women using highly active antiretroviral therapy (HAART) and 139 HIV-matched controls (HIV-) in Maringá City, Brazil. Risk factors were assessed using a standardized questionnaire, and the data regarding HIV infection were obtained from the patients’ medical records. HPV detection and typing were performed using the Kit Multiplex XGEN Multi HPV Chip HS12. Results: HIV infection was well controlled in this cohort, but women who exhibited detectable HIV load were significantly associated with HPV-positive status in overall (P = 0.03) and in cervical mucosa (P = 0.01). HIV+ women had significantly more abnormal cytological findings (P = 0.04) than HIV- women. Of the 115 HIV+ women, 48.7% were positive for cervical and/or oral HPV DNA; of the 139 HIV- women, 41% were positive for cervical and/or oral HPV (P = 0.25). Both HIV+ and HIV- women had a statistically higher prevalence of cervical HPV infection than oral infection. The concurrent HPV infection in two anatomical sites was similar in HIV+ and HIV- women, however HPV type concordance was not observed. HPV type distribution was different between the anatomical sites in both groups, and HIV+ women presented less common types, mainly in oral mucosa. Conclusion: Our data support the importance of HPV infection in HIV+ women, even when the HIV infection is well controlled. Prospective studies are required to better understand the natural history of HPV infection in both anatomical sites, specifically in HIV+ women.

scholarly journals Cervical and oral human papillomavirus infection in women living with human immunodeficiency virus (HIV) and matched HIV-negative controls in Brazil

2020 ◽  
Author(s):  
Tamy Taianne Suehiro ◽  
Gabrielle Marconi Zago Ferreira Damke ◽  
Edilson Damke ◽  
Paloma Luana Rodrigues de Azevedo Ramos ◽  
Marcela de Andrade Pereira Silva ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Hpv Infection ◽  
Hpv Dna ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Oral Hpv ◽  
Hiv Women ◽  
Hiv Negative

Abstract Background: Despite the demonstrated role of human Papillomavirus (HPV) in the etiology of cervical cancer and the strong evidence suggesting the importance of HPV in the development of oropharyngeal cancer, several aspects of the interrelationship between HPV infection in both body sites remain unknown, specifically in female human immunodeficiency virus (HIV)-positive (HIV+) patients. We aimed to assess the prevalence, distribution, and concordance of cervical and oral HPV in HIV+ women and matched HIV-negative (HIV-) controls in Brazil.Material and methods: Cervical and endocervical samples for cytological screening and HPV detection and oral samples were collected from 115 HIV+ women using highly active antiretroviral therapy (HAART) and 139 HIV-matched controls (HIV-) in Maringá City, Brazil. Risk factors were assessed using a standardized questionnaire, and the data regarding HIV infection were obtained from the patients’ medical records. HPV detection and typing were performed using the Kit Multiplex XGEN Multi HPV Chip HS12.Results: HIV infection was well controlled in this cohort, but women who exhibited detectable HIV loads were significantly associated with HPV-positive status overall (P = 0.03) and in cervical mucosa (P = 0.01). HIV+ women had significantly more abnormal cytological findings (P = 0.04) than HIV- women. Of the 115 HIV+ women, 48.7% were positive for cervical and/or oral HPV DNA; of the 139 HIV- women, 41% were positive for cervical and/or oral HPV (P = 0.25). Both HIV+ and HIV- women had a statistically higher prevalence of cervical HPV infection than oral infection. The concurrent HPV infection in two anatomical sites was similar in HIV+ and HIV- women; however, HPV type concordance was not observed. HPV type distribution was different between the anatomical sites in both groups, and HIV+ women presented less common types, mainly in oral mucosa.Conclusion: Our data support the importance of testing HPV infection in HIV+ women, even when the HIV infection is well controlled. Prospective studies are required to better understand the natural history of HPV infection in both anatomical sites, specifically in HIV+ women.

scholarly journals Cervical and oral human papillomavirus infection in women living with human immunodeficiency virus (HIV) and matched HIV-negative controls in Brazil

2020 ◽  
Author(s):  
Tamy Taianne Suehiro ◽  
Gabrielle Marconi Zago Ferreira Damke ◽  
Edilson Damke ◽  
Paloma Luana Rodrigues de Azevedo Ramos ◽  
Marcela de Andrade Pereira Silva ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Hpv Infection ◽  
Hpv Dna ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Oral Hpv ◽  
Hiv Women ◽  
Hiv Negative

Abstract Background: Despite the demonstrated role of human Papillomavirus (HPV) in the etiology of cervical cancer and the strong evidence suggesting the importance of HPV in the development of oropharyngeal cancer, several aspects of the interrelationship between HPV infection in both body sites remain unknown, specifically in female human immunodeficiency virus (HIV)-positive (HIV+) patients. We aimed to assess the prevalence, distribution, and concordance of cervical and oral HPV in HIV+ women and matched HIV-negative (HIV-) controls in Brazil.Material and methods: Cervical and endocervical samples for cytological screening and HPV detection and oral samples were collected from 115 HIV+ women using highly active antiretroviral therapy (HAART) and 139 HIV-matched controls (HIV-) in Maringá City, Brazil. Risk factors were assessed using a standardized questionnaire, and the data regarding HIV infection were obtained from the patients’ medical records. HPV detection and typing were performed using the Kit Multiplex XGEN Multi HPV Chip HS12.Results: HIV infection was well controlled in this cohort, but women who exhibited detectable HIV loads were significantly associated with HPV-positive status overall (P = 0.03) and in cervical mucosa (P = 0.01). HIV+ women had significantly more abnormal cytological findings (P = 0.04) than HIV- women. Of the 115 HIV+ women, 48.7% were positive for cervical and/or oral HPV DNA; of the 139 HIV- women, 41% were positive for cervical and/or oral HPV (P = 0.25). Both HIV+ and HIV- women had a statistically higher prevalence of cervical HPV infection than oral infection. The concurrent HPV infection in two anatomical sites was similar in HIV+ and HIV- women; however, HPV type concordance was not observed. HPV type distribution was different between the anatomical sites in both groups, and HIV+ women presented less common types, mainly in oral mucosa.Conclusion: Our data support the importance of testing HPV infection in HIV+ women, even when the HIV infection is well controlled. Prospective studies are required to better understand the natural history of HPV infection in both anatomical sites, specifically in HIV+ women.

scholarly journals FRI0435 THE CLINICAL SIGNIFICANCE OF SERUM AUTOANTIBODIES AND HLA-B27 MOLECULE TESTING IN UYGUR PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS INFECTION

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 815.3-815
Author(s):  
X. Chen ◽  
L. Wu ◽  
X. Wu ◽  
C. N. Luo ◽  
Y. M. Shi
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Molecular Mimicry ◽  
Molecular Testing ◽  
Hla B27 ◽  
Clinical Value ◽  
Rheumatic Manifestations ◽  
Immunodeficiency Virus ◽  
Positive Rate

Background:AIDS is a deadly infectious disease caused by the HIV. When HIV infects a host, it may induce production of autoantibodies due to the structural antigen similarity between viral proteins and selfantigens.The molecular mimicry between HIV protein and self-antigens could cause antibody cross-reactions and lead to development of autoimmune disease.Objectives:To explore the clinical value of serum autoantibodies and human leukocyte antigen (HLA-B27) molecular testing in Uygur patients with human immunodeficiency virus (HIV) infection.Methods:A total of 727 HIV-infected Uygur patients who visited Kuche Infectious Diseases Hospital during May 2016 to March 2017 were include in this study. The other 390 healthy people were enrolled as controls. Serum antinuclear antibodies (ANA) and ANA Profile, anti-cyclic citrullinated peptide (CCP) antibody, and HLA-B27 molecule were tested.Results:Among 727 HIV-infected Uygur patients, 317 were males and 410 were females with mean age (35.52±13.44) years old. The mean duration of disease was (6.34±3.05)years. There were 697(95.87%) patients receiving Highly active antiretroviral therapy (HAART) with mean duration of treatment (6.34±3.05)years. Rheumatic manifestations were recorded in 238 (32.74%) HIV-infected Uygur patients, mainly with dry mouth and dry eye (15.41%), alopecia (9.90%), arthralgia (8.94%), ect. Compared with the health controls, positive ANA was more common in HIV infected Uygur patients (33.42%vs.17.43%,P< 0.001) with low titers (ANA titer:1:100). HIV-infected Uygur patients had higher positive anti-u1-RNP antibodies positive rate (1.10%), but lower anti-SSA antibodies positive rate (0.14%) and anti-CCP antibodies positive rate (0.28%). Patients with positive ANA in HAART group were significantly less than that in non-treatment group (38.72%vs.50.00%,P=0.049).Only one female patient was HLA-B27 positive (0.14%), which was significantly lower than that in healthy controls (3.08%) (P<0.001). Also, only one patient was diagnosed with rheumatoid arthritis (RA).Conclusion:Rheumatic manifestations are common in HIV-infected Uygur patients. Several autoantibodies are positive, but the coincidence of rheumatic diseases is rare. It’s noted that patients with Rheumatic manifestations and low titre positive ANA should be considered as a differential diagnosis of HIV infection.Disclosure of Interests:None declared

Abstract WP426: Subarachnoid Hemorrhage in patients infected with Human Immunodeficiency Virus

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Haralabos Zacharatos ◽  
Malik M Adil ◽  
Ameer E Hassan ◽  
Sarwat I Gilani ◽  
Adnan I Qureshi
Keyword(s):  
Human Immunodeficiency Virus ◽  
Subarachnoid Hemorrhage ◽  
Blood Transfusion ◽  
Hospital Mortality ◽  
Hiv Infection ◽  
The United States ◽  
Hiv Positive ◽  
Published Data ◽  
Immunodeficiency Virus ◽  
Hiv Negative

Background: There is limited data regarding the unique attributes of ischemic stroke among patients infected with human immunodeficiency virus (HIV). There is no published data regarding the occurrence and outcomes of subarachnoid hemorrhage (SAH) among HIV infected persons. Methods: The largest all-payer Nationwide Inpatient Sample (NIS 2002-2010) data was used to identify and analyze all patients presenting with the primary diagnosis of SAH in the United States. Among this cohort, we identified the patients who were not HIV positive and those who were HIV positive. Patient demographics, medical co-morbidities, in-hospital complications, in-hospital procedures, and discharge disposition were compared between the two groups. The association between HIV infection and outcomes was evaluated in multivariate analysis after adjusting for potential confounders. Results: Of the 351,491 patients admitted with SAH, 1367 (0.39%) were infected with HIV. HIV infected patients were younger, mean age [±SD] of 45 ±14.2 years versus those who were not 58±19 years, (p<0.0001). The rate of blood transfusion [27,286 (7.8%) versus 245.6 (18%), p=0.0003], mechanical ventilation [51,199 (14.6%) versus 316.1(23.1%), p=0.008], and sepsis [14,644 (4.2%) versus 236.1 (17.3%), p<0.0001] was significantly higher among HIV infected patients. After adjusting for age, gender, hypertension, coagulopathy, atrial fibrillation, renal failure, and dyslipidemia, HIV negative patients had a significantly higher rate of discharge to home (odds ratio [OR] 1.9, 95% CI: 1.4-2.6, p<0.0001) and lower in-patient mortality (OR 0.4, 95% CI: 0.3-0.5, p<0.001). Further adjustment for blood transfusion and sepsis reduced the odds of discharge to home for the HIV negative patients, from 1.9 to 1.7 but did not affect in-hospital mortality. Conclusion: The in-hospital mortality in HIV infected patients with SAH is higher despite these patients being younger than non-HIV infected patients. We believe that this study provides a nationwide perspective which may have some important implications for early recognition and diagnosis of HIV-infection in SAH patients.

scholarly journals Human Immunodeficiency Virus Infected Patients are Not at Higher Risk for Hepatitis E Virus Infection: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 7 (12) ◽  
pp. 618
Author(s):  
Pedro Lopez-Lopez ◽  
Mario Frias ◽  
Angela Camacho ◽  
Antonio Rivero ◽  
Antonio Rivero-Juarez
Keyword(s):  
Systematic Review ◽  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Fixed Effects ◽  
Hepatitis E Virus ◽  
Meta Analysis ◽  
Geographical Area ◽  
Hepatitis E ◽  
Immunodeficiency Virus ◽  
Hiv Negative

Hepatitis E virus (HEV) infection is the most common cause of acute hepatitis in the world. It is not well established whether people infected with the human immunodeficiency virus (HIV) are more susceptible to infection with HEV than people not infected with HIV. Many studies have evaluated this relationship, although none are conclusive. The aim of this systematic review and meta-analysis was to assess whether patients with HIV infection constitute a risk group for HEV infection. A systematic review and meta-analysis was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), to find publications comparing HEV seroprevalences among HIV infected and uninfected populations. The analysis was matched by sex, age and geographical area, and compared patients who live with HIV and HIV-negative individuals. The odds ratio (OR) for patients with HIV was 0.87 (95% CI: 0.74–1.03) in the fixed effects meta-analysis and 0.88 (95% CI: 0.70–1.11) in random effects, with I2 = 47%. This study did not show that HIV infection was a risk factor for HEV infection when compared with those who are HIV-negative.

scholarly journals Postoperative Infectious Morbidities of Cesarean Delivery in Human Immunodeficiency Virus-Infected Women

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Helen Cavasin ◽  
Thao Dola ◽  
Olga Uribe ◽  
Manoj Biswas ◽  
Mai Do ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cesarean Section ◽  
Hiv Infection ◽  
Cesarean Delivery ◽  
Multiple Logistic Regression Analysis ◽  
Bivariate Analysis ◽  
Complication Rates ◽  
Immunodeficiency Virus ◽  
Women And Hiv ◽  
Hiv Negative

Objective. To compare the infectious complication rates from cesarean delivery of human immunodeficiency virus (HIV)-infected women and HIV-negative women.Materials and Methods. A retrospective analysis was performed on data derived from HIV-infected women and HIV-negative women, who underwent cesarean delivery at two teaching hospitals. Main outcome measures were infectious postoperative morbidity. Descriptive, comparison analysis, and multiple logistic regression analysis were performed.Results. One hundred and nineteen HIV-infected women and 264 HIV-negative women delivered by cesarean section and were compared. The HIV-negative women were more likely than the HIV-infected women to deliver by emergent cesarean section (78.0% versus 51.3%, resp., ), to labor prior to delivery (69.4% versus 48.3%, resp., ), and to have ruptured membranes prior to delivery (63.5% versus 34.8%, resp., ). In bivariate analysis, HIV-infected and HIV-negative women had similar rates of post-operative infectious complications (16.8% versus 19.7%, resp., ). In a multivariate stepwise logistic analysis, emergent cesarean delivery and chorioamnionitis but not HIV infection were associated with increased rate of post-operative endometritis (odds ratio (OR) 4.10, 95% confidence interval (95% CI) 1.41–11.91, , and OR 3.02, 95% CI 1.13–8.03, , resp.).Conclusion. In our facilities, emergent cesarean delivery and chorioamnionitis but not HIV infection were identified as risk factors for post-operative endometritis.

scholarly journals Levels of Macrophage Inflammatory Protein 1α (MIP-1α) and MIP-1β in Intervillous Blood Plasma Samples from Women with Placental Malaria and Human Immunodeficiency Virus Infection

2003 ◽  
Vol 10 (4) ◽  
pp. 631-636 ◽  
Author(s):  
Sujittra Chaisavaneeyakorn ◽  
Julie M. Moore ◽  
Lisa Mirel ◽  
Caroline Othoro ◽  
Juliana Otieno ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Blood Plasma ◽  
Plasma Levels ◽  
Placental Malaria ◽  
Hiv Positive ◽  
Inflammatory Protein ◽  
Immunodeficiency Virus ◽  
Macrophage Inflammatory Protein ◽  
Hiv Negative

ABSTRACT Macrophage inflammatory protein-1α (MIP-1α) and MIP-1β play an important role in modulating immune responses. To understand their importance in immunity to placental malaria (PM) and in human immunodeficiency virus (HIV)-PM coinfection, we investigated levels of these chemokines in the placental intervillous blood plasma (IVB plasma) and cord blood plasma of HIV-negative PM-negative, HIV-negative PM-positive, HIV-positive PM-negative, and HIV-positive PM-positive women. Compared to HIV-negative PM-negative women, the MIP-1β concentration in IVB plasma was significantly elevated in HIV-negative PM-positive women and HIV-positive PM-positive women, but it was unaltered in HIV-positive PM-negative women. Also, PM-infected women, irrespective of their HIV status, had significantly higher levels of MIP-1β than HIV-positive PM-negative women. The MIP-1α level was not altered in association with either infection. The IVB plasma levels of MIP-1α and MIP-1β positively correlated with the cord blood plasma levels of these chemokines. As with IVB plasma, only cord plasma from PM-infected mothers had significantly elevated levels of MIP-1β compared to PM-negative mothers, irrespective of their HIV infection status. MIP-1β and MIP-1α levels in PM-positive women were positively associated with parasite density and malaria pigment levels. Regardless of HIV serostatus, the IVB MIP-1β level was significantly lower in women with PM-associated anemia. In summary, an elevated level of MIP-1β was associated with PM. HIV infection did not significantly alter these two chemokine levels in IVB plasma.

Interleukin-15 enhances neutrophil functional activity in patients with human immunodeficiency virus infection

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1979-1984
Author(s):  
Claudio M. Mastroianni ◽  
Gabriella d'Ettorre ◽  
Gabriele Forcina ◽  
Miriam Lichtner ◽  
Fabio Mengoni ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Treatment Failure ◽  
Oxidative Burst ◽  
Highly Active Antiretroviral Therapy ◽  
Fungicidal Activity ◽  
Stimulant Effect ◽  
Immunodeficiency Virus ◽  
Vitro Effect

Polymorphonuclear leukocyte (PMN) dysfunction has been reported in human immunodeficiency virus (HIV)-infected patients. Interleukin (IL)-15 is a recently discovered cytokine that potentiates antimicrobial functions of normal PMNs. We evaluated the in vitro effect of IL-15 on chemotaxis and fungicidal activity of PMNs from 9 patients with untreated advanced HIV infection, 8 patients with viral suppression after 52 to 130 weeks of highly active antiretroviral therapy (HAART), and 12 patients with treatment failure. We also studied oxidative burst and apoptosis of PMNs in 5 patients with untreated advanced HIV infection. Twelve healthy donors were included as controls. Chemotaxis and fungicidal activity of unprimed PMNs was significantly lower in patients with untreated HIV infection compared with controls. After incubation with IL-15, a significant increase in PMN chemotaxis and fungicidal activity was found; moreover, IL-15 induced a significant reduction in the number of apoptotic HIV+ PMNs. IL-15 did not modulate oxidative burst of HIV+ PMNs as measured by chemiluminescence production. The in vitro priming of PMNs with IL-15 determined a complete reversal of defective chemotaxis and killing in all HAART-treated patients with long-term HIV suppression. IL-15 significantly enhanced chemotaxis and fungicidal activity also in patients with HAART failure. In conclusion, IL-15 is an important cytokine in the activation of the functional properties of HIV+ PMNs, by delaying apoptosis and enhancing chemotaxis and fungicidal activity. The potent stimulant effect of IL-15 on PMN function was observed in antiretroviral naive patients as well as in individuals who were receiving HAART, including those with treatment failure.

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