Fatal Multiorgan Failure Syndrome in a Strongyloides-HTLV-1 Coinfected Patient, after Treatment with Ivermectin.

Because of its characteristic features of autoinfection, the parasitic nematode Strongyloides stercoralis can infect patients for years. An acceleration of its autoinfective cycle can be triggered by human T-lymphotropic virus-1 (HTLV-1) infection, mainly by the deviation of the protective Th2- to Th1-type immune response and can lead to severe disease by dissemination of Strongyloides stercoralis larvae carrying intestinal bacteria to multiple organs. Meningitis caused by enteric Gram-negative bacteria is a potentially fatal complication of disseminated strongyloidiasis. Herein, we present the case of a Strongyloides-HTLV-1 coinfected patient, admitted for E. coli meningitis. One day after initiation of ivermectin, the patient developed significant S. stercoralis dissemination, complicated by multiorgan failure syndrome, and died from neurological failure. While the initial clinical scenario of our case has already been well described in the literature, its course after antihelminthic treatment initiation remains unclear and needs to be discussed.

Juvenile-Onset Recurrent Respiratory Papillomatosis Aggressiveness: In Situ Study of the Level of Transcription of HPV E6 and E7.

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is a condition related to HPV 6 and 11 infection which is characterized by the repeated growth of benign exophytic papilloma in the respiratory tract. Disease progression is unpredictable: some children experience minor symptoms, while others require multiple interventions due to florid growth. The aim of this study was to explore the biomarkers of JoRRP severity on a bicentric cohort of forty-eight children. We performed a CISH on the most recent sample of papilloma with a probe targeting the mRNA of the E6 and E7 genes of HPV 6 and 11 and an immunostaining with p16INK4a antibody. For each patient HPV RNA CISH staining was assessed semi-quantitatively to define two scores: 1+, defined as a low staining extent, and 2+, defined as a high staining extent. This series contained 19 patients with a score of 1+ and 29 with a score of 2+. Patients with a score of 2+ had a median of surgical excision (SE) per year that was twice that of patients with a score of 1+ (respectively 6.1 versus 2.8, p = 0.036). We found similar results with the median number of SE the first year. Regarding p16INK4a, all patients were negative. To conclude, HPV RNA CISH might be a biomarker which is predictive of disease aggressiveness in JoRRP, and might help in patient care management.

Chromogenic In Situ Hybridization as a Tool for HPV-Related Head and Neck Cancer Diagnosis.

Human papillomavirus (HPV) infection is a major risk factor for a subtype of oropharyngeal squamous cell carcinoma (OPSCC), which tends to be associated with a better outcome than alcohol- and tobacco-related OPSCC. Chromogenic in situ hybridization (CISH) of HPV viral RNA could allow the semiquantitative evaluation of viral transcripts of the oncogenic proteins E6 and E7 and an in situ visualization with a good spatial resolution. This technique allows the diagnosis of an active infection with the visualization of HPV transcription in the tumoral HPV-infected cells. An advantage of this technique is the avoidance of contamination from nonneoplastic HPV-infected cells adjacent to the tumor. Overall, its good diagnosis performances have it considered to be the gold standard for active HPV infection identification. Since E6 and E7 viral protein interaction with cell proteins pRb and p53 is mandatory for cell transformation, HPV RNA CISH is functionally relevant and acutely reflects active oncogenic HPV infection. This technique is clinically relevant as well since "low" or "high" HPV transcription levels helped the identification of two prognosis groups among HPV-related p16-positive head and neck cancer patients. Here we present the protocol for manual HPV RNA CISH performed on formalin-fixed paraffin-embedded (FFPE) slides with a kit obtained from the manufacturer. Instead of chromogenic revelation, RNA in situ hybridization may also be performed with fluorescent revelation (RNA FISH). It may also be combined with conventional immunostaining.

Evaluation of the efficacy of the 4 tests (p16 immunochemistry, polymerase chain reaction, DNA, and RNA in situ hybridization) to evaluate a human papillomavirus infection in head and neck cancers: a cohort of 348 French squamous cell carcinomas.

It is now established that human papillomavirus (HPV) plays a role in the development of a subset of head and neck squamous cell carcinomas (SCCs), notably oropharyngeal (OP) SCCs. However, it is not clear which test one should use to detect HPV in OP and non-OP SCCs. In this study, using 348 head and neck SCCs (126 OP SCCs and 222 non-OP SCCs), we evaluated diagnostic performances of different HPV tests in OP and non-OP SCCs: polymerase chain reaction, p16 immunostaining, in situ hybridization targeting DNA (DNA-CISH) and RNA (RNA-CISH), combined p16 + DNA-CISH, and combined p16 + RNA-CISH. HPV DNA (polymerase chain reaction) was detected in 26% of all tumors (44% of OP SCCs and 17% of non-OP SCCs). For OP SCCs, RNA-CISH was the most sensitive stand-alone test (88%), but p16 + RNA-CISH was even more sensitive (95%). Specificities were the same for RNA-CISH and DNA-CISH (97%), but it was better for p16 + RNA-CISH (100%). For non-OP SCCs, all tests had sensitivities less than 50%, and RNA-CISH, DNA-CISH, and p16 + DNA-CISH had 100%, 97%, and 99% specificities, respectively. As a stand-alone test, RNA-CISH is the most performant assay to detect HPV in OP SCCs, and combined p16 + RNA-CISH test slightly improves its performances. However, RNA-CISH has the advantage of being one single test. Like p16 and DNA-CISH, RNA-CISH performances are poor in non-OP SCCs to detect HPV, and combining tests does not improve performances.