Pleconaril Revisited: Clinical Course of Chronic Enteroviral Meningoencephalitis after Treatment Correlates with <i>In Vitro</i> Susceptibility
Bibliographic record
Abstract
BACKGROUND: Human enteroviruses (HEVs) can cause severe infections, especially in patients with a deficient humoral immune response, such as X-linked agammaglobulinemia. In this patient group, chronic enteroviral meningitis (CEMA) is feared because of extensive morbidity and high fatality rate. Treatment options consist of intravenous immunoglobulin (IVIG), with various outcomes. Pleconaril is an antiviral agent with in vitro activity against HEVs that has been used in the treatment of HEV infections. METHODS: The efficacy of pleconaril and IVIG against HEV isolated from the patients was assessed in vitro in two patients with CEMA. RESULTS: Echovirus 11 was found in the cerebrospinal fluid (CSF) of case 1. Treatment with high-dose IVIG and pleconaril did not provide any clinical improvement and HEV PCR in CSF remained positive. Case 2 (echovirus 13 positive in CSF) was also treated with IVIG and pleconaril. The patient recovered completely and HEV PCR in CSF became negative. Recent IVIG batches contained low titres of neutralizing antibodies against the patient strains. Echovirus 11 (case 1) was resistant to pleconaril in vitro, whereas echovirus 13 (case 2) was susceptible, in accordance with virological response after treatment and subsequent clinical results. CONCLUSIONS: This is the first report that evaluates efficacy of antiviral treatment in CEMA patients in relation to in vitro susceptibility of clinical virus isolates. Since pleconaril is no longer available for compassionate use we strongly propagate that new drugs should be developed against these potential life threatening HEV infections.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".