Commensal Bacteria Calibrate the Activation Threshold of Innate Antiviral Immunity

Two hundred young adults with common colds were studied during a 10-month period. Virus culture, antigen detection, PCR, and serology with paired samples were used to identify the infection. Viral etiology was established for 138 of the 200 patients (69%). Rhinoviruses were detected in 105 patients, coronavirus OC43 or 229E infection was detected in 17, influenza A or B virus was detected in 12, and single infections with parainfluenza virus, respiratory syncytial virus, adenovirus, and enterovirus were found in 14 patients. Evidence for bacterial infection was found in seven patients. Four patients had a rise in antibodies against Chlamydia pneumoniae, one had a rise in antibodies against Haemophilus influenzae, one had a rise in antibodies against Streptococcus pneumoniae, and one had immunoglobulin M antibodies against Mycoplasma pneumoniae. The results show that although approximately 50% of episodes of the common cold were caused by rhinoviruses, the etiology can vary depending on the epidemiological situation with regard to circulating viruses. Bacterial infections were rare, supporting the concept that the common cold is almost exclusively a viral disease.

Viruses and Bacteria in the Etiology of the Common Cold

Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota.

Sixty-six percent of a group of 163 patients with Parkinson's disease exhibited subjective or objective improvement of their akinesia, rigidity, and tremor while receiving amantadine hydrochloride. Of those showing improvement, benefits were sustained in 58% for a period of three to eight months. The maximum daily dose was 200 mg. Side effects occurred in 22% and consisted of increased jitteriness, insomnia, abdominal uneasiness, dizziness, depression, confusion, and, in a few cases, hallucinations. Convulsions have been reported with large doses of 800 mg per day. In most cases, side effects were controlled by adjustment of dosage of [ill] hydrochloride or the patient's concomitant medication.

https://jamanetwork.com/journals/jama/articlepdf/345886/jama_208_7_011.pdf

Amantadine in the treatment of Parkinson's disease.

ContextInfluenza virus neuraminidase is thought to be essential for virus replication
in humans; however, to date, available neuraminidase inhibitors are limited
to zanamivir, which is topically administered.ObjectiveTo determine the safety, tolerability, and antiviral activity of oral
neuraminidase inhibitor oseltamivir (GS4104/Ro64-0796) for prevention and
the early treatment of influenza in experimentally infected humans.DesignTwo randomized, double-blind, placebo-controlled trials conducted between
June and July 1997.SettingIndividual hotel rooms; 2 large US university medical schools.ParticipantsA total of 117 healthy adult volunteers (aged 18-40 years; median age,
21 years) who were susceptible (hemagglutination-inhibition antibody titer ≤1:8).InterventionsAll subjects were inoculated intranasally with influenza A/Texas/36/91(H1N1)
virus. For the prophylaxis study, oral oseltamivir (100 mg once daily [n=12],
100 mg twice daily [n=12], or matching placebo [n=13], starting 26 hours before
virus inoculation) was administered. For the treatment study, the same drug
was given (20 mg, 100 mg, or 200 mg twice daily, 200 mg once daily, or matching
placebo [n=16], in each group starting 28 hours after inoculation). All regimens
were continued for 5 days.Main Outcome MeasuresComparing placebo groups with pooled treatment groups, for prophylaxis,
outcomes included frequency of infection and viral shedding; for treatment,
viral shedding in titers.ResultsIn the prophylaxis study, 8 (67%) of 12 placebo and 8 (38%) of 21 oseltamivir
recipients became infected (P=.16; efficacy, 61%);
6 (50%) placebo compared with 0 oseltamivir recipients shed virus (P<.001; efficacy, 100%), and 33% of placebo but no oseltamivir recipient
had infection-related respiratory illness (P<.01).
Among infected subjects in the treatment study (n=69), the viral titer area
under the curve of the combined oseltamivir groups (n=56) was lower (median
[interquartile range {IQR}], 80 [23-151] vs 273 [79-306] log10
tissue culture-infective doses50 per milliliter×hour; P=.02) than the placebo group (n=13), and the median (IQR)
duration of viral shedding with therapy was reduced from 107 (83-131) to 58
(35-59) hours (P=.003). Oseltamivir treatment also
reduced symptom scores (median [IQR] score-hours, 225 [97-349] vs 400 [189-645]; P=.05), and nasal proinflammatory cytokine levels. Transient
mild to moderate nausea after dosing was observed in 15 (17%) of 88 oseltamivir
and 2 (7%) of 29 placebo recipients (95% confidence interval for difference, −11%
to 68%), which was largely prevented by ingestion with food.ConclusionsIn these trials, prophylaxis and early treatment with oral oseltamivir
were both associated with significant antiviral and clinical effects in experimental
human influenza.

https://jamanetwork.com/journals/jama/articlepdf/191957/joc90230.pdf

Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment.

Serological evidence for prevention of influenzal infection in volunteers by an anti-influenzal drug adamantanamine hydrochloride.

Viruses Causing Common Respiratory Infection in Man. IV. Reoviruses and Adenoviruses

VII. Present Concepts of the Common Cold

Within the past two decades, many new viruses have been isolated and temporally associated with respiratory illness in humans. Initially, the taxonomic position of these viruses could not be assigned, and it was useful to assemble the known characteristics of each of them into a uniform format. With the acquisition of additional data, a more stable taxonomy of the viruses has been created. Nevertheless, the outline used in this manual was helpful for accumulating known and new data about these viruses and has served as a useful reference for

Viruses causing common respiratory infections in man

The antiviral activity of isoprinosine was tested in tissue cultures and mice. In tissue cultures, concentrations of 25 to 100 mug/ml inhibited the infectivity of influenza and herpes hominis viruses but not parainfluenza virus, rhinovirus, or adenovirus. Among different strains of influenza A, there was considerable variability in the inhibitory concentration of isoprinosine. For influenza B, a zone effect was observed in the inhibitory drug concentration. Oral prophylactic administration of isoprinosine beginning 24 hr before infection with an intermediate challenge dose of influenza A and continued as treatment for 5 days produced a significant reduction in mortality. No protection was provided against a high dose challenge. Oral or intraperitoneal treatment of mice beginning 24 hr after infection with influenza A or B viruses significantly delayed or prevented death when the drug was administered for 10 days, but not when treatment was limited to 4 days. An increased fatality rate which occurred in treated mice given a virus dose of low lethality could not be attributed to drug toxicity.

Robert L. Muldoon

Papers

Serological evidence for prevention of influenzal infection in volunteers by an anti-influenzal drug adamantanamine hydrochloride.

Viruses Causing Common Respiratory Infection in Man. IV. Reoviruses and Adenoviruses

VII. Present Concepts of the Common Cold

Viruses causing common respiratory infections in man

Effect of Isoprinosine Against Influenza and Some Other Viruses Causing Respiratory Diseases