Norovirus infectionsA08.1 Akute Gastroenteritis durch Norovirus

Noroviruses are widespread worldwide and are among the most common causes of non-bacterial acute gastrointestinal inflammation. Noroviruses are highly infectious and are characterised by a high level of environmental resistance. As the only known reservoir of the pathogen, it is known to humans. The detection of caliciviruses in animals (pigs, cats and rabbits) is currently not recognizably related to human diseases. Infections usually occur as minor endemics in community facilities and clinics, but also sporadically.

Noroviruses (old name Norwalk viruses) are unenveloped viruses with high environmental resistance. They belong to the Caliciviridae family ( Caliciviridae ), which derives its name from the calix (lat. = calyx), which can be detected on the capsid surface. Noroviruses are characterized by a pronounced genome variability. They are divided into 5 genogroups. Noroviruses have an extremely high degree of contagiousness and can cause endemics that are difficult to control, e.g. in hospitals and nursing homes.

Adsorption of the virus takes place at receptors expressed on the epithelial cells of the gastrointestinal tract. The processes involved in the penetration and release of genomic RNA into the cytoplasm of the luminal cells are still unknown.

The viruses are excreted in large quantities in stool and vomit; accordingly, transmission occurs via direct contact (oral ingestion of virus-containing droplets - aerosols produced during gushing vomiting ) or indirect contact (fecal-oral, e.g., via hand contact with contaminated surfaces). Although viral shedding is possible during the presymptomatic phase, the massive release of infectious viruses begins with the onset of clinical symptoms. This explains the rapid spread of infection, for example, in hospitalized settings. Transmission of noroviruses can also occur through contaminated food or drinking water. Although infections can occur throughout the year, a cluster is observed in the winter months ("winter vomiting disease").

Duration of infectivity: During acute illness and until at least 48h after resolution of clinical symptoms, affected individuals are highly infectious. The virus is excreted for at least 7-14 days, in some cases even for weeks after the symptoms have subsided. Therefore, even after the acute phase, a consequent

Children (about 30% of cases) and adults (about 50% of cases) are affected. Infections with noroviruses can occur all year round. A seasonal accumulation of infections can be observed especially during the cold season (October to March). A high number of unreported cases can be assumed (Karst SM et al. 2015)!

Incubation period: 10-50 hours.

Noroviruses cause acute gastroenteritis with severe diarrhea and violent, gushing vomiting, which can lead to a significant fluid deficit. Accompanying this is an acute, marked feeling of illness with abdominal pain, nausea, headache, lassitude, and myalgias. Body temperature may be slightly elevated; however, high fever usually does not occur. Mild or asymptomatic courses are also possible. Clinical symptoms persist for about 1-2 days, with a maximum of 4 days.

Leucocytosis

Bioptic material shows shortened and widened villi in the jenjunum. During convalescence the microvilli completely regress to the pre-infectious normal state.

There are currently 3 detection methods available for the detection of noroviruses:

• Amplification of viral nucleic acids (reverse transcriptase polymerase chain reaction, RT-PCR)
• Detection of viral proteins (antigen EIA)
• electron microscopic detection of virus particles.

The method with the highest sensitivity and specificity is the detection of virus RNA in stool samples by RT-PCR. This method is suitable for rapid clarification of outbreaks.

Food poisoning (mostly by bacterial toxins), Salmonella gastroenteritis; Rotavirus infection (often in children <5 years). For special questions, molecular biological methods are also available for the detection of other viral gastroenteritis pathogens (astrovirus, aichivirus, picobirnavirus, bocavirus).

Desiccosis (children, older adults); prolonged course in immunocompromised patients)

The therapy is carried out symptomatically by compensating the loss of fluid and electrolytes (still water, black tea, green tea) and, if necessary, by using antiemetics.

The production of an effective vaccine has so far failed due to the immunological variability of the virus.

Cautious gradual food build-up: 1-2 days of tea fasting, possibly grated apples with crushed banana. Followed by rusks, gruel soups (rice or gruel), carrot vegetables, potato soup, low-fat meals.

Warm stomach compresses or a hot-water bottle have a relaxing effect.

In addition, a lightly salted chicken broth is a proven household remedy that is also well tolerated in the acute phase of illness.

A causal antiviral therapy is not available. Patients should stay in bed during the acute phase and consistently limit contact with other people until 48 hours (better 72 hours) after the symptoms have ceased.

Norovirus infections are generally benign. Low lethality (<0.1%). They are self-limiting and have an incubation period of about 6-50h. In old, very young or weakened patients the disease can lead to death.

Recurrent infections are possible (reinfections), since a developed immunity is only of short duration (the most frequent genotype II.4 changes its capsid protein repeatedly).

Due to the high infection rate, immunity appears to be only partial, so that one can be repeatedly infected with different pathogen types (no cross-immunity).

If the infection breaks out in immunocompromised patients, a chronic infection may occur. In this constellation, the norovirus can possibly be detected in the stool for several years (often several pathogens are involved). These patients may suffer from chronic diarrhoea. However, the infection can also be asymptomatic at times. In severe cases, a norovirus-associated enteropathy may occur.

Due to the high infectivity, norovirus outbreaks can only be controlled by consistent and complete adherence to hygiene measures. In case of clinical-epidemiological suspicion of a norovirus infection (abrupt onset, violent gushing vomiting, high rate of illness), the necessary hygiene measures must be implemented immediately, even before laboratory confirmation.

These include in particular:

• Isolation measures
• Careful and frequent hand hygiene
• Precautionary measures during patient transfer
• Temporary closure of wards for new admissions
• Diagnostic measures to detect norovirus outbreaks quickly and as reliably as possible
• Measures for cleaning and disinfecting the contaminated environment
• Temporary release from duty of ill staff, as well as communication and reporting

Help against nausea:

• Fennel Tea
• chamomile tea or
• a combination of fennel, aniseed and caraway tea.

Swelling agents: carrot soup, psyllium and Indian psyllium in particular as seed coat (Silcher H 2015).

Adsorbents: coffee charcoal

Antiphlogistics: Oak bark, tormentill rootstock (Tormentillae rhizoma)

Peristaltic (and antiemetic) drug: Uzara root (Uzara®40mg tbl: adults and adolescents) As an initial dose 4-5x 1-2 doses/day; then 3-6x 1 dose per day; schoolchildren and infants 1-2 doses/day).

Dry yeast from Saccharomycescerevisiae (Syn: Saccharomyces boulardii): as monopreparation Perenterol®forte 250mg Kps. 2x1 Kps/day.

For example, blueberries and pectin-rich fruits (apple or carrot fruits) can be helpful for children.

Ginger rootstock (Zingiberis rhizoma) is also described as helpful for nausea and vomiting: Application: put a few slices of peeled ginger in a container, pour boiling water over them and let them steep for 5-10 minutes, strain, 1 cup before meals. Ready-to-use preparations (e.g. Zintona® Kps 250mg powdered ginger stock; adults and children > 6 years 2 Kps/day) are available as monotherapeutic treatment.

Practical tip: In the acute phase, administer small amounts of cola and salt sticks

Hygiene measures in inpatient facilities, State Center for Health in NRW

Accommodation:

• Single room accommodation (contact isolation) with own wet cell or cohort isolation. If no private toilet is available, use night chair, urine bottle or bedpan on a patient-by-patient basis.
• Restrict staff, patient, resident movement. Bed rest and, if possible, stay exclusively in own patient room until 48 h after symptoms end.
• In case of transfers, the receiving facility must be informed in advance of the infection.

Protective measures:

• Consistent hand hygiene for staff, visitors and patients with a virus-effective disinfectant (virucidal).
• In routine cases, use VAH-listed virucidal agents or products with "limited virucidal activity" test method according to DIN EN 14476,
• In the event of an outbreak, use only disinfectants with the AB range of action with proven "virucidal activity" (test method according to DVV/RKI guideline),

Hand disinfection

• before and after patient contact,
• after contact with contaminated objects, surfaces or materials,
• after removing gloves and protective gowns,
• before leaving the isolation room
• after using the toilet,
• before contact with food.

Train and instruct staff, visitors, and patients regarding hand hygiene, disinfection, and other protective measures.

• Protective gowns, gloves in case of possible contact with pathogen-containing material.
• Use appropriate respiratory protection when in contact with affected patients to prevent infection associated with vomiting.
• If necessary, use protective goggles if patient vomits. - Dispose of protective clothing in appropriate discards in patient room before leaving room.
• Close wards or areas to new admissions as appropriate.

Disinfection and reprocessing

• For surface disinfection, use only agents with proven norovirus efficacy (virucidal) from the list of the Association for Applied Hygiene (VAH) (verifiable inactivation of the virus by products proven by DVV carrier test "virucidal low level" or RKI test method).
• The manufacturer's instructions on concentration and exposure time must be observed.
• At least daily wipe disinfection of the sanitary area and all contact surfaces close to the patient, door handles, door knobs, switches, etc. with a suitable disinfectant. - Visibly contaminated surfaces should be disinfected immediately. - In the case of contamination by vomit, for example, clean immediately with disinfectant.
• Disinfect medical equipment at least once a day.
• Use and disinfect care utensils for specific persons.
• Clean isolation rooms last, wear protective clothing, dispose of mop and cloth. - Place instruments in ready-to-use instrument disinfection solutions, thermally process and transport closed.
• Transport dishes in closed containers (rinse >60°C).
• Treat laundry as infectious (wash chemo-thermally >60°C).

Sick personnel

• Sick personnel should be excused from work even in case of minor gastroenteritic symptoms. Work can be resumed 2 (preferably 3) days after symptoms have subsided, provided that hand hygiene is consistently observed. This also applies to personnel in food occupations (§ 42 IfSG). Infectivity is to be expected for at least 14 days after symptoms have subsided, so that consistent hand hygiene and strict personal hygiene must be observed.

Consultation and special diagnostics Consiliary Laboratory for Noroviruses, FG 15 Molecular Epidemiology of Viral Pathogens Robert Koch Institute Seestraße 10, 13353 Berlin, Tel.: 030 18754-2375 E-Mail: hoehnem@rki.de

1. Karst SM et al (2016) Recent advances in understanding norovirus pathogenesis. J Med Virol 88:1837-1843.
2. Karst SM et al (2014) Advances in norovirus biology. Cell Host Microbe 15:668-680.
3. Karst SM et al. (2015) What is the reservoir of emergent human norovirus strains? J Virol 89:5756-5759.
4. Robilotti E et al. (2015) Norovirus. Clin Microbiol Rev 28:134-164.
5. Silcher H (2015) Guide Phytotherapy. Urban&FischerPublisher p.642-643