Swine flu pandemic

1 July 2009. Related: Special reports.

Nathan Geffen, TAC

This is a summary of key information on the H1N1 pandemic, with emphasis on the treatment and management of this disease in HIV-positive people. The main source for this information is the National Institute of Communicable Diseases (NICD) which together with the National Health Laboratory Services (NHLS) produces a health workers’ handbook on pandemic influenza A(H1N1) 2009. It is regularly updated and available on their website. [1]

Table 1: Contact information

Current NICD position on swine flu

The new pandemic influenza A (H1N1) 2009 virus appears to have a higher attack rate than seasonal influenza and is spreading fast, particularly among young people from ages 10 to 45. The severity of disease ranges from very mild symptoms to severe illnesses that can result in death. The majority of people who contract the virus experience mild disease and recover without antiviral treatment or medical care. Of the more serious cases, more than half of hospitalised people had underlying health conditions or weak immune systems. Although the majority of people affected experience mild, self-limiting illness, a characteristic of pandemic strains is the ability to cause severe disease and fatalities in otherwise healthy, young people. Therefore it is vital that pandemic influenza be considered in the differential diagnosis of all patients currently being admitted with severe acute respiratory illness. The overall severity of this influenza pandemic has been assessed to be moderate.

Pregnant women and people with metabolic conditions at higher risk of death

An analysis of 574 swine flu deaths worldwide published by Vaillant and colleagues in Eurosurveillance indicates that there are two important risk factors for mortality: pregnant women and people with metabolic conditions including obesity. [2] As of 16 July 2009, 16 women (10% of all individually documented female cases who died and 30% of the 20-39 year-old women who died) were pregnant or had delivered at the time of their death. Among these 16 women, at least eight had documented underlying health risks (obesity, heart disease or a respiratory disease such as asthma or tuberculosis). No information was available as to the underlying health status of the eight remaining women who died.

A sub-analysis of swine flu deaths showed that diabetes and obesity were the most frequently identified underlying conditions and were found in fatal cases over the age of 20. In 13 fatal cases with individual detailed data on metabolic conditions, seven had obesity, five had diabetes, and one had both.

The NICD defines the following people to be at high risk of serious complications from swine flu:

1. Adults or children with underlying medical conditions and who are receiving regular medical care for conditions such as chronic pulmonary disease (including asthma) and cardiac disease (excluding hypertension), chronic renal and hepatic diseases, diabetes mellitus and similar metabolic disorders.

2. People who are immunosuppressed (including HIV-positive people, and people on immunosuppressive medications). Currently, there is no good data on the interaction between HIV and swine flu. However, experience with seasonal flu suggests that HIV-positive people may be at higher risk of complications.

3. Adults and children who have any condition (e.g. cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders) that can compromise respiratory function or the handling of respiratory secretions or that can increase the risk for aspiration.

4. Morbid obesity (BMI > 30) has been identified as a risk factor for complications of influenza as well as pulmonary embolic disease.

5. Children and adolescents who are receiving long-term aspirin therapy and who might be at risk for experiencing Reye’s syndrome after influenza virus infection.

6. Residents of nursing homes and other chronic-care facilities.

7. Pregnant women, especially in the third trimester and also in the period after delivery.

NICD positions on HIV and swine flu

There is currently no information on the effect of swine flu in HIV co-infected persons. Evidence that influenza can be more severe for HIV-infected adults and adolescents comes from US studies of HIV-positive people who had seasonal influenza, but these data are limited. However, several studies have reported higher hospitalisation rates, prolonged illness and increased mortality, especially among people with AIDS.

It is now clear that the pandemic virus has been established throughout South Africa and that sustained community transmission is occurring. Moving forward, a strategy that concentrates on the detection, laboratory confirmation and investigation of all cases, including those with mild illness is extremely resource-intensive, leaving little capacity for the monitoring and management of severe cases. In addition, this diverts limited resources away from managing other diseases such as HIV and TB. In line with a WHO recommendation, it is therefore prudent to limit routine laboratory testing of all suspected cases of swine flu infections, to focus on people at risk for complications, those with severe illness and to monitor virus characteristics.

NICD Case definitions

The NICD defines three case definitions of increasing seriousness: (1) Influenza Like Illness (ILI) – mild disease, (2) Severe Acute Respiratory Infection (SARI) – moderate to severe disease and (3) severe illness. High fever, persistent vomiting, and marked prostration with progressive / persistent symptoms may suggest ongoing viral replication and predict progression to more severe illness.

Table 2: NICD Case definitions

NICD recommendations on who should be tested

The NICD does not recommend routine testing for ILI patients. Patients with SARI or severe illness should be tested as well as people who are suspected to have died of swine flu.

NICD treatment guidelines

Patients with HIV who present within 48 hours should receive antiviral therapy

Patients with specific features of severe immunosuppression should be considered for oseltamivir after 48 hours at the discretion of the attending physician, including HIV-positive people with CD4 counts < 200 cells/mm3 or WHO Stage 4 (AIDS) or HIV plus active TB on treatment or other pulmonary infection.

People with moderate to severe illness (based on a clinical assessment) that require hospital admission should be managed as follows:

• Where possible people should be isolated in their own room with the door closed for the duration of hospital stay.
• Droplet and contact precautions should be instituted.
• Health workers should wear a surgical mask on entry into a patient’s room and a properly fitting N95 mask should be used for aerosol-generating procedures.
• The patient should wear a standard surgical mask whenever he or she is required to leave the isolation room.
• Where separate isolation rooms are not available, suspected cases should be cohorted in a designated ward and the above precautions instituted.
• Oseltamivir or zanamivir should be used for treatment of moderate to severe cases.

Given the widespread current outbreak, infection with swine flu must be considered as part of the differential diagnosis in all patients presenting with community acquired pneumonia, Acute Respiratory Distress Syndrome (ARDS), any severe acute respiratory infection (SARI) and myocarditis. Strong consideration must be given to urgent treatment with a neurominadase inhibitor such as oseltamivir or zanamivir without waiting for laboratory confirmation.

NICD notes on zanamivir and oseltamivir

The virus is currently sensitive to zanamivir and oseltamivir but it is resistant to the M2 proton channel inhibitors, amantadine and rimantadine.

There are sporadic reports of oseltamivir-resistant isolates and recommendations for use of antivirals may change as data on antiviral susceptibilities become available. Oseltamivir is orally administered and is registered for use in individuals aged ≥1 year of age. Zanamivir is administered through an inhaler and is registered for use in individuals aged ≥ 12 years of age.

Antiviral treatment with oseltamivir or zanamivir should be initiated as soon as possible after the onset of symptoms. Although benefit is likely to be greatest when therapy is initiated within 48 hours, some benefit may still be obtained in patients whose therapy is started later in the course of illness. The use of antivirals should be guided by the clinical condition of the patient and the clinical judgment of the treating physician, at whose discretion the decision to treat rests.

Recommended duration of treatment is five days, but there is limited data on the optimal dosage and duration for people with severe illness from the virus.

Table 3: NICD dosage recommendations for oseltamivir and zanamivir

ARV interactions

According to the Liverpool Pharmacology Group (LPG), there may be potential interactions between oseltamivir and protease inhibitors. [3]

Oseltamivir can cause neuropsychiatric side-effects that might be made worse with protease inhibitors, although CNS symptoms are more likely caused by influenza itself. The LPG recommends caution when using oseltamivir in renally impaired patients using FTC, tenofovir and lamivudine.

There are no clinically significant interactions expected between zanamivir and any ARVs. The LPG also recommends that zanamivir may be preferable in a patient with renal failure as it is poorly systemically absorbed.

Detailed recommendations on dosage for HIV-positive people are provided at
http://www.hiv-druginteractions.org

References

1. NICD and NHLS. Revised health workers handbook on pandemic influenza A(H1N1) 2009 “Swine Flu” version 3, updated 19 August 2009. (Latest version obtained by personal communication, but website is updated regularly: http://www.nicd.ac.za)
2. Vaillant et al. Epidemiology of fatal cases associated with pandemic H1N1 influenza 2009. Eurosurveillance, Volume 14, Issue 33, 20 August 2009. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19309
3. Liverpool Pharmacology Group. Influenza antiviral interactions. May 2009.
http://www.hiv-druginteractions.org/new/Uploaded_Attachment/76_Flu_Chart_update.pdf

(Thanks to Lucille Blumberg for assistance with this article.)