|Year : 2020 | Volume
| Issue : 1 | Page : 10-16
A review of H1N1: Clinical, diagnostic and infection control strategies
Rohit Vadala1, Isabella Princess2, Pratap Upadhya3
1 Metro Centre for Respiratory Diseases, Metro Multispeciality Hospital, Noida, Uttar Pradesh, India
2 Department of Microbiology, Apollo Speciality Hospital, Chennai, Tamil Nadu, India
3 Department of Pulmonary Medicine, JIPMER, Puducherry, India
|Date of Submission||01-Nov-2020|
|Date of Acceptance||23-Jun-2020|
|Date of Web Publication||4-Sep-2020|
Dr. Rohit Vadala
Metro Centre for Respiratory Diseases, Metro Multispeciality Hospital, Noida, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Evolution of new viruses and their spread across continents are worrisome due to high mortality rates. One of the greatest advantages of handling epidemics and pandemics of H1N1 is the existing global preparedness, public awareness and vaccine availability for this virus. Media and health departments of various countries play a pivotal role in disseminating knowledge as soon as an outbreak is suspected. Currently, H1N1 is easily detectable and controllable compared to other types of Influenza viruses, therefore reducing the anxiety among the public as well as health-care workers. This review would give a comprehensive understanding of clinical manifestations, diagnostic strategies and infection control practices, which should be followed to effectively manage outbreaks of H1N1.
Keywords: H1N1, infection control, influenza, influenza vaccine, swine flu
|How to cite this article:|
Vadala R, Princess I, Upadhya P. A review of H1N1: Clinical, diagnostic and infection control strategies. J Patient Saf Infect Control 2020;8:10-6
|How to cite this URL:|
Vadala R, Princess I, Upadhya P. A review of H1N1: Clinical, diagnostic and infection control strategies. J Patient Saf Infect Control [serial online] 2020 [cited 2021 Jan 21];8:10-6. Available from: https://www.jpsiconline.com/text.asp?2020/8/1/10/294372
| Introduction|| |
Most viruses which cause major public health threats have human-to-human transmission. Narrowing down on the route of transmission, most viruses gain entry into the human body through the inhalation of infective respiratory droplets. This results in easy transmissibility of viruses within close communities. Shift in the recent trend of global patterns such as extensive travel, urbanisation, rearing exotic pets, deforestation and religious practices go hand in hand in easy dissemination of newer viruses from one part of the world to another. Containment of infectious particles before dissemination remains a challenge as they get carried through various modes within a very short duration. The emphasis here is that an outbreak goes unnoticed until clinical manifestations begin, by which time the virus crosses national and continental borders. Once an outbreak begins, high alert is flagged through various modes of communication across the world. The World Health Organisation (WHO) and the Centres for Disease Control and Prevention (CDC) roll out various risk reduction and preventive strategies during each outbreak. Effective vaccine strategies are proposed every year for public use by the WHO, the most recent one being in February 2019.
Swine flu/H1N1 emerged as a respiratory virus causing frequent outbreaks in various parts of the world. The most recent major pandemic caused by H1N1 was in the year 2009 before which epidemics with other strains of the virus have been reported. Ever since this pandemic, the 2009 pandemic Influenza strain has now established itself causing sporadic outbreaks of seasonal Influenza. Early recognition of these outbreaks, coupled with immunoprophylaxis helps in reducing morbidity and mortality to a great extent. The importance of this review is to discuss effective management of an epidemic or pandemic of H1N1 based on clinical features, diagnostic methods and infection control policy.
| Case Definition and Clinical Categorisation of H1N1|| |
Cases of H1N1 Influenza are defined and characterised based on case definitions given by the Government of India are as follows.
A person with acute febrile respiratory illness (temperature ≥38°C) along with one of the followings:
- onset of illness, 7 days within close contact with a confirmed H1N1 patient
- onset of illness, 7 days within travel to a place with one or more confirmed swine flu (H1N1) cases
- Residing in a community with one or more confirmed swine flu (H1N1) cases.
A person with acute febrile respiratory illness along with one of the followings:
- Positive for Influenza A (unsubtypable by polymerase chain reaction [PCR] into H1/H3/seasonal influenza)
- Meets the criteria of the suspected case along with positivity to Influenza A by a rapid test or immunofluorescence assay
- Individual with a clinically compatible illness who died of an unexplained acute respiratory illness who is considered to be epidemiologically linked to a probable or confirmed case.
A person with acute febrile respiratory illness with laboratory confirmation of swine Influenza A virus (H1N1) by one of the following tests from a WHO-approved laboratory:
- Real-time reverse transcriptase PCR (rtRT PCR)
- Viral isolation by the culture of virus
- Four-fold rise in viral neutralising antibodies to H1N1.
Every patient should be categorised into either one of these above categories to diagnose and proceed with further evaluation. These guidelines on the clinical categorisation of swine flu (H1N1) patients have been framed by the Ministry of Health and Family Welfare (MOHF), India.
Clinically, H1N1 cases should be categorised into three, as depicted in [Figure 1]. The treatment of H1N1 solely depends on this categorisation.
|Figure 1: Clinical categorisation of swine flu cases.*Risk groups include children with mild illness but with predisposing factors, people over 65 years, pregnant women, patients on long term corticosteroids, patients with any of these diseases: Diabetes, lung disease, heart disease, liver disease, renal disease, cancer, HIV/AIDS, blood or neurological disorders.|
Click here to view
Complications of H1N1 include bronchitis, respiratory distress, secondary bacterial pneumonia, exacerbation of chronic illnesses, myocarditis, encephalopathy, toxic shock syndrome, sepsis.
| Laboratory Diagnosis of H1N1|| |
As discussed above, laboratory testing is done only for patients falling under category C of illness. Category A and B patients do not require testing or treatment. These recommendations are put forth by the Government of India, but it is often challenging to convince patients as well as clinicians to prevent outliers. It should be reiterated that H1N1 testing is not necessary for patients in categories A and B.
The Indian government recommends the use of real-time PCR (rt RT PCR), viral culture, neutralisation tests for diagnosis of swine flu (H1N1). An exclusive document by the National Institute of Communicable Diseases provides details on sample collection, transport and tests for diagnosis of H1N1. This is detailed and clarifies simple doubts on all aspects of Influenza diagnosis.
Sample collection for H1N1 diagnosis,
What to collect?
Throat swabs, nasal swabs, nasopharyngeal aspirates/washes/swabs, oropharyngeal washes/aspirates/swabs, bronchoalveolar lavage and tracheal aspirates can be collected.
When to collect?
Specimens should be collected as early as possible after the onset of symptoms and ideally before the initiation of antiviral therapy. Patients who present after a week of onset of symptoms can also be subjected to testing. Multiple samples can be collected if necessary and if the patient is available.
How to collect?
The health-care professional must don all components of Personal Protective Equipment (PPE) before initiating sample collection. Mandatory PPEs to be used are N95 mask, gloves, gown, hair cover, goggles and boots (if exposure is anticipated). Samples should be collected and transported in viral transport medium (VTM)-containing bovine serum albumin, antimicrobials, phenol red indicator, sodium bicarbonate. Swabs used should have a synthetic tip (polyester/dacron) and a plastic/aluminium shaft. Cotton or alginate swabs and swabs with wooden sticks are toxic to the virus and therefore be avoided.,
Who should collect?
Samples should be collected by trained professionals such as physicians, microbiologists, nurses, preferably before the initiation of antiviral therapy. It is not recommended by laboratory staff to collect samples for H1N1 diagnosis. However, in laboratory technicians who are trained as phlebotomists can collect samples.
Transport of specimens for influenza diagnosis,
Transport of collected specimens is equally crucial as the collection process. In the case of sample transport to a laboratory away from the collection site, samples must be meticulously packed according to documented guidelines., Sample labelling is mandatory with information such as the name of the patient, age, specimen number, hospital name and unique identification number. Samples collected in VTM should be stored at 4°C before and during transportation within 48 h of sample collection. After 48 h, samples should be stored at -70°C, avoiding freeze-thaw cycles. A standard triple packing system given by the WHO should be followed with an accompanying form filled with all clinical and epidemiological details of the patient. Personnel handling these specimens should wear appropriate PPE and wash hands frequently. In the case of spills during transportation, disinfection is mandatory using sodium hypochlorite (bleach). Waste should be handled appropriately according to current biomedical waste management guidelines. Work surfaces in laboratories should be cleaned and disinfected before and after processing samples.,
Diagnostic tests for H1N1
Although many diagnostic tests exist, the Government of India recommends only three methods for confirmatory diagnosis of H1N1.
- Viral isolation in cell culture: Specific cell lines are used for the culture of different viruses. The Madin–Darby Canine Kidney cell line is used for the culture of Influenza viruses; inoculation should be done in the Class II biosafety cabinet. This is of limited use to clinicians since the average turnaround time for viral isolation in culture is 4–5 days. Viral isolation is of much importance to extract viral antigens which can be used for other tests such as immunofluorescence, neutralisation and haemagglutination assays
- Embryonated egg inoculation: Allantoic cavity of an embryonated chicken egg is ideal for the inoculation of Influenza A virus. Cytopathic effects can be detected after a week of incubation by candling. In recent years, this procedure has gained importance solely for vaccine production and not of much importance for the diagnosis of the virus
- Antigen detection: Direct immunofluorescence assay is used for direct detection of viral antigens from respiratory epithelial cells using fluorescent-tagged antibodies against the Influenza virus. Other antigen detection methods are lateral flow rapid immunochromatography and dipstick assays, which can be used as a point of care tests in emergency rooms, clinics, etc., Since the Government of India does not recommend antigen detection as a confirmatory test, positive-antigen detection should always be confirmed using one of the recommended methods of diagnosis,
- Antibody detection: Paired serum samples collected during the acute phase and convalescent phase should be tested for neutralising antibodies by neutralisation, haemagglutination inhibition assays. An acute-phase serum specimen (3–5 ml whole blood) should be taken immediately and not later exceeding 7 days after the onset of clinical symptoms. A convalescent-phase serum specimen should be collected 2–4 weeks later. Only a four-fold rise in antibody titre is confirmatory of H1N1 infection; therefore, a single serum specimen can never be used for the diagnosis of Influenza infection. Conventional neutralisation assays have been replaced by microneutralisation using microtitre plates with a turnaround time of 2 days. Neuraminidase assay and neuraminidase inhibition assays are done to detect the inhibitory effect of a patient's serum on the neuraminidase enzyme of the Influenza virus. Antibodies in the serum can then be quantified
- Molecular diagnosis of influenza A H1N1: The most common molecular method used for the diagnosis of H1N1 is RT-PCR using specific oligonucleotide probes. rt RT-PCR for viral RNA amplification can be performed by conventional as well as real-time PCR. The viral RNA is first converted to complementary DNA, which is then amplified using specific primers which are tagged to enzyme/fluorescent dye to make the amplification product detectable. Subtyping of the virus can be done by other methods such as phylogenetic gene sequence analysis, Restriction Fragment Length Polymorphism, probe hybridisation. simple amplification-based assay PCR is a single cartridge-based point of care amplification assay used to detect viral nucleic acid directly from the patient sample within 2 h 15 min. More than 25 platforms of PCR-based assays have been approved by the Food and Drug Administration and authorised by the CDC for Influenza diagnosis. The names of these assays and platforms can be accessed from the CDC website.
It is recommended to collect multiple samples if feasible and in view of the availability of diagnostic tests. It is wise to time the diagnostic tests right according to the time of detection of virus/antigen/antibodies. Viral shedding occurs on day one of illness, whereas antibodies begin to rise by the end of 1st week after viral exposure. Therefore, RT-PCR, viral culture and antigen detection tests can be performed from day 1 of illness, but antibody detection tests should be performed only after day 7 of illness.
[Table 1] comprehensively explains the sensitivity, specificity of various supportive Influenza diagnostic tests along with reference methods used for comparison of the tests. Gold standard tests for Influenza diagnosis are viral culture and rtRT-PCR.
|Table 1: Sensitivities and specificities of various Influenza diagnostic tests|
Click here to view
| Treatment Strategies for H1N1|| |
Antiviral drugs, supportive therapy, respiratory support (mechanical ventilation) are the treatment strategies employed for the management of H1N1 cases based on the clinical category.
Oseltamivir (oral) and Zanamivir (inhalational) are the drugs recommended by the MOHF, India. Both these drugs are neuraminidase inhibitors, but Zanamivir cannot be used in children <5 years of age. On the other hand, Oseltamivir has been approved for use in children >1 year of age. Oseltamivir dosing for children is as follows [Table 2]:
In adults, Oseltamivir dosing for therapy is 75 mg BD for 7 days. For chemoprophylaxis, Oseltamivir is given until 10 days after the individual's exposure at a dose of 75 mg once daily for 5 days. Similarly, Zanamivir dosing for therapy is 10 mg BD (two 5 mg inhalations) for 5 days. For chemoprophylaxis, Zanamivir is given for 7 days as 10 mg (two 5 mg inhalations) once daily. Antiviral drugs are more effective only if initiated within 48 h after the onset of symptoms., Other drugs effective yet not recommended in national guidelines are the adamantanes (amantadine, rimantadine), other neuraminidase inhibitors such as peramivir and laninamivir. It is noteworthy to keep in mind that resistance to antivirals has emerged and been documented. Adverse reactions to antiviral drugs are minimal. Oseltamivir usage may cause nausea, vomiting with increasing doses. Other reported side effects are pseudomembranous colitis, bronchitis, insomnia, vertigo, angina, peritonsillar abscess, etc.
Supportive therapy for H1N1 [Table 3]
The MOHFW of India recommends hospitalisation only for Category C patients. Patients in Category A and B1/B2 patients should confine themselves at home and avoid mixing up with public and high-risk members in the family. Category A patients should not be subjected to testing for H1N1 as well.
Patients can be discharged after 7 days of symptomatic relief. However, children treated for swine flu (H1N1) should be discharged only after 14 days of symptomatic relief.
| Infection Control Practices|| |
Preventing the spread of H1N1 encompasses various aspects is depicted in [Figure 2]. Inevitable outbreaks can be efficiently managed only if good infection control practices are implemented and stringently followed. Staff, patient, public education and awareness need to be key goals in effective infection control during community as well as health-care outbreaks [Figure 3].
|Figure 3: Process flow for health-care workers handling H1N1-infected patients|
Click here to view
Self-explanatory pictorial representations with thought-provoking quotes should be displayed in crowded and common areas of hospitals to draw the attention of patients and their attendants. These displays are educative and create awareness on how to prevent the generation of infective aerosols. Visual alerts are put up, especially during outbreaks and epidemics. Steps of cough etiquette to be followed include coughing into a paper towel, if unavailable, into the upper sleeve, disposing the soiled paper towel into the “infectious waste” closed bin, performing hand hygiene immediately after coughing, wearing a surgical mask to protect others. Cough etiquette posters are available on the CDC and MOHFW webpages, which can be readily printed and displayed in areas such as outpatient departments, emergency, canteens, wards, critical care areas. These visual alerts depicting cough etiquette are a simple yet vital form of communication in health-care settings.
Standard precautions and transmission-based precautions
Components of standard precautions include appropriate use of PPEs, hand hygiene, proper disposal of biomedical waste and sharps, proper handling of infected linen. All Influenza infected patients should be placed in separate rooms with appropriate “Droplet isolation” signage displayed on the door. Appropriate PPEs (Gown, surgical mask), alcohol-based hand rubs should be placed outside patient rooms. N95 masks are not recommended for use in droplet isolation; however, based on availability, clinical judgement and high exposure-prone procedures, one can use these masks. Bins to discard used PPEs should be placed inside the patient room just before exiting to ensure appropriate disposal of waste before leaving the room. An alcohol-based hand rub should be placed inside the patient's room to ensure hand hygiene after touching patient's surroundings. If dedicated single-patient rooms are unavailable, cohorting of patients should be done with bed placement at least one meter away from each other. All health-care workers, including doctors, nurses, housekeeping staff and allied health staff who provide care, should be vaccinated with the current recommended influenza vaccine. Dedicated medical equipment should be used for these patients which should be cleaned and disinfected with an appropriate disinfectant after each patient's use.,,
Inanimate objects in patient surroundings, fomites, bed rails are major reservoirs of the virus through which indirect transmission may occur., Hand hygiene is the best available entity to ensure the prevention of the spread of the virus to humans from contaminated environmental surfaces. Another major aspect is the decontamination of environmental surfaces with either one of the disinfectants such as phenol, quaternary ammonium compounds, alcohol or 1%–2% sodium hypochlorite. Failure in following any one of these practices may be deleterious, leading to viral transmission.
Immunoprophylaxis against H1N1
Every year, the WHO convenes two consultations in February and September to formulate vaccine recommendations in northern and southern hemispheres. Vaccine preparations should contain these predominant strains recommended in the WHO congress for maximum efficacy. Vaccines available in India have been elicited in [Table 4].
High-risk groups listed above and health-care workers working in emergency rooms, critical care areas, crowded outpatient departments and cohort isolation wards should be vaccinated with the recommended strains every year. It should be mandatorily emphasised to high-risk groups the importance of getting immunoprophylaxis on a yearly basis. Since all influenza vaccines are egg-based (prepared from hen's egg containing ovalbumin), it is wise to avoid vaccinating individuals with egg allergy. These individuals can be given chemoprophylaxis in case of exposure to an infected person. Chemoprophylaxis can also be given to close contacts and for geographic containment of the virus within 5 km from the epicentre.
| Current World Health Organisation Vaccination Strategy for 2019–2020|| |
The most recent WHO congress for vaccine recommendation was held on February 21'st, 2019. Strains to be included in vaccines for the 2019–2020 Influenza season were decided to take into consensus the seasonal influenza activity between September 2018 and January 2019. Strains co-circulating between this period were Influenza A (H1N1) pdm 09, A (H3N2) and B viruses. Over 95% of viruses in most countries were Influenza A type with minimal Influenza B viral infections. The predominant viral subtypes reported in Asia were Influenza A (H1N1) pdm 09 and Influenza A (H3N2). Based on these evidence, the WHO recommends 2019–2020 quadrivalent vaccine to contain the following strains of viruses:
- An A/Brisbane/02/2018 (H1N1) pdm09-like virus,
- An A/Kansas/14/2017 (H3N2) virus (component announced on 21st March 2019),
- A B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) and
- A B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage).
For trivalent vaccines, the WHO recommends the use of B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) along with the two strains of Influenza A viruses.
These are specifications provided for countries in Northern Hemisphere. According to a document released by the WHO regarding countries of tropics and subtropics, India belongs to the Southern Hemisphere vaccination zone. Tropical and subtropical countries may, however, choose their vaccine strains between northern and southern hemisphere formulations from the WHO website.
| Conclusion|| |
Epidemics of H1N1 are inevitable every year. Although the burden of this infection has remarkably reduced compared to the past, mortality and morbidity is definitely alarming. Early suspicion, viral detection, effective management and prompt infection control practices are key determinants during H1N1 epidemics. One has to remain updated on different vaccine strains every year, depending on the geographic location. Preparedness in health-care settings also plays a pivotal role in managing H1N1 epidemics.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dikid T, Jain SK, Sharma A, Kumar A, Narain JP. Emerging re-emerging infections in India: An overview. Indian J Med Res 2013;138:19-31.
] [Full text]
Shekhar R, Sharma P, Tyagi LK, Gupta AK, Kori ML. Swine Flu (Swine Influenza-A (H1N1) Virus): A review. Global J Pharmacol 2009;3:131-6.
Guidelines for Sample Collection and Handling of Human Clinical Samples for Laboratory Diagnosis of H1N1 Influenza. Directorate General of Health Services MINISTRY of Health and Family Welfare Government of India; 2016.
Pandemic Influenza A H1N1. Clinical Management Protocol and Infection Control Guidelines; 2009.
Clinical Management Protocol for Seasonal Influenza; 2017.
WHO Global Influenza Surveillance Network Manual for the Laboratory Diagnosis and Virological Surveillance of Influenza; 2011.
Drexler JF, Helmer A, Kirberg H, Reber U, Panning M, Muller M, et al
. Poor clinical sensitivity of rapid antigen test for influenza A pandemic (H1N1) 2009 virus. Emerg Infect Dis 2009;15:1662-4.
Faix DJ, Sherman SS, Waterman SH. Rapid-test sensitivity for novel swine-origin influenza A (H1N1) virus in humans. N
Engl J Med 2009;361:728-9.
Wang R, Taubenberger JK. Methods for molecular surveillance of influenza. Expert Rev Anti-Infective Ther 2010;8:517-27.
Wu L, Thomas I, Curran MD, Ellis JS, Parmar S, Goel N, et al
. Duplex molecular assay intended for point-of-care diagnosis ofinfluenza A/B virus infection. J Clin Microbiol 2013;51:3031-8.
Hawkes M, Richardson SE, Ipp M, Schuh S, Adachi D, Tran D. Sensitivity of rapid influenza diagnostic testing for swine-origin 2009 a (H1N1) influenza virus in children. Pediatrics 2010;125:e639-44.
Yu S, Bui CT, Hoang Kim DT, Nguyen AV, Thi Trinh TT, Yeo S. Clinical evaluation of rapidfluorescent diagnostic immunochromatographic test for influenza a virus (H1N1). Nature Sci Rep 2018;8:13468.
Veguilla V, Hancock K, Schiffer J, Gargiullo P, Lu X, Aranio D, et al
. Sensitivity and specificity of serologic assays for detection of humaninfection with 2009 pandemic H1N1 virus in U.S. Populations. J ClinMicrobiol 2011;49:2210-5.
Angoulvant F, Bellettre X, Houhou N, Dexpert JB, Morin L, Siriez JY, et al
. Sensitivity and specificity of a rapid influenza diagnostic test in children and clinical utility during influenza A (H1N1) 2009 outbreak. Emerg Med J 2011;28:924-6.
Rewar S, Mirdha D, Rewar P. Treatment and prevention of pandemic H1N1 influenza. Ann Global Health 2015;81:645-53.
Bridges CB, Kuehnert MJ, Hall CB. Transmission of influenza: Implications for control in health care settings. Clin Infect Dis 2003;37:1094-101.
Ryan MA, Christian RS, Wohlrabe J. Handwashing and respiratory illness among young adults in military training. Am J Prev Med 2001;21:79-83.
Hillyard DR. Novel swineorigin influenza A (H1N1) virus investigation team. N
Engl J Med 2009;360:25.
World Health Organization. Recommended Composition of Influenza Virus Vaccines for Use in the 2019-2020 Northern Hemisphere Influenza Season; 21 February, 2019. p. 1-9.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]