Treatment with oseltamivir in Influenza like illness reduces lower respiratory tract complications by 55%, antibiotic use by 26%, and hospitalization by 59%.[7
] Thus, use of neuraminidase inhibitors for treatment of H1N1 patients with risk factors such as extremes of age, pregnancy, immune suppression, and co-morbid conditions is non-controversial. But US Food and Drug Administration (FDA) and World Health Organization (WHO) guidelines do not support the use of neuraminidase inhibitors for therapeutic use in healthy adults with mild disease.[8
Post-exposure prophylaxis entails giving oseltamivir to exposed persons before the symptoms develop, and the effectiveness of oseltamivir in preventing influenza in household contacts has been proved.[9
Systematic review and meta-analysis by Acute Respiratory Infections Group, Cochrane Collaboration, Rome,[10
] evaluated two studies[11
] in which oseltamivir (75 mg daily) was used for chemoprophylaxis. No conclusion could be drawn as evidence was insufficient to support or refute the use of oseltamivir for chemoprophylaxis against flu-like illness.
The meta-analysis also highlighted the safety data of neuraminidase inhibitors. Nausea was the most commonly reported adverse effect of oseltamivir (OR: 1.79; 95% CI: 1.1–2.93) and was higher with the dose of 150 mg given daily. Evidence for possibility of oseltamivir to induce sudden behavioral changes in recipients (hallucination, suicidal tendencies, and sudden death while asleep) came after a review was ordered by the Japanese government, triggered by the 567 serious neuropsychiatric cases received since the launch of the drug.[13
] Thereafter, prospective clinical trials have reported neuropsychiatric events at a rate of 0.5% with use of oseltamivir,[14
] whereas retrospective studies have mentioned an incidence of 20–27 neuropsychiatric adverse events per 1000 adults at 14 days and 30–40 neuropsychiatric adverse events per 1000 adults at 30 days.[13
Most of the studies evaluating the role of neuraminidase inhibitors have been conducted during seasonal influenza outbreaks. In pandemics, large population of healthy adults are at risk of acquiring influenza, but with a low incidence of severe respiratory tract complications. Neuraminidase inhibitors do not prevent infection or stop nasal viral excretion and are thus a suboptimal means of interrupting viral spread in a pandemic.
Novel influenza viruses are very efficient agents causing rapid spread and transmission of disease, and thus lead to outbreaks in healthcare settings. But evidence-based data available to guide infection control measures during pandemics are scarce. The use of N95 respirators instead of surgical masks for all close contacts during a pandemic is recommended based on evidence-based studies.[15
] A study conducted in Hong Kong during 2009 H1N1 epidemic also concluded that not wearing a surgical mask either by the exposed persons during contact with the index cases (4/4 vs. 264/832, P
= 0.010) or vice versa (4/4 vs. 300/832, P
= 0.017, Fisher's exact test) was one of the most significant risk factors for nosocomial acquisition of H1N1.[16
Incidence rates of H1N1 infection among HCP during 2009 pandemic have been described in two previous studies.[1
] Attack rates were high when infection control measures were not followed,[1
] but low when proper measures were undertaken.[2
] Till date, no study compares the incidence rates in HCP with and without chemoprophylactic intake of neuraminidase inhibitors. We, in our study, attempt to highlight the advantages and disadvantages of chemoprophylactic intake of oseltamivir by HCP following infection control measures in places of high aerosol generation – Swine Flu ICU.
The results of our study report no significant difference in the incidence of flu-like illness and H1N1 infection among those who took chemoprophylaxis in comparison to those who did not. There was no significant difference in the incidence of flu-like illness among close contacts of HCP in the two groups. Instead, 57% of HCP who took oseltamivir reported an ADR – nausea, gastritis, and headache in decreasing order of frequency. But none reported any severe or life-threatening complication. Thus, we conclude that chemoprophylaxis with oseltamivir is not required by healthy HCP using PPE in areas of high aerosol generation like ICU. There is no clinically significant advantage in terms of protective efficacy. In contrast, incidence of adverse effects is high.
ADRs of therapeutic and prophylactic doses of oseltamivir were also studied during the 2009 H1N1 pandemic by Anovadiya et al
] Causality, severity, and preventability assessments were also done. Frequency of ADRs in therapeutic and prophylactic groups was compared with phase III trial of oseltamivir. Therapeutic group reported significantly higher incidence (62%) and severity of ADRs in comparison to prophylactic group (41%). Common ADRs in both the groups were gastritis, nausea, vomiting, diarrhea weakness, sedation, loneliness, sadness, headache, and abdominal pain. Results of our study also report an incidence of 57% of ADRs among HCP. Though nausea and gastritis were the most common similar to the previous study, headache was reported as the third most frequently reported ADR, which is in contrast to the previous study.
Limitations of our study include its retrospective design and recall bias of HCP interviewed. However, the recall period did not extend beyond 15 days, and thus likelihood of this limitation is low. Another possible bias may be regarding exposure to H1N1 infection from external sources, e.g. community, neighborhood. To prevent this, we did inquire all HCP for any contact with a suspected H1N1-positive patient outside the hospital, but none of them reported any such exposure. Testing for H1N1 was not done in all HCP and we identified “flu-like illness” based on clinical features. Testing was limited to HCP with severe manifestations only. This could probably underestimate the number of HCP infected as the subclinical forms and those with mild illness could be missed out. Use of neuraminidase inhibitors for therapeutic use in healthy adults with mild disease is not recommended, and thus we did not attempt to identify or treat these mild forms which are self-limiting in nature and without any adverse sequel.
Indiscriminate use of oseltamivir increases the risk of development of oseltamivir-resistant H1N1 virus[18
] and is discouraged. During influenza pandemics, emphasis should be laid on infection control procedures, use of PPE, and hand washing. There is a paucity of clinical trials on the use of oseltamivir during pandemics, as highlighted by Gupta et al
] Our study makes an attempt to describe the protective efficacy and safety of oseltamivir when used for chemoprophylaxis for HCP in contact with H1N1 infected patients. Further research is needed in the form of randomized controlled trials with a large sample size.