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Lee VJ, Yap J, Cook AR, et al.
Oseltamivir Ring Prophylaxis for Containment of 2009 H1N1 Influenza Outbreaks
New England Journal of Medicine; Volume 362:2166-2174; 10 June 2010; Number 23
This study reports the effectiveness of post-exposure ?ring chemo-prophylaxis? using the antiviral oseltamivir in controlling four outbreaks of 2009 pandemic influenza A(H1N1) that occurred from June 22nd to June 25th 2009 in the semi-closed environment of four different military camps in Singapore. The authors defined ?ring chemo-prophylaxis? as a ?geographically targeted containment by means of prophylaxis?. To conduct the study, all personnel with confirmed infection were isolated and the affected military units were segregated and administered post-exposure ?ring chemo-prophylaxis? with oseltamivir with the purpose of containing the spread of the virus. All personnel were subsequently screened for signs of infection using questionnaires three times a week, both for virologic infection and for clinical symptoms. The total number of at-risk personnel was 1175, of which 75 (6.4%) were confirmed infected before the intervention, and the remaining 1100 received, thus, oseltamivir prophylaxis. The results show that after the intervention only 7 of the 1100 personnel that received oseltamivir prophylaxis were infected after receiving the antiviral. Moreover, the study concludes that there was a significant reduction in the effective reproductive number, from 1.91 (before the intervention) to 0.11 (after the intervention), and that three of the four outbreaks showed a significant reduction in the rate of infection after the intervention. Molecular analysis of samples obtained from cases within the same outbreak indicated that these cases were due to transmission within the camp, ruling out the possibility of unrelated episodes of infection. Concerning possible adverse effects of the oseltamivir the study notes that of the 816 personnel treated with oseltamivir who were surveyed for these effects, 63 of them (7.7%) reported only mild non-respiratory side effects and no severe adverse effects were described.
Health Protection Agency UK The role of the Health Protection Agency in the ?containment? phase during the first wave of pandemic influenza in England in 2009
Health Protection Agency, March 2010
This overview of the role of the Health Protection Agency (HPA) in the ?containment phase? of the first wave of the 2009 influenza A(H1N1) pandemic gives a preliminary assessment of the effectiveness of the measures taken to attempt to contain the 2009 influenza A(H1N1) pandemic during the Spring and Summer wave in England. The ?containment? measures taken by the HPA with regards to antivirals were:
* Treatment of ?cases? meeting a sensitive case definition (without waiting for diagnostic confirmation)
* Antiviral prophylaxis of close contacts of cases
* In school settings, those with clinical illness were offered treatment with oseltamivir and only allowed to return to school when symptom free. Close contacts of confirmed cases (and of suspected cases in confirmed outbreaks) were offered prophylaxis but no restriction was placed on activity unless they became unwell. Often, contacts of cases identified in schools could not be individually identified and the whole year or school was offered prophylaxis.
The evaluation reports that as a result of the general implementation of these measures, and in particular of the combination of treatment of index cases and prophylaxis of close contacts, there was a reduction of symptomatic infection in close contacts was observed (especially if treatment and prophylaxis were provided rapidly). The report also states that, although the effects of treatment and prophylaxis occurred together and cannot be separated, most of the effect will have been due to prophylaxis, having into account the time delay observed with the index cases, i.e. from the moment they are infected until they are identified as suitable candidates for antiviral treatment. For this reason, as peak infectivity occurs close to the onset of symptoms, treatment alone is never likely to have much impact on transmission. The second part of this report is especially interesting as it summarises the key operational issues identified by the HPA and comes to preliminary conclusions that though containment measures, implemented by the HPA working with the clinical services (the NHS) were demonstrated to be very effective in households, and have some protective effect in other settings (schools) these measures could not be expected to prevent the possibility of transmission in the community. It was noted that in May and June an increasing number of cases were identified with no links to other known cases so that during June, mounting evidence of sustained community transmission indicated that the benefit of containment measures was increasingly doubtful. There was a formal move to a treatment only approach. A difficulty with this pandemic was that although severe illness, and deaths, occurred in a minority of cases, especially in children and young adults and particularly in those with conditions placing them at high risk of the complications of influenza, most cases experienced a mild illness or no symptoms at all. Hence it was difficult to ?sell? large scale sue of antivirals to the public and some professionals. It was noted that there is insufficient information at present to come to conclusions as to whether the measures taken slowed the spread of infection in the population or affect the ultimate size of the spring summer wave of the pandemic in England which peaked in late July and then declined. The report documented how the HPA mounted a substantial sustained and coordinated emergency response throughout the containment period, including the provision of advice to professionals and the public which was a novel care delivery system for patients with influenza that had not been part of previous planning. The demand placed on the HPA during this period was considerable and resources needed to maintain the containment approach became stretched, particularly towards the end of this phase.
ECDC Comment (19/08/10)
On the surface these two evaluations suggest different outcomes while in reality they are compatible. Both found that if antivirals are used intensively in small defined populations in combination with personal health measures even pandemic influenza can be halted at least for a while. That is consistent with other observations of the effectiveness of oseltamivir against the pandemic strain.(1) However when scaling up to the macro-level such containment is simply impossible as well as being very resource intensive and exhausting. That is what was suggested by WHO in April and the UK experience was reported to the Swedish Presidency meetings in July 2009 which led to the abandonment of containment policies in Europe.(2,3) It had been pointed out in the UK by their official evaluation that containment was never part of the original plan.(4) Whether or not to use antivirals in a pandemic remains a controversial area. In some EU countries it was policy to offer them to all people when they developed symptoms, in others only to those at higher risk of severe disease and in yet others to confine their use to those ill enough to require hospital treatment. Dilemmas for clinicians were that it is generally agreed that to be effective antivirals had to be given early, hence waiting for someone to become very ill was risky. Equally the policy of giving treatment to only those in the risk group was confronted with the fact that around 30% of those who eventually died from the pandemic infection were outside any risk group.(5)
Oseltamivir Ring Prophylaxis for Containment of 2009 H1N1 Influenza Outbreaks
New England Journal of Medicine; Volume 362:2166-2174; 10 June 2010; Number 23
This study reports the effectiveness of post-exposure ?ring chemo-prophylaxis? using the antiviral oseltamivir in controlling four outbreaks of 2009 pandemic influenza A(H1N1) that occurred from June 22nd to June 25th 2009 in the semi-closed environment of four different military camps in Singapore. The authors defined ?ring chemo-prophylaxis? as a ?geographically targeted containment by means of prophylaxis?. To conduct the study, all personnel with confirmed infection were isolated and the affected military units were segregated and administered post-exposure ?ring chemo-prophylaxis? with oseltamivir with the purpose of containing the spread of the virus. All personnel were subsequently screened for signs of infection using questionnaires three times a week, both for virologic infection and for clinical symptoms. The total number of at-risk personnel was 1175, of which 75 (6.4%) were confirmed infected before the intervention, and the remaining 1100 received, thus, oseltamivir prophylaxis. The results show that after the intervention only 7 of the 1100 personnel that received oseltamivir prophylaxis were infected after receiving the antiviral. Moreover, the study concludes that there was a significant reduction in the effective reproductive number, from 1.91 (before the intervention) to 0.11 (after the intervention), and that three of the four outbreaks showed a significant reduction in the rate of infection after the intervention. Molecular analysis of samples obtained from cases within the same outbreak indicated that these cases were due to transmission within the camp, ruling out the possibility of unrelated episodes of infection. Concerning possible adverse effects of the oseltamivir the study notes that of the 816 personnel treated with oseltamivir who were surveyed for these effects, 63 of them (7.7%) reported only mild non-respiratory side effects and no severe adverse effects were described.
Health Protection Agency UK The role of the Health Protection Agency in the ?containment? phase during the first wave of pandemic influenza in England in 2009
Health Protection Agency, March 2010
This overview of the role of the Health Protection Agency (HPA) in the ?containment phase? of the first wave of the 2009 influenza A(H1N1) pandemic gives a preliminary assessment of the effectiveness of the measures taken to attempt to contain the 2009 influenza A(H1N1) pandemic during the Spring and Summer wave in England. The ?containment? measures taken by the HPA with regards to antivirals were:
* Treatment of ?cases? meeting a sensitive case definition (without waiting for diagnostic confirmation)
* Antiviral prophylaxis of close contacts of cases
* In school settings, those with clinical illness were offered treatment with oseltamivir and only allowed to return to school when symptom free. Close contacts of confirmed cases (and of suspected cases in confirmed outbreaks) were offered prophylaxis but no restriction was placed on activity unless they became unwell. Often, contacts of cases identified in schools could not be individually identified and the whole year or school was offered prophylaxis.
The evaluation reports that as a result of the general implementation of these measures, and in particular of the combination of treatment of index cases and prophylaxis of close contacts, there was a reduction of symptomatic infection in close contacts was observed (especially if treatment and prophylaxis were provided rapidly). The report also states that, although the effects of treatment and prophylaxis occurred together and cannot be separated, most of the effect will have been due to prophylaxis, having into account the time delay observed with the index cases, i.e. from the moment they are infected until they are identified as suitable candidates for antiviral treatment. For this reason, as peak infectivity occurs close to the onset of symptoms, treatment alone is never likely to have much impact on transmission. The second part of this report is especially interesting as it summarises the key operational issues identified by the HPA and comes to preliminary conclusions that though containment measures, implemented by the HPA working with the clinical services (the NHS) were demonstrated to be very effective in households, and have some protective effect in other settings (schools) these measures could not be expected to prevent the possibility of transmission in the community. It was noted that in May and June an increasing number of cases were identified with no links to other known cases so that during June, mounting evidence of sustained community transmission indicated that the benefit of containment measures was increasingly doubtful. There was a formal move to a treatment only approach. A difficulty with this pandemic was that although severe illness, and deaths, occurred in a minority of cases, especially in children and young adults and particularly in those with conditions placing them at high risk of the complications of influenza, most cases experienced a mild illness or no symptoms at all. Hence it was difficult to ?sell? large scale sue of antivirals to the public and some professionals. It was noted that there is insufficient information at present to come to conclusions as to whether the measures taken slowed the spread of infection in the population or affect the ultimate size of the spring summer wave of the pandemic in England which peaked in late July and then declined. The report documented how the HPA mounted a substantial sustained and coordinated emergency response throughout the containment period, including the provision of advice to professionals and the public which was a novel care delivery system for patients with influenza that had not been part of previous planning. The demand placed on the HPA during this period was considerable and resources needed to maintain the containment approach became stretched, particularly towards the end of this phase.
ECDC Comment (19/08/10)
On the surface these two evaluations suggest different outcomes while in reality they are compatible. Both found that if antivirals are used intensively in small defined populations in combination with personal health measures even pandemic influenza can be halted at least for a while. That is consistent with other observations of the effectiveness of oseltamivir against the pandemic strain.(1) However when scaling up to the macro-level such containment is simply impossible as well as being very resource intensive and exhausting. That is what was suggested by WHO in April and the UK experience was reported to the Swedish Presidency meetings in July 2009 which led to the abandonment of containment policies in Europe.(2,3) It had been pointed out in the UK by their official evaluation that containment was never part of the original plan.(4) Whether or not to use antivirals in a pandemic remains a controversial area. In some EU countries it was policy to offer them to all people when they developed symptoms, in others only to those at higher risk of severe disease and in yet others to confine their use to those ill enough to require hospital treatment. Dilemmas for clinicians were that it is generally agreed that to be effective antivirals had to be given early, hence waiting for someone to become very ill was risky. Equally the policy of giving treatment to only those in the risk group was confronted with the fact that around 30% of those who eventually died from the pandemic infection were outside any risk group.(5)
