Characterizing the epidemiology of the 2009 influenza A/H1N1 pandemic in Mexico

Background

Mexico''s local and national authorities initiated an intense public health response during the early stages of the 2009 A/H1N1 pandemic. In this study we analyzed the epidemiological patterns of the pandemic during April–December 2009 in Mexico and evaluated the impact of nonmedical interventions, school cycles, and demographic factors on influenza transmission.

Methods and Findings

We used influenza surveillance data compiled by the Mexican Institute for Social Security, representing 40% of the population, to study patterns in influenza-like illness (ILIs) hospitalizations, deaths, and case-fatality rate by pandemic wave and geographical region. We also estimated the reproduction number (R) on the basis of the growth rate of daily cases, and used a transmission model to evaluate the effectiveness of mitigation strategies initiated during the spring pandemic wave. A total of 117,626 ILI cases were identified during April–December 2009, of which 30.6% were tested for influenza, and 23.3% were positive for the influenza A/H1N1 pandemic virus. A three-wave pandemic profile was identified, with an initial wave in April–May (Mexico City area), a second wave in June–July (southeastern states), and a geographically widespread third wave in August–December. The median age of laboratory confirmed ILI cases was ∼18 years overall and increased to ∼31 years during autumn (p<0.0001). The case-fatality ratio among ILI cases was 1.2% overall, and highest (5.5%) among people over 60 years. The regional R estimates were 1.8–2.1, 1.6–1.9, and 1.2–1.3 for the spring, summer, and fall waves, respectively. We estimate that the 18-day period of mandatory school closures and other social distancing measures implemented in the greater Mexico City area was associated with a 29%–37% reduction in influenza transmission in spring 2009. In addition, an increase in R was observed in late May and early June in the southeast states, after mandatory school suspension resumed and before summer vacation started. State-specific fall pandemic waves began 2–5 weeks after school reopened for the fall term, coinciding with an age shift in influenza cases.

Conclusions

We documented three spatially heterogeneous waves of the 2009 A/H1N1 pandemic virus in Mexico, which were characterized by a relatively young age distribution of cases. Our study highlights the importance of school cycles on the transmission dynamics of this pandemic influenza strain and suggests that school closure and other mitigation measures could be useful to mitigate future influenza pandemics. Please see later in the article for the Editors'' Summary     

Ethical principles of management and planning during influenza pandemic

The article is dedicated to an actual problem of ethical component inclusion into the system of management and planning of epidemic control measures during threat emergence and in the course of influenza pandemic (epidemic) progress. Data regarding development of international ethical guidelines during influenza including WHO recommendations are presented and analysis of normative documents in Russian Federation is given. A necessity of comprehension and accounting of ethical values in pandemic preparedness is shown, main directions of action and responsibility are revealed. Key ethical positions of planning and implementation of measures during influenza pandemic are outlined, compliance with those determines the level of public support and thus provides the effectiveness of the implemented measures.     

Effective, robust design of community mitigation for pandemic influenza: a systematic examination of proposed US guidance

Background

The US government proposes pandemic influenza mitigation guidance that includes isolation and antiviral treatment of ill persons, voluntary household member quarantine and antiviral prophylaxis, social distancing of individuals, school closure, reduction of contacts at work, and prioritized vaccination. Is this the best strategy combination? Is choice of this strategy robust to pandemic uncertainties? What are critical enablers of community resilience?

Methods and Findings

We systematically simulate a broad range of pandemic scenarios and mitigation strategies using a networked, agent-based model of a community of explicit, multiply-overlapping social contact networks. We evaluate illness and societal burden for alterations in social networks, illness parameters, or intervention implementation. For a 1918-like pandemic, the best strategy minimizes illness to <1% of the population and combines network-based (e.g. school closure, social distancing of all with adults'' contacts at work reduced), and case-based measures (e.g. antiviral treatment of the ill and prophylaxis of household members). We find choice of this best strategy robust to removal of enhanced transmission by the young, additional complexity in contact networks, and altered influenza natural history including extended viral shedding. Administration of age-group or randomly targeted 50% effective pre-pandemic vaccine with 7% population coverage (current US H5N1 vaccine stockpile) had minimal effect on outcomes. In order, mitigation success depends on rapid strategy implementation, high compliance, regional mitigation, and rigorous rescinding criteria; these are the critical enablers for community resilience.

Conclusions

Systematic evaluation of feasible, recommended pandemic influenza interventions generally confirms the US community mitigation guidance yields best strategy choices for pandemic planning that are robust to a wide range of uncertainty. The best strategy combines network- and case-based interventions; network-based interventions are paramount. Because strategies must be applied rapidly, regionally, and stringently for greatest benefit, preparation and public education is required for long-lasting, high community compliance during a pandemic.     

Health system resource gaps and associated mortality from pandemic influenza across six Asian territories

Background

Southeast Asia has been the focus of considerable investment in pandemic influenza preparedness. Given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations. We aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in Asia.

Methods and Findings

We collected health system resource data from Cambodia, Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam. We applied a mathematical transmission model to simulate a “mild-to-moderate” pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory. The results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as “avoidable” mortalities), particularly in poorer areas. Severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except Taiwan. Other resources (oseltamivir, hospital beds and human resources) are inequitably distributed within countries. Estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario. However, geographic patterns observed within and across territories remained similar for the range of parameter values explored.

Conclusions

The findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic. Effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths.     

Panalysis: a new spreadsheet-based tool for pandemic planning

Publicly available influenza modeling tools are of limited use to hospitals and local communities in planning for a severe pandemic. We developed Panalysis, a new tool to estimate the likely healthcare consequences of a pandemic and to aid hospitals in the development of mitigation and response strategies. By way of example, we demonstrate how Panalysis can be used to plan for a 1918-like flu pandemic. We discuss potential future applications of this tool.     

禽流感:一种人畜共患病

禽流感 (AvianInfluenza ,AI)是严重危害畜牧业与人类健康的一种传染性疾病。多年来在世界上许多国家和地区都发生过此病 ,危害严重 ,经济损失巨大。禽流感病毒可感染多种动物 ,包括人、猪、马、鲸、海豹和雪貂。禽流感病毒经变异或基因重组 ,已具备感染人的能力 ,有可能成为人类新型流感流行的潜在病原。本文对与禽流感病毒相关的流感疫情进行历史性的回顾 ,并对其人畜共患机制做了初步探讨     

Adaptive Vaccination Strategies to Mitigate Pandemic Influenza: Mexico as a Case Study

Background

We explore vaccination strategies against pandemic influenza in Mexico using an age-structured transmission model calibrated against local epidemiological data from the Spring 2009 A(H1N1) pandemic.

Methods and Findings

In the context of limited vaccine supplies, we evaluate age-targeted allocation strategies that either prioritize youngest children and persons over 65 years of age, as for seasonal influenza, or adaptively prioritize age groups based on the age patterns of hospitalization and death monitored in real-time during the early stages of the pandemic. Overall the adaptive vaccination strategy outperformed the seasonal influenza vaccination allocation strategy for a wide range of disease and vaccine coverage parameters.

Conclusions

This modeling approach could inform policies for Mexico and other countries with similar demographic features and vaccine resources issues, with regard to the mitigation of the S-OIV pandemic. We also discuss logistical issues associated with the implementation of adaptive vaccination strategies in the context of past and future influenza pandemics.     

What hospitals should do to prepare for an influenza pandemic

This article offers recommendations on what hospitals should do to prepare for an influenza pandemic and proposes specific actions and priorities for the purpose of making the discussion of hospital pandemic preparedness issues more operationally useful.     

Avian flu pandemic: Can we prevent it?

Outbreaks of highly pathogenic H5N1 avian influenza in Southeast Asia, Europe and Africa have led to devastating consequences for poultry, and have resulted in numerous infections in humans. Although these infections from the animal reservoir continue to accumulate, the virus does not seem to spread extensively among humans. However, for example, a process of genetic reassortment could occur in a human who is co-infected with avian influenza A virus and a human strain of influenza A virus. The resulting new virus might then be able to easily infect humans and spread from human to human. Therefore, many experts expect the occurrence of a pandemic due to a mutant virus which can be easily transmitted among humans. Thus, currently, a major public health concern is the next influenza pandemic; yet it remains unclear how to control such a crisis. In this paper, we investigate relations between the evolution of virulence and an effectiveness of pandemic control measures after the emergence of mutant avian influenza; one is an elimination policy of infected birds with avian influenza and the other is a quarantine policy of infected humans with mutant avian influenza. We found that each of these prevention policies can be ineffective (i.e., increase human morbidity or mortality). Further, interestingly, the same intervention might, under the same conditions, increase human morbidity and decrease human mortality, or vice versa. Our practical findings are that the quarantine policy can effectively reduce both human morbidity and mortality but the elimination policy increases either human morbidity or mortality in a worst case situation.     

People at Risk of Influenza Pandemics: The Evolution of Perception and Behavior

Influenza pandemics can severely impact human health and society. Understanding public perception and behavior toward influenza pandemics is important for minimizing the effects of such events. Public perception and behavior are expected to change over the course of an influenza pandemic, but this idea has received little attention in previous studies. Our study aimed to understand the dynamics of public perception and behavior over the course of the 2009 H1N1 influenza pandemic. Three consecutive cross-sectional surveys were administered among Beijing residents with random-digit dialing techniques in March 2008 and August and November 2009. Effective samples of 507, 508 and 1006 respondents were interviewed in each of the three surveys, respectively. The mean scores of risk perception were low to moderate across the three surveys. The perceived risk of infection of self was significantly lower than that of the community, revealing an optimistic bias. Longitudinally, the perceived risk of contracting H1N1 increased, whereas the perceived risk of being unable to obtain medicine and medical care once influenza permeated the community first increased and then decreased. Responsive actions toward influenza varied. Most respondents took actions that required little extra effort, such as ventilating rooms; these actions did not change over time. Comparatively, a smaller number of respondents took actions for coping with influenza, such as vaccination; however, these actions were taken by an increasing number of respondents over time. The association between risk perception and behavior was unstable. Positive, insignificant, and negative associations were obtained in the three surveys. In conclusion, the evolving patterns of risk perception and responsive behavior over the course of an influenza pandemic are sensitive to how risk and behavior are defined and scoped.     

Coinfection can trigger multiple pandemic waves

Sequences of epidemic waves have been observed in past influenza pandemics, such as the Spanish influenza. Possible explanations may be sought either in mechanisms altering the structure of the network of contacts, such as those induced by changes in the rates of movement of people or by public health measures, or in the genetic drift of the influenza virus, since the appearance of new strains can reduce or eliminate herd immunity. The pandemic outbreaks may also be influenced by coinfection with other acute respiratory infections (ARI) that increase transmissibility of influenza virus (by coughing, sneezing, running nose). In fact, some viruses (e.g., Rhinovirus and Adenovirus) have been found to induce “clouds” of bacteria and increase the transmissibility of Staphylococcus aureus. Moreover, Rhinovirus and Adenovirus were detected in patients during past pandemics, and their presence is linked to superspreading events. In this paper, by assuming increased transmissibility in coinfected individuals, we propose and study a model where multiple pandemic waves are triggered by coinfection with ARI. The model agrees well with mortality excess data during the 1918 pandemic influenza, thereby providing indications for potential pandemic mitigation.     

Efficacy of vaccination with different combinations of MF59-adjuvanted and nonadjuvanted seasonal and pandemic influenza vaccines against pandemic H1N1 (2009) influenza virus infection in ferrets

Serum antibodies induced by seasonal influenza or seasonal influenza vaccination exhibit limited or no cross-reactivity against the 2009 pandemic swine-origin influenza virus of the H1N1 subtype (pH1N1). Ferrets immunized once or twice with MF59-adjuvanted seasonal influenza vaccine exhibited significantly reduced lung virus titers but no substantial clinical protection against pH1N1-associated disease. However, priming with MF59-adjuvanted seasonal influenza vaccine significantly increased the efficacy of a pandemic MF59-adjuvanted influenza vaccine against pH1N1 challenge. Elucidating the mechanism involved in this priming principle will contribute to our understanding of vaccine- and infection-induced correlates of protection. Furthermore, a practical consequence of these findings is that during an emerging pandemic, the implementation of a priming strategy with an available adjuvanted seasonal vaccine to precede the eventual pandemic vaccination campaign may be useful and life-saving.     

Removing barriers to global pandemic influenza vaccination

This article clarifies the regulatory issues surrounding influenza pandemic vaccine for the larger policy community and describes the need for regulatory harmonization. Vaccination would save lives in an influenza pandemic, but a lack of global manufacturing capacity will leave most of the world without access to vaccine. Capacity can be expanded if governments harmonize their regulatory policies. This article details the regulatory approaches taken by the United States, the European Union, and Japan for pandemic vaccine development, three regions that produce the majority of the world's seasonal influenza vaccine. They should quickly converge on regulatory requirements, intellectual property considerations, the use of recombinant DNA techniques for vaccine production, and technical issues about the composition of pandemic vaccine.     

Epidemiologic and economic effectiveness of school closure during influenza epidemics and pandemics

Epidemiologic and economic effectiveness of school closure during influenza epidemics and pandemics is discussed. Optimal effect of school closure is observed when this measure is taken at the start of the epidemic or pandemic and for a sufficiently long time. School closure during high morbidity among schoolchildren, in the middle (at the peak) and by the end of epidemic or pandemic does not influence significantly the spread of influenza or morbidity. Significant economic losses and other negative consequences of school closure are noted. School closure may be the most appropriate during the emergence of influenza pandemic when the pandemic vaccine is not yet available, however timely mass immunization of schoolchildren against influenza may be a more appropriate measure than school closure for the reduction of influenza morbidity and spread during seasonal influenza epidemics.     

A cross-sectional study of pandemic influenza health literacy and the effect of a public health campaign

ABSTRACT: BACKGROUND: To ascertain the understanding of 2009 pandemic (H1N1) influenza and relevant infection control measures in an emergency department population and to assess the effectiveness of education campaigns in informing the public about the pandemic. METHODS: Questionnaires were administered to patients, visitors, non-clinical staff and volunteers. Data were collected on knowledge, preventative measures, information sources, attitudes to government and media reporting, perceived seriousness, behaviour change and intended compliance with future measures. Results were used to construct an overall knowledge score. RESULTS: There were 252 participants. Traditional forms of mass media (138 [55%]) remained the principal information source. Approximately 70% (176) accurately described mode of transmission and recommended precautions and 68% (175) reported behaviour change because of the pandemic. Gaps in knowledge included failure to identify certain high risk groups. Recall of government campaigns was significantly associated with a higher knowledge score. 60% (151) thought that authorities and media had exaggerated the threat; only 40% (101) would comply with recommended measures in a future pandemic. CONCLUSIONS: The knowledge regarding pandemic influenza was high in this population and positively affected by official campaigns. Pandemic planning should address knowledge gaps and the impression that authorities had exaggerated the public-health threat.     

Emergence of drug resistance: implications for antiviral control of pandemic influenza

Given the danger of an unprecedented spread of the highly pathogenic avian influenza strain H5N1 in humans, and great challenges to the development of an effective influenza vaccine, antiviral drugs will probably play a pivotal role in combating a novel pandemic strain. A critical limitation to the use of these drugs is the evolution of highly transmissible drug-resistant viral mutants. Here, we develop a mathematical model to evaluate the potential impact of an antiviral treatment strategy on the emergence of drug resistance and containment of a pandemic. The results show that elimination of the wild-type strain depends crucially on both the early onset of treatment in indexed cases and population-level treatment. Given the probable delay of 0.5-1 day in seeking healthcare and therefore initiating therapy, the findings indicate that a single strategy of antiviral treatment will be unsuccessful at controlling the spread of disease if the reproduction number of the wild-type strain (R0s) exceeds 1.4. We demonstrate the possible occurrence of a self-sustaining epidemic of resistant strain, in terms of its transmission fitness relative to the wild-type, and the reproduction number R0s. Considering reproduction numbers estimated for the past three pandemics, the findings suggest that an uncontrollable pandemic is likely to occur if resistant viruses with relative transmission fitness above 0.4 emerge. While an antiviral strategy is crucial for containing a pandemic, its effectiveness depends critically on timely and strategic use of drugs.     

Age-matched comparison of children hospitalized for 2009 pandemic H1N1 influenza with those hospitalized for seasonal H1N1 and H3N2

BACKGROUND: A wide spectrum of clinical manifestation ranging from deaths to a mild course of disease has been reported in children infected with the 2009 pandemic H1N1 (pH1N1) influenza. METHODOLOGY/MAJOR FINDINGS: We conducted an age-matched control study comparing children hospitalized for pH1N1 with historic controls infected with seasonal H1N1 and H3N2 influenza to correct for the effect of age on disease susceptibility and clinical manifestations. We also compared children with pH1N1 to children concurrently admitted for seasonal influenza during the pandemic period to adjust for differences in health-seeking behavior during the pandemic or other potential bias associated with historic controls. There was no death or intensive care admission. Children with pH1N1 were more likely to have at least one risk condition for influenza, an underlying chronic pulmonary condition, more likely to have asthma exacerbation and to be treated with oseltamivir. There was no difference in other aspects of the clinical course or outcome. CONCLUSION: Disease manifestation of children hospitalized for pH1N1 infection was mild in our patient population.     

Public health strategies for distribution of influenza vaccine during an influenza pandemic

In order to consider the ethical issues around vaccine distribution during an influenza pandemic, it is critical to have an understanding of the role of influenza vaccine in a pandemic, the rate at which vaccine is likely to be come available, who will likely produce and "own" the vaccine, how vaccine distribution and administration might be accomplished, and which are the groups that might be deemed highest priority to be vaccinated against influenza. The United States and Connecticut have been considering the more challenging of these issues and have learned from Canada, which previously discussed and made decisions on the challenges related to vaccine distribution. Although there is still some critical advance thinking that needs to be done, planning for the response to an influenza pandemic is now at an advanced stage. The keys to preparedness at this stage are to be aware of the vaccine distribution options, to know the benefits and limitations of each option, and to be flexible but nimble in dealing with a real pandemic.     

The age-specific cumulative incidence of infection with pandemic influenza H1N1 2009 was similar in various countries prior to vaccination

Background

During the influenza pandemic of 2009 estimates of symptomatic and asymptomatic infection were needed to guide vaccination policies and inform other control measures. Serological studies are the most reliable way to measure influenza infection independent of symptoms. We reviewed all published serological studies that estimated the cumulative incidence of infection with pandemic influenza H1N1 2009 prior to the initiation of population-based vaccination against the pandemic strain.

Methodology and Principal Findings

We searched for studies that estimated the cumulative incidence of pandemic influenza infection in the wider community. We excluded studies that did not include both pre- and post-pandemic serological sampling and studies that included response to vaccination. We identified 47 potentially eligible studies and included 12 of them in the review. Where there had been a significant first wave, the cumulative incidence of pandemic influenza infection was reported in the range 16%–28% in pre-school aged children, 34%–43% in school aged children and 12%–15% in young adults. Only 2%–3% of older adults were infected. The proportion of the entire population infected ranged from 11%–18%. We re-estimated the cumulative incidence to account for the small proportion of infections that may not have been detected by serology, and performed direct age-standardisation to the study population. For those countries where it could be calculated, this suggested a population cumulative incidence in the range 11%–21%.

Conclusions and Significance

Around the world, the cumulative incidence of infection (which is higher than the cumulative incidence of clinical disease) was below that anticipated prior to the pandemic. Serological studies need to be routine in order to be sufficiently timely to provide support for decisions about vaccination.     

Perspectives on antiviral use during pandemic influenza.

Antiviral agents could potentially play a major role in the initial response to pandemic influenza, particularly with the likelihood that an effective vaccine is unavailable, by reducing morbidity and mortality. The M2 inhibitors are partially effective for chemoprophylaxis of pandemic influenza and evidence from studies of interpandemic influenza indicate that the neuraminidase inhibitors would be effective in prevention. In addition to the symptom benefit observed with M2 inhibitor treatment, early therapeutic use of neuraminidase inhibitors has been shown to reduce the risk of lower respiratory complications. Clinical pharmacology and adverse drug effect profiles indicate that the neuraminidase inhibitors and rimantadine are preferable to amantadine with regard to the need for individual prescribing and tolerance monitoring. Transmission of drug-resistant virus could substantially limit the effectiveness of M2 inhibitors and the possibility exists for primary M2 inhibitor resistance in a pandemic strain. The frequency of resistance emergence is lower with neuraminidase inhibitors and mathematical modelling studies indicate that the reduced transmissibility of drug-resistant virus observed with neuraminidase inhibitor-resistant variants would lead to negligible community spread of such variants. Thus, there are antiviral drugs currently available that hold considerable promise for response to pandemic influenza before a vaccine is available, although considerable work remains in realizing this potential. Markedly increasing the quantity of available antiviral agents through mechanisms such as stockpiling, educating health care providers and the public and developing effective means of rapid distribution to those in need are essential in developing an effective response, but remain currently unresolved problems.