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Keywords:

  • Burden of disease;
  • costs;
  • epidemiology;
  • influenza;
  • influenza-like illness;
  • Latin America & Caribbean;
  • use of resources

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Conflict of interest
  10. Funding
  11. References
  12. Supporting Information

Please cite this paper as: Savy et al. (2012) Burden of influenza in Latin America and the Caribbean: a systematic review and meta-analysis. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12036.

Objective  Influenza causes severe morbidity and mortality. This systematic review aimed to assess the incidence, etiology, and resource usage for influenza in Latin America and the Caribbean.

Design  Meta-analytic systematic review. Arcsine transformations and DerSimonian Laird random effects model were used for meta-analyses.

Setting  A literature search from 1980 to 2008 in MEDLINE, Cochrane Library, EMBASE, LILACS, Ministries of Health, PAHO, proceedings, reference lists, and consulting experts.

Sample  We identified 1092 references, of which 31 were finally included, in addition to influenza surveillance reports. We also used information from the 10 reports from the collaborative group for epidemiological surveillance of influenza and other respiratory virus (GROG), and information retrieved from the WHO global flu database FLUNET.

Main outcome measures  Incidence, percentage of influenza specimens out of the total received by influenza centers and resource-use outcomes.

Results  A total of 483 130 specimens of patients with influenza were analyzed. Meta-analysis showed an annual rate of 36 080 (95%CI 28 550 43 610) influenza-like illness per 100 000 persons-years. The percentage of influenza out of total specimens received by influenza centers ranged between 4.66% and 15.42%, with type A the most prevalent, and A subtype H3 predominating. The mean length of stay at hospital due to influenza ranged between 5.8 12.9 days, total workdays lost due to influenza-like illnesses were 17 150 days, and the mean direct cost of hospitalization was US$575 per laboratory-confirmed influenza case.

Conclusions  Our data show that seasonal influenza imposes a high morbidity and economic burden to the region. However, the vaccine-uptake rate has been low in this region. Population-based cohort studies are required to improve the knowledge about incidence and resource utilization, which would inform healthcare authorities for decision making.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Conflict of interest
  10. Funding
  11. References
  12. Supporting Information

Influenza virus is a highly contagious etiological agent that spreads rapidly and causes an acute respiratory illness, mostly characterized by sudden onset of high fever, myalgia, headache, sore throat, and inflammation.1,2 It is usually self-limited, and the patient recovers within 1 or 2 weeks. However, in some cases it may lead to serious complications such as pneumonia, bronchitis, and sometimes death, particularly in young children (6–23 months), the elderly (>65 years), and people with underlying chronic health problems.3,4

The knowledge of influenza incidence by country and region is an important public health topic that helps taking measures to organize health care services during peaks of circulation. About 10–20% of the general population is usually affected during the cold season. In the United States (US), influenza-related consultations vary from 6 to 29 per 100 children annually;3,5–7 the rate of hospitalization in children aged <5 years varies from 500 (high-risk) to 100 (healthy) per 100 000 children.8–14 Studies conducted in the temperate regions of Europe have revealed influenza-related hospitalization rates ranging from 11 to 237 per 100 000 children,12,15–18 while higher rates have been reported in Hong Kong.19 During the influenza season, H1N1 and H3N2 influenza A and influenza B viruses usually circulate according to different patterns: either two types/subtypes can circulate at the same time or sequentially, or one type/subtype can replace the previous one. These different patterns can impact with a different burden.20 Besides, influenza A (H1N1) has emerged as a new strain responsible for the influenza pandemic in 2009, which has so far resulted in more than 182 000 laboratory-confirmed cases and 1799 deaths in 177 countries.21

In the region of Latin America and the Caribbean (LA&C), scarce information on influenza mortality and morbidity is available, most likely due to underreporting.22–25 The poor quality of accessible data makes the estimation of the burden of disease difficult. The actual impact of influenza in LA&C is often obscured by the lack of usage of specific diagnostic methods by physicians to confirm etiology, as most reported data come from clinical diagnoses of influenza-like illnesses (ILI).3 This was particularly the case before the 2009 flu pandemic. The lack of laboratory confirmation in the diagnosis of co-circulating pathogens and the occurrence of diseases clinically similar to influenza act as major barriers for estimating the true incidence.

We conducted a systematic review and meta-analysis of the available epidemiological and virological data to assess the incidence, etiology, and use of healthcare resources in people with influenza in LA&C. The results of this analysis will help inform public health decision makers.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Conflict of interest
  10. Funding
  11. References
  12. Supporting Information

We performed a meta-analysis of observational studies following guidelines the Meta-analysis Of Observational Studies in Epidemiology (MOOSE)26 and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).27,28

Search strategy and selection criteria

We conducted a systematic search of the following electronic databases: Cochrane CENTRAL register and specialized register of the Cochrane Acute Respiratory Infections Group, MEDLINE, EMBASE, and LILACS, between January 1980 and September 2008 (Appendix S1). We also performed a generic and academic Internet search and meta-search. An annotated search strategy for ‘gray literature’ was included to retrieve information from relevant sources like regional Ministries of Health, PAHO, hospital reports, databases containing regional proceedings or congresses’ annals and doctoral theses, reference lists of included studies, and consultations with expert and institutions related to the topic. Authors were contacted to obtain missing or extra information when needed. Other sources searched were SLIPE (Latin-American Society of Pediatric Infectious Diseases) for annals and proceedings from international congresses and the World Health Organization (WHO)’s FluNet. This is a global tool for influenza virological surveillance. Data entered into FluNet are publically available. Data are provided remotely by National Influenza Centres (NICs) of the Global Influenza Surveillance and Response System (GISRS) and other national influenza reference laboratories collaborating actively with GISRS or are uploaded from WHO regional databases.29 In the WHO Region of the Americas, the majority of specimens are from children.30

We included the control arms of controlled trials, cohort studies, case–control studies, case series, surveillance, and cross-sectional studies without language restriction. Systematic reviews and meta-analyses with original data were also included for qualitative synthesis of the data. Studies were included only if at least 20 cases of ILI or laboratory-confirmed influenza were reported. We included studies enrolling patients of any age since 1995.

We included studies in which influenza diagnosis was confirmed by viral isolation, detection of viral protein or viral RNA in nasal, throat, or respiratory tract secretion samples, rapid diagnostic tests, and seroconversion (defined as greater than fourfold increase in antibody titers in 2 weeks).

We included studies that assessed at least one of the following outcomes in the context of ILI: incidence of clinical and laboratory-confirmed cases of influenza, mortality and pneumonia due to influenza, mixed pneumonia, secondary bacterial pneumonia, lower respiratory tract complications, exacerbations of chronic obstructive pulmonary disease, central nervous system complications, myocarditis and pericarditis, toxic shock syndrome, and influenza-related admissions. We assessed the proportion of influenza among all specimens reported to the FluNet, proportion of type A in influenza-positive specimens, and proportion of subtypes H1 and H3 in type A-positive specimens. We also evaluated viral subtype etiology distribution and use of healthcare resources in terms of laboratory tests, treatment methods, absenteeism from school and work, number of physician visits, and overall impact on economy.

Selection of eligible articles and data abstraction

Two reviewers independently screened titles and abstracts of all identified citations and selected all potentially eligible studies. Full-text versions of these articles were independently assessed by two reviewers to evaluate whether they met the inclusion criteria. Disagreements were solved by consensus in both phases. Data were abstracted using a previously piloted electronic chart.

Quality assessment of included studies

The methodological quality of all included studies was independently assessed by three reviewers (AB, AC, DG), based on the checklist of essential items stated in Strengthening the Reporting of Observational studies in Epidemiology (STROBE),31 the results of a systematic review evaluating tools for assessing quality and susceptibility to bias in observational studies,32 and the guidelines for appraising medical research published by Fowkes et al.33 We used an algorithm (Appendix S2) to estimate an overall risk of bias taking into account five potential sources of bias: methods for selecting study participants, methods for measuring exposure and outcome variables, methods to control confounding, design-specific sources of bias, and statistical methods. Disagreements were solved by consensus.

Statistical analyses

A proportion meta-analysis was performed. We applied an arcsine transformation to stabilize the variance of proportions (Freeman–Tukey variant of the arcsine square root of transformed proportions method).34 The pooled proportion was calculated as the back-transformation of the weighed mean of the transformed proportions, using inverse arcsine variance weights for the fixed and random effects model. The estimates and its 95% confidence interval (CI) were calculated using the DerSimonian–Laird weights for the random effects model where heterogeneity between studies was found.35 We calculated the I2 statistic as a measure of the proportion of the overall variation that was attributable to between-study heterogeneity.36 Stats-direct (StatsDirect Ltd, Altrincham, Cheshire, UK) and stata 9.0 (StataCorp LP, College Station, TX, USA) were used for all analyses.

We expressed incidence as the number of patients with at least one episode of influenza (ILI or laboratory confirmed) per 100 000 person, years. We calculated proportions (percentages) of total specimens remitted to influenza centers or of influenza-positive specimens. Subgroup analyses by age and by country were performed. We used maps to represent the yearly proportion of influenza-positive samples among total specimens analyzed and among rates reported in FluNet. When data were missing from FluNet, we complemented it with data from the Collaborative Group For Epidemiological Surveillance Of Influenza and Other Respiratory Viruses in Argentina (GROG). Cutoff points for categories were selected according to the quartiles of proportions observed for all countries in the period 1999–2008. Country proportion was represented only if the total number of samples reported for a given year for that country was ≥100. Maps also reflect the distribution of influenza types and A-subtypes in 1999 and 2008. The distribution of influenza subtypes was reported for a particular year and country if the total number of influenza-positive samples was ≥30. The denominator for the subtype pie charts presented in the maps is the reported number of influenza-positive samples.

To estimate the burden of ILI in the region for year 2008—before the H1N1 influenza pandemic—we used the upper and lower limits of the 95% CI of incidence obtained from the meta-analysis of the prospective studies reporting incidence. We also projected the total number of confirmed influenza cases and influenza A and B cases for the year 2008 applying the influenza incidence obtained from prospective studies to the countries’ populations, and pooled type proportion rates obtained from the FluNet.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Conflict of interest
  10. Funding
  11. References
  12. Supporting Information

The study selection process is shown in Figure 1. The literature search retrieved 1092 potential articles. Of these, 95 full-text articles, one book, 10 GROG reports for Argentina, and a database were included for detailed assessment. A total of 64 articles were excluded due to inability to meet the inclusion criteria, irrelevant information, or data duplication. Finally, 31 articles, 10 GROG reports for Argentina (1999–2008), and 75 sub-studies from FluNet (1999–2008) were included for analyses. These sources encompassed a total of 483 130 samples from patients diagnosed with influenza or ILI. Seven studies were excluded due to duplication of information with the FluNet,37–39 GROG,40–42 or due to the recruitment date being prior to 1995.43

image

Figure 1.  Flow diagram for study selection.

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Table 1 describes the included studies’ characteristics. Most data were from Argentina (36·6%), Brazil (22·0%), Chile (17·1%), Cuba (4·9%), and Mexico (4·9%). Most were surveillance studies (39·0%) or case series (39·0%). The majority (82·9%) of the cases reported in these studies were laboratory-confirmed influenza, 75·6% had the influenza type reported, 58·5% were low respiratory tract infections (LRTI), and 41·5% were ILI.

Table 1. Characteristics and Influenza detection of included studies
ID (Author, reporting date)CountryDate for recruitmentFollow-up (m)No influenza seasonsDesignComplexity level hospitalSetting (in/outpatient)Cohort sample sizeMedian age (m)Mean age (m)Lower age (m)Upper age (m) N with ILIInpatients with LRTIConfirmed influenza (N)H1H3A (H1 + H3 + Not typed)
StartEnd
  1. ILI, influenza-like illnesses.

Arg GROG 199962,106ArgentinaJan-99Nov-99111SurveillanceHighBoth   All ages 16 297972  89379
Arg GROG 200063ArgentinaJan-00Nov-00111SurveillanceHighBoth   All ages 21 116454  39856
Arg GROG 200164ArgentinaJan-01Nov-01111SurveillanceHighBoth   All ages79620 356869  79574
Arg GROG 200265ArgentinaJan-02Nov-02111SurveillanceHighBoth   All ages67818 041425  182243
Arg GROG 200366ArgentinaJan-03Nov-03111SurveillanceHighBoth   All ages149926 5771323  130419
Arg GROG 200467ArgentinaJan-04Nov-04111SurveillanceHighBoth   All ages167528 9181130  990140
Arg GROG 200568ArgentinaJan-05Nov-05111SurveillanceHighBoth   All ages299026 029894  779115
Arg GROG 200669ArgentinaJan-06Nov-06111SurveillanceHighBoth   All ages235126 570716  560156
Arg GROG 200770ArgentinaJan-07Nov-07111SurveillanceHighBoth   All ages191728 928986  95333
Arg GROG 2008107ArgentinaJan-08Jul-0860·5SurveillanceHighBoth   All agesN/A18 628781  448333
Canas 2000108ArgentinaJan-97Dec-98242SurveillanceHighN/A   N/AN/A  27  261
Lopez 200871ArgentinaMar-05Sep-0561Case seriesHighInpatient   024 63343  376
Parra 200578ArgentinaJan-98Dec-98121Case seriesHighInpatient  18N/AN/A 38861    
Parra 2005109ArgentinaJan-02Dec-02121Case seriesHighInpatient  16·4N/AN/A 56513    
Viegas 200477ArgentinaJan-98Dec-02475Retrospective Case seriesHighInpatient   060 18 561523  50813
Bellei 200758BrazilJun-01Dec-0171Case seriesHighOutpatient   216Older412 83  4736
Coelho 20072BrazilJan-96Dec-01725Retrospective case seriesHighInpatient   024 103345  3114
Costa 2006110BrazilJan-01Dec-04485Case seriesHighInpatient   060  36    
De Freitas Souza 200349BrazilMay-96Apr-97121Case seriesLowOutpatient138  024  8  71
Diniz 200572BrazilNov-00Sep-02232Cross-sectionalHighInpatient 4 days 01 7811  110
Mixeu 2002111BrazilMar-97Oct-9771RCTLowOutpatient29934 216768203      
Straliotto 200275BrazilMay-90Dec-92243Prospective Case seriesHighN/A   060 862170222217
Thomazelli 200776BrazilJan-03Jan-04121Prospective Case seriesHighInpatient 5 060 33617  17 
Tsuchiya 200556BrazilJan-00Jan-03364Cross-sectionalHighBoth   08402731348125  9728
Avendaño 199983ChileMar-98Sep-9861SurveillanceHighInpatient   060 500     
Avendaño 1996-200683ChileJan-96Dec-0612010Cross-sectionalHighInpatient   060 3672118    
Delpiano 200384ChileMay-99Sep-9951Prospective cohort studyHighInpatient  14060 175   1669
Perret Perez 200473ChileJun-04Jul-041N/ACase seriesHighInpatient 9 0780 3053892    
Rabagliati 200474ChileMay-04Jun-0421Case seriesHighInpatient   816180 16355  592
Rabagliati 200682ChileMay-04Jul-0431Retrospective Case seriesHighInpatient  681801212 8361  4021
Sotomayor 2008112ChileJan-08Nov-08101SurveillanceN/AN/A   N/AN/A509 56  533
Duque 2001113ColombiaMar-97Aug-9761RCTHighOutpatient246  1860225      
Herrera 200880ColombiaSep-03Dec-0331SurveillanceHighInpatient   0Older 648 771
Morales 20041ColombiaOct-00May-0181Prospective cohort studyN/AOutpatient335 32216780158      
Cancio 200081CubaJan-95Dec-98363Case seriesHighInpatient   0Older 301195  12966
Oropesa Fernandez 199854CubaJan-92Dec-95484Case seriesHighN/A   N/AN/A148 13647519838
Canas 2000108EcuadorJan-97Dec-98242SurveillanceHighN/A   N/AN/A  4  31
Jackson 200457JamaicaJan-03Feb-04131Cross-sectionalHighInpatient   N/AN/A318 7044852 
Cabello 200648MexicoJan-97Feb-98131Prospective cohort studyLowOutpatient290 35060  86  6026
Talavera 200755MéxicoDec-99Dec-02363Prospective Case seriesN/AN/A  32·606098 28 2828 
Gordon 200947NicaraguaJan-06Jan-07121Community-based cohortLowOutpatient3999  241441156      
Canas 2000108PeruJan-97Dec-98242SurveillanceHighN/A   N/AN/A  48  417

The overall risk of bias was high in 71·0% (22/31), medium in 3·0% (1/31), and low in 26·0% (8/31) of the studies (Appendix S2).

Cases and deaths

We estimated that about 164 and 251 million ILI cases occurred in LA&C in 2008 (Table 2), including the estimated total number of Influenza A and B cases. For this period, considering theses estimations, Chile presented the highest testing rate (using number of tests registered in the FluNet as nominator, and the 95% CI lower and upper bounds of estimated ILI cases as denominator) between 0·275% and 0·419%, while Brazil showed the lowest one (0·005–0·007%).

Table 2. Projection of annual number of ILI, confirmed Influenza, Influenza A and B cases for 2008
CountryILI casesConfirmed Influenza casesInfluenza A casesInfluenza B cases
Lower 95%CIUpper 95%CILower 95%CIUpper 95%CILower 95%CIUpper 95%CILower 95%CIUpper 95%CI
  1. *Countries with available data to obtain specific estimations. Note: Estimations based on the 46 countries of LA&C and global proportions from meta-analysis.

  2. ILI, influenza-like illnesses.

Argentina*11 386 59717 392 976477 098728 766256 727443 527186 736285 239
Brazil*54 808 00683 718 9894 170 8896 371 0152 121 7313 976 1511 567 8372 394 865
Chile*4 797 5427 328 224163 596249 892149 936238 472747611 420
Mexico*4 797 5427 328 224746 9181 140 914599 0281 056 03055 57184 884
Panama*970 4151 482 30484 135128 51657 136111 30711 26617 208
All LA&C*164 487 970251 254 6547 665 13911 708 4675 988 0079 969 7601 138 2731 738 707

Influenza-specific mortality was often unavailable, and countries reported ‘influenza and pneumonia’ (I&P) combined mortality to PAHO. I&P-related mortality was the highest in the youngest and eldest age groups in most of the countries. In Latin America, in children under 5 years of age, I&P deaths were the highest in Ecuador representing 14·4% of all deaths (for the year 2003), 13·5% in Brazil (2004), 4·8% in Paraguay (2001–2003), and 4·0% in Argentina (2004). In the Caribbean, the highest I&P death rate was recorded in Barbados (85·0%) in 2002 for the ≥65, year age group. Across all age groups, I&P were responsible for 2·1% of total deaths in Bermuda (2001–2002), 5·6% in the Cayman Islands (1998–2000), 5·8% in Haiti (2003), 3·5% in Puerto Rico (2004), 7·0% in St. Kitts & Nevis (2002–2004), 14·7% in Guatemala (2001–2003), and 4·3% in Honduras (2003).

Further details can be found in the supplemental material (Appendix S3).44 In Chile, a country that uses population-based nationwide Sentinel Units to record data, the influenza-specific mortality rate was 0·4 per 100 000 population, and 2633 cases of influenza occurred per 100 000 population in 2001.

Incidence

Information on ILI incidence was provided by four studies (two randomized controlled trials, one prospective study, and one cohort study).1,45–47 Incidence of influenza-related acute respiratory infections (ARI) in children of 5 years of age and younger was described in a prospective study conducted in Mexico,48 while influenza-related LRTIs incidences were described in a longitudinal prospective study conducted in Brazil49 in children attending day care center and aged between 0 and 2 years. The ages of patients included ranged from 18 months to 65 years. The median duration of follow-up in the above-mentioned four studies was 12 months. The random effect meta-analysis of the ILI incidence showed an annual incidence rate of 36 080 (95% CI: 28 550–43 610) episodes per 100 000 person, years, with the highest annual incidence rate recorded in the <5, year age group (45 730 per 100 000 person, years; 95% CI: 39 760–51 710). The incidence of influenza-related ARI48 in children <5 years of age was the highest in the 3- to 4, year age group (57 500 per 100 000 person, years; 95% CI: 34 000–81 000) and lowest in the 1 to 2, year age group (15 090 per 100 000 person, years; 95% CI: 7700–22 490).

LRTI incidence was 5800 per 100 000 person, years (95% CI: 1780–9810) in children aged 0–2 years.49 Incidence rates across all age groups are presented in Table 3, Figure 2.

Table 3. Incidence of ILI, ARI, and LRTI
IncidenceStudy and age groupEvents/Persons, yearsIncidence per 100 000 persons-years (95% CI)Annual mean rate per 100 000 persons-years (95% CI)
  1. ILI, influenza-like illnesses.

ILI (meta-analyzed data)Duque 200150 (18 months–5 years)225/49245 730 (39 760–51 710)36 080 (28 550–43 610)
Morales 20041 (18–65 years)158/50331 410 (26 510–36 310)
Mixeu 200251 (21–58 years)203/51339 570 (34 130–45 010)
Gordon 200952 (2–12 years)1156/399928 910 (27 240–30 570)
ARICabello 200653 (0–1 year)13/2944 830 (20 460–69 200)
Cabello 200653 (1–2 years)16/10615 090 (7700–22 490)
Cabello 200653 (2–3 years)14/5326 420 (12 580–40 250)
Cabello 200653 (3–4 years)23/4057 500 (34 000–81 000)
Cabello 200653 (4–5 years)20/3951 280 (28 810–73 760)
LRTIDe Freitas Souza 200354 (0–2 years)8/1385800 (1780–9810)
image

Figure 2.  Incidence of Influenza-like illness.

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Proportion of confirmed influenza, influenza types, and subtypes among total influenza specimens processed at national reference laboratories

In the meta-analysis performed to estimate the proportion of influenza-positive specimens among total respiratory specimens received at influenza centers, the pooled percentage of specimens positive for influenza (all types) ranged between 4·7% and 15·4% per year, with an overall percentage of 8·2% (95% CI: 7·3–9·3) between 1999 and 2008 (Table 4). During the same period, meta-analyses of influenza types and subtypes showed that the pooled percentage of influenza-positive type A samples ranged between 60·2% and 96·2%, and the pooled percentage of type B samples ranged between 3·7% and 39·8%. The pooled percentage of influenza type A samples that were H1 subtyped was 9·3%, and H3 subtyped was 19·3% (Table 5).

Table 4. Percentage of influenza among all specimens analyzed at influenza centers
YearNumber of sub-studies N*Percentage of influenza % (95% CI)
  1. *Number of specimens received for analysis at all influenza centers.

  2. **Argentinean GROG 2008107 was not analyzed because complete influenza season’s data were not available.

19992302110·13 (4·52–17·66)
2000428 0848·42 (1·90–18·95)
2001422 81810·95 (4·26–20·23)
2002741 44215·42 (7·64–25·29)
2003870 28011·39 (5·99–18·24)
20041063 6768·35 (5·92–11·15)
2005861 78110·62 (7·12–14·73)
2006965 6626·13 (4·64–7·83)
20071070 4615·13 (3·82–6·62)
2008**1255 9054·66 (3·45–6·04)
All74483 1308·23 (7·25–9·28)
Table 5. Percentage of influenza types (A and B*) and subtypes (H1, H3, and NT**)***
YearNumber of sub-studies N Percentage of type A % (95% CI)Percentage of type B % (95% CI)
1999442985·49 (82·03–88·65)14·51 (11·35–17·97)
20005144896·25 (91·61–99·08)3·75 (0·92–8·39)
20015250376·96 (63·20–88·27)23·04 (11·73–36·80)
20029195260·16 (42·08–76·91)39·84 (23·09–57·92)
20038329895·19 (89·56–98·72)4·81 (1·28–10·44)
20048305175·51 (66·86–83·22)24·49 (16·78–33·14)
20058287584·88 (78·46–90·34)15·12 (9·66–21·54)
20068204882·44 (71·59–91·11)17·56 (8·89–28·41)
20078249583·63 (73·36–91·78)16·37 (8·22–26·64)
20088220672·67 (56·31–86·37)27·33 (13·63–43·69)
All7122 30581·77 (78·12–85·15)18·23 (14·85–21·88)
Number of studies N Type A subtypePercentage % (95% CI)
  1. *Number of cases with influenza.

  2. **Not typed.

  3. ***The percentages do not add up to 100% because each one is a different meta-analysis with a different subset of studies.

  4. Argentinean GROG 2008107 was not analyzed because complete FLU season’s data were not available.

  5. Number of cases with influenza type A.

  6. §NT, Not subtyped.

6318 586H19·27 (5·68–13·62)
H319·32 (13·77–25·55)
NT§63·85 (58·22–69·30)

The proportion of influenza (all types), influenza types, and subtypes is presented by year (1999–2008) and by country in Tables 6 and 7. Initial and final maps are shown in Figure 3. In Appendix S4, the proportion forest plot and the entire map series are shown. The highest percentage of influenza among countries under surveillance was recorded in Peru (69·5%; 95% CI: 66·4–72·5) in 2002 followed by Uruguay (42·6%; 95% CI: 36·6–48·6) in 2005.

Table 6. Percentage of influenza of all specimens analyzed at influenza centers, and its Type A, and Type B percentage by country and year
CountryYearInfluenza N Percentage* % (95% CI)Percentage type A** % (95% CI)Percentage type B** % (95% CI)
AllType AType B
  1. *The denominator is the number of specimens received by influenza centers.

  2. **The denominator is the number of specimens positive for influenza.

Argentina19991861543226167·11 (6·15–8·16)82·80 (76·59–87·92)17·20 (12·08–23·41)
20004543985621 1162·15 (1·96–2·35)87·67 (84·28–90·55)12·33 (9·45–15·72)
20018697957421 1524·11 (3·84–4·38)91·48 (89·43–93·25)8·52 (6·75–10·57)
200242518224318 7192·27 (2·06–2·49)42·82 (38·07–47·68)57·18 (52·32–61·93)
2003132313041928 0764·71 (4·47–4·97)98·56 (97·77–99·13)1·44 (0·87–2·23)
2004113099014030 5933·69 (3·49–3·91)87·61 (85·55–89·48)12·39 (10·52–14·45)
200589477911529 0193·08 (2·88–3·29)87·14 (84·76–89·26)12·86 (10·74–15·24)
200671656015628 9212·48 (2·30–2·66)78·21 (75·01–81·18)21·79 (18·82–24·99)
20079869533330 8453·20 (3·00–3·40)96·65 (95·33–97·69)3·35 (2·31–4·67)
200878144833318 6284·19 (3·91–4·49)57·36 (53·81–60·86)42·64 (39·14–46·19)
Brazil199947688·68 (76·97–95·73)11·32 (4·27–23·03)
2001162044·44 (27·94–61·90)55·56 (38·10–72·06)
2002123127·91 (15·33–43·67)72·09 (56·33–84·67)
200310197410809·35 (7·68–11·25)96·04 (90·17–98·91)3·96 (1·09–9·83)
20041571263119398·10 (6·92–9·40)80·25 (73·16–86·17)19·75 (13·83–26·84)
200599574223504·21 (3·44–5·11)57·58 (47·23–67·45)42·42 (32·55–52·77)
20062391875231317·63 (6·73–8·62)78·24 (72·47–83·30)21·76 (16·70–27·53)
200758391944571·30 (0·99–1·68)67·24 (53·66–78·99)32·76 (21·01–46·34)
200829816912939187·61 (6·79–8·48)56·71 (50·87–62·41)43·29 (37·59–49·13)
Chile1999 11321 84·33 (77·05–90·03)15·67 (9·97–22·95)
20003563479274912·95 (11·72–14·26)97·47 (95·26–98·84)2·53 (1·16–4·74)
2001585120621819 2323·04 (2·80–3·29)84·69 (82·71–86·52)15·31 (13·48–17·29)
20025545364919 9122·78 (2·56–3·02)91·62 (89·08–93·74)8·38 (6·26–10·92)
20031037553124 1374·30 (4·04–4·56)99·82 (99·00–100·00)0·18 (0·00–1·00)
200491487316423 6263·87 (3·63–4·12)84·19 (81·82–86·35)15·81 (13·65–18·18)
200571074417024 8582·86 (2·65–3·07)81·40 (78·72–83·87)18·60 (16·13–21·28)
20067996763424 0293·33 (3·10–3·56)95·21 (93·37–96·66)4·79 (3·34–6·63)
200768661818120 1253·41 (3·16–3·67)77·35 (74·28–80·21)22·65 (19·79–25·72)
2008566434340513·83 (10·62–17·58)93·73 (91·65–95·43)6·27 (4·57–8·35)
Colombia1999325334886·56 (4·53–9·13)94·64 (85·13–98·88)5·36 (1·12–14·87)
2000213204145·07 (3·17–7·65)100·00 (89·11–100·00)0·00 (0·00–10·89)
2002312295176·00 (4·11–8·40)70·97 (51·96–85·78)29·03 (14·22–48·04)
20036766138117·59 (13·90–21·79)98·51 (91·96–99·96)1·49 (0·04–8·04)
20046722457129·41 (7·37–11·80)32·84 (21·85–45·40)67·16 (54·60–78·15)
2005777079727·92 (6·30–9·80)90·91 (82·16–96·27)9·09 (3·73–17·84)
2006494726177·94 (5·93–10·36)95·92 (86·02–99·50)4·08 (0·50–13·98)
Costa Rica200824820·97 (0·62–1·44)
Ecuador200740295·24 (83·84–99·42)4·76 (0·58–16·16)
El Salvador2006223985·53 (3·50–8·25)
200824––3696·50 (4·21–9·52)
French Guiana20027268427326·37 (21·25–32·02)94·44 (86·38–98·47)5·56 (1·53–13·62)
2008 276 81·82 (64·54–93·02)18·18 (6·98–35·46)
Honduras200751393·60 (1·18–8·19)
200862562·34 (0·86–5·03)––
México200056854622373115·22 (14·09–16·42)96·13 (94·19–97·56)3·87 (2·44–5·81)
2001838129918·38 (6·73–10·28)97·59 (91·57–99·71)2·41 (0·29–8·43)
2002108614716556·53 (5·38–7·82)56·48 (46·60–66·00)43·52 (34·00–53·40)
200337635719309812·14 (11·01–13·34)94·95 (92·22–96·93)5·05 (3·07–7·78)
200461273423752·57 (1·97–3·29)44·26 (31·55–57·55)55·74 (42·45–68·45)
200529727423272110·92 (9·77–12·15)92·26 (88·61–95·03)7·74 (4·97–11·39)
200697494841892·32 (1·88–2·82)50·52 (40·17–60·83)49·48 (39·17–59·83)
20073893513854977·08 (6·41–7·79)90·23 (86·84–92·99)9·77 (7·01–13·16)
20081261101652322·41 (2·01–2·86)87·30 (80·20–92·56)12·70 (7·44–19·80)
Panama200771521961211·60 (9·17–14·41)73·24 (61·41–83·06)26·76 (16·94–38·59)
20088365189578·67 (6·97–10·64)78·31 (67·91–86·61)21·69 (13·39–32·09)
Paraguay2000 380 100·00 (90·75–100·00)0·00 (0·00–9·25)
200191395226134·87 (29·09–40·99)42·86 (32·53–53·66)57·14 (46·34–67·47)
200231151615020·67 (14·49–28·03)48·39 (30·15–66·94)51·61 (33·06–69·85)
20033731615 5160·24 (0·17–0·33)83·78 (67·99–93·81)16·22 (6·19–32·01)
2004118111713178·96 (7·47–10·63)94·07 (88·16–97·58)5·93 (2·42–11·84)
20058375810897·62 (6·12–9·36)90·36 (81·89–95·75)9·64 (4·25–18·11)
2008179361·82 (1·06–2·89)
Peru200262337724689669·53 (66·40–72·53)60·51 (56·55–64·37)39·49 (35·63–43·45)
2003757637120191239·59 (37·39–41·82)84·15 (81·35–86·68)15·85 (13·32–18·65)
200443535085187423·21 (21·32–25·19)80·46 (76·42–84·08)19·54 (15·92–23·58)
200539437420172922·79 (20·83–24·84)94·92 (92·27–96·87)5·08 (3·13–7·73)
20061311141726105·02 (4·21–5·93)87·02 (80·04–92·26)12·98 (7·74–19·96)
200784592523703·54 (2·84–4·37)70·24 (59·27–79·73)29·76 (20·27–40·73)
2008119863321845·45 (4·53–6·48)72·27 (63·32–80·08)27·73 (19·92–36·68)
Uruguay2002 1024 29·41 (15·10–47·48)70·59 (52·52–84·90)
20038380330527·21 (22·30–32·58)96·39 (89·80–99·25)3·61 (0·75–10·20)
200446361043210·65 (7·90–13·95)78·26 (63·64–89·05)21·74 (10·95–36·36)
2005117863127542·55 (36·63–48·62)73·50 (64·55–81·23)26·50 (18·77–35·45)
20065452215135·76 (28·14–43·96)96·30 (87·25–99·55)3·70 (0·45–12·75)
20076658851612·79 (10·03–15·98)87·88 (77·51–94·62)12·12 (5·38–22·49)
200880354537621·28 (17·25–25·76)43·75 (32·68–55·30)56·25 (44·70–67·32)
Venezuela2004121866·45 (3·38–11·00)
20065232207876·61 (4·97–8·57)61·54 (47·02–74·70)38·46 (25·30–52·98)
Table 7. Percentage of subtype H1, H3, and NT out of Type A strains by country and year
CountryYearSubtype H1Subtype H3Subtype non-specifiedNPercentage subtype H1 % (95% CI)Percentage subtype H3 % (95% CI)Percentage subtype NTb % (95% CI)
Argentina19998451011545·19 (2·27–9·98)29·22 (22·18–37·08)65·58 (57·51–73·04)
20001171028139829·40 (24·96–34·14)0·00 (0·00–0·92)70·60 (65·86–75·04)
2001141737727950·13 (0·00–0·70)52·45 (48·91–55·97)47·42 (43·90–50·96)
2002231014918212·64 (8·18–18·36)5·49 (2·67–9·87)81·87 (75·49–87·18)
2003263249792130420·17 (18·02–22·45)19·10 (17·00–21·34)60·74 (58·03–63·40)
200404835079900·00 (0·00–0·37)48·79 (45·63–51·95)51·21 (48·05–54·37)
200504533267790·00 (0·00–0·47)58·15 (54·60–61·64)41·85 (38·36–45·40)
20062652626956047·32 (43·12–51·55)4·64 (3·06–6·73)48·04 (43·83–52·26)
200703216329530·00 (0·00–0·39)33·68 (30·68–36·78)66·32 (63·22–69·32)
20082004284484·46 (2·75–6·81)0·00 (0·00–0·82)95·54 (93·19–97·25)
Brazil19990146470·00 (0·00–7·55)2·13 (0·05–11·29)97·87 (88·71–99·95)
20032526469725·77 (17·42–35·65)26·80 (18·32–36·76)47·42 (37·19–57·82)
2004434881263·17 (0·87–7·93)26·98 (19·47–35·62)69·84 (61·03–77·69)
20053351575·26 (1·10–14·62)5·26 (1·10–14·62)89·47 (78·48–96·04)
2006412612018721·93 (16·22–28·55)13·90 (9·29–19·71)64·17 (56·85–71·04)
2007412233910·26 (2·87–24·22)30·77 (17·02–47·57)58·97 (42·10–74·43)
20089607316956·80 (48·98–64·39)0·00 (0·00–2·16)43·20 (35·61–51·02)
Chile1999133791130·89 (0·02–4·83)29·20 (21·03–38·50)69·91 (60·57–78·18)
20002151319334743·52 (38·23–48·91)0·86 (0·18–2·51)55·62 (50·22–60·92)
2001424595712060·33 (0·09–0·85)20·32 (18·08–22·70)79·35 (76·96–81·61)
2002105043153619·59 (16·31–23·21)0·00 (0·00–0·69)80·41 (76·79–83·69)
200323162355530·36 (0·04–1·30)57·14 (52·90–61·31)42·50 (38·33–46·74)
200404783958730·00 (0·00–0·42)54·75 (51·38–58·09)45·25 (41·91–48·62)
200504682767440·00 (0·00–0·49)62·90 (59·32–66·38)37·10 (33·62–40·68)
200615119233367622·34 (19·25–25·67)28·40 (25·03–31·97)49·26 (45·43–53·10)
2007731030136181·13 (0·46–2·32)50·16 (46·15–54·18)48·71 (44·70–52·73)
2008393025064361·12 (57·23–64·91)0·00 (0·00–0·57)38·88 (35·09–42·77)
Colombia199904310530·00 (0·00–6·72)81·13 (68·03–90·56)18·87 (9·44–31·97)
200022553268·75 (49·99–83·88)15·63 (5·28–32·79)15·63 (5·28–32·79)
20031578661·52 (0·04–8·16)86·36 (75·69–93·57)12·12 (5·38–22·49)
20050268700·00 (0·00–5·13)2·86 (0·35–9·94)97·14 (90·06–99·65)
20060047470·00 (0·00–7·55)0·00 (0·00–7·55)100·00 (92·45–100·00)
Ecuador200738024095·00 (83·08–99·39)0·00 (0·00–8·81)5·00 (0·61–16·92)
French Guiana20020599680·00 (0·00–5·28)86·76 (76·36–93·77)13·24 (6·23–23·64)
México20004235195460·73 (0·20–1·87)4·21 (2·69–6·25)95·05 (92·89–96·72)
2001966678111·11 (5·21–20·05)7·41 (2·77–15·43)81·48 (71·30–89·25)
20023652614·92 (1·03–13·71)9·84 (3·70–20·19)85·25 (73·83–93·02)
200324792543576·72 (4·35–9·84)22·13 (17·93–26·80)71·15 (66·15–75·80)
200526941542749·49 (6·29–13·59)34·31 (28·70–40·26)56·20 (50·11–62·17)
2006831432496·12 (1·28–16·87)28·57 (16·58–43·26)65·31 (50·36–78·33)
2007769518035121·65 (17·46–26·33)27·07 (22·49–32·04)51·28 (45·92–56·62)
200816633111014·55 (8·55–22·54)57·27 (47·48–66·66)28·18 (20·02–37·56)
Panama20070052520·00 (0·00–6·85)0·00 (0·00–6·85)100·00 (93·15–100·00)
20080065650·00 (0·00–5·52)0·00 (0·00–5·52)100·00 (94·48–100·00)
Paraguay20000038380·00 (0·00–9·25)0·00 (0·00–9·25)100·00 (90·75–100·00)
20010039390·00 (0·00–9·03)0·00 (0·00–9·03)100·00 (90·97–100·00)
200301516310·00 (0·00–11·22)48·39 (30·15–66·94)51·61 (33·06–69·85)
2004051601110·00 (0·00–3·27)45·95 (36·45–55·67)54·05 (44·33–63·55)
200522746752·67 (0·32–9·30)36·00 (25·23–47·91)61·33 (49·38–72·36)
Peru2002902226537723·87 (19·66–28·50)58·89 (53·73–63·90)17·24 (13·57–21·44)
200347855056377·38 (5·47–9·69)13·34 (10·80–16·23)79·28 (75·92–82·36)
2004786620635022·29 (18·03–27·01)18·86 (14·89–23·36)58·86 (53·50–64·06)
20051454218737438·77 (33·80–43·91)11·23 (8·21–14·88)50·00 (44·82–55·18)
2006211111141·75 (0·21–6·19)0·88 (0·02–4·79)97·37 (92·50–99·45)
20070059590·00 (0·00–6·06)0·00 (0·00–6·06)100·00 (93·94–100·00)
20082084862·33 (0·28–8·15)0·00 (0·00–4·20)97·67 (91·85–99·72)
Uruguay20031637278020·00 (11·89–30·44)46·25 (35·03–57·76)33·75 (23·55–45·19)
20040531360·00 (0·00–9·74)13·89 (4·67–29·50)86·11 (70·50–95·33)
200522658862·33 (0·28–8·15)30·23 (20·79–41·08)67·44 (56·48–77·16)
2006100425219·23 (9·63–32·53)0·00 (0·00–6·85)80·77 (67·47–90·37)
200703226580·00 (0·00–6·16)55·17 (41·54–68·26)44·83 (31·74–58·46)
2008250103571·43 (53·70–85·36)0·00 (0·00–10·00)28·57 (14·64–46·30)
Venezuela2006181403256·25 (37·66–73·64)43·75 (26·36–62·34)0·00 (0·00–10·89)
image

Figure 3.  Percentage of influenza in samples by country and year: initial (1999) and final (2008) reports.

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ILI and LRTI rates

The ILI rate was reported in four countries: Argentina (2644·9 per 100 000 persons -2005-), Chile (633 per 100 000 persons -2005-), Dominica (605 per 100 000 persons -2003-), and Panama (cases increased from 6250 to 9822 per 100 000 persons -1995–2004-). This large increase of ILI burden in Panama may have been attributed to the influenza epidemic in 1999 that resulted in an annual ILI rate of 46 262 per 100 000 persons.44

Information from the Ministries of Health and viral surveillance centers of Argentina and Brazil was available on ILI and LRTI. In Argentina, a median of 874 809 ILI cases and 48 728 LRTI were notified between 2003 and 2007.50 The rate of ILI notification until August 2007 was 2264·19 per 100 000 persons in adults and 6062·38 per 100 000 persons in children <5 years of age.51 Between 2000 and 2008, the influenza surveillance system in Brazil revealed that ILI led to a total of 4·39–16·92% of hospital consultations.52

Influenza-like illnesses activity in LA&C for the period 1999–2008 is presented in Appendix S4 (data taken from the FluNet). Each national influenza center defines the geographical spread of influenza based on the WHO global influenza surveillance system as follows: Region, No report, No activity, Sporadic, Local outbreak, Regional activity, and Widespread activity.53

In the meta-analysis of ILI by age, we included six studies and the Argentinean GROG reports 2001–2007.54–70 The proportion of confirmed influenza in ILI cases was high in children aged 5–14 years, while in children younger than 5 years and older than 14 years the proportion of confirmed influenza in ILI cases was low. Meta-analysis of the proportion of confirmed influenza in LRTI reported in 16 studies2,55,60–83 showed that the highest proportion occurred in the adolescent population. Type A was more prevalent than type B in confirmed cases of ILI and LRTI (Table 8).

Table 8. Percentage of confirmed influenza in ILI and LRTI by age groups
 Age groupsNumber of studies N Influenza Percentage % (95% CI)Number of studies N Percentage Type A % (95% CI)Percentage Type B % (95% CI)
  1. *Studies without a specific age range.

  2. ILI, influenza-like illnesses.

Confirmed influenza in ILI0–5 years5151324·53 (16·94–33·01)539094·29 (83·05–99·66)5·71 (0·34–16·95)
5–14 years4119329·98 (23·19–37·25)438283·36 (45·88–99·98)16·64 (0·02–54·12)
14–59 years4189119·21 (15·59–23·12)435284·01 (60·02–98·10)15·99 (1·90–39·98)
60 or more314918·55 (12·79–25·10)32783·89 (50·73–99·77)16·11 (0·23–49·27)
Any age*712 58416·32 (10·41–23·26)7189885·62 (73·84–94·30)14·38 (5·70–26·16)
NR397541·57 (5·09–85·05)326280·86 (65·07–92·72)19·14 (7·28–34·93)
Confirmed influenza in LRTI0–2 years1867164·48 (3·07–6·14)722383·53 (69·70–93·74)16·46 (6·26–30·30)
0–5 years16142 1493·00 (2·20–3·91)15407887·12 (79·31–93·29)12·88 (6·71–20·69)
5 to 14/16 years10685611·35 (5·06–19·73)979676·16 (57·11–90·92)23·84 (9·08–42·89)
14/16 to ≥59 years5230319·38 (16·47–22·47)543579·20 (55·22–95·48)20·80 (4·52–44·78)
≥60 years44576·66 (4·57–9·11)42992·25 (80·87–98·76)7·75 (1·24–19·13)
All ages*18217 7842·98 (2·91–3·06)18711179·22 (70·25–86·94)20·78 (13·06–29·75)
NR3127111·79 (2·04–28·01)

Use of resources

The impact of influenza, ILI, LRTI, and ARI on healthcare resources was reported in eight studies.1,2,45,46,71,72,74,84 A meta-analysis on the use of healthcare resources was not performed due to the heterogeneity of the designs and included populations.

Many of the influenza cases were severe and led to hospitalization. The mean duration of stay in hospitals ranged between 5·8 and 12·9 days in non-intensive care units (ICU);2,71,72 for patients who were admitted to ICU, the median duration of stay (one study) was 32 days,71 although it ranged between 5·9 and 13·6 days in another study.84

The use of antibiotic and/or neuraminidase inhibitors in the treatment of patients with influenza was reported in three studies.2,71,72 Oseltamivir resistance of influenza A (H1N1) 2009 virus was reported in two studies in Argentina.85,86

Influenza-like illnesses also resulted in absenteeism and workdays lost, being the total number of work days lost (in unvaccinated population) of 17,1 102,45 and 150 days45 in the three analyzed studies, respectively.

Hospitalization due to influenza or ILI led to several direct (e.g., hospitalization, diagnosis, and treatment) and indirect costs (domestic help, transportation, loss of productivity due to absenteeism). The mean direct cost at the time of discharge from hospitals was US$575 per laboratory-confirmed influenza case, US$473 for other respiratory diseases, and US$657 for subjects who tested negative for all viral pathogens. Overall, societal cost at discharge, which takes into account direct and indirect costs, was US$620 per laboratory-confirmed influenza case, US$453 for other respiratory viruses, and US$669 for subjects who were negative for all viral pathogens.71

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Conflict of interest
  10. Funding
  11. References
  12. Supporting Information

Influenza virus has an unparalleled potential to cause epidemics and global pandemics.87 The disease affects millions of people all over the world and leads to fatal complications in approximately 1 million people every year.88 In LA&C, seasonal influenza has been the major cause of respiratory infection-associated morbidity and mortality in older adults and younger children.89,90

In this systematic review, 31 articles, 75 sub-studies from the FluNet database, the book Health in the Americas 2007 Edition, and 10 reports from collaborative groups were analyzed. We included information mostly derived from surveillance systems, case series, and cross-sectional studies, which were based on samples from patients who attended healthcare centers or specific sub-populations. The annual incidence rate of ILI per 1000 person, years was found to be 36 080 per 100 000 person, years. Meta-analysis was performed on four prospective studies with the highest incidence observed in the <5, year age group. It is important to acknowledge that there may have been underreporting of ILI cases in these studies and thus the rates calculated here may be lower than the true value, highlighting the need of alternative methods, as presented in this report, to estimate the real burden of influenza.

The burden of influenza was high, with increased risk of morbidity and mortality in children under 5 years of age and in the elderly population having underlying medical problems. Consequently, these patients also contributed significantly to the economic burden of the country in terms of hospitalization, treatment, and other resource costs. The rate of hospitalization due to respiratory diseases in children in the United States aged <5 years varied from 100 to 500 per 100 000 children in different reports.8–14 Studies in temperate regions in Europe show similar figs.12,16–18 In Hong Kong, where the epidemiological pattern is similar to the tropical zone, higher hospitalization rates (2093–2882 per 100 000) were reported.19

No meaningful conclusions could be drawn on influenza-related mortality since Chile was the only country with available mortality data attributable to influenza (overall 0·4 per 100 000 persons; 4·1 per 100 000 persons in ≥65, year age group). Influenza and all-cause pneumonia deaths are reported together for the majority of LA&C official MOH databases.44,91 While these deaths were originated both from laboratory-confirmed and ILI cases, and from bacterial pneumonia cases, they still provide a broad complementary perspective of the upper limit of influenza burden. Chilean data were in line with previous studies demonstrating that influenza-related mortality rate was the highest in the <5, year and >65, year age groups.92,93 One study in the United States used a regression model to attribute an annual average of 41 400 deaths (95% CI: 27 100–55 700) to influenza between 1979 and 2001.94 Other studies in the United States and England have also shown that influenza infections were seldom fatal in younger adults, but led to deaths (range: 0·8–6·7 per 100 000 persons) in the <5, year age group.95,96

Meta-analysis of the proportion of influenza-positive specimens among all specimens received by influenza centers over a 10, year period (1999–2008) showed a range of 4·7–5·4%. Of all influenza-positive specimens analyzed during the period of study, type A was more frequent than type B, accounting for 81·8% and 18·2% of influenza-positive samples, respectively. The percentages of laboratory-confirmed influenza appeared to fluctuate within the period studied, probably due to the severity of annual epidemics. Assessment of the percentage of influenza-positive specimens per country demonstrated diverse rates between different countries. This could be due to the sampling of patients with different case definitions. Additionally, each country used different baseline and epidemic curves to determine the situation at a given moment, so comparison of the percentages of influenza clinical specimens between countries was not possible. When all studies were grouped, influenza type A predominated in all the years assessed. However, when analyzed by country and year, influenza B was the most prevalent type in Argentina, Brazil, and Uruguay in 2002, Colombia and Mexico in 2004, and Paraguay in 2001. With respect to the proportion of type A-positive samples accounted for by the different influenza subtypes, H3 influenza viruses were found to be more frequent, although a high proportion of viruses were not subtyped.

As a limitation, substantial heterogeneity was observed; however, the use of a random effect model provided conservative estimations (e.g., on the proportion of influenza cases meta-analyses).

When conducting seasonal influenza circulation studies using specimens collected at international reference centers, it was generally considered sufficient to analyze only a minimal proportion of isolates to determine the influenza strain in circulation. The circulation of H3 or H1 subtypes did not appear to show a definite trend when analyzed by season or by country. Some calendar years were characterized by the circulation of one unique subtype, while in others there was co-circulation of H3 and H1.

While sentinel surveillance is not adequate for capturing ILI incidence, it is still useful to learn about flu yearly seasonality patterns and to obtain information related with flu types and subtypes, genetic changes, and the emergence of antiviral resistance. Different surveillance systems coexist in the region and even in a country: virological surveillance, sentinel sites or units, population-based studies, outbreak investigations. In general, it is not possible to estimate what proportion of the ILI cases has been confirmed as influenza cases because the mentioned systems do not circumscribe a definite population, except for Chilean data where samples are provided by hospitals attending a restricted population. Important underreporting could have arisen from mild episodes that may have not sought medical attention, and also due to the passive nature of the surveillance in LAC countries.

Respiratory syncytial virus (RSV) is the most frequent viral agent causing severe acute LRTI, needing hospitalization in infant and young children worldwide.97–99 The diagnosis of viral respiratory infections improved in the last years, and currently comprises 21 national influenza centers in the region, including detection of RSV, adenovirus, and para-influenza viruses. Weekly information on the circulation of respiratory viruses started to be organized by PAHO in 2009. Besides, epidemiological data on bronchiolitis notifications started to be analyzed at the Ministries of Health of several countries. In Argentina, bronchiolitis notifications started in 2004.

The emergence of the H1N1 2009 pandemic virus triggered a number of new investigations, some of them reflecting ILI incidence data in previously non-studied regions,100 in an active population-based surveillance in 2008–2009 in the Amazon Basin, Peru, estimated an age-adjusted incidence of ILI of 46·7 episodes/1000 person-years and an age-adjusted incidence rate of 16·5 symptomatic influenza virus infections/1000 person, years.

Besides, different testing methods have been employed in the literature analyzed with marked differences in sensitivity and specificity for detection of influenza virus and co-circulating viruses of relevance as RSV. In general, virological influenza surveillance before H1N1 2009 pandemics has been performed by immunofluorescence as well as for etiological studies. Special facilities proportionate new etiological approaches as in the studies by Laguna Torres et al. in Peru101–103 or Douce et al. in Ecuador.104 Even though, most of them are biased by the selection of the population or the recruitment sites.

Laboratory-confirmed influenza hospitalizations and deaths underestimate influenza burden because influenza rarely appears on medical records, and death can occur after secondary bacterial infection or exacerbation of comorbidities several weeks after the primary viral infection has subsided. Charu et al.105 estimate influenza-related mortality rates for interpandemic and pandemic seasons during 2000–2010, applying Serfling cyclical regression models to monthly death rates due to I&P, respiratory causes, cardiac causes, and all-cause mortality, with data obtained from the vital statistics at the Mexican Ministry of Health.24 Results obtained estimate that the excess pandemic mortality was 0·6–2·6 times higher than the seasonal mean excess mortality.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Conflict of interest
  10. Funding
  11. References
  12. Supporting Information

We critically reviewed data collected over the last decade on the circulation of the influenza virus and of its types and subtypes in LA&C. Although we could not draw solid conclusions on incidence and use of resources due to heterogeneity between populations, sampling methods, and definitions used, this review could be informative for decision makers in adopting measures to control the disease.

Although there has been a considerable improvement in the influenza surveillance systems in the region, the ILI notification rate is still unsatisfactory. Limited conclusions can be drawn from trends identified in the circulation of different influenza types or subtypes, or their geographical distribution and spread. In LA&C, pneumonia and influenza are placed together between the first and eighth leading causes of death in men and women alike. The highest rates of pneumonia and influenza-related deaths are seen in the <5, year and ≥60, year age groups. To improve our knowledge about incidence and resource use for influenza in LA&C, more data from population-based cohort studies are needed.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Conflict of interest
  10. Funding
  11. References
  12. Supporting Information

The authors express their gratitude to the librarian Daniel Comandé for his crucial contribution to this study; Geetha Subramanyam and Juliette Gray for medical writing, Camilo Moreno and Jessica Mattos for editorial assistance and coordination of this publication (all four employees or on behalf of GSK).

Conflict of interest

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Conflict of interest
  10. Funding
  11. References
  12. Supporting Information

IECS authors and Vilma Savy declare no conflicts of interest. Eduardo Ortega-Barría and Rómulo E. Colindres are employees of GlaxoSmithKline Biologicals.

Funding

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Conflict of interest
  10. Funding
  11. References
  12. Supporting Information

This work was supported by GlaxoSmithKline Biologicals and by the Institute for Clinical Effectiveness and Health Policy.

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  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Conflict of interest
  10. Funding
  11. References
  12. Supporting Information
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Supporting Information

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Conflict of interest
  10. Funding
  11. References
  12. Supporting Information

Appendix S1. Search strategy in electronic databases.

Appendix S2. Tool for assessing susceptibility to bias in observational studies.

Appendix S3. Country-wise reports on national health situations on influenza and ARI.

Appendix S4. Prevalence of influenza by country and year.

Appendix S5. Yearly ILI activity report1999–2008 by country in LA&C# (FLUNET reports).

Map S1. Prevalence and Type/Subtype distribution 1999.

Map S2. Prevalence and Type/Subtype distribution 2000.

Map S3. Prevalence and Type/Subtype distribution 2001.

Map S4. Prevalence and Type/Subtype distribution 2002.

Map S5. Prevalence and Type/Subtype distribution 2003.

Map S6. Prevalence and Type/Subtype distribution 2004.

Map S7. Prevalence and Type/Subtype distribution 2005.

Map S8. Prevalence and Type/Subtype distribution 2006.

Map S9. Prevalence and Type/Subtype distribution 2007.

Map S10. Prevalence and Type/Subtype distribution 2008.

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