Elsevier

The Lancet

Volume 372, Issue 9640, 30 August–5 September 2008, Pages 744-749
The Lancet

Articles
Factors associated with case fatality of human H5N1 virus infections in Indonesia: a case series

https://doi.org/10.1016/S0140-6736(08)61125-3Get rights and content

Summary

Background

Indonesia has had the most human cases of highly pathogenic avian influenza A (H5N1) and one of the highest case-fatality rates worldwide. We described the factors associated with H5N1 case-fatality in Indonesia.

Methods

Between June, 2005, and February, 2008, there were 127 confirmed H5N1 infections. Investigation teams were deployed to investigate and manage each confirmed case; they obtained epidemiological and clinical data from case-investigation reports when possible and through interviews with patients, family members, and key individuals.

Findings

Of the 127 patients with confirmed H5N1 infections, 103 (81%) died. Median time to hospitalisation was 6 days (range 1–16). Of the 122 hospitalised patients for whom data were available, 121 (99%) had fever, 107 (88%) cough, and 103 (84%) dyspnoea on reaching hospital. However, for the first 2 days after onset, most had non-specific symptoms; only 31 had both fever and cough, and nine had fever and dyspnoea. Median time from onset to oseltamivir treatment was 7 days (range 0–21 days); treatment started within 2 days for one patient who survived, four (36·4%) of 11 receiving treatment within 2–4 days survived, six (37·5%) of 16 receiving treatment within 5–6 days survived, and ten (18·5%) of 44 receiving treatment at 7 days or later survived (p=0·03). Initiation of treatment within 2 days was associated with significantly lower mortality than was initiation at 5–6 days or later than 7 days (p<0·0001). Mortality was lower in clustered than unclustered cases (odds ratio 33·3, 95% CI 3·13–273). Treatment started at a median of 5 days (range 0–13 days) from onset in secondary cases in clusters compared with 8 days (range 4–16) for primary cases (p=0·04).

Interpretation

Development of better diagnostic methods and improved case management might improve identification of patients with H5N1 influenza, which could decrease mortality by allowing for earlier treatment with oseltamivir.

Funding

None.

Introduction

As of Feb 12, 2008, highly pathogenic avian influenza A (H5N1) had affected 360 human beings since October, 2003,1 and there is concern that these infections could be the prelude to a global pandemic if sustained human-to-human transmission develops. The high case-fatality rate of 62·8%1 would be devastating if maintained in a pandemic. Indonesia has had the most patients with H5N1 influenza and one of the highest case-fatality rates worldwide. The first confirmed human H5N1 infection in Indonesia was in June, 2005,2 and since then the number of patients has increased steadily, and case fatality increased year-on-year from 2005 to 2007. Although there have been many hypotheses about the reasons behind the high case-fatality rates of H5N1 influenza infection, there is little evidence pointing to specific causes.

Indonesia has built surveillance and referral systems for human H5N1 infections since February, 2004. Health officers at the central, provincial, and district levels have been trained on surveillance and case identification and reporting according to WHO case definitions.3 Health officers are constantly on the lookout for cases that meet the definition of a suspect case for preliminary investigation and to obtain samples for confirmatory testing. Where clinically possible, suspected human cases are treated with oseltamivir, which is available at government hospitals and primary health-care centres throughout the country. Suspect cases are also immediately sent to one of 44 avian influenza referral hospitals (currently being increased to 100) that are equipped with isolation and intensive-care facilities, as well as case-management guidelines and expertise. In the areas where H5N1 cases have occurred, referral hospitals are all within 1 day's travel by land.

We describe the factors obtained from case investigations that are associated with case-fatality of human H5N1 infection in Indonesia.

Section snippets

Patients and data

127 people infected with H5N1 were confirmed with onset from June 22, 2005, to Feb 1, 2008. The 127 patients included the first 54 in Indonesia mentioned in a previous paper,4 although this study uses a new dataset from the case-investigation reports.

All patients with suspected H5N1 had specimens (throat and nasal swabs) taken and sent to national laboratories for testing by RT-PCR and sequencing,4 with results available within a few days. For cases before 2007, specimens were sent to WHO

Results

The case-fatality rate from 2005 to 2008 increased from 65·0% in 2005 (13 of 20 cases), to 81·8% in 2006 (45 of 55 cases), to 86·8% in 2007 (37 of 42 cases), and 80·0% up to Feb 2, 2008 (eight of ten cases). The yearly trend was significant (p=0·05) from 2005 to 2007.

From the exposure history, 54 patients had direct exposure, 50 had indirect exposure, and 23 had inconclusive exposure. There were 63 infections in men and boys. Median age of patients was 20 years (range 2–67). 58 patients lived

Discussion

H5N1 case fatality rates in Indonesia have increased from 2005 to 2007, even though case management protocols, surveillance, and equipment across the country have improved since 2005. Not being part of a cluster, residence in an urban area, and indirect exposure were positively associated with mortality. From the multivariate analysis, only patients that were part of clusters had significantly lower case fatality than did those who were not part of clusters. Secondary cases in clusters were

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