To identify risk factors for death from pandemic (H1N1) 2009, we obtained data for 157 hospitalized patients with confirmed cases of this disease. Multivariate analysis showed that diabetes and class III obesity were associated with death. These findings helped define priority vaccination groups in Brazil.
In May 2009, pandemic (H1N1) 2009 was identified in Brazil (
This study was conducted in 11 hospitals in 4 cities (Passo Fundo, Caxias do Sul, Santa Maria, and Uruguaiana) in Rio Grande do Sul (population 10,914,128 in 2009), the southernmost state in Brazil (
All laboratory-confirmed (real-time reverse transcription PCR–positive) pandemic (H1N1) 2009 case-patients hospitalized in July 2009 who had shortness of breath or radiologic evidence of pneumonia and either died (case-patients) or were discharged (controls) were included. A standardized form was used that included data reported by patients who survived or their families (patients who died and patients <18 years of age) and information from medical chart review.
We analyzed factors associated with death by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Variables with a p value <0.10 calculated by bivariate analysis were included in a multivariate unconditional logistic regression model adjusted for age and sex. All statistical analyses were conducted by using Epi Info for Windows version 3.5.1 (Centers for Disease Control and Prevention, Atlanta, GA, USA). A p value <0.05 was considered significant.
The number of confirmed pandemic (H1N1) 2009 case-patients enrolled in each city is shown in
Location of Rio Grande do Sul, Brazil (A) and distribution of 157 patients with pandemic (H1N1) 2009 in 4 cities in this state (B). Values in parentheses are numbers of patients.
Sample selection process for 201 patients with pandemic (H1N1) 2009, Rio Grande do Sul, Brazil, 2009.
| Characteristic | Value | No. patients |
|---|---|---|
| Demographic | ||
| Male sex | 78 (50) | 157 |
| Age, y | 33 (0–73) | 157 |
| Family income, US$ | 678 (0–6,780) | 146 |
| Education level, y† | 8 (0–19) | 129 |
| Residence city different from hospitalization city | 46 (29) | 157 |
| Smoking habits† | ||
| Current smoker | 34 (24) | 142 |
| Years exposed to tobacco | 14 (1–47) | 33 |
| Cigarettes/day | 12 (1–60) | 33 |
| Pack-years | 8 (0–93) | 33 |
| Former smoker | 19 (13) | 142 |
| Years exposed to tobacco | 11 (1–54) | 18 |
| Cigarettes/day | 20 (3–60) | 18 |
| Pack-years | 6.5 (0–162) | 18 |
| Signs and symptoms | ||
| Cough | 155 (99) | 157 |
| Fever | 152 (97) | 157 |
| Shortness of breath | 152 (97) | 157 |
| Myalgia | 110 (70) | 157 |
| Chills | 110 (70) | 157 |
| Arthralgia | 73 (47) | 157 |
| Sore throat | 74 (47) | 157 |
| Hemoptysis | 18 (11) | 157 |
| Diarrhea | 52 (33) | 157 |
| Vomiting | 69 (44) | 157 |
| Conjunctivitis | 9 (6) | 157 |
| Headache | 56 (36) | 157 |
| Seasonal influenza vaccination in the previous year‡ | 13 (13) | 101 |
| Pneumonia vaccination in the previous year‡ | 5 (5) | 101 |
| Health care treatment before hospitalization | 136 (87) | 157 |
| Risk factor for influenza complication§ | 87 (55) | 157 |
| Diabetes | 23 (18) | 125 |
| Chronic lung disease | 23 (18) | 125 |
| Immunosuppression | 11 (9) | 125 |
| Chronic cardiovascular disease | 8 (6) | 125 |
| Chronic renal disease | 6 (5) | 125 |
| Pregnancy trimester¶ | 15 (25) | 59 |
| Second | 5 (33) | 15 |
| Third | 10 (67) | 15 |
| Age | 16 (10) | 157 |
| Age | 7 (5) | 157 |
| Obesity# | 53 (38) | 138 |
| Class III obesity** | 10 (7) | 138 |
| Hospitalization | ||
| Admitted to intensive care unit | 80 (51) | 157 |
| Mechanical ventilation | 61 (39) | 157 |
| Invasive procedures | 69 (44) | 157 |
| Clinical complications | 54 (34) | 157 |
*Values are no. (%) or median (range).
†Children <8 years of age were excluded from the denominator.
‡Influenza and pneumonia vaccination were checked on the vaccination card.
§Obesity was not included.
¶Percentage of pregnancy among women of reproductive age (15–49 years) was included.
#Body mass index (BMI) data were available for 138 patients. Obesity in adults was BMI
Taking medication was reported by 107 (68%) case-patients, but none received oseltamivir before hospitalization. Hospitalization occurred a median of 5 days (range 0–15 days) after symptom onset. Most case-patients (94%) received antimicrobial drugs during hospitalization, and most (81%) began antimicrobial drug therapy on the day of hospitalization. Steroids were administered to 83 (53%) case-patients a median of 1 day (range 0–11 days) after admission.
Three deaths occurred during the first 24 hours of hospitalization. The case-fatality rate was higher among patients admitted to the intensive care unit (47 [59%] of 80 died). No difference was observed between patients who died and those who survived for median number of days between symptom onset and hospitalization (case-patients 6 days, range 0–6 days; controls 5 days, range 0–15 days; p = 0.25) or initiation of oseltamivir treatment (case-patients 6 days, range 1–16 days; controls 5 days, range 0–19 days; p = 0.10). After we adjusted for age and sex, diabetes (OR 4.4, 95% CI 1.5–12.8) and class III obesity (OR 6.2, 95% CI 1.3–29.2) were independently associated with death from pandemic (H1N1) 2009. No association was found between oseltamivir treatment within 48 hours of symptom onset and death (
| Characteristic | Outcome, no. (%) case-patients | Unadjusted | Adjusted† | |||||
|---|---|---|---|---|---|---|---|---|
| Died | Survived | OR (95% CI) | p value | OR (95% CI) | p value | |||
| Demographic | ||||||||
| Male sex | 30 (58) | 48 (46) | 1.6 (0.8–3.2) | 0.16 | NC | NC | ||
| Current smoker | 15 (30) | 19 (21) | 1.6 (0.7–3.6) | 0.21 | NC | NC | ||
| Former smoker | 4 (8) | 15 (18) | 0.4 (0.1–1.3) | 0.13 | NC | NC | ||
| Underlying medical condition‡ | 30 (58) | 57 (54) | 1.1 (0.6–2.2) | 0.69 | NC | NC | ||
| Diabetes | 14 (27) | 9 (9) | 3.9 (1.6–9.8) | 0.01 | 4.4 (1.5–12.8) | <0.01 | ||
| Chronic lung disease | 9 (19) | 14 (18) | 1.1 (0.4–2.7) | 0.87 | NC | NC | ||
| Immunosuppression | 2 (4) | 9 (12) | 0.3 (0.1–1.7) | 0.14 | NC | NC | ||
| Chronic cardiovascular disease | 5 (11) | 3 (4) | 3.0 (0.7–13.1) | 0.13 | NC | NC | ||
| Chronic renal disease | 1 (2) | 5 (6) | 0.3 (0.1–2.8) | 0.27 | NC | NC | ||
| Pregnancy§ | 5 (28) | 10 (24) | 1.2 (0.3–4.2) | 0.51 | NC | NC | ||
| Age | 2 (4) | 14 (13) | 0.3 (0.1–1.2) | 0.06 | NC | NC | ||
| Age | 4 (8) | 3 (3) | 2.8 (0.6–13.2) | 0.17 | NC | NC | ||
| Class III obesity¶ | 26 (57) | 27 (29) | 5.3 (1.3–21.7) | <0.01 | 6.2 (1.3–29.2) | 0.02 | ||
| Oseltamivir treatment | 25 (48) | 64 (61) | 0.6 (0.3– 1.2) | 0.12 | NC | NC | ||
| Oseltamivir | 2 (12) | 12 (19) | 0.4 (0.1–1.8) | 0.18 | NC | NC | ||
| Steroid treatment | 32 (71) | 51 (57) | 0.5 (0.3–1.2) | 0.12 | NC | NC | ||
| Antimicrobial drug treatment | 99 (94) | 49 (94) | 1.0 (0.2–4.1) | 0.99 | NC | NC | ||
*OR, odds ratio; CI, confidence interval; NC, not calculated.
†Adjusted for sex and age group (reference age 0–5 years).
‡Obesity excluded.
§Women of reproductive age included (15–49 years).
¶Class III obesity was a body mass index
This study confirmed findings from other countries suggesting that at the beginning of the epidemic, pandemic (H1N1) 2009 virus showed a pattern similar to that in the Northern Hemisphere. Consequently, vaccine recommendations in Brazil were made on the basis of epidemiology of pandemic (H1N1) 2009 in Brazil and other countries.
Identification of diabetes and class III obesity as independent risk factors for death caused by pandemic (H1N1) 2009 among hospitalized patients in Brazil was also consistent with findings from other regions (
Diabetes and obesity were overrepresented among case-patients in this study compared with the general population of Rio Grande do Sul. A telephone survey conducted in Porto Alegre (capital of Rio Grande do Sul) found a 14.3% prevalence of self-reported obesity and 6.2% prevalence of self-reported diabetes in 2009 (
Our study had several limitations. Data were collected retrospectively (median 54 days, range 1–93 days after symptom onset) and by proxy interview for case-patients who died and pediatric patients and were therefore subject to recall bias. Data for analysis, including underlying illnesses and patient weight and height, were not systematically recorded in medical charts. Therefore, these data could not be used to validate questionnaire responses. Furthermore, hospitalized case-patients from whom nasopharyngeal aspirates or swab samples were not obtained were excluded from the study. Thus, the sample analyzed might not be representative of all hospitalized case-patients with severe pandemic (H1N1) 2009 during the study. However, demographic characteristics of study patients were similar to those of reported hospitalized case-patients with suspected pandemic (H1N1) 2009. Conclusions from small case series are limited, and results from this study should be considered in the context of studies in different populations. Quality of hospital care is likely to have a major role in survival rates but is difficult to compare between settings.
To reduce incidence of illness and death, the Brazilian Ministry of Health obtained 110 million doses of monovalent pandemic (H1N1) vaccine for distribution in the first 3 months of 2010. Persons with chronic medical conditions, including diabetes and obesity, received priority for vaccination on the basis of international recommendations (
We thank Brendan Flannery, Douglas Hatch, Jeremy Sobel, and Suely Tuboi for reviewing the article and making other contributions.
This study was supported by the Secretariat of Health Surveillance, Brazilian Ministry of Health and Health Department of Rio Grande do Sul State, and the National Council of Scientific and Technological Development (grant no. 552051/2009-8).
Ms Yokota is an epidemiology trainee of the Brazilian Field Epidemiology Training Program, Brasilia, Brazil. Her research interests are public health surveillance and biostatistics.