aDepartment of Pediatrics, University Federico II, Italy
bSantobono Pediatric Hospital, Naples, Italy.
Received 23 March, 2010
Revised 29 May, 2010
Accepted 10 June, 2010
Correspondence to Professor Alfredo Guarino, Department of Pediatrics, University Federico II, Via S. Pansini 5, 80131 Naples, Italy. Tel: +39 081 7464232; fax: +39 081 7464232; e-mail: firstname.lastname@example.org
Eleven HIV-infected and 30 otherwise healthy children hospitalized for H1N1 influenza were studied. Leukopenia was recorded in 64% of HIV-infected and in 20% of healthy children (P = 0.01). Chest radiograph was abnormal in 18 (46%) children. Interstitial pneumonia was more frequent in HIV-positive children and consolidation was more frequent in HIV-negative children. Although the duration of symptoms and hospital stay was significantly longer in HIV-negative than in HIV-positive children, only 37% of HIV-negative children and 91% of HIV-positive received oseltamivir. The H1N1 influenza attack rate was very high (20%) in HIV-infected children, but it consistently ran a mild course.
Selected chronic conditions have been associated with risk of a more severe course of new influenza . An underlying medical condition was reported in 73% of 272 American patients hospitalized for influenza H1N1 . Fifteen percent of them (40 patients, 29 adults and 11 children) had an underlying immunosuppression and this was the second most frequent at-risk condition for severe H1N1 . Because symptoms of classic flu may be prolonged and complications be more frequent in HIV-infected people [3,4], AIDS was considered a risk condition in the preparedness plans for flu pandemic and a priority for H1N1 vaccination . Although a decrease in hospital admissions and mortality rate from influenza has been reported in HIV-infected patients after highly active antiretroviral therapy (HAART) introduction , the hospitalization rate for influenza in this category exceeds that of the general population . However, during the pandemic, WHO officers reported that patients with HIV/AIDS did not appear to be ‘at special risk’ from H1N1 flu . On the contrary, a fatal case of pneumonia associated with H1N1 influenza in a HIV-positive patient has been reported . This death occurred in an adult with concurrent type 1 diabetes, diagnosis of AIDS and poor compliance to HAART . Whether children with HIV infection were truly at risk for an increased rate of H1N1 infection or its complications remains unclear.
In this study, we comparatively analyzed the major clinical, laboratory and radiographic features of HIV-infected children and children without risk factors hospitalized for H1N1 infection.
Children with a microbiological diagnosis of influenza H1N1, hospitalized for at least 24 h, were enrolled between 20 October and 20 November 2009, during the year of pandemic flu in Italy.
Thirty HIV-negative children (22 males; mean age 4 ± 3.4, range 5–11.3 years) and 11 HIV-infected children (six males; mean age 12.9 ± 5.4, range 3.7–18 years; P = 0.0001) attending our Reference Center for Pediatric HIV infection were admitted because of H1N1 influenza. This corresponded to 22% of the total HIV-infected children in Campania (n = 49). Four of the 11 children (36%) had received H1N1 influenza vaccine 3–10 days before hospital admission. All HIV-infected patients were on HAART; all but two children had undetectable serum HIV RNA; the mean CD4+ lymphocyte count was 975 ± 458 cells/μl.
The clinical presentation of H1N1 influenza was similar in HIV-positive and in HIV-negative children. The most common symptoms at presentation were fever (98%) and cough (71%) (Table 1).
Leukopenia was detected in 13 (32%) and thrombocytopenia in five (12%) patients (Table 1). The incidence of leukopenia was significantly higher in HIV-infected children (7/11) compared with healthy children (6/30). Six of these seven HIV-infected children showed leukopenia during H1N1 infection, whereas one child had leukopenia also before H1N1 influenza due to sclerosing cholangitis-associated hypersplenism.
A chest radiograph was performed in 95% of patients and abnormal findings were observed in 18 (46%) patients (Table 1). The most common feature was interstitial pneumonia (in 11/18 children, 61%). This pattern was more common in HIV-infected children compared to HIV-negative children, who, conversely, showed a more frequent pattern of consolidation.
Invasive medical procedures (O2 therapy, i.v. antibiotic, i.v. rehydration) were more frequent in HIV-negative than in HIV-infected children (14/30, 47%, vs. 1/11, 9%; P = 0.03). Twenty-one out of 41 (51%) children were treated with oseltamivir. Although the total duration of symptoms and hospital stay was significantly longer in HIV-negative than in HIV-positive children, only a third of children without risk factors received oseltamivir treatment compared to all but one HIV-infected child (Table 1). A HIV-positive girl did not receive oseltamivir because she was in good clinical condition, and was found positive 6 days after the onset of fever, too late for starting an effective therapy. A shorter total duration of fever was observed in children who received early (within 48 h from the onset of fever) oseltamivir (duration of fever 74.4 ± 30.7 h) compared to children who received late (after 48 h) treatment (168 ± 59.7 h) or no oseltamivir (163.2 ± 120 h) (P = 0.03, ANOVA test). Thirty-six (90%) patients received antibiotics (amoxi-clavulanate in 12 cases; clarithromycin in four; ceftriaxone in four; a combination of these antibiotics in nine; others in seven). The main reason for antibiotic prescription was the presence of consolidation or infiltrates at chest radiograph associated or not with high level of C-reactive protein and leukocytosis. Seven out of 19 (37%) patients had a serologically confirmed Mycoplasma infection (Table 1). There were no deaths in the series described.
This is the first study on the clinical course of H1N1 infection in HIV-infected children compared with children with no risk factors. Interestingly, the attack rate of H1N1 virus was more than 20% in our at-risk population of 49 children with HIV infection. Such a high attack rate can be explained, at least in part, by the close medical surveillance of these patients, as they were rapidly tested for H1N1 in case of flu-like symptoms. On the contrary, considering that the overall rate of H1N1 infection registered in the general Italian population was about 7% , it may be hypothesized that patients with HIV are highly susceptible to H1N1 influenza.
Leukopenia and relative lymphopenia were common findings, mainly in HIV-infected children. A transient leukopenia has been occasionally reported in association with influenza A infection [10–12] and may be a specific feature of H1N1 in HIV infection. About half the patients showed abnormal findings at chest radiograph, with a different pattern in HIV-positive and negative children. However, both leukopenia and pneumonia ran a transient and benign course in HIV-infected children.
Pandemic flu ran a mild course in all children with HIV infection, supporting the WHO indication that HIV is a ‘mild-risk category’. In fact, the clinical course of new flu was slightly longer in HIV-negative than in positive children. However, none of our HIV-infected patients was severely immune-suppressed and only two had a detectable HIV-RNA load. In addition, the medical intervention was rapid in all children, leading to prompted hospital admission for H1N1 infection. All HIV-infected patients were hospitalized during the first 2 weeks of November, corresponding to the epidemic peak in Italy and the ‘swine influenza phobia’. A higher percentage of HIV-infected children received oseltamivir compared to HIV-negative children, probably because of fear of a severe course of H1N1 infection in at-risk children.
In conclusion, the attack rate of H1N1 infection was high in HIV-infected children leading to hospital admission and aggressive treatment. However, pandemic flu ran a benign course, which suggests that HIV is not at risk of a severe course, but possibly of a high attack rate compared to otherwise healthy children.
The research was supported by a grant from Sky Italia s.r.l.
A. Giannattasio prepared the case report form, drafted the manuscript, participated in its review and performed the analysis of data. A. Lo Vecchio participated in drafting the manuscript and performing the analysis of data. M.T. Russo and E. Ruberto collected data on HIV-infected children. M. R. Pirozzi and A. Barbarino collected data on children without HIV. A. Campa provided patients without HIV. A. Guarino conceived and coordinated the study.
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