Investigation of Duke University cluster of oseltamivir-resistant H1N1 cases revealed patient-to-patient transmission of H275Y mutation; Health-care professionals had influenza symptoms

A multi-agency team of public health experts recently presented the results of their investigation into the cluster of four immunocompromised patients admitted to Duke University Medical Center over the 21-27 Sep, 2009 timeframe, who were found to have oseltamivir-resistant H1N1 (the H275Y mutation). Three of the patients died.

The investigation involved reviews of patient medical records and infection control measures and interviews with healthcare personnel (HCP) Oseltamivir-resistance was confirmed in virus isolates via serologic and DNA chain-reaction tests, as well as from viral genomic sequencing.

Key excerpts from the report:


“During September 21–27, 2009, four patients were admitted to the hematology ward for reasons unrelated to influenza infection (Figure). All were ambulatory and had opportunity to interact outside their rooms before onset of influenza-related illness. Three patients were located in adjacent rooms. An index patient experienced fever on October 6, 8 days after completing 5 days of oseltamivir prophylaxis following exposure to an ill family member. Isolation precautions were instituted 9 days after symptom onset. The remaining three patients experienced fever or respiratory symptoms 1, 3, and 5 days after the index patient. All four patients were immunocompromised and had concurrent problems that can mimic infection or respiratory illness. Twelve HCPs reported influenza symptoms during the study period; none were tested for pH1N1. Five reported working while ill; one of these received oseltamivir. Viral isolates from the four patients had complete genomic homology and the H275Y mutation for oseltamivir resistance, which was not identified in other pH1N1 specimens obtained from the hospital or throughout the state.”


“Geographic proximity, temporal association of hospital stay, presence of H275Y mutation and genetic homology strongly indicate patient-to-patient transmission of oseltamivir-resistant pH1N1. An index patient experienced oseltamivir-resistant pH1N1 after receiving oseltamivir; however, the source of resistant virus is unknown. Three remaining patients probably acquired oseltamivir-resistant pH1N1 before diagnosis and isolation of this index patient. Transmission by HCPs cannot be established. Diagnosis of pH1N1 is difficult among immunocompromised hosts with complex comorbidities. Although we detected no other cases, increased diagnostic vigilance and aggressive isolation are necessary to limit potential transmission of oseltamivir-resistant pH1N1 among immunocompromised hosts.”

Comment: Available data indicates severely immunocompromised patients make up the plurality of oseltamivir-resistant cases worldwide. It is not clear from this abstract exactly when Duke University Medical Center staff confirmed the H275Y mutation in the cluster of cases. Earlier, the World Health Organization (WHO) had reported “In 3 of the 4 cases, the H275Y mutation was identified before oseltamivir was administered.” Moreover, the abstract does not explore the cause of death among three of the patients, nor any potential connection to “patient-to-patient transmission” of oseltamivir-resistant H1N1.

The Duke University Medical Center press release on the situation stated that:

“Our extensive investigation thus far has revealed that appropriate infection control procedures have been diligently practiced on this isolated unit, and throughout the hospital, and we have experienced no illness among employees taking care of these patients in the affected unit over this period of time.”

The fact that 12 HCPs were symptomatic for influenza, and that five reported working while ill, calls into question the quality of infection control procedures.

Life Extension - Health And Medical Findings

Duke UMC: CDC Confirms Four New Cases of Oseltamivir (Tamiflu)-Resistant H1N1
SHEA: Cluster of Oseltamivir-Resistant 2009 Pandemic Influenza A (H1N1) Virus Among Immunocompromised Patients on a Hospital Ward — North Carolina

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