By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.

H1N1 in HIV Infection

Source: Perez CM, et al. Pandemic influenza A (H1N1) in HIV-infected patients. AIDS. 2010; 24: Epub ahead of publication.

Although there is little data to support this, I routinely counsel my HIV-infected patients to get seasonal and H1N1 vaccine, explaining that while they are probably at no greater risk for "catching the flu," they may be at greater risk for more severe symptoms and complications than someone without HIV.

During the first epidemic wave of H1N1 in Santiago, Chile between May and August 2009, the incidence and severity of influenza infection in the HIV clinic population was examined. During those months, a total of 1,720 HIV-infected patients sought clinical care in Santiago at six different clinical sites, 30 (1.74%) of whom were diagnosed with H1N1 influenza. The diagnosis was made on clinical grounds in 25 patients, and confirmed by PCR in five. The majority of influenza cases at that time were due to circulating H1N1.

Of the 30 patients, five had recognized risk factors for more severe influenza, including one pregnant patient, two with diabetes, one with hypertension, and one who was obese. Twenty-eight of the patients were receiving HAART therapy, and 23 patients (76.6%) had effective virologic suppression on antiretroviral therapy. The mean CD4 count was 423 cells/mm3 (range, 95 – 771 cells/mm3); two patients had CD4 counts < 200 cells/mm3. Only 37% had received a seasonal flu vaccine.

All patients received antiviral therapy with oseltamivir (the pregnant patient received zanamivir). Symptoms on presentation were fairly typical, with more than 80% of patients presenting with fever, cough, and myalgias. Nearly one-fourth had gastrointestinal symptoms with vomiting and/or diarrhea. The mean duration of symptoms was 5.6 days. Four patients had abnormal chest radiographs consistent with either viral or bacterial pneumonia, two of whom required hospitalization. None of the patients required mechanical ventilation, and none died. In total, three patients (10%) required hospitalization; their average CD4 count was 506 cells/mm3.

This report suggests that the incidence of infection in HIV+ persons (1.74%) during a local outbreak of H1N1 is similar to that for non-HIV-infected persons. The risk for someone with HIV acquiring H1N1 is, therefore, probably not significantly greater than that of an otherwise healthy person without HIV. Compared with non-HIV-infected persons, the authors assert that the presentation and outcome for HIV-infected patients appears similar. However, in this report, which examines a small group of HIV-infected patients with influenza, the risk of hospitalization (10%) does appear greater than that of the general public. The risk of pneumonia and hospitalization in HIV-infected persons with H1N1 did not appear to be associated with the degree of immune deficiency, as reflected by the CD4 count. I will continue to counsel my HIV+ patients to get the flu shot.

Seizures in Children with H1N1

Source: Rellosa N, et al. Neurologic manifestations of pediatric novel H1N1 influenza infection. The Pediatric Infection Disease Journal. 2011;30: epub (ahead of print).

Neurologic manifestations of influenza virus infection are well recognized, ranging from seizures, encephalopathy and encephalitis, transverse myelitis, and acute disseminated encephalomyelitis (ADEM), to the rare but potentially devastating acute necrotizing encephalopathy (ANE). In fact, I just saw a 40-year-old computer engineer with persisting neurologic complaints following a recent episode of viral encephalomyelitis, believed to be secondary to influenza A infection. He was suffering from persistent gait disorder and tremors so severe, suggestive of residual basal ganglia impairment, he had trouble functioning at his job at the computer.

Neurologic involvement with H1N1 in children was first described in MMWR in May 2009 (MMWR. 2009;58:773-778), with a description of four children who developed mild encephalitis and seizures, all of whom fully recovered. CSF pleocytosis was absent in those cases. Subsequently, a number of other pediatric cases with neurologic involvement from H1N1 have been described in the literature, including one child who died from ANE, none with reported CSF pleocytosis.

These authors describe three children with severe neurologic manifestations and seizures from H1N1 influenza infection, two of whom developed mild lymphocytic pleocytosis. The children ranged in ages from 23 months to 9 years, and all were previously healthy (one had sickle cell trait). None of the children had received influenza vaccine, and all three had confirmed H1N1 infection by PCR of respiratory specimens. One child developed acute viral symptoms and, 4-5 days later, developed progressive confusion, loss of consciousness, and facial grimacing and twitching, with a diagnosis of encephalitis. EEG demonstrated partial complex status epilepticus, and MRI scanning was consistent with ADEM. He required critical care and phenobarbital coma for two weeks in the ICU but slowly recovered and was transferred to a rehab facility. He was left with a residual speech abnormality.

A second child developed a febrile illness nine days earlier and was treated for an ear infection. He then developed rapid onset of fever and frequent grand mal seizures, with ankle clonus on exam. He was hospitalized but quickly responded to antiviral and antiepileptic therapy and was released from the hospital fully recovered (before an MRI was performed). A third child was diagnosed with influenza H1N1 at a local urgent care center but received only a single dose of oseltamivir. Five days later he developed progressive lethargy with increasing seizure activity. MRI was consistent with bilateral increased signal intensity in the basal ganglia and thalamus. He quickly improved, with resolution of neurologic symptoms within six days on antiepileptic therapy.

The CSF results in two of the children demonstrated mild-to-moderate pleocytosis (12 to 32 cells/mm3), with a predominance of lymphocytes (85%-90%) and mildly increased protein levels; the 3rd had normal-appearing CSF, with only four WBC/mm3. CSF PCR for influenza A was negative in two of two patients tested.

The fact that neurologic manifestations were delayed by 5-9 days after the onset of influenza-like symptoms in these children, and CSF PCRs were negative in two patients tested, suggests that neurologic infection with influenza virus may not be directly responsible for the neurologic manifestations. Radiographic studies frequently demonstrate involvement of specifically the deep nuclei and basal ganglia, and patchy deep white matter involvement, suggesting an immunologic mechanism for the acute neurologic deterioration. Fortunately, the symptoms appear to respond favorably to time and treatment, with only modest neurologic impairment in one of the three children.

Infectious Disease Curbsides: What are They Worth?

Source: Grace C, et al. The complexity, relative value, and financial worth of curbside consultations in an academic infectious diseases unit. Clin Infect Dis. 2010;51:651-655.

How many times in your id career have you been asked whether Endolimax nana requires treatment (just because many textbooks don't specifically state it does not)? Or whether that positive FTA needs to be treated? There are days where I joke I feel like a walking reference text. Curbside consultations play a significant role in infectious disease practice. Studies suggest that infectious diseases are the most heavily curbsided specialty service. And as reimbursements are increasingly diminished, and time constrained, there may be an increased demand for informal consultation from our primary care and other colleagues. But what is the value of that service, both in potential revenue but also in the recognition of the service provided?

The University of Vermont College of Medicine conducted a one-year prospective study of the burden and financial worth of curbside consultation on the university infectious disease service. Inpatient and outpatient consultations could be performed in person, by telephone or email, and were tracked on a daily basis. Each consult was assigned a CPT code (we all know those by heart now) based on the complexity of the case and the severity of the patient's illness. The Centers for Medicare & Medicaid Services' 2005 conversion factor for reimbursement, adjusted for the geographic area, was used to calculate the potential financial worth of the added work effort (at $37.89 per work RVU).

During the period of observation, 1,001 curbside consultations were performed an average of 2.84 per day, which seems just about right to me. One-third concerned inpatients, most of which were initial consultations and 84% were believed to be complex in nature. The remainder were regarding outpatient consultations, most of which also were initial consultations, 75% of which were considered complex in nature. Only a small number (< 4%) were follow-up consultations.

During the same time period, there were a total of 6,982 formal consultations performed, with an estimated work value of $459,265. Of these, 69% were inpatient consultations, most of which were follow-up consults, and 77% were considered complex in nature (presumably some of these were follow-up visits).

The estimated value of curbside consultations represented 17% of the total infectious disease services provided to the institution. The estimated value of the added work effort for curbside consultation was $93,979, which is essentially unreimbursed time on the part of the infectious disease specialists on service.

Curbsides are a time-honored practice for physicians; it's a way we share our experiences, how we learn from one other, and seek advice and assistance. However, an increasing number of reports indicate that infectious diseases are disproportionately affected by curbsides relative to other specialties. Various studies of curbside consultations have found that an infectious disease specialist performs anywhere from 23 to 121 curbside consultations per month, representing 0.5 to 2.4 of his or her formal consults.

The 17% in potential lost reimbursement to the infectious disease service identified above is, I suspect, fairly typical and, at a minimum, represents a loss of recognition of that effort and time. At our large multi-specialty clinic, I was recently asked to calculate the FTE effort of all physicians in my department, based solely on their "face time" with patients — with the assumption that physicians spend about 20% additional time doing charting, phone calls, etc ("non-face-time") (which is "built in" to their work effort). Factors such as time on call at night and weekends and curbside consultations were not included in these FTE estimates, although disproportionately require considerably more time and effort for infectious disease specialists than for other specialties.