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Update in Infectious Diseases

Posted on: Friday, 10 December 2004, 03:00 CST

This year's Update in Infectious Diseases incorporates articles on common infections, HIV medicine, therapeutics, bioterrorism, and emerging infections.

Common Infections

A Multivitamin and Mineral Supplement Reduced Infection and Absenteeism in Patients with Type 2 Diabetes Mellitus Barringer TA, Kirk JK, Santaniello AC, et al. Effect of a multivitamin and mineral supplement on infection and quality of life. A randomized, double- blind, placebo-controlled trial. Ann Intern Med. 2003; 138:365-71. [PMID: 12614088]

Although about 20% of U.S. adults take a combination multivitamin and mineral supplement daily, the health benefits are largely unknown. Supplements may improve the immunologic defects associated with micronutrient malnutrition. To learn more, the investigators in this randomized, double-blind trial divided 130 community-based adults by age (45 to 64 years or ≥65 years) and presence of type 2 diabetes mellitus and assigned them randomly to receive a daily multivitamin and mineral supplement or placebo. The primary end point was the incidence of participant-reported infection.

After 1 year, 43% of the participants receiving the supplement reported infectious illness compared with 73% of the participants receiving placebo (P < 0.001). Most of the reported infections were upper respiratory tract infections. Infection-related absenteeism from work was also lower in the supplement group (21% vs. 57%; P < 0.001).

Most of the treatment benefit occurred in the one third of study participants (n = 51) who had type 2 diabetes mellitus. Seventeen percent of persons with diabetes who were treated with supplements reported infections compared with 93% of diabetic persons who received placebo (P < 0.001). Absenteeism occurred in 0% of diabetic persons who received supplements and 89% of diabetic persons who received placebo. The supplements had no effect on quality of life, as assessed by physical or mental health scores, or on energy level.

In summary, these surprising and important findings showed that a daily multivitamin and mineral supplement dramatically reduced the frequency of infection-related illness and absenteeism in adults with type 2 diabetes who were older than 45 years of age. It will be important to evaluate the value of supplements in other groups with chronic illness. In the meantime, on the basis of this study, it seems simple, safe, and inexpensive to recommend a daily multivitamin and mineral supplement for adults with type 2 diabetes.

Extended Doxycycline Treatment or Combination Therapy with Ceftriaxone Failed To Enhance Therapeutic Efficacy in Lyme Disease

Wormser GP, Ramanathan R, Nowakowski J, et al. Duration of antibiotic therapy for early Lyme disease. A randomized, double- blind, placebo-controlled trial. Ann Intern Med. 2003;138:697-704. [PMID: 12729423]

Lyme disease is the most common vector-borne disease in the United States. The appropriate duration of treatment for the most common manifestation of Lyme disease, erythema migrans (the classic expanding rash), is unclear. Over time, the treatment for erythema migrans has become longer-up to a month or more-primarily because many patients still report symptoms at the end of the course of treatment. In this randomized, double-blind trial, the investigators evaluated different lengths of treatment with oral doxycycline and oral doxycycline plus a single intravenous dose of ceftriaxone in patients with early Lyme disease. They randomly assigned 180 patients with erythema migrans to 1 of 3 treatment groups: one 2-g dose of intravenous ceftriaxone followed by 10 days of oral doxycycline, then 10 days of placebo; 1 dose of intravenous placebo followed by 10 days of oral doxycycline, then 10 days of placebo; or 1 dose of intravenous placebo followed by 20 days of oral doxycycline. Initially, 75% of patients had systemic illness, and 35% had multiple erythema migrans lesions.

At 20 days, 3 months, 12 months, and 30 months, the investigators assessed clinical outcomes and tested neurocognitive performance. The clinical outcomes in the 3 groups were identical at each time point. About two thirds of the individuals in each group achieved a complete response at 20 days. At 30 months, the complete response rate was 83.9% in the 20-day doxycycline group, 90.3% in the 10-day doxycycline group, and 86.5% in the doxycycline-ceftriaxone group (P > 0.2). One treatment failure occurred in a patient who developed meningitis on day 18 of the 10-day doxycycline regimen. The group that received doxycycline-ceftriaxone had more diarrhea (35%) than the other 2 groups (P < 0.001). No neurologic deficits occurred in any of the treatment groups. Six percent to 11% of the patients in each group developed a new erythema migrans rash (P > 0.5). In summary, this study showed that 10 days of oral doxycycline is equivalent to longer courses of antibiotics and led to excellent long-term outcomes without neurologic sequelae.

College Campus Computers Aided in Investigation of a Conjunctivitis Outbreak

Martin M, Turco JH, Zegans ME, et al. An outbreak of conjunctivitis due to atypical Streptococcus pneumonias. N Engl J Med. 2003;348: 1112-21. [PMID: 12646668]

Pneumococci are a common cause of sporadic conjunctivitis, but outbreaks have been rare. In February 2002, clinicians at the Dartmouth College Health Service in Hanover, New Hampshire, recognized an outbreak of conjunctivitis and launched an investigation. They reviewed their database for diagnoses of conjunctivitis from January through mid-April 2002, obtained viral and bacterial cultures from ill students, and had the Centers for Disease Control and Prevention perform identification and typing on isolates from conjunctival swabs. They then performed a cohort study on the college-protected Web site to assess risk factors; responses were forwarded electronically to a database. The health service also launched control measures, using the college newspaper, posters, and e-mails to spread the message that people should wash their hands, avoid sharing utensils, and seek help through the college health service if symptoms developed. The health service also distributed an alcohol-based hand gel through the college mailroom 2 days before spring break.

From 1 January through 12 April 2002, 13.8% of Dartmouth students (698 of 5060) received a diagnosis of conjunctivitis, and 5% had a second episode. Among first-year students, 22% received a diagnosis of conjunctivitis. Of interest, no health service clinicians became ill, indicating that they had protective antibody or were careful about washing their hands. The epidemic ended soon after the hand gel distribution and after spring break.

No viruses were isolated. Unencapsulated Streptococcus pneumoniae grew from 43.3% (110 of 254) of the conjunctival swabs. Infection with unencapsulated pneumococci is unusual, and current vaccines do not protect against it. Of more than 14 000 isolates of pneumococci causing invasive disease in the United States from 1998 to 2001, 99.6% had an identifiable capsular serotype.

Survey data from 1832 students suggested that risk factors for acquiring conjunctivitis included having close contact with a student with conjunctivitis, wearing contact lenses, being a member of a sports team, and attending parties at or living in a fraternity or sorority house. At Princeton University in Princeton, New Jersey, an outbreak clue to an identical isolate and involving 274 students occurred during February and March of the same year, a time when many students from the Dartmouth and Princeton campuses visited each other. The Dartmouth epidemic was particularly interesting because it showed how electronic sources within a school could facilitate recruitment of study participants, data acquisition, and public health action.

Pneumococcal Antibiotic Resistance Did Not Predict Clinical Outcome

Yu VL, Chiou CC, Feldman C, et al. An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome. Clin Infect Dis. 2003;37:230-7. [PMID: 12856216]

There has been an alarming and well-publicized increase in the prevalence of penicillin-resistant S. pneumoniae. In response, new regimens have been widely used for the empirical therapy of community-acquired pneumonia. However, the clinical relevance of resistance is unclear, and although in vitro data are plentiful, very little is known about treatment outcome in individuals with penicillin-resistant pneumococci. This prospective, international, observational study assessed the clinical impact of emerging pneumococcal drug resistance.

The investigators enrolled 844 consecutive hospitalized patients (mean age, 52 years) with blood cultures positive for S. pneumoniae at 21 hospitals in 10 countries; approximately half of the patients had at least 1 comorbid condition. The authors evaluated risk factors for drug resistance; performed susceptibility testing; and recorded data on antibiotics given, including the timing in relation to symptom onset, the dose and duration, and the route of administration. The investigators defined concordant therapy as the administration, for the first 2 days after obtaining a blood culture, of a single antibiotic with in vitro activity against S. pneumoniae; discordant therapy was defined as administration of an antibiotic that was not active in vitro.

The investigators found that 15% \of pneumococcal isolates had intermediate susceptibility to penicillin in vitro (minimum inhibitory concentration, 0.12 to 1 g/mL) and 9.6% were resistant (minimum inhibitory concentration, ≥2 g/mL). The prevalence of penicillin-nonsusceptible S. pneumoniae was 30.8% in the United States and varied widely by country, from as little as 2.6% in Argentina to 57% in Taiwan. On the basis of data from the 360 patients they could evaluate, the investigators found that 93% of the patients in this study received concordant therapy and 7% received discordant therapy.

Overall mortality was 16.9%, and 65% of deaths occurred within the first 3 days. Age, severity of illness, and underlying disease with immunosuppression were significantly associated with mortality. Receipt of discordant therapy (penicillins, cefotaxime, and ceftriaxone) was not associated with a higher mortality rate. Duration of fever and suppurative complications did not differ between treatment-concordant and treatment-discordant groups.

In summary, pneumococcal susceptibility did not prediet clinical outcome. Although in vitro resistance is increasing among pneumococci, it has not yet become clinically relevant for treatment. β-Lactam antibiotics, including penicillins, are still useful for the treatment of nonmeningitic pneumococcal infections, regardless of in vitro susceptibility as determined by current standards. This paper is important because it suggests that using quinolone and macrolide antibiotics as empirical therapy for community-acquired pneumonia is unnecessary and may promote the emergence of resistance to these agents without conferring any benefit.

Pneumococcal Conjugate Vaccine Administered to Young Children Prevented Disease in Adults

Whitney CG, Parley MM, Hadler J, et al. Decline in invasive pneumococcal disease after the introduction of protein- polysaccharide conjugate vaccine. N Engl J Med. 2003;348:1737-46. [PMID: 12724479]

In 2000, the United States licensed a protein polysaccharide conjugate vaccine targeting 7 serotypes of pneumococci for use in infants and young children. This conjugate vaccine, administered in a 4-dose regimen, was efficacious in preventing bacteremia, meningitis, and septic arthritis and was somewhat efficacious against otitis media and pneumonia. It is now recommended for routine use in all children younger than 2 years of age. Young children have the highest risk for invasive disease and are carriers for pneumococci, but most cases of and deaths from pneumococcal disease occur in adults. Nasopharyngeal carriage of pneumococci is higher in adults who have young children than in other adults.

In this study, the investigators analyzed populationbased data from the Active Bacterial Core Surveillance of the Centers for Disease Control and Prevention to assess the clinical impact of vaccination on pneumococcal infection. Drawing on data from 7 large geographic areas with a total population of about 16 million, they performed serotyping and susceptibility testing of isolates and tracked changes in the burden of invasive disease, defined by isolation of 5. pneumoniae from a normally sterile site. The authors found that the rate of invasive pneumococcal disease decreased from an average of 188.0 cases per 100 000 to 59.0 per 100 000 (P < 0.001) among children younger than 2 years of age, a 69% reduction. Invasive disease due to one of the 7 vaccine serotypes decreased by 78%. Of note, disease rates also decreased in adults, in particular by 32% among adults between the ages of 20 and 39 years, many of whom might be parents of young vaccinated children. The rate of disease decreased 8% among adults age 40 to 64 years and 18% among adults older than 65 years, some of whom might be grandparents of young vaccinated children. In summary, childhood vaccination appeared to provide an effective new tool for reducing disease caused by pneumococci in both children and adults.

HIV Medicine

Enfuvirtide Added to an Optimized Antiretroviral Regimen Provided Significant Benefits in Patients with Multidrug-Resistant HIV Infection

Lalezari JP, Henry K, O'Hearn M, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med. 2003;348:2175-85. [PMID: 12637625]

Viral resistance is common in treated HIV-infected persons. Salvage therapy after the virus rebounds is more effective if the drug is from an antiretroviral class to which the patient was not previously exposed. Enfuvirtide, also known as T-20, is the first of a new class of antiretroviral drugs known as fusion inhibitors. The novel peptide binds to the envelope glycoprotein 41 of the virus and prevents it from fusing with the CD4 cell.

This randomized, open-label, phase 3 study of enfuvirtide (T-20) involved 501 patients from 48 sites in the United States, Canada, Mexico, and Brazil. Patients had at least 6 months of previous treatment with agents in 3 classes of antiretroviral drugs, were resistant to drugs in these classes, or both. Their viral load was at least 5000 copies/mL. Patients were randomly assigned in a 2:1 ratio to receive either enfuvirtide (90 mg subcutaneously twice daily) plus an optimized background regimen of 3 to 5 antiretroviral drugs or the optimized regimen alone (control group). The 2 groups had similar median baseline HIV RNA levels, median CD4^sup +^ cell counts, demographic characteristics, and previous antiretroviral therapy. After treatment began, 491 patients received at least 1 dose of the study drug and had at least 1 measurement of plasma HIV RNA. At baseline, the patients were very sick: The average viral load was more than 50 000 copies/mL in both groups, and the median CD4^sup +^ cell count was 0.075 109 cells/L in the enfuvirtide group and 0.087 10 cells/L in the control group.

The study's primary end point was the change in viral load from baseline to week 24. At 24 weeks, the investigators found that the viral load decreased 1.696 log,0 copies/ mL in the enfuvirtide group and 0.764 log]0 copies/mL in the control group (P < 0.001). The CD4+ cell count increased by a mean of 0.076 X 109 cells/L in the enfuvirtide group and 0.032 X 109 cells/L in the control group (P < 0.001). Almost all of the patients in the enfuvirtide group (98%) reported reactions at the site where the drug was injected, and this group also experienced more cases of pneumonia. In summary, the addition of enfuvirtide to an optimized antiretroviral regimen resulted in significant antiretroviral and immunologic benefit in seriously ill, treatment-resistant patients.

Corroborative Study Confirmed That Adding Enfuvirtide to an Optimized Antiretroviral Regimen Benefited Patients with Multidrug- Resistant HIV Infection

Lazzarin A, Clotet B, Cooper D, et al. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N Engl J Med. 2003;348:2186-95. [PMID: 12773645]

The methodology of the T-20 vs. Optimized Regimen Only 2 (TORO 2) study, a European and Australian study involving patients from 67 centers, was essentially the same as that of the preceding study (TORO 1). Like TORO 1, TORO 2 showed that the addition of this new antifusion agent to an optimized regimen provided significant viral load suppression and immunologic benefit after 24 weeks in people with very advanced disease who had received multiple antiretroviral agents and in whom therapy was failing. The U.S. Food and Drug Administration has approved enfuvirtide for those with previous treatment and evidence of viral replication despite ongoing antiretroviral therapy. Physicians treating HIV-infected patients have a new therapeutic tool. However, the drug has 3 major problems, which may limit its long-term value: It is administered twice daily by subcutaneous injection, almost all patients developed local reactions, and the yearly cost for an individual patient is nearly $25 000.

Therapeutics

Physicians Used More Expensive Broad-Spectrum Agents but Fewer Antibiotics Overall

Steinman MA, Gonzales R, Linder JA, et al. Changing use of antibiotics in community-based outpatient practice, 1991-1999. Ann Intern Med. 2003;138:525-33. [PMID: 12667022]

Sensible use of antibiotics has the potential to decrease medical costs as well as the emergence of resistance. Most studies of antibiotic use have focused on excessive use; relatively few have looked at the types of antibiotics that physicians prescribe. In this study, the investigators evaluated the patterns and types of outpatient antibiotic use in the United States using 3 study periods- 1991 to 1992, 1994 to 1995, and 1998 to 1999 -of the National Ambulatory Medical Care Survey, a large, cross-sectional sample of community-based outpatient visits. They compared antibiotics used in the first study period (1991 to 1992) and the final study period (1998 to 1999).

Between the 2 time periods, the proportion of office visits that involved an antibiotic prescription decreased from 13% to 10% for adults and from 33% to 22% for children. In particular, physicians prescribed antibiotics less frequently to treat common colds and unspecified upper respiratory tract infections in adults (the proportion of antibiotics prescribed for these indications declined from 56% to 43%). Although an improvement, this finding still means that doctors often prescribed unnecessary antibiotics.

The investigators also found that use of broad-spectrum agents, including azithromycin, clarithromycin, the fluoroquinolones, amoxicillin- clavulanate, and secondand third-generation cephalosporins, increased in adults from 24% to 48% of antibiotic prescriptions and in children from 23% to 40% of antibiotic prescriptions (P < 0.001 for both comparisons). Physicians did not use broadspectrum antibiotics only for infections where increasing resistance might justify their use; in fact, in 1998 to 1999, 22% of adult and 14% of pediatric prescriptions for broadspe\ctrum antibiotics were for conditions such as the common cold, for which antibiotics are unwarranted.

In summary, community-based physicians used fewer antibiotics and prescribed them less often for illnesses for which the drugs had no utility. When physicians did use antibiotics, however, they increasingly turned to broadspectrum, costly drugs, a dismaying trend. Physicians should follow expert recommendations about which antibiotics to use for specific infections and when to use them.

Bioterrorism

Mass Smallpox Vaccinations Were Conducted Safely, with Very Low Rates of Serious Adverse Events

Grabenstein JD, Winkenwerder W Jr. US military smallpox vaccination program experience. JAMA. 2003;289:3278-82. [PMID: 12824209]

Halsell JS, Riddle JR, Atwood JE, et al. Myopericarditis following smallpox vaccination among vaccinia-naive US military personnel. JAMA. 2003;289:3283-9. [PMID: 12824210]

Update: Adverse events following civilian smallpox vaccinationUnited States, 2003. MMWR Morb Mortal Wkly Rep. 2003;52:360, 362-3. [PMID: 12749475]

The attacks of 11 September 2001 and the subsequent acts of anthrax bioterrorism in the United States made terrorism a frightening reality for Americans. Concerns about using smallpox as a weapon of war led to military and civilian vaccination programs. These reports described the effects of smallpox vaccination in military personnel and civilian health care and public health workers.

From 13 December 2002 through 28 May 2003, 450 293 military personnel received vaccination against smallpox (70.5% were primary vaccinees and 29.5% were revaccinees). Eczema vaccinatum or progressive vaccinia did not occur. Smallpox was not transmitted from vaccinated health care workers to patients, and no deaths were attributable to vaccination. Fewer than 3% of vaccinees needed short- term sick leave (mostly because they had fever that lasted for a day, had a headache, or simply could not function). One case of encephalitis, 48 instances of selfinoculation (which occurs when individuals touch their vaccine site and scratch another part of their body, creating another lesion), and 21 instances in which vaccinia was transmitted to a close contact were reported; all of these cases were mild. Unexpectedly, however, 37 vaccinees developed acute myopericarditis, all after primary vaccination; the rate was 1 per 12819 vaccinees, 3.6 times higher than among nonvaccinated personnel. From January through August 2003, 38 257 civilian health care and public health workers received smallpox vaccine. Adverse events included 3 cases of generalized vaccinia, 24 instances of self-inoculation (3 ocular), 1 case of encephalitis, and 22 episodes of myopericarditis.

These experiences showed that mass smallpox vaccination programs can have very low rates of adverse events. Myopericarditis emerged as an unexpected untoward event at a rate that was more than 7 times higher among vaccinated civilians than among vaccinated military personnel. The risks in the general population and in those with significant illness remain unknown.

Emerging Infections

SARS Outbreak Caused Significant Morbidity and Mortality

Lee N, Hui D, Wu A, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003 ;348:198694. [PMID: 12682352]

Severe acute respiratory syndrome (SARS) is a contagious disease that was first identified in humans in early 2003. Its rapid spread throughout the world demonstrated the potential for international air travel to widen a pathogen's range. This case study, involving 138 patients exposed to SARS at Prince of Wales Hospital in Hong Kong between 11 March and 25 March 2003, was one of the first publications to describe the disease and helped to define its features. The 138 patients-66 men and 72 women, 50% health care workers and 11 % medical students-were all admitted to an isolation ward. The investigators collected clinical, laboratory, and radiologic findings and determined demographic, clinical, laboratory, and radiologic characteristics of SARS.

The investigators identified the following features of the clinical illness and their frequency: fever (100% of cases), chills and rigors (73.2%), myalgia (60.9%), cough (>50%), headache (>50%), lymphopenia (69.6%), thrombocytopenia (44.8%), and increased lactate dehydrogenase (71%) and creatine kinase (32.1%) levels. At the onset of fever, 78% of patients had an abnormal chest radiograph showing airspace consolidation. All patients eventually developed respiratory disease and had abnormal radiographs, and chest computed tomography scans also showed peripheral airspace consolidation. Thirty-two patients (23.2%) were admitted to the intensive care unit, and 5 patients (3.6%) died. Independent predictors of adverse outcomes included advanced age, high peak lactate dehydrogenase level, and leukocytosis at the time of admission.

The attack rate of this serious illness was particularly high among health care workers. In 2003, 1700 of the 8000 cases of SARS worldwide occurred among health care workers. Physicians must learn the clinical picture of this illness to ensure prompt diagnosis and to initiate measures to prevent transmission. The SARS phenomenon is a good reminder that frightening epidemic illness is more likely to come from nature than from bioterrorism.

Cause of SARS Identified

A multicentre collaboration to investigate the cause of severe acute respiratory syndrome. Lancet. 2003;361:1730-3. [PMID: 12767752]

This paper tells one of the most amazing stories in the history of medicine. In February 2003, SARS, a new infectious disease in humans, was first recognized in Hanoi, Vietnam. During the same month, 305 cases and 5 deaths due to atypical pneumonia occurred in Guangdong Province, China. The illness rapidly spread around the world, and within 2 months, 25 countries on 5 continents had reported cases. The scientific and epidemiologic communities responded, placing the highest priority in their containment strategy on identifying the causal agent and developing a diagnostic test. At the outset of the epidemic, the epidemiology and pathogenesis of the illness were poorly understood and no definitive diagnostic test or treatment was available.

On 15 March 2003, the World Health Organization set up a worldwide network of 11 laboratories that agreed to share all information, have daily teleconferences, and use a secure Web site to post electron micrographs, polymerase chain reaction primers, and protocols. Within 3 days, electron microscopy of respiratory samples showed a candidate virus. Within another 2 days, investigators had ruled out influenza and many other respiratory pathogens. By 21 March, they had isolated a virus in cell culture. Almost simultaneously, they demonstrated antibodies to this new virus in the blood of patients. By 23 March, they had identified the candidate virus as a novel coronavirus by sequencing polymerase chain reaction-amplified products. During the first week of April, monkeys infected with the newly found coronavirus developed a SARS- like illness. Three diagnostic tests were developed. On 16 April, 1 month from the start of the investigation, all participating laboratories collectively announced that the new coronavirus was the cause of SARS.

This sequence of events was an extraordinary and unprecedented example of international scientific cooperation and the power of modern science used to solve a new and serious problem. The authors dedicated the paper to the memory of Carlo Urbani, the World Health Organization infectious disease physician who contracted SARS in Hanoi and died on 29 March 2003.

The Transmission of West Nile Virus by Organ Transplantation

Iwamoto M, Jernigan DB, Guasch A, et al. Transmission of West Nile virus from an organ donor to four transplant recipients. N Engl J Med. 2003;348:2196-203. [PMID: 12773646]

The first case of West Nile virus infection in the United States occurred in 1999 in New York. From 1999 to 2001, 149 U.S. cases were diagnosed. The attack rate increased rapidly, with more than 4000 cases in 2002 and more than 9000 in 2003. The 2003 cases occurred in all but 2 states, and almost half occurred in Colorado and Nebraska.

In 2002, a single organ donor from Georgia transmitted West Nile virus to 4 recipients: 2 recipients of kidneys in Georgia and a heart recipient and a liver recipient in Florida. Symptoms began 7 to 17 days after transplantation. Three of the affected individuals developed encephalitis and were seropositive for West Nile virus IgM antibody. The fourth recipient developed a febrile illness; subsequently, investigators isolated the virus from brain tissue and identified the virus by using nucleic acid and antigen assays.

The investigators reviewed medical records, conducted interviews, and collected blood and tissue samples for testing with a variety of assays. Although the organ donor showed no antibodies to the West Nile virus before and immediately after blood transfusions, serum and plasma samples obtained at the time of organ recovery were positive for West Nile virus on viral nucleic acid testing and viral culture. The investigators determined that the organ donor had received blood from 63 donors from 8 states. One of these blood donors was viremic at the time of donation and became seropositive for West Nile virus IgM antibodies during the next 2 months. In summary, this report was the first to show transmission of West Nile virus through organ donation. These cases suggest that West Nile virus-infected organ transplant recipients taking immunosuppressive drugs might be at risk for severe disease.

Investigation Documented the Transmission of West Nile Virus by Blood Transfusion

Realer LN, Marfin AA, Petersen LR, et al. Transmission of West Nile virus through blood transfusion in the United States in 2002. N Engl J Med. 2003;349:1236-45. [PMID: 14500806]

In this study, the investigators identified 23 pat\ients who developed West Nile virus infection within 4 weeks of a transfusion of leukoreduced and nonreduced erythrocytes, platelets, or fresh frozen plasma. They linked 16 donors with evidence of viremia at donation to the 23 infected recipients. Of these donors, 9 reported viral symptoms before or after donation, 5 were asymptomatic, and 2 were lost to follow-up. At donation, all 16 blood donors were negative for West Nile virus-specific IgM antibody and were often near the limits of sensitivity of nucleic acid assays.

Forty-three percent of patients who received transfusions (n = 10) were immunocompromised, had recently undergone transplantation, or had cancer. In addition, 35% (n = 8) were at least 70 years of age and had significant illnesses. Illness in patients who received transfusions began 2 to 21 days (median, 10 days) after the transfusion; immunocompromised recipients tended to have longer incubation periods. All of the transfusion recipients from these donors developed antibodies, showing that transmission was highly efficient.

This study proved that transfused erythrocytes, platelets, and fresh frozen plasma could transmit West Nile virus. Beginning in June 2003, transfusion facilities began using a nucleic acid assay to screen all U.S. blood for West Nile virus. During the next 8 weeks, blood banks screened 1 million donations and removed 163 positive donations from the blood supply. Screening is particularly important because research has shown that 80% of West Nile virusinfected persons are asymptomatic and have viremia that lasts about a week.

West Nile virus is not a passing phenomenon. Immunosuppressed patients receiving contaminated organs or blood products appear to be at increased risk for severe disease, and the incubation period and period of viremia may be prolonged. The virus has also been transmitted through breastfeeding, after physical trauma in the laboratory, and vertically from mother to child.

Infection with Vasculotropic Virus Human Herpesvirus-8 May Cause Primary Pulmonary Hypertension

Cool CD, Rai PR, Yeager ME, et al. Expression of human herpesvirus 8 in primary pulmonary hypertension. N Engl J Med. 2003;349: 1113-22. [PMID: 13679525]

Pulmonary hypertension is a serious condition characterized by complex, lumen-occluding vascular lesions. The only viral infection associated with severe pulmonary hypertension is HIV disease, but no one has demonstrated the viral genome or viral antigens in pathologic lesions. In this study, the investigators tested for human herpesvirus-8 (HHV-8), the cause of Kaposi sarcoma, in lung tissue samples from 16 patients with sporadic primary pulmonary hypertension and 14 patients with secondary pulmonary hypertension. They identified HHV-8 infection by using an antibody directed against latency-associated nuclear antigen 1 (LANA-1). They also detected the viral cyclin gene of HHV-8 by using lung DNA sequence analysis and polymerase chain reaction assay.

Lung tissue from 10 of the 16 patients with primary pulmonary hypertension (62%) was positive for LANA-1 and contained viral cyclin. None of the patients with secondary pulmonary hypertension had LANA-1-positive lung tissue. These findings show a link between HHV-8 and pulmonary hypertension, which adds to the growing list of chronic illnesses that appear to be caused by infectious agents. This instance again raises the following question: Are all diseases infectious?

Bennett Lorber, MD

From Temple University School of Medicine and Temple University Hospital, Philadelphia, Pennsylvania.

Contributing Editor: Jennifer Fisher Wilson

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Bennett Lorber, MD, Department of Medicine, Temple University School of Medicine and Temple University Hospital, Broad and Ontario Streets, Philadelphia, PA 19140; email, lorberb@tuhs.temple.edu.

Copyright American College of Physicians Dec 7, 2004

Source: Annals of Internal Medicine

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