Other Infectious Diseases Studies
Scholes D, Hooton TM, Roberts PL, Gupta K, Stapleton AE, Stamm WE. Risk factors associated with acute pyelonephritis in healthy women. Ann Intern Med. 2005;142:20-27 . The goal was to identify the risk factors for pyelonephritis among healthy women. The method was an analysis of a large health maintenance organization (HMO), Group Health Cooperative in Seattle, Washington, with a population-based case-control format. Case patients included 242 women with pyelonephritis identified through a computerized database, and controls were 546 women matched by age without pyelonephritis in the previous 5 years. Participants underwent a structured interview to identify the variables associated with pyelonephritis. The results showed several interesting observations: The estimated annual incidence of pyelonephritis was 27.6 cases/10,000 persons;
The 2 most frequently reported symptoms within 2 weeks of the infection were flank pain in 86% and fever in 77%;
The dominant pathogen was Escherichia coli in 85% followed by Staphylococcussaprophyticus in 3.4% and K pneumoniae in 1.7%;
Sensitivity tests of the E coli showed 99% sensitive to ciprofloxacin; 91% to nitrofurantoin, ceftriaxone; and gentamicin; 85% to trimethoprim-sulfamethoxazole; and 60% to ampicillin; and
Only 7% of those with a diagnosis of pyelonephritis were hospitalized.
The risk factors that proved most important in multivariant analysis were a urinary tract infection in the previous 30 days and sexual intercourse on an average of 3 or more times per week. The data are summarized in Table 7 .
The investigators conclude that (as with cystitis) young, healthy, nonpregnant women are at risk for pyelonephritis on the basis of sexual behavior and a history of urinary tract infections.
Comment: The findings of this study support the recommendation of ciprofloxacin or a similar quinolone for the empirical treatment of pyelonephritis in nonpregnant, healthy women under 50 years of age. The finding that the predominant pathogens and risk factors apply to both cystitis and pyelonephritis supports the conventional teaching that the ascending infection accounts for the pathogenesis of upper tract involvement.
BSE, Bovine - Canada. ProMED-AHEAD Digest. January 8, 2005 . Pro-MED summarizes the second report of a case of bovine spongiform encephalopathy (BSE) in Canada, as reported by the Canadian Food Inspection Agency on January 2, 2005. This cow was born in 1996, prior to the introduction of a feed ban in 1997. This brings the total number of cases in North America to 3, all from Canada: The first was detected in May 2003, the second in Washington State in December 2003 (involving cows born in Canada), and the third noted above. All 3 were born at a "period of time suggesting a common source of contaminated feed."
Recovery of a Patient From Clinical Rabies — Wisconsin, 2004. CDC MMWR. 2004;53:1171-1173 . This is the CDC report of the Wisconsin patient who recovered from rabies, the first person known to have recovered from rabies without a rabies vaccine. Details have been previously reported in this series on the basis of information from ProMED . In brief: The patient was a 15-year-old girl who picked up a bat at a church service in September and released it outside. The bat bit her left index finger and the wound was cleaned with hydrogen peroxide.
One month later, the girl complained of fatigue and tingling in the left hand. Two days later, she felt unsteady and had diplopia, then nausea and vomiting. A neurologist reported partial bilateral sixth-nerve palsy and magnetic resonance imaging (MRI) was normal.
On day 4 of illness, the patient was hospitalized where a lumbar puncture showed a white blood cell count of 23 cells/mL, with 93% lymphocytes and a protein level of 50 mg/dL. She then developed fever and slurred speech with tremors of the left arm and lethargy.
On day 6, the bat-bite history was reported; rabies was considered for the first time, and she was transferred to a tertiary care hospital. A lumbar puncture indicated positive serology for rabies by an immunofluorescent antibody test with a titer of 1:32, which increased to 1:2048. She was treated with drug-induced coma, ventilator support, and IV ribavirin. The coma was discontinued at 7 days; she became progressively alert, was extubated on day 33, and then transferred to a rehabilitation unit. She is now able to walk, solve math problems, and eat.
Rabies postexposure prophylaxis (PEP) has been given to 5 family members, 5 of 35 healthcare workers, and 27 of 55 community contacts. No healthcare workers at the tertiary care hospital received PEP because appropriate precautions were established at the time of admission.
The study authors note that this is the sixth patient known to recover from rabies infection, but all 5 prior cases were treated with rabies vaccine, and 4 of the 5 had persistent neurologic deficits. It is also noted that no treatment has proven effective, but treatments that have been proposed include rabies vaccine, rabies immunoglobulin, monoclonal antibodies, ribavirin, interferon-alpha, and/or ketamine. The report also notes that between 1980 and 2000, there were a total of 26 rabies virus variants obtained from patients in the United States, representing 74% of all cases. With regard to recommendations, first, avoid bats. Second, with a bite from a potentially rabid animal — wash the wound with soap and water; capture the animal for quarantine (if this can be done safely); contact public health officials; and seek medical attention regarding the need for PEP. The investigators note that the long-term prognosis for this patient is unknown.
Mikszta JA, Sullivan VJ, Dean C, et al. Protective immunization against inhalational anthrax: a comparison of minimally invasive delivery platforms. J Infect Dis. 2005;191:278-288 . The investigators represent a collaboration between BD Technologies and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Maryland. The goal was to determine the effectiveness of microneedle-based cutaneous (intradermal [ID]) and nasal mucosal (topical) delivery of Bacillus anthracis protective antigen (PA) in mice and rabbits. The microneedles are stainless steel and have the approximate dimensions of a strand of hair; this is integrated into a hub that limits the depth of penetration and is inserted perpendicular to the skin. Mice were immunized with 10 mcg of PA on days 0, 21, and 42 with or without adjuvant. The PA immunogen was tested for serologic response when delivered by ID, intramuscular (IM), epidermal, and topical (nostril installation with both liquid and powder antigens) delivery systems. The most effective delivery was ID with 90% seroconversion with a single injection with adjuvant. Without adjuvant, the rate was 60% with a single dose. By contrast, results with IM delivery resulted in seroconversion in only 20%, with a single dose of PA with adjuvant. Titers by enzyme-linked immunosorbent assay (ELISA) were 4-fold higher with ID delivery compared with IM delivery following the 3-dose series. Intranasal delivery resulted in essentially no seroconversions with a single dose; 3 doses were required to achieve seroconversion rates comparable to those achieved with single-ID delivery. In addition to the above, the study authors tested the vaccine efficacy in vivo with aerosol challenge with about 100 times the dose of anthrax spores (Ames strain) that is lethal to 50% of animals (LD50) at 6 weeks after immunization. This showed complete protection in animals with a serologic response following immunization IM, ID, or by intranasal challenge. The investigators conclude that the use of novel delivery systems, such as ID, permits vaccine protection with the potential to reduce the need for adjuvant and the number of immunizations required.
Comment: The science behind the use of ID challenge with vaccines is based on observations that the skin has robust immunostimulatory properties and abundance of antigen-presenting cells. The study authors claim that this is the first systematic comparison of 5 methods of delivering anthrax vaccine: IM, ID, nasal installation of liquid, nasal installation of powder, and epidermal by microabrasion. The antigen used in this study, PA, mediates the entry of lethal factor and edema factor, which are the toxins of anthrax; antibody to PA blocks the entry of these toxins. Efficacy was further studied and supported by the rabbit model of inhalation anthrax; the investigators note that this is the first reported use of the rabbit model. These results are particularly attractive for anthrax vaccine, which is a high priority in bioterrorism planning. The current FDA anthrax vaccine requires 6 IM injections, and this study suggests that other vaccine strategies may be much better. Of note is the controversial, recent allocation of $877 million to VaxGen for a new anthrax vaccine as the first product of the BioShield legislation.
Brown DR, Shew ML, Qadadri B, et al. A longitudinal study of genital human papillomavirus infection in a cohort of closely followed adolescent women. J Infect Dis. 2005;191:182-192 . This is a report from Indianapolis, Indiana, of a cohort of adolescent girls aged 14-17 years who were attending 1 of 3 primary care clinics and enrolled in a 27-month longitudinal study. Sexual activity was not a criterion for participation. Participants made quarterly visits for interviews and had weekly, self-collected vaginal swabs for sexually transmitted infections, including human papillomavirus (HPV). The results showed that HPV was detected in 45% by polymerase chain reaction (PCR). HPV types that represent high oncogenic risks were detected in 38.6%. During the entire study period, 49 of 60 participants tested positive for HPV for a cumulative prevalence of 82%. The most frequent types were 52 (285 of 2107 total swabs or 13.5%), 16 (245 of 2107 total swabs or 11.6%), and 59 (138 of 2107 total swabs or 6.5%). The results are shown in Table 8 .
The study authors conclude that the prevalence HPV infection in adolescent girls is extremely high and involves numerous HPV types.
Comment: The natural history of this infection is quite unclear. Specific HPV types were inconsistent with sequential observations, but the study authors acknowledge that failure to detect by PCR is not proof of clearance, because these may persist at very low levels and reactivate later in life. All of this is now quite relevant in the context of the probability of an HPV vaccine directed against the most common oncogenic types.
Ozolins M, Eady EA, Avery AJ, et al. Comparison of five antimicrobial regimens for treatment of mild to moderate inflammatory facial acne vulgaris in the community: randomised controlled trial. Lancet. 2004;364:2188-2195 . The report is from the United Kingdom of a study to determine optimal therapy for mild-to-moderate facial acne. Participants were recruited from general practices and randomized to 1 of 5 regimens: (1) oxytetracycline (500 mg orally twice daily), (2) minocycline (100 mg orally once daily), (3) 5% benzoyl peroxide (topical twice daily), (4) 5% benzoyl peroxide plus 3% erythromycin (topical twice daily), or (5) 2% erythromycin (topical in the morning) plus 5% benzoyl peroxide (topical in the evening). Participants were required to have at least 15 inflamed and 15 noninflamed lesions on the face and were required to discontinue prior therapy for at least 4 weeks before participation. The 2 primary outcomes were (1) at least moderate improvement based on a 6-point Likert scale, with a baseline photograph and mirror to assist patient interpretation, and (2) counts of inflamed lesions on the face. The assessment was made at 18 weeks. There were 127-131 participants assigned to each of the 5 treatment groups. This was a placebo-controlled trial, so topical treatment was accompanied by oral placebo and oral treatment was accompanied by placebo topical agents. Baseline microbiology showed that 96% to 99% of participants in each of the 5 groups were colonized by Propionibacteria acnes , and in vitro sensitivity tests showed erythromycin resistance in 44% to 48%, clindamycin resistance in 38% to 45%, and tetracycline resistance in 12% to 27%. The results of the trial showed that all 5 regimens were nearly equally effective, as summarized in Table 9 .
The study authors also assessed cost-effectiveness by queries to participants about willingness to pay for treatment they had received. The median at baseline that participants were willing to pay for a treatment that is "almost certain to cure your spots" was 25 British pounds ($47); after 18 weeks, the median amount that they were willing to pay for the treatment that they had received in the study was again 25 British pounds ($47). On the basis of cost-benefit, the best treatment was topical benzoyl peroxide and the least cost-effective was oral minocycline. Analysis of outcome showed that the counts of inflamed lesions decreased less in patients treated with tetracycline if they had tetracycline-resistant P acnes at baseline vs those with tetracycline-sensitive strains at baseline. The investigators acknowledge that topical retinoids became popular treatments for acne after the study was completed, so that a study of these agents now needs to be done. With respect to the regimens tested, the conclusion is that they were all quite similar, but the topical benzoyl peroxide seemed to be the most cost-effective and not affected by antibiotic resistance.
Falagas ME, Vergidis PI. Narrative review: diseases that masquerade as infectious cellulitis. Ann Intern Med. 2005;142:47-55 . The study authors review the conditions that mimic infectious cellulitis and consequently do not respond to antibiotics and may present a diagnostic challenge. Table 10 lists these conditions and their appropriate treatment. Printer- Friendly Email This