Robert A. Gasser

Rapid diagnostic testing for malaria

Malaria rapid diagnostic devices (MRDD) have been developed with the hope that they would offer accurate, reliable, rapid, cheap and easily available alternatives to traditional methods of malaria diagnosis. The results from early malaria rapid diagnostic studies were quite promising, especially for detecting Plasmodium falciparum at densities of more than 100–500 parasites/μl. Despite the introduction of these devices over a decade ago, only a few target antigens have been introduced. Of greater concern, these devices have shown limitations in sensitivity, ability to differentiate species and robustness under field conditions in the tropics. Recent trials have revealed wide variability in sensitivity both within and between products. We review the recent trials assessing MRDD use for the diagnosis of P. falciparum and non‐P. falciparum infections in endemic and non‐endemic countries and describe the various aspects of these devices which need further improvement. High quality, accurate, rapid and affordable diagnostic tools are urgently needed now that new antimalarial regimens, characterized by higher cost and increased toxicity, have been introduced more widely in response to emerging multi‐drug resistance.

White Blood Cell Counts and Malaria

White blood cells (WBCs) were counted in 4697 individuals who presented to outpatient malaria clinics in Maesod, Tak Province, Thailand, and Iquitos, Peru, between 28 May and 28 August 1998 and between 17 May and 9 July 1999. At each site and in each year, WBC counts in the Plasmodium falciparum-infected patients were lower than those in the Plasmodium vivax-infected patients, which, in turn, were lower than those in the uninfected patients. In Thailand, one-sixth of the P. falciparum-infected patients had WBC counts of <4000 cells/microL. Leukopenia may confound population studies that estimate parasite densities on the basis of an assumed WBC count of 8000 cells/microL. For instance, in the present study, use of this conventional approach would have overestimated average asexual parasite densities in the P. falciparum-infected patients in Thailand by nearly one-third.

Safety and Efficacy of Intravenous Sodium Stibogluconate in the Treatment of Leishmaniasis: Recent U.S. Military Experience

The efficacy and toxicity of sodium stibogluconate (SSG) at a dosage of 20 mg/(kg.d) for either 20 days (for cutaneous disease) or 28 days (for visceral, mucosal, or viscerotropic disease) in the treatment of leishmaniasis is reported. Ninety-six U.S. Department of Defense health care beneficiaries with parasitologically confirmed leishmaniasis were prospectively followed for 1 year. One patient was infected with human immunodeficiency virus; otherwise, comorbidity was absent. Clinical cure occurred in 91% of 83 cases of cutaneous disease and 93% of 13 cases of visceral/viscerotropic disease. Adverse effects were common and necessitated interruption of treatment in 28% of cases, but they were generally reversible. These included arthralgias and myalgias (58%), pancreatitis (97%), transaminitis (67%), headache (22%), hematologic suppression (44%), and rash (9%). No subsequent mucosal leishmaniasis was identified, and there were no deaths attributable to SSG or leishmaniasis.

Malaria Rapid Diagnostic Devices: Performance Characteristics of the ParaSight F Device Determined in a Multisite Field Study

ABSTRACT Microscopic detection of parasites has been the reference standard for malaria diagnosis for decades. However, difficulty in maintaining required technical skills and infrastructure has spurred the development of several nonmicroscopic malaria rapid diagnostic devices based on the detection of malaria parasite antigen in whole blood. TheParaSight F test is one such device. It detects the presence of Plasmodium falciparum-specific histidine-rich protein 2 by using an antigen-capture immunochromatographic strip format. The present study was conducted at outpatient malaria clinics in Iquitos, Peru, and Maesod, Thailand. Duplicate, blinded, expert microscopy was employed as the reference standard for evaluating device performance. Of 2,988 eligible patients, microscopy showed that 547 (18%) had P. falciparum, 658 (22%) had P. vivax, 2 (0.07%) had P. malariae, and 1,750 (59%) were negative for Plasmodium. Mixed infections (P. falciparum and P. vivax) were identified in 31 patients (1%). The overall sensitivity of ParaSight F forP. falciparum was 95%. When stratified by magnitude of parasitemia (no. of asexual parasites per microliter of whole blood), sensitivities were 83% (>0 to 500 parasites/μl), 87% (501 to 1,000/μl), 98% (1,001 to 5,000/μl), and 98% (>5,000/μl). Device specificity was 86%.

Comparison of IsoCode STIX and FTA Gene Guard Collection Matrices as Whole-Blood Storage and Processing Devices for Diagnosis of Malaria by PCR

ABSTRACT We compared two collection devices, IsoCode and FTA, with whole blood for the diagnosis of malaria by PCR (n = 100). Using whole blood as the reference standard, both devices were sensitive for the detection of single-species malaria infections by PCR (≥96%). However, the detection of mixed infections was suboptimal (IsoCode was 42% sensitive, and FTA was 63% sensitive).

Prolonged Recurrence of Pentamidine-Induced Torsades de Pointes

OBJECTIVE: To report a case of recurrent pentamidine-induced torsades de pointes (TdP) and to review previously reported cases in the literature. DATA SOURCES: Medical records of the subject patient, case reports, and relevant studies identified by MEDLINE. DATA EXTRACTION: Data were abstracted from pertinent published sources by one author and reviewed by the remaining authors. DATA SYNTHESIS: A 43-year-old woman with AIDS experienced pentamidine-induced TdP. TdP and other cardiac arrhythmias recurred repeatedly for 13 days after pentamidine therapy was discontinued and in the presence of normal magnesium and potassium serum concentrations. Infusions of magnesium, lidocaine, and isoproterenol were used to treat the arrhythmias. The exact mechanism of pentamidine-induced TdP has not been clearly established. It is postulated, however, that the similarity of pentamidines structure to procainamide may contribute to its proarrhythmic effects. The tissue-binding capacity of pentamidine may result in a prolongation of its effects. No distinctive characteristic appears to predispose people to the development of cardiac arrhythmias. Laboratory values that should be monitored include serum magnesium, potassium, and creatinine. The corrected QT interval also should be monitored. CONCLUSIONS: Recurrent arrhythmias may be seen for many days after intravenous administration of pentamidine has been discontinued. Clinicians should consider this phenomenon as they decide how to monitor patients who have received this drug.

Fever in Patients with Mixed-Species Malaria

BACKGROUND Clinical symptoms of mixed-species malaria infections have been variously reported as both less severe and more severe than those of single-species infections. METHODS Oral temperatures were taken from and blood slides were prepared for 2308 adults who presented at outpatient malaria clinics in Tak Province (Thailand) during May-August 1998, May-July 1999, and May-June 2001 with malaria infections diagnosed by 2 expert research microscopists, each of whom was blinded to the others reports. RESULTS In each year, temperatures of patients with mixed Plasmodium vivax-Plasmodium falciparum infections were higher than temperatures of patients with P. vivax or P. falciparum infections. In every mixed-species case, P. falciparum parasitemia was higher than P. vivax parasitemia, but patient temperature was not correlated with the parasitemia of either species or with the total parasitemia. CONCLUSIONS Among adults who self-report to malaria clinics in western Thailand, patients with mixed P. vivax-P. falciparum infections have higher fevers than patients with single-species infections, a distinction that cannot be attributed to differences in parasitemia. This observation warrants more detailed investigations, spanning wider ranges of ages and transmission environments.

Fulminant supraglottitis from Neisseria meningitidis.

To the Editor: A 68-year-old Caucasian woman with non–insulin-dependent diabetes mellitus, hypertension, and peripheral vascular disease sought treatment at an emergency department after experiencing 2 days of pharyngitis and 1 day of fatigue and dysphagia for solid food. The morning of admission she noted dysphagia for solid food and liquids, dysphonia, severe anterior neck pain, swelling, and erythema, dyspnea, and a temperature of 102.3°F (39°C). A computed tomographic (CT) scan demonstrated substantial neck soft tissue edema and narrowing of the oropharynx and hypopharynx. She received single doses of intravenous ampicillin/sulbactam, clindamycin, dexamethasone (10 mg), and methylprednisolone (125 mg) before being evacuated by air to our intensive care unit (ICU) at Walter Reed Army Medical Center. Intravenous ampicillin/sulbactam, 3 g every 6 hours, and clindamycin, 900 mg every 8 hours, were continued after the transfer. Two doses of intravenous vancomycin, 1 g every 12 hours, were given before vancomycin was discontinued. Results of laboratory studies were the following: leukocyte count 13.3/mm3 (71% polymorphonuclear leukocytes, 18% bands) and normal hematocrit, platelet count, blood urea nitrogen and creatinine concentrations, and liver-associated enzymes. A marker pen was used to track the rapid advance of erythema overnight from her anterior, inferior chin to the top of her breasts (Figure). The infectious disease service was consulted the next morning. When she was examined, her condition had improved; she had normal vital signs, a slightly hoarse voice, and the ability to swallow some saliva. She had no headache or meningismus. The chest erythema was receding. Oral examination demonstrated erythema and an abrasion in the posterior pharynx. Her tongue was not elevated and her uvula was midline. Anterior firm edema without crepitus extended from her chin to the mid-neck. Results of her examination were otherwise unremarkable. The infectious disease consultant recommended restarting a course of vancomycin and discontinuing clindamycin. Figure Top, anterior and lateral views of patient on day 1 of receiving antimicrobial drugs, demonstrating neck erythema and edema. Bottom, anterior and lateral views of patient on day 8 of receiving antimicrobial drugs, demonstrating resolution of neck erythema ... A follow-up CT scan with contrast demonstrated anterior cervical soft tissue edema and patent airway with surrounding abnormal thickness and soft tissue density. No abscess or clot was seen. Endoscopic examination in the ICU showed diffuse erythema and generalized supraglottic edema affecting mostly the epiglottis and arytenoids. Dental examination demonstrated no acute pathologic features. Blood cultures at our hospital yielded no growth, and throat culture was negative for group A streptococci. The patient recovered without requiring intubation (Figure). On the day of discharge, a blood culture from the referring hospital’s emergency department was reported to be positive for Neisseria meningitidis, serogroup Y. Immediate family members and the otolaryngologists who conducted the endoscopic examination were given postexposure prophylaxis. The patient also received terminal prophylaxis. Results of a screening CH50 for terminal complement deficiency were normal. This patient’s condition is consistent with fulminant meningococcal supraglottitis. Supraglottitis implies involvement of the epiglottis and surrounding structures and is more commonly used to describe adult infection than is epiglottitis (1). Epiglottitis has become more common in adults than in children since the introduction of the Haemophilus influenzae type b vaccine. Other organisms responsible for epiglottitis in adults include H. influenzae, H. parainfluenzae, pneumococci, Staphylococcus aureus, and group A streptococci (2). Despite its propensity to colonize the upper respiratory tract, N. meningitidis has rarely been identified as a cause of supraglottitis or other deep neck infections. Only 6 cases have been reported, the first in 1995 (3–8). Previously reported cases were equally apportioned by sex, and patients were 44 to 95 years of age (3–8). Including our patient, 3 of 7 were diabetic (6,7). None showed evidence of meningitis or fulminant meningococcemia, but all had fever, pharyngitis, and airway compromise. Five required airway intervention: 3 intubations and 2 urgent tracheostomies. Two received steroids (3,4), a 54-year-old man required urgent tracheostomy before receiving steroids, and a 60-year-old man’s condition “deteriorated rapidly,” but the report does not indicate the interval between receipt of steroids and intubation. Although steroids have been used, their benefit is unproven, and no controlled clinical trials have been conducted (9). Blood cultures have been positive from all reported case-patients. Two isolates were typed as serogroup B, 4 as serogroup Y, and the serotype of 1 was unreported. Meningococcal strains causing supraglottitis appear to be more locally aggressive but cause less disseminated disease, possibly due to decreased tropism for endothelial cells (8). To our knowledge, ours is the second case of meningococcal supraglottitis reported with severe neck edema and cellulitis; a 44-year-old woman in a prior review had features similar to our patient (8). An 81-year-old woman with diabetes was noted to have “reddish swelling” on the right side of the neck (7), but little was described beyond that. All 3 had serogroup Y infection. We wondered whether serogroup Y might have a propensity to cause cellulitis; however, a review of 10 cases of meningococcal cellulitis included patients with multiple serogroups: C (4 cases), B (2 cases), Y (2 cases), and unknown (2 cases) (10). N. meningitidis may cause supraglottitis more frequently than is recognized (3). Timely drawing of blood cultures in relation to administration of antimicrobial drugs is most likely to identify this pathogen in this setting. Because of its public health implications and potential for rapid progression to airway compromise, N. meningitidis should be considered among the differential diagnoses of supraglottitis/epiglottitis.