24. Bruce S, Schroeder TL, Ellner K, Rubin H, Williams T, Wolf JE Jr. Armadillo exposure and Hansen’s disease: an epidemiologic survey in southern Texas. J Am Acad Dermatol. 2000;43:223–8. http://dx.doi.org/10.1067/mjd.2000.106368 25. Clark BM, Murray CK, Horvath LL, Deye GA, Rasnake MS, Longfield RN. Case–control study of armadillo contact and Hansen’s disease. Am J Trop Med Hyg. 2008;78:962–7. 26. Deps PD, Alves BL, Gripp CG, Aragao RL, Guedes B, Filho JB, et al. Contact with armadillos increases the risk of leprosy in Brazil: a case–control study. Indian J Dermatol Venereol Leprol. 2008;74:338–42. http://dx.doi.org/10.4103/0378-6323.42897 27. Lopez A, Dietz VJ, Wilson M, Navin TR, Jones JL. Preventing congenital toxoplasmosis. MMWR Recomm Rep. 2000;49:59–68. 28 Deps PD, Antunes JM, Tomimori-Yamashita J. Detection of Mycobacterium leprae infection in wild nine-banded armadillos (Dasypus novemcinctus) using the rapid ML Flow test. Rev Soc Bras Med Trop. 2007;40:86–7. http://dx.doi.org/10.1590/ S0037-86822007000100019 29. Cardona-Castro N, Beltran JC, Ortiz-Bernal A, Vissa V. Detection of Mycobacterium leprae DNA in nine-banded armadillos (Dasypus novemcinctus) from the Andean region of Colombia. Lepr Rev. 2009;80:424–31. 30. Zumarraga MJ, Resoagli EH, Cicuta ME, Martinez AR, Oritiz de Rott MI, de Millan SG, et al. PCR-restriction fragment length polymorphism analysis (PRA) of Mycobacterium leprae from human lepromas and from a natural case of an armadillo of Corrientes, Argentina. Int J Lepr Other Mycobact Dis. 2001;69:21–5. 31. Pedrini SC, Rosa PS, Medri IM, Mourao G, Bagagli E, Lopes CA. Search for Mycobacterium leprae in wild mammals. Braz J Infect Dis. 2010;14:47–53. http://dx.doi.org/10.1016/S1413-8670(10)70010-6 32. Truman RW, Kumaresan JA, McDonough CM, Job CK, Hastings RC. Seasonal and spatial trends in the detectability of leprosy in wild armadillos. Epidemiol Infect. 1991;106:549–60. http://dx.doi.org/10.1017/S0950268800067613 33. Spencer JS, Duthie MS, Geluk A, Balagon MF, Kim HJ, Wheat WH, et al. Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy. Mem Inst Oswaldo Cruz. 2012;107(Suppl 1):79–89. http://dx.doi.org/ 10.1590/S0074-02762012000900014 34. Duthie MS, Balagon MF, Maghanoy A, Orcullo FM, Cang M, Dias RF, et al. Rapid quantitative serological test for detection of infection with Mycobacterium leprae, the causative agent of leprosy. J Clin Microbiol. 2014;52:613–9. http://dx.doi.org/ 10.1128/JCM.02085-13 35. da Conceição Oliveira Coelho Fabri A, Carvalho AP, Araujo S, Goulart LR, de Mattos AM, Teixeira HC, et al. Antigen-specific assessment of the immunological status of various groups in a leprosy endemic region. BMC Infect Dis. 2015;15:218. http://dx.doi.org/10.1186/s12879-015-0962-4 36. Smith NH, Gordon SV, de la Rua-Domenech R, Clifton-Hadley RS, Hewinson RG. Bottlenecks and broomsticks: the molecular evolution of Mycobacterium bovis. Nat Rev Microbiol. 2006;4:670–81. http://dx.doi.org/10.1038/nrmicro1472 37. Morris RS, Pfeiffer DU. Directions and issues in bovine tuberculosis epidemiology and control in New Zealand. N Z Vet J. 1995;43:256–65. http://dx.doi.org/10.1080/00480169./1995.35904 38. Palmer MV. Tuberculosis: a reemerging disease at the interface of domestic animals and wildlife. Curr Top Microbiol Immunol. 2007;315:195–215. http://dx.doi.org/10.1007/ 978-3-540-70962-6_9 39. Wheat WH, Casali AL, Thomas V, Spencer JS, Lahiri R, Williams DL, et al. Long-term survival and virulence of Mycobacterium leprae in amoebal cysts. PLoS Negl Trop Dis. 2014;8:e3405. http://dx.doi.org/10.1371/journal.pntd.0003405 40. Riley LW. Molecular epidemiology of infectious diseases: principles and practices. Washington (DC): American Society for Microbiology; 2004.

OBJECTIVES:To study prospectively HIV-positive patients admitted to the hospital because of pneumonia by extensive laboratory tests to determine specific microbiologic diagnoses and to establish the best clinical diagnosis after review of all available data by expert clinicians.METHODS:Patients admitted to one of two hospitals had extensive questionnaires completed and defined diagnostic tests performed on blood, sputum, urine and bronchoalveolar lavage specimens, when available.RESULTS:A total of 230 patients had a diagnosis of pneumonia verified. A definite or probable etiologic diagnosis was made in 155 (67%) of these patients. Pneumocystis carinii caused 35% of all cases of pneumonia. Twenty-seven percent of cases of pneumonia with a single etiology had a definite or probable bacterial etiology. 'Atypical agents' were distinctly uncommon. Few clinical or laboratory parameters could differentiate specific etiologies.CONCLUSIONS:P. carinii continues to be a common cause of pneumonia in these patients. The rarity of 'atypical agents' could simplify the empiric approach to therapy. Despite the use of extensive testing we did not find a definite etiology in a large number of cases.

BACKGROUND:Investigators have reported that patients infected with Pneumocystis carinii containing mutations in the DHPS (dihydropteroate synthase) gene have a worse outcome than those infected with P carinii containing wild-type DHPS. We investigated patients with HIV-1 infection and P carinii pneumonia to determine if DHPS mutations were associated with poor outcomes in these patients. METHODS:We compared presence of mutations at the DHPS locus with survival and response of patients to co-trimoxazole or other drugs. FINDINGS:For patients initially given co-trimoxazole, nine (14%) of 66 with DHPS mutant died, compared with nine (25%) of 36 with wild type (risk ratio50.55 [95% CI=0.24-1.25]; p=0.15). Ten (15%) of 66 patients with a DHPS mutant did not respond to treatment, compared with 13 (36%) of 36 patients with the wild type (0.42 [0.20-0.86]; p=0.02). For patients aged 40 years or older, four (14%) of 29 with the mutant and nine (56%) of 16 with the wild type died (0.25 [0.09-0.67]; p=0.005). INTERPRETATION:These results, by contrast with those of previous studies, suggest that patients with wild-type P carinii do not have a better outcome than patients with the mutant when given co-trimoxazole. Our results suggest that presence of a DHPS mutation should be only one of several criteria guiding the choice of initial drug treatment of P carinii pneumonia in patients with HIV-1 infection.

Journal of Eukaryotic MicrobiologyVolume 48, Issue s1 p. 137s-138s Pneumocystis carinii Dihydropteroate Synthase Genotypes in HIV-infected Persons Residing in San Francisco: Possible Implications for Disease Transmission LAURENCE HUANG, Corresponding Author LAURENCE HUANG Vision of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110Corresponding author: L. Huang-Telephone: 415–476–4082; Fax: 415–476–6953; E-mail: lhuang@php.ucsf.eduSearch for more papers by this authorJANNA FRIEDLY, JANNA FRIEDLY Vision of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110Search for more papers by this authorALISON M. MORRIS, ALISON M. MORRIS Vision of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110Search for more papers by this authorJANE L. CARTER, JANE L. CARTER Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341, USASearch for more papers by this authorJOAN R. TURNER, JOAN R. TURNER Vision of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110Search for more papers by this authorCYNTHIA MERRIFIELD, CYNTHIA MERRIFIELD Vision of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110Search for more papers by this authorTHOMAS R. NAVIN, THOMAS R. NAVIN Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341, USASearch for more papers by this authorCHARLES B. BEARD, CHARLES B. BEARD Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341, USASearch for more papers by this author LAURENCE HUANG, Corresponding Author LAURENCE HUANG Vision of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110Corresponding author: L. Huang-Telephone: 415–476–4082; Fax: 415–476–6953; E-mail: lhuang@php.ucsf.eduSearch for more papers by this authorJANNA FRIEDLY, JANNA FRIEDLY Vision of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110Search for more papers by this authorALISON M. MORRIS, ALISON M. MORRIS Vision of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110Search for more papers by this authorJANE L. CARTER, JANE L. CARTER Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341, USASearch for more papers by this authorJOAN R. TURNER, JOAN R. TURNER Vision of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110Search for more papers by this authorCYNTHIA MERRIFIELD, CYNTHIA MERRIFIELD Vision of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110Search for more papers by this authorTHOMAS R. NAVIN, THOMAS R. NAVIN Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341, USASearch for more papers by this authorCHARLES B. BEARD, CHARLES B. BEARD Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341, USASearch for more papers by this author First published: 11 July 2005 https://doi.org/10.1111/j.1550-7408.2001.tb00487.xCitations: 7Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume48, Issues1June 2001Pages 137s-138s RelatedInformation

BACKGROUND:Although the incidence of toxoplasmosis is low in the United States, up to 6000 congenital cases occur annually. In September 1998, the Centers for Disease Control and Prevention held a conference about toxoplasmosis; participants recommended a survey of the toxoplasmosis-related knowledge and practices of obstetrician-gynecologists and the development of professional educational materials for them.METHODS:In the fall of 1999, surveys were mailed to a 2% random sample of American College of Obstetricians and Gynecologists (ACOG) members and to a demographically representative group of ACOG members known as the Collaborative Ambulatory Research Network (CARN). Responses were not significantly different for the random and CARN groups for most questions (p value shown when different).RESULTS:Among 768 US practicing ACOG members surveyed, 364 (47%) responded. Seven per cent (CARN 10%, random 5%) had diagnosed one or more case(s) of acute toxoplasmosis in the past year. Respondents were well-informed about how to prevent toxoplasmosis. However, only 12% (CARN 11%, random 12%) indicated that a positive Toxoplasma IgM test might be a false-positive result, and only 11% (CARN 14%, random 9%) were aware that the Food and Drug Administration sent an advisory to all ACOG members in 1997 stating that some Toxoplasma IgM test kits have high false-positive rates. Most of those surveyed (CARN 70%, random 59%; chi2 p < 0.05) were opposed to universal screening of pregnant women.CONCLUSIONS:Many US obstetrician-gynecologists will encounter acute toxoplasmosis during their careers, but they are frequently uncertain about interpretation of the laboratory tests for the disease. Most would not recommend universal screening of pregnant women.

To examine survival after diagnosis of Pneumocystis carinii pneumonia (PCP) and factors associated with early death (during the month of or the month after diagnosis of PCP), data were analyzed from the Adult and Adolescent Spectrum HIV Disease project. Among 4412 patients with 5222 episodes of PCP during follow-up (1992-1998), survival at >1 month after diagnosis was 82%, and survival at > or =12 months after diagnosis was 47%; 12-month survival increased from 40% in 1992-1993 to 63% in 1996-1998. By multiple logistic regression analysis, early death was associated with history of PCP (odds ratio [OR], 1.4), age 45-59 years (OR, 1.9) or > or =60 years (OR, 3.7), and CD4 cell count of 0-24 cells/microL (< or =5 months before PCP; OR, 1.8) or 25-49 cells/microL (OR, 1.4) (P<.05). Concurrent prescription of combination antiretroviral therapy (OR, 0.2) and other antiretroviral therapy (OR, 0.4) was associated with surviving the early period. This study shows improved survival after diagnosis of PCP in recent years, despite emergence of antibiotic-resistant mutant P. carinii strains.

Two hundred eleven adults with human immunodeficiency virus (HIV) infection hospitalized for community-acquired pneumonia, including Pneumocystis carinii pneumonia (PCP; patients), and 192 matched HIV-infected hospitalized patients without pneumonia (controls) were interviewed to determine risk factors for pneumonia. Multivariate logistic regression showed that patients were less likely than controls to have used trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.12-0.41) and more likely to have been hospitalized previously with pneumonia (OR, 6.25; CI, 3.40-11.5). Patients were also more likely than controls to have gardened (OR, 2.24; CI, 1.00-5.02) and to have camped or hiked (OR, 4.95; CI, 1.31-18.7), but stratified analysis by etiologic agent showed this association only for PCP. These findings reconfirm the efficacy of TMP-SMZ in preventing community-acquired pneumonia. In addition, hospitalization for pneumonia might represent a missed opportunity to encourage HIV-infected patients to enter into regular medical care and to adhere to prescribed antiretroviral and prophylaxis medications.

To determine factors associated with mutations in the Pneumocystis carinii dihydropteroate synthase (DHPS) gene, a prospective study of human immunodeficiency virus (HIV)—infected patients with confirmed P. carinii pneumonia was conducted in Atlanta, Seattle, and San Francisco. Clinical information was obtained from patient interview and chart abstraction. DHPS genotype was determined from DNA sequencing. Overall, 76 (68.5%) of 111 patients had a mutant DHPS genotype, including 22 (81.5%) of 27 patients from San Francisco. In multivariate analysis, sulfa or sulfone prophylaxis and study site were independent predictors of a mutant genotype. Fourteen (53.8%) of 26 patients who were newly diagnosed with HIV infection and had never taken prophylaxis had a mutant genotype. The significance of geographic location as a risk factor for mutant genotype and the high proportion of mutant genotypes among persons never prescribed prophylaxis, including those newly diagnosed with HIV infection, provide indirect evidence that these mutations are transmitted from person to person either directly or through a common environmental source.

To study transmission patterns of Pneumocystis carinii pneumonia (PCP) in persons with AIDS, we evaluated P. carinii isolates from patients in five U.S. cities for variation at two independent genetic loci, the mitochondrial large subunit rRNA and dihydropteroate synthase. Fourteen unique multilocus genotypes were observed in 191 isolates that were examined at both loci. Mixed infections, accounting for 17.8% of cases, were associated with primary PCP. Genotype frequency distribution patterns varied by patients' place of diagnosis but not by place of birth. Genetic variation at the two loci suggests three probable characteristics of transmission: that most cases of PCP do not result from infections acquired early in life, that infections are actively acquired from a relatively common source (humans or the environment), and that humans, while not necessarily involved in direct infection of other humans, are nevertheless important in the transmission cycle of P. carinii f. sp. hominis.

SCOPE OF THE PROBLEM:Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. Acute infections in pregnant women can be transmitted to the fetus and cause severe illness (e.g., mental retardation, blindness, and epilepsy). An estimated 400-4,000 cases of congenital toxoplasmosis occur each year in the United States. Of the 750 deaths attributed to toxoplasmosis each year, 375 (50%) are believed to be caused by eating contaminated meat, making toxoplasmosis the third leading cause of foodborne deaths in this country.ETIOLOGIC FACTORS:Toxoplasma can be transmitted to humans by three principal routes: a) ingestion of raw or inadequately cooked infected meat; b) ingestion of oocysts, an environmentally resistant form of the organism that cats pass in their feces, with exposure of humans occurring through exposure to cat litter or soil (e.g., from gardening or unwashed fruits or vegetables); and c) a newly infected pregnant woman passing the infection to her unborn fetus. RECOMMENDATIONSFOR PREVENTION: Toxoplasma infection can be prevented in large part by a) cooking meat to a safe temperature (i.e., one sufficient to kill Toxoplasma); b) peeling or thoroughly washing fruits and vegetables before eating; c) cleaning cooking surfaces and utensils afterthey have contacted raw meat, poultry, seafood, or unwashed fruits or vegetables; d) pregnant women avoiding changing cat litter or, if no one else is available to change the cat litter, using gloves, then washing hands thoroughly; and e) not feeding raw or undercooked meat to cats and keeping cats inside to prevent acquisition of Toxoplasma by eating infected prey.RESEARCH AGENDA:Priorities for research were discussed at a national workshop sponsored by CDC in September 1998 and include a) improving estimates of the burden of toxoplasmosis, b) improving diagnostic tests to determine when a person becomes infected with Toxoplasma, and c) determining the applicability of national screening programs.CONCLUSION:Many cases of congenital toxoplasmosis can be prevented. Specific measures can be taken by women and their health-care providers to decrease the risk for infection during pregnancy and prevent severe illness in newborn infants.

From January 1991 through September 1994, we observed people who were infected with HIV to assess the impact of enteric parasite-associated diarrhea. Respondents answered comprehensive questionnaires covering clinical and epidemiologic information and provided stool specimens monthly, which were examined unstained as well as stained with trichrome, chromotrope 2R, and with Kinyoun carbol-fuchsin, and with indirect immunofluorescence for Cryptosporidium. In all, 602 participants, who were interviewed, provided stool specimens at 3254 monthly visits. Parasites were associated with 50 of 354 (14.1%) acute diarrheal episodes (lasting < or = 28 days) and with 97 of 279 (34.8%) chronic episodes (lasting > 28 days). A parasite was associated with 31 of 222 (14.0%) episodes that occurred when CD4+ counts were > or = 200 cells/microl and with 150 of 566 (26.5%) episodes that occurred when CD4+ counts were < 200 cells/microl. The most commonly identified parasite was C. parvum, which was associated with 18 of 354 (5.1%) acute episodes and 36 (12.9%) of the 279 chronic episodes of diarrhea. In this patient population, enteric protozoan parasites were commonly associated with illness, particularly as immunosuppression worsened, and were more likely to be associated with chronic rather than acute diarrhea.

Risk factors for the development of a first episode of Pneumocystis carinii pneumonia (PCP) were investigated in the Adult and Adolescent Spectrum of Disease Project, a medical record review study involving longitudinal follow-up of human immunodeficiency virus-infected adults in 9 US cities. Risk factors included decreasing CD4 lymphocyte count and history of AIDS-defining illness, non-P. carinii pneumonia, oral thrush, or unexplained fever for > or = 2 days; PCP prophylaxis was protective. PCP incidence/100 person-years of observation among persons not prescribed PCP prophylaxis was higher in those with CD4 lymphocyte counts < 250 cells/microL or CD4 cell percent < 14% (8.3; 95% confidence interval [CI], 7.7-9.0) than in persons with CD4 cell counts < 200 or history of thrush or fever, which constitute current criteria for prophylaxis against PCP (5.9; 95% CI, 5.5-6.4). Because of increased efficiency in capturing persons at highest risk, CD4 cell count < 250 or CD4 cell percent < 14% should be considered as criteria for prophylaxis against first episodes of PCP.

CONTEXT Cryptosporidium parvum infection, a common cause of diarrhea in persons infected with the human immunodeficiency virus (HIV), is difficult to treat or prevent. OBJECTIVE To evaluate relative rates of cryptosporidiosis in HIV-infected patients who were either receiving or not receiving chemoprophylaxis or treatment for Mycobacterium avium complex. DESIGN Analysis of prospectively collected data from HIV-infected patients' visits to their physicians since 1992. SETTING Ten (8 private, 2 publicly funded) HIV clinics in 9 US cities. PATIENTS A total of 1019 HIV-infected patients with CD4+ cell counts less than 0.075 x 10(9)/L. MAIN OUTCOME MEASURES Incidence of clinical cryptosporidiosis during treatment with clarithromycin, rifabutin, and azithromycin. RESULTS Five of the 312 patients reportedly taking clarithromycin developed cryptosporidiosis vs 30 of the 707 patients not taking clarithromycin (relative hazard [RH], 0.25 [95% confidence interval (CI), 0.10-0.67]; P=.004). Two of the 214 patients taking rifabutin developed cryptosporidiosis vs 33 of the 805 not taking rifabutin (RH, 0.15 [95% CI, 0.04-0.62]; P=.01). Prophylactic efficacy of either drug was 75% or greater. No protective effect was seen in the 54 patients reportedly taking azithromycin (RH, 1.48 [95% CI, 0.44-5.04]; P=.46). CONCLUSIONS Clarithromycin and rifabutin were highly protective against development of cryptosporidiosis in immune-suppressed HIV-infected persons in this analysis; further study is warranted.

Although reactivation of latent infections has long been considered the primary explanation for PCP in immunosuppressed patients, over the years a steady flow of reports has described clusters of PCP cases (2). In addition, recent studies have suggested that the duration of latency is very limited, i.e., usually less than 1 year (3,4). Still other studies have demonstrated genetic variation in PCR-amplified P. carinii DNA from the lungs of patients during subsequent PCP episodes (5). Together, these observations provide strong circumstantial evidence of person-to-person transmission of P. carinii. Consequently, establishing the role that person-to-person transmission plays in the epidemiology of PCP is urgent. Another important area of PCP epidemiology is determining the predisposing factors for disease. The most frequently discussed predictor of disease is CD4+ cell count, specifically as it relates to care and management of AIDS patients (6); however, it has long been known that malnutrition can be an important contributor (7). The degree to which other factors such as viral infections or pneumonitis of other causes, may come into play, is yet to be shown. Much can also be learned regarding the epidemiology of PCP in HIV-infected infants. Recent studies report that primary infections in these infants often develop when the child is 3 to 6 months old (8,9). The source of these patients’ P. carinii infections (i.e., the hospital setting, their mothers, other children, or an environmental source) is not known. Clinicians working with AIDS patients need a sensitive, reliable, and noninvasive tool for early detection and diagnosis of PCP infections (10,11). Besides the standard procedures of bronchoalveolar lavage (BAL) and induced sputum (IS) sampling, recent studies indicate that it is possible to amplify P. carinii DNA sequences by polymerase chain reaction (PCR) directly from blood or serum samples and from nasopharyngeal aspirates of PCP patients (11,12). Further studies are needed to confirm that a PCR-based diagnostic tool superior to microscopy can be adapted for use in clinical settings. A serologic tool that will distinguish recent PCP infections from those past is also needed. Prophylaxis failures have been reported for both trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine (13-16). Studies evaluating these cases, however, are frequently complicated by the difficulties in assessing and confirming patient compliance with the prophylaxis regimen. The only factor that has a significant correlation with failure in most cases, however, is the patient’s CD4+ T lymphocyte count (14). Although this correlation would be expected because of the general increased risk for PCP associated with CD4+ cell depletion (6) and the increase in prophylaxis complications in HIV-infected patients (17), these drugs may not eliminate all organisms, and some degree of patient immunity may be required to clear or control the infection. What role, if any, specific antimicrobial resistance mechanisms play in the reported treatment failures has not been shown; however, the emergence of resistance is always a threat. Likewise, long-term TMP-SMX prophylaxis increases the possibility for the selection of antimicrobial resistance in bacterial pathogens, some of which are important potential causes of pneumonia in HIV-infected patients (18). Identifying potential antimicrobial resistance mechanisms in P. carinii is difficult because of the lack of an established culture system for human P. carinii that would allow traditional antimicrobial sensitivity testing. At least three separate lines of data suggest that P. carinii is a commonly encountered organism: the high seroprevalence rates reported in normal populations (19), the rapid rate at which infants acquire primary infections (8) and AIDS patients become reinfected after successful treatment (20), and the amplification of P. carinii-specific DNA from ambient air sampled from the environment (e.g., an apple orchard) (21) and from rooms of animals and patients with PCP (22). Airborne transmission has been demonstrated for PCP in rats (23-26) and is by far the most likely mechanism proposed for natural exposure to P. carinii in humans (2,22). Given the similarities Commentary

Objective: To evaluate the incidence of and risk factors for toxoplasmic encephalitis among HIV-infected persons. Design: Medical facility-based prospective medical record reviews of consecutive patients. Methods: We analysed data collected from January 1990 through August 1995 in more than 90 inpatient and outpatient medical facilities in nine US cities. Incidence was calculated as cases per 100 person-years and risk ratios (RR) for annual incidence were calculated using proportional hazards regression while controlling for city, sex, race, age, county of birth, HIV exposure mode, and prior prescription of trimethoprim–sulfamethoxazole (TMP–SMX). Results: The incidence of TE was 4.0 cases per 100 person-years among persons with a CD4+ T-lymphocyte count of < 100×106/l. In multivariate analysis, among the nine cities the annual incidence of toxoplasmosis was significantly lower only in Denver [RR, 0.3; 95% confidence interval (CI), 0.1–0.7; referent city, Seattle]. Persons prescribed TMP–SMX were half as likely to develop toxoplasmic encephalitis as those who were not (RR, 0.5; 95% CI, 0.4–0.7). Of the 4173 persons with AIDS (1987 Centers for Disease Control and Prevention definition) who died during the study period, 267 (6.4%) had toxoplasmic encephalitis in the course of HIV disease. Conclusions: Toxoplasmic encephalitis in HIV-infected persons varies by geographic area in the United States. TMP–SMX reduces the risk for toxoplasmic encephalitis.

To evaluate the incidence of and risk factors for toxoplasmic encephalitis among HIV-infected persons.Medical facility-based prospective medical record reviews of consecutive patients.We analysed data collected from January 1990 through August 1995 in more than 90 inpatient and outpatient medical facilities in nine US cities. Incidence was calculated as cases per 100 person-years and risk ratios (RR) for annual incidence were calculated using proportional hazards regression while controlling for city, sex, race, age, county of birth, HIV exposure mode, and prior prescription of trimethoprim-sulfamethoxazole (TMP-SMX).The incidence of TE was 4.0 cases per 100 person-years among persons with a CD4+ T-lymphocyte count of < 100 x 10(6)/l. In multivariate analysis, among the nine cities the annual incidence of toxoplasmosis was significantly lower only in Denver [RR, 0.3; 95% confidence interval (CI), 0.1-0.7; referent city, Seattle]. Persons prescribed TMP-SMX were half as likely to develop toxoplasmic encephalitis as those who were not (RR, 0.5; 95% CI, 0.4-0.7). Of the 4173 persons with AIDS (1987 Centers for Disease Control and Prevention definition) who died during the study period, 267 (6.4%) had toxoplasmic encephalitis in the course of HIV disease.Toxoplasmic encephalitis in HIV-infected persons varies by geographic area in the United States. TMP-SMX reduces the risk for toxoplasmic encephalitis.

Although the incidence of Pneumocystis carinii pneumonia (PCP) among adults infected with human immunodeficiency virus (HIV) has declined, no decline in PCP incidence has been observed among HIV-infected children, and PCP remains the most common serious opportunistic infection among both adults and children in the United States. Some evidence of airborne transmission of P. carinii exists, and some clusters of cases of PCP have been reported; however, data are insufficient to recommend that persons with PCP be separated from immunosuppressed persons as a standard practice. The incidence of PCP can be reduced substantially if persons at risk for PCP are identified and receive adequate chemoprophylaxis. Several drugs and drug combinations are highly effective in preventing PCP. For both adults and children, oral trimethoprim-sulfamethoxazole (TMP-SMZ) is the preferred form of prophylaxis. Adverse effects are commonly associated with the use of TMPSMZ and in some cases may necessitate withdrawal of the drug until the effects resolve. However, reintroduction at the same dose or at a lower and gradually increasing dose will often permit the continued use of TMP-SMZ. For persons intolerant of TMP-SMZ, dapsone alone and dapsone plus pyrimethamine are effective alternatives. A third alternative is aerosolized pentamidine. Additional drugs of unproven efficacy but of potential use in exceptional cases are available.

Sixty-six Guatemalan men with parasitologically confirmed cutaneous leishmaniasis, due most commonly to Leishmania braziliensis, were randomly assigned to receive one of three treatment regimens: meglumine antimonate (meglumine) for 20 days; meglumine for 10 days; and meglumine for 10 days plus alternate-day injections of interferon-gamma. In each group, meglumine was given intravenously as 20 mg of antimony/(kg of body weight.d). All treatment regimens were associated with similar response rates: the lesions of 19 (90%) of 21 patients who received meglumine for 20 days, 18 (90%) of 20 patients who received meglumine for 10 days, and all 22 patients who received meglumine plus interferon-gamma were completely reepithelialized by 13 weeks. In addition, for patients receiving all treatment regimens, test-of-cure cultures for Leishmania were negative and reactivation of lesions did not occur during 12 months of follow-up. The high efficacy of our 10-day course of meglumine indicates that the currently recommended duration of 20 days may be unnecessary for infections caused by L. braziliensis and suggests that a 10-day course of high-dose antimony should be tested as therapy for cutaneous leishmaniasis in other geographic areas.

The natural history of American cutaneous leishmaniasis was studied in Guatemala by analyzing the characteristics of 355 untreated leishmanial lesions, observing the evolution of 57 lesions on persons who received a placebo in treatment trials, and analyzing data from a population-based survey concerning the duration of 82 untreated lesions. Of 25 lesions caused by Leishmania mexicana that were followed prospectively, 22 (88%) completely reepithelialized by a median lesion age of 14 weeks, and 17 (68%) were classified as cured (no residual wound inflammation or reactivation during at least 6 months of follow-up). In contrast, 7 (22%) of 32 lesions caused by Leishmania braziliensis reepithelialized by a median lesion age of 13 weeks, and only 2 (6%) cured. These data demonstrate that the species of Leishmania is the primary determinant of the clinical course and outcome of untreated lesions and underscore the need for field-applicable diagnostic techniques that provide rapid species identification.