Coccidioidomycosis: A Contemporary Review.

Coccidioidomycosis, colloquially known as Valley Fever, is an invasive dimorphic fungal infection caused by Coccidioides immitis and C. posadasii. The fungi are found in the arid desert soils of the southwestern US, as well as in parts of Mexico and Central and South America. Acquisition is typically via inhalation of arthroconidia which become airborne after both natural (e.g., earthquakes, dust storms, and fires) and human-related events (e.g., military maneuvers, recreational activities, agriculture, and construction). The incidence of infection in increasing likely a result of both climatic and populational changes. Further, the recognized geographic distribution of Coccidioides spp. is expanding, as cases are being diagnosed in new areas (e.g., eastern Washington, Oregon, and Utah). Most coccidioidal infections are asymptomatic (60%); however, approximately one-third develop a pulmonary illness which is a leading cause of community-acquired pneumonia in highly endemic areas. Uncommonly (0.5-2% of cases), the infection disseminates to extrapulmonary locations (e.g., skin, bones/joints, and the central nervous system), and is most commonly seen among persons with cellular immunodeficiencies (e.g., transplant recipients, HIV, and pregnancy) and non-Caucasian races (especially African Americans and Filipinos). The diagnosis of coccidioidomycosis requires astute clinical suspicion and laboratory findings, including positive serology, cultures, and/or histopathology results. Treatment is warranted among persons with pneumonia who have risk factors for complicated disease and among those with extrapulmonary disease. Novel antifungals with improved fungicidal activity and rapidity of action with fewer side effects and drug interactions are needed. Preventive strategies (e.g., education regarding the disease, dust avoidance, mask wearing, including among select groups, antifungal prophylaxis, and surveillance laboratory testing) are advised for residents and travelers to endemic areas. Currently, no preventive vaccine is available. Coccidioidomycosis has been recognized for over a century, and an expanding wealth of knowledge has been gained regarding this emerging infectious disease which will be reviewed here.

Pneumonia outbreak associated with group a Streptococcus species at a military training facility.

BACKGROUND: Although group A streptococci (GAS) infections are a major cause of morbidity and mortality, outbreaks of associated pneumonia are rare. We report an outbreak of GAS pneumonia that occurred at a US military training camp. METHODS: Standard epidemiologic and laboratory procedures were used to characterize the outbreak and causative organism(s). A case-control study and determination of the prevalence of GAS infection among camp personnel were also performed. RESULTS: A total of 162 of 4500 Marine Corps personnel were hospitalized for respiratory symptoms during the period of 1 November and 20 December 2002, and 127 (78%) had radiographically confirmed pneumonia. The attack rate was 1.6 cases per 100 person-months. Thirty-four (27%) of 127 patients with pneumonitis had definite or probable GAS pneumonia; an additional 22 (17.3%) were coinfected with GAS and another pathogen. Pathogens, in addition to GAS, included Chlamydia pneumoniae (27 patients), Mycoplasma pneumoniae (19), adenovirus (5), and Streptococcus pneumoniae (2). A survey revealed that the pharyngeal carriage rate of GAS among camp personnel was 16%. Molecular characterization of the GAS isolates found emm type 3, multilocus sequence type 15. The epidemic ended after administration of additional prophylaxis with a single dose of intramuscular benzathine penicillin (1.2 million U) or azithromycin (1 g orally). Because the number of days from the last penicillin injection was correlated with a positive throat culture result and the occurrence of pneumonia, the dosing interval of benzathine penicillin was shortened from every 28-35 days to every 21 days. CONCLUSIONS: This is the largest outbreak of GAS pneumonia reported in >30 years. This outbreak emphasizes the potential for GAS to cause epidemics of severe infection and demonstrates the need for surveillance and consideration of appropriate antibiotic prophylaxis among particularly high-risk populations.

Infections associated with tumor necrosis factor-alpha antagonists.

Tumor necrosis factor (TNF)-alpha antagonists are promising therapeutic agents for patients with severe autoimmune and rheumatologic conditions. Unfortunately, their use has been associated with an increased rate of tuberculosis, endemic mycoses, and intracellular bacterial infections. Infliximab, 1 of 3 available drugs in this novel class, appears to be associated with the greatest risk of infection, likely because of its long half-life and induction of monocyte apoptosis. Prospective trials are necessary to determine the exact risk associated with these agents, particularly the newer TNF-alpha antagonists. More specific TNF-alpha blockers, which reduce inflammation while maintaining adequate immunity, are needed. In the meantime, a thorough work-up is mandatory for all febrile illness occurring in TNF-alpha blocker recipients. We present 4 patients who developed severe infections during TNF-alpha antagonist therapy, review the literature, and discuss current guidelines for surveillance and prophylaxis.

New issues in infectious diarrhea.

Infectious diarrhea remains a leading cause of both mortality and morbidity worldwide. Novel organisms recently have been described as causes of previously undiagnosed diarrhea. In addition, changes in epidemiologic trends of known pathogens, such as Clostridium difficile, are occurring, including multiple outbreaks of a newly recognized epidemic strain associated with increased severity of cases and poor response to current antibiotics. Given rising resistance rates, new antimicrobial agents are being studied. Rifaximin is a nonabsorbable, gut-selective antibiotic recently approved by the US Food and Drug Administration for the treatment of travelers' diarrhea caused by noninvasive Escherichia coli. This novel antibiotic has also shown promise in the prevention of travelers' diarrhea, as well as a host of other gastrointestinal disorders. Development of a vaccine against diarrheagenic organisms is of high global importance but has been a challenge, owing to the multiple causative serotypes of E. coli and other organisms.

A review of hypogonadism and erectile dysfunction among HIV-infected men during the pre- and post-HAART eras: diagnosis, pathogenesis, and management.

Hypogonadism and erectile dysfunction (ED) appear to be more common among men infected with HIV compared to age-matched men within the general U.S. population. HIV providers should consider these conditions and utilize standardized evaluation and diagnostic criteria. Treatment of both hypogonadism and ED increases sexual function and quality of life; testosterone supplementation in the setting of hypogonadism may also improve lean body mass, mental status, and anemia. We review the epidemiology, diagnosis, pathogenesis, and treatment options of both hypogonadism and ED among HIV-infected men.

Cytomegalovirus retinitis after immune reconstitution.

Cytomegalovirus (CMV) infection is the most common opportunistic infection that affects the retina in HIV-positive patients; it typically occurs in the setting of severe immune suppression (CD4 count less than 50 cell/microL). We present a case report of an HIV-infected patient in whom recurrent CMV retinitis developed after HAART and apparent immune reconstitution (CD4 count of greater than 500 cells/microL). This case report underscores that CMV infection may occur despite high CD4 counts among patients who experience only partial immune reconstitution.

HIV care in the U.S. Navy: a multidisciplinary approach.

We provide a review of the medical care provided to human immunodeficiency virus (HIV)-positive service members in the U.S. Navy and Marine Corps. An overview of the history of HIV and its impact on the U.S. Navy is presented. We also explain the policies of mandatory HIV testing within the U.S. Navy and the evaluation process for those found to have HIV infection. We specifically describe the multidisciplinary HIV medical care provided at Naval Medical Center San Diego, which is one of three HIV specialty clinics within the U.S. Navy.

History of U.S. military contributions to the study of parasitic diseases.

U.S. military researchers have made major contributions to the discovery, diagnosis, treatment, and prevention of a number of parasitic diseases. We review the paramount U.S. military contributions to the understanding of leishmaniasis, filariasis, schistosomiasis, trypanosomiasis, gastrointestinal parasites, intestinal capillariasis, and angiostrongyliasis.

A novel use for drotrecogin alfa (activated): successful treatment of septic shock associated with coccidioidomycosis.

We present 2 cases of septic shock associated with coccidioidomycosis that were successfully treated with drotrecogin alfa (activated) in combination with antifungal agents. The favorable outcomes, in light of the high mortality usually associated with this condition, suggest that drotrecogin alfa (activated) may be a valuable adjunct for treating septic shock due to endemic mycoses.

An outbreak of conjunctivitis due to a novel unencapsulated Streptococcus pneumoniae among military trainees.

BACKGROUND: Bacterial conjunctivitis usually occurs as sporadic cases; outbreaks are uncommon and usually are associated with school campuses. We report an outbreak of Streptococcus pneumoniae conjunctivitis at a military training facility. METHODS: An outbreak investigation was done. Each case of conjunctivitis was evaluated with an assessment tool including demographic and clinical data. Conjunctival swabs were obtained. Pneumococci underwent standard testing, including serotyping with the Quellung reaction, capsular staining, and multilocus sequence typing. Sequence types were compared with previous reported outbreak strains by construction of dendrograms. Carriage rates of S. pneumoniae were determined among previously undiagnosed case patients with conjunctivitis, and a case-control study was performed. Control measures included education to increase hand washing, distribution of alcohol-based hand gel, and prompt treatment of patients with conjunctivitis. RESULTS: During a 6-week period, 92 cases of conjunctivitis occurred among 3500 persons, with an attack rate of 1.75 cases per 100 person-months. Eighty cases (87%) were due to S. pneumoniae; 45 (49%) were confirmed, and 35 (38%) were probable. Ten percent of recruits surveyed carried the outbreak strain. Twenty-two percent self-reported symptoms consistent with conjunctivitis during the outbreak period; sharing washcloths was associated with conjunctivitis (odds ratio, 11.7; P=.03). The causative organism was resistant to azithromycin but susceptible to telithromycin. The outbreak strain was an unencapsulated S. pneumoniae that has not been previously described; it was most closely related to the sequence type causing the Dartmouth College (Hanover, NH) outbreak of conjunctivitis in 2002. CONCLUSIONS: We report a conjunctivitis outbreak among military trainees caused by a novel, unencapsulated strain of S. pneumoniae.

A case series and focused review of nocardiosis: clinical and microbiologic aspects.

Nocardia species are ubiquitous soil organisms that often infect patients with underlying immune compromise, pulmonary disease, or a history of surgery or trauma. We report 5 cases of nocardiosis representing various aspects of this "great imitator": 1) pneumonia in the setting of underlying malignancy, 2) chronic pneumonia with drug-resistant organism, 3) bacteremia and empyema with chronic hematologic malignancy, 4) primary cutaneous disease, and 5) sternal wound infection. We present a summary of the English literature from 1966 to 2003 with a focus on the teaching points of each of our 5 cases as well as the background epidemiology and microbiology of the Nocardia genus. Isolation of the organism may be achieved with routine media but longer incubation times may be necessary, delaying diagnosis and appropriate therapy. Treatment with a sulfa-containing regimen is standard of care, but resistance testing is warranted given emerging drug resistance, high rates of discontinuation due to adverse reactions, and the potential for nephrotoxicity in transplant recipients on cyclosporine.

Coccidioidomycosis: a descriptive survey of a reemerging disease. Clinical characteristics and current controversies.

Coccidioidomycosis is a fungal disease with protean manifestations endemic to the Lower Sonoran Life Zone, which includes the hot deserts of the southwestern United States and areas of Mexico. Two hundred and twenty-three patients were found to have coccidioidomycosis at our institution from 1994-2002, the largest reported cohort of coccidioidomycosis patients since the 1950s. Of these patients, 58% presented with isolated pulmonary disease, 14% had high (>1:16) complement fixation titers without clear evidence of dissemination, 22% had definite disseminated disease, and 5% had unclassified disease. Enzyme immunoassay was a reliable diagnostic tool in those with symptomatic disease, but had a low specificity in those who were asymptomatic. Complement fixation titers of > or =1:16 were associated with dissemination to bone or skin but were not helpful in evaluating central nervous system disease. Thirteen percent of patients with high complement fixation titers (>1:16) without clear evidence of dissemination on presentation and 7% of those with isolated pulmonary disease eventually progressed to disseminated disease; 30% of Filipino patients with pulmonary disease progressed to disseminated disease. Nonwhite race was a predictor for dissemination; African American patients more often developed disseminated bony disease while Filipinos were more likely to develop cutaneous or central nervous system disease. Relapse of disseminated coccidioidomycosis occurred in 24% of patients; the risk was highest (71%) among those with central nervous system disease. Azole therapy was generally inferior to amphotericin B in disseminated disease. Predictors of permanent disability included African American or Filipino race, central nervous system disease, and bony disease.

Bacterial pyomyositis in the United States.

The incidence of reported bacterial pyomyositis is increasing in the United States, especially among immunocompromised persons. This review summarizes all reported cases of pyomyositis among human immunodeficiency virus (HIV)-infected persons worldwide and HIV-negative persons in the United States since 1981. During the era of combination antiretroviral therapy, bacterial pyomyositis among HIV-infected persons typically occurred in those with end-stage acquired immunodeficiency syndrome. Among non-HIV-infected patients, about half have a serious underlying medical problem, most commonly diabetes mellitus, malignancy, or a rheumatologic condition. These patients are more likely to have a gram-negative infection, a normal white blood cell count, multifocal involvement, or higher mortality than those without an underlying medical condition. The characteristics of cases in temperate areas are similar to tropical cases, except that the former occurs more often in immunocompromised persons; this may change with the HIV epidemic in tropical regions.

Halting a pneumococcal pneumonia outbreak among United States Marine Corps trainees.

BACKGROUND: Streptococcus pneumoniae is the leading cause of bacterial pneumonia in all age groups. Identifying outbreaks of pneumococcal disease and key risk factors may lead to improvements in vaccination and prevention strategies for high-risk groups. A significant outbreak of S. pneumoniae pneumonia that occurred among Marine recruits is reported here. METHODS: An outbreak was investigated using standard microbiologic procedures and epidemiologic evaluation to define the extent of the outbreak, determine the microbiologic causative agent(s), identify risk factors for the development of disease, and institute preventive measures against further cases of pneumonia among recruits. RESULTS: Fifty-two cases of radiographically confirmed pneumonia occurred among 3367 Marine recruits over a 2-week period in November 2000. Twenty-five of these cases occurred in a single company of 481 men, with an attack rate of 5.2%. Twelve of the 25 cases were caused by S. pneumoniae, serotypes 4 and 9v. The outbreak rapidly ended following isolation of cases, prophylaxis with oral azithromycin, and administration of the 23-valent pneumococcal vaccine. CONCLUSIONS: This outbreak of pneumococcal disease occurred in the setting of intense military training and a crowded environment. The use of the pneumococcal vaccine year-round in military trainees and other high-risk populations to reduce pneumococcal disease should be considered.

Sweet's syndrome masquerading as facial cellulitis.

Sweet's syndrome, or acute febrile neutrophilic dermatosis, is a cutaneous condition that typically occurs as tender red plaques or nodules. However, atypical presentations may occur and, in our case, Sweet's syndrome masqueraded as facial cellulitis and soft tissue infections of the extremities in a sporotrichoid pattern. Despite treatment with broad-spectrum antibiotics, the cutaneous lesions progressed. Results of skin biopsy specimens of the facial plaque and a nodule on the right upper extremity were diagnostic of Sweet's syndrome. Simultaneous to diagnosis, the patient also was found to have acute myelogenous leukemia (AML).

A case series of group A Streptococcus necrotizing fasciitis in military trainees.

We describe a case series of group A Streptococcus (GAS) necrotizing fasciitis occurring over a 10-week period in military recruits undergoing intense physical training. These cases highlight that GAS may cause life-threatening infections in addition to mild diseases such as pharyngitis. This series suggests that the incidence of severe GAS infections may be increasing in certain populations and it emphasizes the importance of considering prophylactic measures against GAS in high-risk populations.

A cluster of disseminated coccidioidomycosis cases at a US military hospital.

We recently evaluated a cluster of cases of disseminated coccidioidomycosis referred to the Naval Medical Center San Diego. Between March and June of 2002, seven cases were diagnosed and treated. In a 5-year record review (March 1997-February 2002), we found only seven cases of disseminated disease attributable to Coccidioides immitis at the same institution. This report of seven cases over a 3-month period represents a 20-fold increase in the number of complicated C. immitis infections. All cases were non-Caucasians, had disseminated disease to bone and/or skin without meningeal involvement, and had a delay of 1.5 to 6 months from symptom onset until the diagnosis of coccidioidomycosis. Four of our cases occurred in previously healthy, young active duty members, emphasizing the importance of this mycosis in U.S. military personnel.