Histoplasmosis complicating tumor necrosis factor-α blocker therapy: a retrospective analysis of 98 cases.

BACKGROUND: Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. METHODS: We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. RESULTS: The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. CONCLUSIONS: In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.

Postexposure prophylaxis for common infectious diseases.

Postexposure prophylaxis (PEP) is effective in preventing illness after potential or documented exposure to a variety of microbial pathogens and in reducing the risk of secondary spread of infection. Guidelines have been published by the Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices for proper use of PEP for bloodborne pathogens, for microorganisms transmitted by either airborne or droplet spread or through direct contact, and for infections acquired after traumatic injuries. Depending on the type of exposure, different forms of PEP are available, including vaccines, immune globulins, antibiotics, and antiviral medications. Physicians should assess a patient's potential need for PEP based on several factors, including the type of exposure, the timing and severity of illness in the source patient, the exposed person's susceptibility to infectious diseases of concern, and the relative risks and benefits of the PEP regimen in an individual situation. Immunity to certain infectious diseases can be ensured with prior infection or vaccination, and by serologic testing in patients with a negative or uncertain history. PEP should be given to persons exposed to index cases of pertussis and invasive meningococcal infection regardless of immunization history, and should be given following rabies and tetanus exposure regardless of the length of delay. In general, PEP should be given as soon as possible following a high-risk exposure. Persons exposed to bloodborne pathogens should have baseline testing for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus antibodies, and follow-up testing at six weeks, three months, and six months postexposure.

A multicenter evaluation of tests for diagnosis of histoplasmosis.

BACKGROUND: The sensitivity of the MVista Histoplasma antigen enzyme immunoassay (MiraVista Diagnostics) has been evaluated in disseminated histoplasmosis in patients with AIDS and in the "epidemic" form of acute pneumonia. Moreover, there has been no evaluation of the sensitivity of antigenemia detection in disseminated histoplasmosis after the implementation of methods to dissociate immune complexes and denature released antibodies. The goal of this study was to determine the sensitivity of the current antigen assay in different categories of histoplasmosis. METHODS: Urine and serum specimens obtained from 218 patients with histoplasmosis and 229 control subjects, including 30 with blastomycosis, were tested. RESULTS: Antigenuria was detected in 91.8% of 158 patients with disseminated histoplasmosis, 83.3% of 6 patients with acute histoplasmosis, 30.4% of 46 patients with subacute histoplasmosis, and 87.5% of 8 patients with chronic pulmonary histoplasmosis; antigenemia was present in 100% of 31 tested cases of disseminated histoplasmosis. Among patients with disseminated cases, antigenuria was detected more often and at higher concentrations in immunocompromised patients and those with severe disease. Specificity was 99.0% for patients with nonfungal infections (n = 130) and in healthy subjects (n = 69), but cross-reactivity occurred in 90% of patients with blastomycosis. CONCLUSIONS: The sensitivity of antigen detection in disseminated histoplasmosis is higher in immunocompromised patients than in immunocompetent patients and in patients with more severe illness. The sensitivity for detection of antigenemia is similar to that for antigenuria in disseminated infection.

Pulmonary histoplasmosis.

Pulmonary histoplasmosis is an important cause of morbidity in the United States. Several outbreaks of acute pulmonary histoplasmosis have been linked to potentially preventable environmental exposures. Progressive disseminated histoplasmosis, which is seen frequently in the growing population of immunocompromised hosts, often presents with prominent pulmonary manifestations and is more commonly encountered in hospitalized patients than acute, subacute, or chronic pulmonary histoplasmosis. A battery of diagnostic studies including serology, antigen, cytology/histopathology, and culture should be obtained in suspected cases of histoplasmosis. The yield of antigenuria detection is highest when the multiple body fluids are tested; the level of antigenuria correlates with severity of disease. Amphotericin B is the treatment of choice for severe pulmonary or disseminated histoplasmosis, and itraconazole is effective for mild to moderately severe infection. Posaconazole exhibits promise as a salvage agent. Antifungal prophylaxis is not routinely recommended for at-risk populations. Measures to minimize environmental contamination may reduce the risk of epidemic-type acute pulmonary histoplasmosis related to high-risk exposures.

Treatment and Prevention of Histoplasmosis in Adults Living with HIV.

Histoplasmosis causes life-threatening disseminated infection in adult patients living with untreated HIV. Although disease incidence has declined dramatically in countries with access to antiretroviral therapy, histoplasmosis remains prevalent in many resource-limited regions. A high index of suspicion for histoplasmosis should be maintained in the setting of a febrile multisystem illness in severely immunosuppressed patients, particularly in persons with hemophagocytic lymphohistiocytosis. Preferred treatment regimens for initial therapy include liposomal amphotericin B for severe disease, or itraconazole for mild to moderate disease. Subsequently, itraconazole maintenance therapy should be administered for at least one year and then discontinued if CD4 count increases to ≥150 cells/µL. Antiretroviral therapy, which improves outcome when administered together with an antifungal agent, should be instituted immediately, as the risk of triggering Immune Reconstitution Syndrome is low. The major risk factor for relapsed infection is nonadherence. Itraconazole prophylaxis reduces risk for histoplasmosis in patients with CD4 counts <100/µL but is not associated with survival benefit and is primarily reserved for use in outbreaks. Although most patients with histoplasmosis have not had recognized high-risk exposures, avoidance of contact with bird or bat guano or inhalation of aerosolized soil in endemic regions may reduce risk. Adherence to effective antiretroviral therapy is the most important strategy for reducing the incidence of life-threatening histoplasmosis.

A comprehensive approach to ending an outbreak of rare blaOXA-72 gene-positive carbapenem-resistant Acinetobacter baumannii at a Community Hospital, Kansas City, MO, 2018.

We identified a cluster of extensively drug-resistant, carbapenemase gene-positive, carbapenem-resistant Acinetobacter baumannii (CP-CRAB) at a teaching hospital in Kansas City. Extensively drug-resistant CRAB was identified from eight patients and 3% of environmental cultures. We used patient cohorting and targeted environmental disinfection to stop transmission. After implementation of these measures, no additional cases were identified.

The Jonas Hypertension Program: An Academic-Community Partnership to Address Hypertension in Four Dominican Bateyes.

INTRODUCTION: Adults living in bateyes (i.e., sugarcane plantation villages) in the Dominican Republic have minimal access to health care services. Hypertension (HTN) is a serious and often unrecognized health problem among batey residents. The Jonas Batey Hypertension Program was built on existing social networks to address the detection and treatment of HTN. METHODS: An ongoing community-based participatory research endeavor involves a partnership among three organizations and collaboration with promotoras who engage their batey communities in a mobile HTN screening and treatment program. Adults are screened and, if indicated, are treated with antihypertensive medications. Data collection includes project documentation, participant observation, demographic data, blood pressure (BP) measurements, and pill counts. RESULTS: To date, 243 adults have received HTN treatment in four batey communities. A within-group, as-treated, repeated-measures, pre-/postanalysis showed that among participants who had been receiving antihypertensive treatment for 12 months ( n = 70), there was a significant decrease in BP ( p < .005). CONCLUSION: Results of an interim data analysis indicate that the program model has been implemented successfully and is making a positive impact on BP control. Evaluation is ongoing with regard to the long-term HTN-related health outcomes of batey residents. Ensuring program sustainability is an important consideration for the future.

Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America.

Evidence-based guidelines for the management of patients with histoplasmosis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (Clin Infect Dis 2000; 30:688-95). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. Since 2000, several new antifungal agents have become available, and clinical trials and case series have increased our understanding of the management of histoplasmosis. Advances in immunosuppressive treatment for inflammatory disorders have created new questions about the approach to prevention and treatment of histoplasmosis. New information, based on publications from the period 1999-2006, are incorporated into this guideline document. In addition, the panel added recommendations for management of histoplasmosis in children for those aspects that differ from aspects in adults.

Gastrointestinal histoplasmosis in the acquired immunodeficiency syndrome: report of 18 cases and literature review.

No large case series of gastrointestinal histoplasmosis (GIH) in patients with AIDS has been published. We report 18 cases and review 34 published cases in the medical literature. We did a retrospective chart review from patients seen in our medical practices between 1989 and 2004. Most of our patients were men who had sex with men and who were not receiving highly active antiretroviral therapy. Median CD4 count was 34/muL. The most common presenting symptoms were diarrhea, fever, abdominal pain, and weight loss. The most commonly involved site was the colon or cecum. Biopsies revealed visible Histoplasma capsulatum organisms in 89%. Cultures from any site were positive in 76.9%. Four patients died from GIH. Gastrointestinal histoplasmosis occurs in severely immunocompromised patients with AIDS not receiving highly active antiretroviral therapy. Typical manifestations include diarrhea, fever, abdominal pain, and weight loss. Diagnosis is confirmed by blood or gastrointestinal tissue culture. Improvements in antiretroviral and antifungal therapies appear to have reduced the incidence of GIH and may improve the prognosis of this disease.

Viral infections in the elderly. The challenges of managing herpes zoster, influenza, and RSV.

Viral diseases are an important cause of morbidity and mortality in elderly patients, whether they live in the community or in long-term care facilities. Management of viral infections in older adults is complicated by factors that include the infrequency or absence of common signs and symptoms of infection and adverse drug reactions. In this article, Drs Bader and McKinsey discuss the clinical features and treatment of herpes zoster and the respiratory diseases caused by influenza and respiratory syncytial virus (RSV).

Assessment of readiness for adherence by HIV-positive males who had previously failed treatment.

The purpose of this prospective pilot study was to examine the relationship between the level of readiness for health behavior change and adherence by HIV-positive males (n = 19) who had previously failed treatment due to nonadherence. Participants completed the Index of Readiness (IR), an instrument measuring readiness to initiate health behavior change, prior to beginning new antiretroviral medications. After 6 months, participants were divided into two mutually exclusive groups: those who reached and sustained viral suppression and those who did not. Participants who experienced and sustained viral suppression had statistically significantly higher scores on the Identification of Barriers/Creating Strategies subscale of the IR compared to participants who did not reach viral suppression. Results from this preliminary study indicate that readiness may be a key component in successful adherence and that the IR may be a useful tool in assessing readiness for adherence to antiretroviral medications.

Syphilis presenting as inflammatory tumors of the liver in HIV-positive homosexual men.

Syphilis, a sexually transmitted infection caused by the spirochete Treponema pallidum, has seen a resurgence since 2001, particularly in men who have sex with men. Syphilis can affect the liver during the secondary stage as syphilitic hepatitis and during the tertiary stage as gummas. We describe 3 cases of syphilis in human immunodeficiency virus-positive homosexual men that presented as hepatic mass lesions clinically suspected of being malignant tumors. Histologically, 2 of the 3 cases showed a plump spindle cell proliferation, mixed inflammatory infiltrate with numerous neutrophils, and abscesses, whereas the third case showed granulomas and pericholangitis/cholangitis. Immunohistochemical staining for T. pallidum showed innumerable organisms in 2 of the cases. Pathologists must be aware of the possibility of syphilis causing hepatic inflammatory masses in human immunodeficiency virus-positive men who have sex with men in order to avoid misdiagnosis or delayed treatment.

Strategies to improve HIV treatment adherence in developed countries: clinical management at the individual level.

REMARKABLE ADVANCES IN THE TREATMENT OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) DISEASE HAVE BEEN BLUNTED BY WIDESPREAD SUBOPTIMAL ADHERENCE (IE, NONADHERENCE), WHICH HAS EMERGED AS A MAJOR BARRIER TO ACHIEVING THE PRIMARY GOAL OF ANTIRETROVIRAL (ARV) THERAPY: suppression of HIV viral load. Nonsuppressed HIV viral load is associated with drug resistance, increased morbidity and mortality, and a higher risk of person-to-person HIV transmission. For HIV-infected individuals who are failing HIV treatment due to nonadherence, becoming adherent is a life-saving behavior change. However, overcoming nonadherence is one of the most daunting challenges in the successful management of HIV disease. The purpose of this paper is to provide clinicians with a better understanding of nonadherence to ARV treatment and to review the various factors that have been associated with either adherence or nonadherence. Strategies are presented that may help the nonadherent individual become ready to take HIV medications as prescribed.