Subacute histoplasmosis with focal involvement of the epiglottis: importance of differential diagnosis.

Histoplasmosis is an endemic mycosis of the Americas, Africa, and Asia. In Spain, it is the most common imported endemic mycosis appearing in the literature, and its incidence is on the rise. Proper differential diagnosis of the disease must be taken into consideration by otorhinolaryngologists, as the clinical manifestations of histoplasmosis may simulate more prevalent diseases such as cancer or tuberculosis. We present the case of a Spanish patient with focal involvement of the larynx and offer a review of the relevant literature.

[Understanding current practice of clinical medicine in the tropics (II). Bacterial and viral diseases. Malnutrition]. / Aspectos básicos en la práctica actual de la medicina clínica en el trópico (II). Enfermedades bacterianas y virales. Malnutrición.

In recent years, a significant number of physicians want to spend part of their medical training in health facilities in developing countries. In this setting, clinical skills are extremely important due to the limited available diagnostic resources. Bacterial diseases are common, but bacterial cultures are rarely accessible. In Africa, tuberculosis affects over 200 cases per 100,000 persons, and more than 22 million people live with HIV infection; both diseases are a serious public health problem. Malnutrition is endemic in many countries in Africa and is compounded by the continuous humanitarian and food crisis. In this paper, basic concepts of epidemiology, clinical features, diagnosis and treatment of major diseases that can be found in a rural health post in the tropics are discussed.

[Basic features in the current practice of clinical medicine in the tropics (I). Parasitic diseases]. / Aspectos básicos en la práctica actual de la medicina clínica en el trópico (I). Enfermedades parasitarias.

In recent years an increasing number of physicians want to spend part of their medical training in health facilities in developing countries. Working in these areas requires good clinical skills, particularly where diagnostic resources are limited. Trainees will attend patients with many different parasitic diseases such as malaria and soil transmitted helminthic infections. The aim of this work is to provide basic concepts of epidemiology, clinical characteristics, diagnosis and treatment of the principal parasitic diseases that could occur in a rural health post in the tropics.

Nephrotic syndrome complicating chronic visceral leishmaniasis: re-emergence in patients with AIDS.

Leishmania infection may be associated with immunecomplex-mediated glomerular injury. Contrary to immune-competent individuals, leishmaniasis in HIV patients is a chronic, relapsing disease. Despite the increasing frequency of the Leishmania/ HIV co-infection, there is a paucity of information on the effects of such co-infection in the kidney. We present a patient with AIDS and refractory, relapsing visceral leishmaniasis who developed nephrotic syndrome associated with renal involvement by Leishmania in the absence of immunecomplex glomerular deposition. For the first time, the relapsing nature of renal injury in this context is documented.

Infections of implantable cardioverter-defibrillators: frequency, predisposing factors and clinical significance.

The prognosis for patients with ventricular arrhythmias has improved dramatically with the aid of implantable cardioverter-defibrillators (ICDs). Although infection is a serious complication that frequently causes dysfunction and loss of ICDs, the frequency, predisposing risk-factors, and clinical and microbiological features are only partially understood. This study describes a retrospective review of 423 procedures in 278 patients with ICD primary implants and replacements performed at a tertiary-care hospital. Generators were placed in either a pectoral (68%) or abdominal (32%) site, and electrodes were placed transvenously in 97% of the patients. Most (95%) interventions were performed in a one-stage procedure. Infection developed with ten (2.4%) implanted devices. Four cases occurred within 30 days of surgery ('early infections') and six occurred > 1 month after surgery ('late infections'). In univariate analysis, factors associated with the development of an early infection were: two-stage surgery, a sub-costal approach, and abdominal generator placement. In patients with late infections, a significant association was found with trauma or decubitus ulcer in the generator area. Infection presented with local signs without systemic complications. Seven of the ten patients required complete removal of the system.

Nosocomial enterococcal endocarditis: a serious hazard for hospitalized patients with enterococcal bacteraemia.

OBJECTIVES: Enterococci are a major leading cause of infectious endocarditis and also a common cause of hospital-acquired bacteraemia, which is not believed to represent a serious hazard for the endocarditis. The incidence and risk factors for infectious endocarditis in patients with hospital-acquired enterococcal bacteraemia is determined. METHODS: Prospective analysis of 116 patients with enterococcal bacteraemia admitted to medical or surgical wards of a tertiary-care, university affiliated hospital during a period of 5 years. Echocardiography was performed when indicated by clinical criteria. RESULTS: Seventy-five (61.4%) episodes were hospital-acquired and 47 (38.5%) were community-acquired. Most patients had one or more underlying chronic diseases and major abdominal (58.6%) or genitourinary (38.6%) surgery. Seventeen patients (14.6%) developed enterococcal endocarditis. By univariate analysis the risk factors associated with endocarditis were community-acquired infection (P 0.012); monomicrobial bacteraemia (P 0.006); three or more positive blood cultures (P < 0.001); underlying valvulopathy (P < 0.001); presence of a prosthetic valve (P < 0.001) and age (P 0.012). Six patients (8%) developed nosocomial endocarditis. In this group of patients, three or more positive blood cultures (P < 0.01), bacteraemia as a result of Enterococcus faecalis (P 0.007); underlying valvulopathy (P < 0.001) and presence of a prosthetic valve (P < 0.001) were associated with endocarditis. By logistic regression, the presence of underlying valvulopathy and three or more positive blood cultures were associated with endocarditis (OR 21.0; CI 95% 1.65-26.9; P 0.019). CONCLUSIONS: The risk of developing infectious endocarditis in patients with hospital-acquired enterococcal bacteraemia is significant. Patients with underlying valvulopathy and three or more positive blood cultures with E. faecalis are prone to nosocomial enterococcal endocarditis.

[Relation between erythrocyte sedimentation rate, clinical and immune status and virus load in non-hospitalized HIV-infected patients]. / Relación entre velocidad de sedimentación globular, situación clínica e inmunitaria, y carga viral en pacientes infectados por el VIH no hospitalizados.

The objective of this study was to analyze the clinical, immunitary and virological implications of an elevated erythrocyte sedimentation rate (ESR) in HIV-positive patients. A retrospective crossover study of 350 HIV-positive patients undergoing periodic evaluations (942 follow-ups) at the outpatient service of the Division of Infectious Diseases of the Fundación Jiménez Díaz in Madrid was carried out from January 1993 to July 1998. The relationship between the ESR (cut-off point: 20 mm/h), the clinical status (symptomatic or asymptomatic), the immune status (CD4, cut-off point: 200 cells/microl), and viral status (viral load, cut-off point: 3 log) of the patients was analyzed. Information on other possible confounding factors was also collected. It was found that in 667 cases (71%), the ESR was normal and in 275 (29%) it was >20 mm/h. In the univariate analysis, a statistically significant relation was found between the ESR and the clinical, immune and viral status of the patients: a normal ESR was associated with a CD4 >200 cells/ml, viral load <3 log, and an asymptomatic clinical status (p <0.05). A significant inverse relation was found between ESR and hematocrit (p <0.05, CI 95%: 3.87-5.1) and between ESR and gammaglobulin (p <0.05). The multivariate analysis did not show a significant relation between ESR and clinical status (OR: 1.98, IC95%: 1-3.9), nor between ESR and the CD4 level (in the case of hematocrit 42-43%, OR: 0.755, p >0.005). However, in patients with low hematocrit the risk of having CD4 < or = 200 cells/microl when the ESR was >20 mm/h was significant (OR: 9.34, IC95%: 4.56-11.35). When adjusting for clinical factors such as age, sex, gammaglobulin, hematocrit and co-infection with hepatitis C or B virus, we did not find a relation between the ESR and the clinical, immune or viral status of the seropositive patients. We believe that it is not necessary to determine the ESR when monitoring HIV-positive patients, since it does not appear to be a good marker for a deterioration in clinical, immune or viral status.

[Listeria monocytogenes infections in the adult. Clinical and microbiological issues of a changing disease]. / Infecciones por Listeria monocytogenes en el adulto. Aspectos clínicos y microbiológicos de una enfermedad cambiante.

Thirty-one cases of human listeriosis seen from 1971-1999 were reviewed. cases were grouped as follows: Group I composed of 14 patients were studied in the period 1971-1984; and group II composed of 17 cases studied in the period 1985-1999. We tried to assess changes in the incidence, clinical findings and outcome in both periods. The incidence of listeriosis remained constant along the years, 1.2 cases/20,000 discharges. The mean age of the patients significantly increased along the years (55 11 years versus 68 12 years; p 0.002). 77% of cases had one or more underlying diseases predisposing to listeriosis. We observed an increasing number of listeriosis in patients without chronic diseases in recent years. Listeriosis presented as meningitis or primary sepsis. Mortality was 61% and was strictly associated with the severity of the underlying disease. Patients with meningoencephalitis and seizures had a worse prognosis. We did not observe differences in mortality of patients who were treated with beta-lactam monotherapy in comparison with those who were treated with beta-lactam/aminoglucoside combination. Cotrimoxazole was uniformly successful treatment of human listeriosis in this series.

Mycobacterium tuberculosis bacteremia in a university hospital.

SETTING: Patients with blood cultures positive for Mycobacterium tuberculosis between 1988 and 1999. OBJECTIVE: To study the clinical and microbiological characteristics of patients with tuberculous bacteremia, including data about evolution and management. DESIGN: Retrospective review of the clinical charts and microbiological records of patients with culture-proven tuberculous bacteremia between 1988-1999. RESULTS: During the study period, 19 patients with culture-proven M. tuberculosis bacteremia were detected (1.42 isolates/patient, 4.7% of all patients with blood cultures for mycobacteria). Four patients were non-infected with the human immunodeficiency virus and 15 were HIV-infected. In four patients blood was the only positive sample. Five patients were diagnosed simultaneously with tuberculosis and HIV infection. Only 13 had a temperature higher than 37.5 degrees C. Most patients had symptoms or signs of respiratory tract involvement, and 11 patients died (10 from tuberculosis). The average time for detection of positive blood cultures was 33.25 days for lysis-centrifugation cultures and 26.46 days for BACTEC cultures. The incidence of M. tuberculosis bacteremia remained stable during the study period. CONCLUSIONS: Although blood cultures are useful for definitive diagnosis of disseminated tuberculosis, the long incubation times made them of limited usefulness in the clinical management of patients. Mortality remains high in these patients.

[Infection by resistant Mycobacterium tuberculosis in a hospital population. A longitudinal study of incidental cases at the Fundación Jiménez Díaz]. / Infección por Mycobacterium tuberculosis resistente en una población hospitalaria. Estudio longitudinal de casos incidentes en la Fundación Jiménez Díaz (1991-1997).

OBJECTIVE: Evaluation of epidemiologic, clinical and prognostic characteristics in cases of resistant tuberculosis (MRTB). METHODS: Retrospective longitudinal and observational study of resistant cases of tuberculosis at Fundación Jiménez Díaz (1991-1997). Statistical analysis of conventional tests and significance level at p < 0.05. RESULTS: Twenty patients out of 558 with recovery of Mycobacterium tuberculosis showed resistance to some drugs (isoniazid, rifampicin, ethambutol, streptomycin or pyrazinamide). Information was gathered from 19 patients: eight (42%) HIV-positive patients; eight (42%) with the antecedent of tuberculosis (2 abandoned treatment). There were eleven cases (58%) of secondary resistance and eight of primary resistance but only five (25%) with multi-resistance criteria (1 primary and 4 secondary); five cases showed primary resistance to isoniazid. The number of resistances and HIV seropositivity or antecedent of prophylaxis was not statistically significant. In contrast, the higher number of resistances and tuberculosis antecedent were indeed statistically significant. CONCLUSIONS: There was a low resistance rate at our institution. All multi-resistant cases had antecedents of therapy or prophylaxis abandon or previous tuberculosis. Only one case was MRTB. The relevance of complying with a proper therapy is emphasized (consider therapies directly monitored if there is risk of abandon). In patients with epidemiologic risk factors susceptibility studies should be performed and also start therapy with four drugs. The objective is to decrease the percentages of resistance and morbi-mortality.

[In old age ... AIDS. Is it worth to initiate antiretroviral treatment? Review of 37 patients more than 60 years of age]. / A la vejez ... el SIDA. Merece la pena iniciar tratamiento antirretroviral? Revision de 37 pacientes con más de 60 años.

INTRODUCTION: HIV infection is common in young persons and its clinical picture, outcome and response to antiretroviral therapy is well known, but it is not the case in the elderly. OBJECTIVES: To evaluate the clinical characteristics and response to antiretroviral therapy of HIV elderly patients. DESIGN: Retrospective study of 37 patients elder than 60 years. The control group comprised of 64 HIV positive patients with less than 60 years. None of them were drug abusers. RESULTS: The mean age of patients was 65 years (range 60-79), 86% were males. The most frequent causes for HIV testing were: wasting (22%), P. carinii pneumonia (19%), tuberculosis (13%) and Kaposi sarcoma (10%), but in the control group voluntary testing was the most common reason (64%). The mean CD4 count at diagnosis was lower in the elderly group (233 cells/microL vs 323 cells/microL). During follow up, the most frequent complications for those with less than 200 CD4 cells were: oral candidiasis (44%), P. carinii pneumonia (27%), Kaposi sarcoma (22%) and esophageal candidiasis (22%), while in the young group P. carinii pneumonia (22%), Kaposi sarcoma (9%) and esophageal candidiasis (9%) were less frequent. 67% of the elderly received antiretroviral therapy. Zidovudine had to be discontinued due to anaemia in half of them. Survival at 6 and 12 months was significantly longer in treated patients compared to those who did not received antiretrovirals (100% vs 14% at 6 months, P < 0.001; and 54% vs 0% at 12 months, p = 0.03); and at 2 years it was almost similar to that of the young group (36% vs 52%, p = 0.38). CONCLUSIONS: HIV infection in the elderly is generally diagnosed in an advance stage, but antiretroviral therapy prolongs survival. Zidovudine should be reserve as a second line drug because its frequent haematological toxicity.

[Disseminated histoplasmosis in AIDS patients. A study of 2 cases and review of the Spanish literature]. / Histoplasmosis diseminada en pacientes con sida. Estudio de 2 casos y revisión de la bibliografía española.

The characteristics of two cases of histoplasmosis in AIDS patients in our institution are presented together with a review of the 11 cases published in Spain since 1988 in addition to the current knowledge on histoplasmosis in patients with human immunodeficiency virus infection (HIV). In all except 2 of the 13 patients there was epidemiologic history of a stay in a country in which histoplasmosis is endemic. The 12 cases described in which this information is available had CD4 counts under 100/microL. The clinical manifestations of presentation were fever (92.3%) associated or not with other unspecific symptoms (asthenia, anorexia, cough, diarrhea) with a subacute course of two or three months. Physical examination demonstrated hepatosplenomegaly in 76.9% of the cases and 61.5% of the patients presented cutaneous lesions. Thoracic radiography was abnormal in 55% (61.5% had respiratory symptoms). Diagnosis was achieved by isolation of the fungus in the cutaneous biopsies in all the patients with dermatologic involvement and in 7 cases identification was performed in the bone marrow. In all the cases induction treatment was with anphotericin B and in those who reached the maintenance phase itraconazol was used in 7 cases and ketoconazol in one case. None of the patients treated with itraconazol, including the two in our center, presented recurrence at the time of completion of follow up. In conclusion, histoplasmosis is frequently presented as a prolonged febrile syndrome with unspecific characteristics, thus emphasizing the importance of including travel history to other countries in the anamnesis. The increase in journeys to endemic countries and immigration from these areas had led to an increase in the number of cases of histoplasmosis in patients with HIV infection in Spain.

[Brain abscess. Clinicomicrobiologic study and prognostic analysis of 59 cases]. / Absceso cerebral. Estudio clinicomicrobiológico y análisis pronóstico de 59 casos.

INTRODUCTION: Clinical, microbiological, therapeutic and prognostic characteristics of brain abscesses were analyzed as well as the influence of CT in their evolution. MATERIALS AND METHODS: Retrospective study of 59 patients with the diagnosis of brain abscess of bacterial source before (group A) and after (group B) the introduction of CT (25 and 34 patients, respectively). RESULTS: The most common symptom was headache (76.3%) and the most common abnormality in physical examination was a decrease in the level of consciousness (61%) and this abnormality was associated with a higher mortality rate (13% versus 41.6%; p < 0.05) and also a higher proportion of neurologic sequelae (50% versus 85.7%; p < 0.05). The diagnosis was obtained earlier in group B. The hematogenous source predominated (32.2%); an adjacent source was identified in 28.8% and an apparent source was not recognized in 27.2% (40% in group A versus 17.6% in group B). Anaerobic and microaerophilic streptococci were the bacteria recovered most frequently. Gram-negative aerobic bacteria were the most common in otogenic abscesses. The use of corticosteroids had no influence upon mortality, but it was associated with a lower percentage of neurological sequelae (40% versus 14%; p < 0.05). The introduction of CT decreased mortality (40% in group A versus 23.5% in group B, although this difference was not significant) and also sequelae (86.6% in group A versus 57.6% in group B; p < 0.05). Leaving apart cases of bacterial endocarditis, in which death was due to the underlying heart disease and a systemic sepsis picture, mortality attributed to brain abscess was 20.3%. CONCLUSIONS: The introduction of CT has meant a significant breakthrough for the diagnosis, treatment and follow-up of these patients and has contributed to improvement in survival. In our series, the diagnosis of brain abscess was obtained earlier and the number of brain abscesses with no apparent source has decreased since the introduction of CT. Moreover, CT sensitivity is really good for locating multiple abscesses. Overall, the prognosis of these patients has improved since the introduction of this technique. Nevertheless, brain abscess is still associated with a relevant morbi-mortality rate.

[Spontaneous meningitis caused by gram-negative bacilli]. / Meningitis espontánea por bacilos gramnegativos.

OBJECTIVE: To analyze the causative factors, clinical and microbiological characteristics, and prognosis in spontaneous meningitis caused by Gram-negative rods in adult patients. METHODS: Descriptive and retrospective study of all clinical records and microbiological findings in patients diagnosed of meningitis by Gram-negative bacilli, from 1973 to 1995, at Fundación Jiménez Díaz. RESULTS: Twenty patients had spontaneous meningitis caused by Gram-negative bacilli (2.1% of all diagnosed meningitis during this period). Fourteen patients were older than 65 years (range: 36-81; p < 0.05). Ninety-five percent of cases had an extranosocomial origin (p < 0.001). Ninety percent of patients had some underlying disease (p < 0.001). Twelve patients were immunosuppressed. Seven patients had changes in the urinary tract or repeated UTI infections. The most common clinical symptoms were a decrease in consciousness level, fever, and neck stiffness. Cerebrospinal fluid (CSF) in 18 patients showed cellular and biochemical changes. The CSF smear revealed the presence of Gram-negative bacilli in 15 patients. E. coli was the microorganism recovered most frequently. Immunosuppression (p < 0.05), septic shock (p < 0.001) and antimicrobial therapy not including a third generation cephalosporin (p < 0.01) were independently associated with mortality. CONCLUSIONS: Spontaneous meningitis by Gram-negative bacilli is an uncommon infection. It occurs mainly in immunosuppressed patients older than 65 years or with changes in the urinary tract. It usually has an extranosocomial origin. The investigation of CSF is a highly effective for diagnosis. Therapy with third generation cephalosporins has notably improved its prognosis.

Focal infections due to non-typhi Salmonella in patients with AIDS: report of 10 cases and review.

Bacteremia due to non-typhi Salmonella is frequent in human immunodeficiency virus (HIV)-infected patients; however, focal complications rarely have been reported. Ten of 38 HIV-infected patients (26.3%) with salmonellosis documented over a period of 9 years had focal suppurative complications; only 19 (3.9%) of 490 adults without HIV infection who were seen during the same period had focal complications (P = .001). Infections of the urinary tract, lungs, and soft tissue, followed by arthritis, endocarditis, and meningitis were most frequently seen. Although salmonellosis occasionally heralded HIV infection, most patients were severely immunocompromised and had CD4 cell counts of <100/mm3. The mortality rate was 50%, equivalent to that observed among patients with other immunosuppressive disorders (52.6%). Major emphasis must be put on intensive therapy for salmonella bacteremia and prevention of its complications.

Bone marrow biopsy in the diagnosis of fever of unknown origin in patients with acquired immunodeficiency syndrome.

BACKGROUND: Fever is commonly observed in patients with human immunodeficiency virus (HIV) disease and frequently eludes diagnosis. The role of bone marrow biopsy in the diagnosis of fever of unknown origin in patients infected with HIV remains controversial. PATIENTS AND METHODS: One hundred twenty-three consecutive patients with 137 episodes of fever lasting 10 or more days without diagnosis after 1 week of hospitalization were evaluated by bone marrow biopsy. RESULTS: Overall, a specific diagnosis was achieved in 52 episodes by means of culture and histopathological examination (diagnostic yield, 37.9%). Three types of disease were found: mycobacterial infections (n = 36, 69% of documented episodes), including 18 patients with disseminated tuberculosis and 14 with Mycobacterium avium-intracellulare complex infections; non-Hodgkin lymphomas (n = 12, 23%); and visceral leishmaniasis (n = 4, 8%). Although bone marrow cultures were more sensitive than microscopic examination with special stains for the diagnosis of mycobacterial infections, the pathological examination of bone marrow led to a more rapid diagnosis of disease. In addition, the histopathological examination of bone marrow alone led to the diagnosis of a specific condition in 43 episodes (31.3% of all episodes). CONCLUSIONS: Bone marrow biopsy is a useful procedure for the diagnosis of fever in patients with advanced HIV disease, particularly in areas where tuberculosis and leishmaniasis are prevalent. Involvement of the marrow may be the first indication of the existence of extranodal non-Hodgkin lymphoma. For Mycobacterium avium-intracellulare complex infection, blood cultures were more sensitive than bone marrow biopsy.

Circulating immune complexes from HIV-1+ patients induces apoptosis on normal lymphocytes.

Isolated immune complexes from sera of 49 out of 67 human immunodeficiency virus-1-positive (HIV-1+) patients (CIC-HIV+), composed of anti-HIV-HIV-Ag, could induce apoptosis on normal phytohaemagglutinin (PHA)-activated lymphocytes. DNA degradation was detected by propidium iodide staining. This activity is directed against CD4+ lymphocytes as demonstrated by double binding of CIC-HIV+ and anti-CD4 on apoptosis cells. Expression of Fas antigen is prior to apoptotic phenomena. CIC-HIV+ apoptosis inducers belong mainly to asymptomatic HIV-infected patients, indicating that immune complexes from these patients can destroy CD4+ lymphocytes.