Manuel L. Fernández-Guerrero

Visceral leishmaniasis in immunocompromised hosts

Visceral leishmaniasis is infrequently reported in immunocompromised hosts; hence, the clinical manifestations and outcome of the disease in these patients are unknown. In a series of 10 patients with visceral leishmaniasis complicating renal transplantation (three), hematologic neoplasms (two), systemic lupus erythematosus (two), or infection with human immunodeficiency virus (three), typical hallmarks of kalaazar such as enlargement of spleen or hyperglobulinemia were absent in three and six patients, respectively. Extensive visceral involvement was noted by biopsies or autopsies in four patients. Diagnosis was made during evaluation for fever of unknown origin. Myriads of amastigotes were seen in bone marrow smears. Measurement of antibodies against Leishmania donovani was positive in each patient tested. Ultimately, three patients died, and chronic infections refractory to treatment developed in two other patients. Visceral leishmaniasis is a potentially fatal infection in immunocompromised hosts. Current antiparasitic therapy frequently fails to eradicate L. donovani from infected tissues.

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

Abstract.  Fernández‐Guerrero ML, Herrero L, Bellver M, Gadea I, Roblas RF, de Górgolas M (Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spain). Nosocomial enterococcal endocarditis: a serious hazard for hospitalized patients with enterococcal bacteraemia. J Intern Med 2002; 252: 510–515.

Infective Aortitis due to Brucella melitensis

Infective aneurysms caused by Brucella sp. are extremely rare. B. suis and B. abortus have been implicated in a few cases but to our knowledge, B. melitensis has not been reported as a cause of mycotic aneurysm of the abdominal aorta. We here report the first case of this described in the English literature. The patient was successfully treated with resection of the infected aneurysm, placement of an axillo-bifemoral graft, and prolonged antibiotic treatment (doxycycline and streptomycin). Extended antimicrobial therapy and extra-anatomical bypass grafting procedures are advisable in the management of brucella infections of the abdominal aorta.

Long-Term Efficacy and Safety of Protease Inhibitor Switching to Nevirapine in HIV-Infected Patients with Undetectable Virus Load

BACKGROUND Simplified highly active antiretroviral therapy (HAART) regimens are becoming widely used, particularly as a result of the side effects of and difficult compliance with protease inhibitor (PI) therapy. However, the long-term efficacy of HAART has not been properly assessed. METHODS We performed a prospective study of 110 patients infected with human immunodeficiency virus type 1 (HIV-1) with undetectable virus load who discontinued PI therapy and initiated therapy with nevirapine without changing nucleoside analogues. Reasons for switching were treatment simplification (45%), lipodystrophy (24%), renal problems (23%), and dyslipidemia (8%). HIV-1 load, CD4 cell count, and fasting biochemistry profiles were performed at the time of switching (baseline) and every 3-4 months thereafter. The aim of the study was to evaluate the long-term efficacy and safety of this combination. RESULTS Sixty-eight patients (61.8%) had a duration of follow-up of 3 years. The mean increase in the CD4 cell count after 3 years was 90 cells/microL (13.8% from baseline). Virus loads remained undetectable in all patients but 9 (8.2%). Triglyceride levels dramatically improved at 12 months (a 75% decrease; P<.02) and remained statistically significant over time (P<.04). The same occurred with serum cholesterol levels: there was an initial reduction of 25% (P<.02) and at the end of the follow-up period (P<.015). However, at the long-term evaluation, complete normalization of mean serum cholesterol and triglyceride levels could not be achieved. Sixteen patients (14.5%) had to stop therapy as a result of nevirapine-associated side effects. CONCLUSIONS The switching of a PI to nevirapine is a safe and well-tolerated option for maintaining long-term virological suppression and immunological control. Three years after starting nevirapine therapy, rates of hypercholesterolemia and hypertriglyceridemia improved, although normal cholesterol and triglyceride values were not achieved.

Long term failure of miltefosine in the treatment of refractory visceral leishmaniasis in AIDS patients

We carried out a retrospective and descriptive study of 4 HIV infected patients with relapsing visceral leishmaniasis (VL) seen at 2 tertiary-care hospitals in Spain during the last 6 y, in whom miltefosine was used as a compassionate use treatment at a dosage of 50 mg b.i.d. Patients had a medium CD4 lymphocyte count of 69 cells/µl and were C stage. All patients received at least 2 different anti-leishmanial drugs and had at least 3 relapses before miltefosine treatment (range 3–7). Three patients were treated with miltefosine at a standard dose of 50 mg b.i.d. for 28 d, and the other during 12 months. Despite an initial symptomatic improvement, miltefosine treatment failed to eradicate the infection in all cases. We conclude that the use of miltefosine alone is not strong enough to cure relapsing VL in HIV-1 controlled infected patients.

Q Fever Endocarditis on Porcine Bioprosthetic Valves: Clinicopathologic Features and Microbiologic Findings in Three Patients Treated with Doxycycline, Cotrimoxazole, and Valve Replacement

Three patients developed Q fever endocarditis on porcine bioprosthetic valves. They had a subacute or chronic course with nonspecific symptoms, enlargement of the liver and spleen, and cardiac failure due to destruction of the cusps, without disruption of the valve ring. High-phase I-specific IgG and IgA antibody titers against Coxiella burnetii were found. C. burnetii was isolated in each patient by inoculating suspensions of valve tissue into a human fetal diploid fibroblast cell line, which was grown as monolayers on slides contained inside rubber-stoppered tube cultures. Patients were treated successfully with doxycycline, cotrimoxazole, and valve replacement and were followed up for periods of 24 to 42 months; no evidence of deterioration was found. The human fetal diploid cell culture may be an expeditious, easy, and safe method to isolate C. burnetii from cardiac valves. Valve replacement seemed necessary to cure prosthetic-valve endocarditis due to C. burnetii infection. Combined therapy with doxycycline and cotrimoxazole may control the disease and prevent reinfection of the homografts replacing the valves.

Q fever endocarditis in Spain. Clinical characteristics and outcome.

OBJECTIVES To describe the clinical presentation of a large number of Q fever endocarditis (QFE) and its management considering the role of serology. PATIENTS AND METHODS Eighty-three patients with definite QFE (56 native and 27 prosthetic valve) with a long-term follow-up after stopping treatment (median: 48 months) were included. Final outcome (cure or relapse) was compared according with the serological titre at the end of therapy: less than 1:400 of phase I Ig G antibodies by indirect immunofluorescence (group 1, N=23) or more than 1:400 (group 2, N=30). RESULTS Eleven patients (13.2%) died from QFE and other 8 died for other reasons not related to endocarditis during follow-up. Surgery was performed in 61 (73.5%) patients and combined antimicrobial treatment was long (median: 23 months, IQR: 12 - 36). Seven relapses were observed, but five of them had received an initial incomplete antibiotic regimen. In patients who completed the programmed treatment (range: 12 - 89 months), serological titres at the end of therapy were not useful for predicting the final outcome: one relapse in each group. CONCLUSIONS QFE requires a prolonged antimicrobial treatment, but serological titres are not useful for determining its duration.

Cutaneous and Medullar Gnathostomiasis in Travelers to Mexico and Thailand

Gnathostomiasis is a rare nematode disease acquired by travelers to endemic areas. The most common clinical presentations are cutaneous forms; however, neurologic involvement can also occur. We present two cases of gnathostomiasis, one of them with severe neurologic complications, in Spanish travelers to Thailand and Mexico, who consumed local food and became infected.

Acute hepatitis C outbreak among HIV-infected men, Madrid, Spain.

To the Editor: In the past decade, hepatitis C virus (HCV) has emerged as a sexually transmitted infection (STI) among HIV-infected men who have sex with men (MSM). The epidemic was originally reported in several northern European countries (England, France, Germany, and the Netherlands) (1) and soon after in Australia (2) and the United States (3). Acute HCV acquisition was associated with group sex, unprotected receptive anal intercourse, and according to some studies, concomitant STI (4). Molecular phylogenetic studies suggested evidence of an international transmission network of MSM within northern Europe (1). However, expansion of the HCV epidemic among MSM to Spain (5) or to other countries of the Mediterranean area had not previously been reported. We report 4 cases of acute HCV in HIV-infected MSM in Madrid, Spain, 2010. These patients were monitored at a university-affiliated hospital in downtown Madrid, which provides health care to a large MSM community in the Chueca District. Diagnosis of acute HCV was made by using the following criteria of the European AIDS Treatment Network (6): 1) positive HCV RNA; 2) an acute rise in alanine aminotransferase level >5× the normal upper limit, with documented normal alanine aminotransferase level within 12 months; and 3) negative results for anti–hepatitis A virus immunoglobulin M and anti–hepatitis B core immunoglobulin M (when other causes of acute hepatitis were excluded). An HCV RNA load fluctuation of >1 log10 IU/mL, if present, was considered further evidence of acute HCV infection (7). All 4 patients were MSM with well-controlled HIV infection who were receiving antiretroviral treatment. During routine medical screening, they were found to have newly elevated liver transaminase levels, and further assessment confirmed the diagnosis of acute HCV infection (Table). Three patients had received a diagnosis of STI in the previous 6 months, but only 1 patient acknowledged having unprotected anal intercourse. In addition, only 1 patient acknowledged using any recreational drugs (amyl nitrate); all denied using injection drugs (Table). All patients had lived in Madrid for at least 5 years before receiving a diagnosis of acute HCV. No patients reported having sex during international travel, using sex toys, or fisting. Table Description of 4 HIV-infected men with HCV infection, Madrid, Spain, 2010* The patients described here lived in the Chueca District of Madrid, the largest MSM community in Spain, which is frequented by MSM traveling from smaller cities in Spain and other countries. Two of the 3 patients were infected with HCV genotype 4, which is unusual in patients from outside the Middle East and Africa (8) yet unexpectedly common in northern European HCV outbreaks (1), which suggests that the patients reported here may have been part of the social network originating in the north. Further sequencing of these isolates is under way to address this issue. The third patient with an identifiable HCV genotype was infected with HCV genotype 1, the most common genotype among HIV-infected MSM in northern Europe (1). These findings suggest that a larger, undetected outbreak of HCV infection is taking place in Madrid. Although the patients reported here described fewer risks for sexual acquisition of HCV than patients from northern Europe or the United States, 3 had recent STI, which suggests that they underreported their risks for HCV acquisition. This temporal association between STI and acute HCV in these patients suggests that the pattern of emergence of sexually transmitted HCV among MSM in Spain might be similar to that seen in northern Europe, following regional epidemics of syphilis (starting in 2000) (9,10). We therefore encourage HIV specialists and general practitioners, when investigating an STI, to perform HCV testing on MSM as well as on persons with newly elevated liver aminotransferase levels.

Circulating immune complexes from HIV‐1+ patients induces apoptosis on‘qc 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 apoptotic 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.