[Manifestations of histoplasmosis]. / Manifestaties van histoplasmose.

Two patients, a 34-year old man-to-woman transsexual and a 32-year-old man, with aids presented with pulmonary symptoms, fever, serious weight loss and an oral ulcer. A third patient, a 16-year-old boy, had signs of transverse myelitis and meningitis without immunodeficiency. All were South American citizens and had disseminated histoplasmosis. After antifungal treatment they recovered, although the third patient remained a wheelchair user. If pulmonary or miliary tuberculosis is suspected in a patient originating from South America, histoplasmosis should be considered. Oral ulcers and skin lesions can be diagnostic clues. Specific stainings of direct preparations and longer-lasting cultures of various materials, especially of biopsy samples, then provide the diagnosis.

Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.

BACKGROUND: Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. OBJECTIVES: In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. METHODS: Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). RESULTS: Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery. CONCLUSIONS: Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported for immune recovery in adults after chemotherapy and bone marrow transplantation.

Management of benign lymphoepithelial lesions of the parotid gland in human immunodeficiency virus-positive patients.

The diagnosis and radiotherapeutic treatment of these HIV-associated benign lymphoepithelial lesions in the parotid gland are discussed. As an example of these lesions, a case is presented involving a 43-year-old HIV-infected man with a 2-year history of enlargements in both parotid glands. After evaluation by computer tomography and cytology, the diagnosis of benign lymphoepithelial lesions was made. Treatment by low-dose radiotherapy (15 Gy) caused regression of both lesions. The lesion on the left regressed completely, but the one on the right side responded only partially. A second course of high-dose radiotherapy (24 Gy) to the right lesion caused regression to a cosmetically acceptable size.

Quinine pharmacokinetics: ototoxic and cardiotoxic effects in healthy Caucasian subjects and in patients with falciparum malaria.

OBJECTIVE: To study the pharmacokinetic behaviour of quinine in Caucasians with and without malaria. METHOD: Quinine-dihydrochloride was administered intravenously as a single dose of 300 mg to 12 healthy subjects and as multiple doses of 600 mg in 4 h every 8 h in 10 patients with falciparum malaria. Plasma quinine concentrations were measured by high-performance liquid chromatography RESULTS: Quinine pharmacokinetics are time-dependent: the apparent elimination halftime is shorter in the accumulation phase than in the elimination phase; in malaria patients the maximal quinine concentration was reached in half the time calculated on the basis of the elimination phase after the last quinine infusion. Nevertheless a loading dose seemed advisable to reach adequate therapeutic levels quickly. In malaria patients the highest plasma concentrations during or at the end of the infusions were positively correlated with body weight. There was no correlation between body weight and the volume of distribution of quinine as calculated during the elimination phase. Hearing loss was audiometrically documented in 9 healthy subjects at a mean maximal plasma quinine concentration of only 2 mg/l. All malaria patients suffered serious cochlear hearing impairment. The ototoxic effects in both healthy subjects and patients appeared to be reversible. No electrographic changes were noted in the healthy subjects, whereas a clinically insignificant mean lengthening of the corrected QT interval was seen in the malaria patients. CONCLUSION: Intravenous quinine pharmacokinetics in healthy Caucasians were similar to those reported for Nigerian or Thai subjects. At effective doses quinine causes considerable but reversible cochlear hearing losses in both healthy persons and in patients. Our findings do support the need for a loading dose. The fact that in malaria patients there was no correlation between body weight and quinine VD as calculated during the elimination phase renders questionable the usefulness of dosing quinine according to body weight.

Ototoxic reactions of quinine in healthy persons and patients with Plasmodium falciparum infection.

Audiometric changes following quinine administration were studied in healthy Caucasian subjects and patients suffering from falciparum malaria disease. Quinine-dihydrochloride was administered intravenously as a single dose of 300 mg to 12 healthy subjects and as multiple doses of 600 mg in 4 h every 8 h in 10 Plasmodium falciparum malaria patients. The hearing function was monitored by conventional and high frequency audiometry. In nine healthy subjects hearing loss was documented at 2-4 h after infusion of Quinine-dihydrochloride at a mean maximal plasma quinine concentration of only 2 mg/l. In one healthy subject a persistent loss occurred of 20 dB at 14 kHz in one ear. In all malaria patients severe hearing losses and adverse effects related to ototoxicity were documented, but all the audiograms had returned to normal after 1 week and side effects disappeared. This study has shown that ototoxicity induced by quinine is almost completely reversible in healthy volunteers and in malaria patients.

An unexpected guest in follicular fluid.

Parasitic infection as the only or concomitant cause of infertility in Caucasian women is rare. A parasitic infection may also present itself quite unexpectedly as a coincidental finding as shown with this case report. Moving microfilariae of Mansonella perstans were found in the aspirated follicular fluid of a patient who underwent in-vitro fertilization (IVF) with embryo transfer because of tubal pathology due to Chlamydia trachomatis. The patient also appeared to have a Schistosoma infection. To our knowledge, the presence of parasites in follicular fluid has never been reported before. We expect that infertility physicians may be confronted with parasitic infections more often, not only in patients originating from tropical countries but also in Western women as a result of a tendency to travel more frequently to exotic and (sub)tropical countries.

Viro-immunological studies in acute HIV-1 infection.

OBJECTIVE: To monitor a patient who presented with symptomatic HIV-1 infection for virological and immunological parameters in relation to the clinical course. METHODS: Virological studies included determination of frequency of productively HIV-1-infected peripheral blood mononuclear cells (PBMC) and viral RNA load in plasma and p24 antigenaemia. Immunological studies included the analysis of T-cell subsets, the expression of activation markers, CD45RO and CD45RA antigens, the frequency of cells programmed for death, and T-cell function. RESULTS: During the first week post onset of primary HIV-1 infection symptoms high plasma titres of p24 and HIV-1 RNA were observed. The number of productively HIV-1-infected PBMC peaked, coinciding with CD4+ T lymphocytopaenia, during week 2 when clinical improvement started. CD8+ T lymphocytosis was observed 10 days post onset of clinical symptoms, the expanded cell population being of the CD8+CD38+, CD8+CD27+ and CD8+CD28- phenotype. CD8+ T lymphocytosis was paralleled by a high percentage of cells undergoing programmed cell death on in vitro culture. In vitro T-cell function was severely depressed during the first 10 days post onset of clinical symptoms. Within about 3 weeks, following resolution of clinical symptoms, phytohaemagglutinin-induced proliferation was restored to normal levels while responses to the CD3 monoclonal antibody only showed a partial restoration. During follow-up, concomitant with the rise of activated CD8+ T cells, p24 antigen levels and viral RNA load in serum as well as the number of HIV-producing PBMC steeply declined after 2 weeks. CONCLUSION: These findings demonstrate HIV-1-induced abnormalities during severe clinical symptoms of primary HIV-1 infection. The subsequent strong immune response, which is believed to be responsible for efficient control of viral replication, appears to precede clinical improvement.

[Exogenous reinfection with Mycobacterium tuberculosis caused by nosocomial transmission by a patient with AIDS]. / Exogene reïnfectie met Mycobacterium tuberculosis door nosocomiale transmissie bij een patiënt met AIDS.

A 55-year-old AIDS patient relapsed with tuberculosis as a result of exogenous reinfection, 1.5 years after a prior diagnosis of tuberculosis, for which he had been treated. He was reinfected after exposure to another AIDS patient, a 25-year-old man with tuberculosis, when they were hospitalized together during 5 days. The diagnosis of tuberculosis in the latter patient was delayed because the clinical picture was obscured by another infection. Reinfection and nosocomial transmission were demonstrated by analysis of the restriction-fragment-length polymorphism patterns on serial isolates of Mycobacterium tuberculosis. Increased alertness to tuberculosis, especially among HIV-infected persons, and implementation of effective infection control precautions are important in the prevention of nosocomial transmission.

Human immunodeficiency virus exanthem.

The human immunodeficiency virus (HIV) exanthem can be the primary manifestation of HIV infection. We report three cases of an exanthematous skin eruption associated with acute HIV infection. HIV antigen (p24 core antigen) was present, whereas results of the HIV antibody test were negative.