Search

Summary Objectives Staphylococcus aureus skin and soft tissue infection (Sa-SSTI) places a significant burden on healthcare systems. New Zealand has a high incidence of Sa-SSTI, and here most morbidity is caused by a polyclonal methicillin-susceptible (MSSA) bacterial population. However, MSSA also colonise asymptomatically the cornified epithelia of approximately 20% of the population, and their divide between commensalism and pathogenicity is poorly understood. We aimed to see whether MSSA are genetically differentiated across colonisation and SSTI; and given the close interactions between people and pets, whether strains isolated from pets differ from human strains. Methods We compared the genomes of contemporaneous colonisation and clinical MSSA isolates obtained in New Zealand from humans and pets. Results Core and accessory genome comparisons revealed a homogeneous bacterial population across colonisation, disease, humans, and pets. The rate of MSSA colonisation in dogs was comparatively low (5.4%). Conclusions In New Zealand, most Sa-SSTI morbidity is caused by a random sample of the colonising MSSA population, consistent with the opportunistic infection model rather than the paradigm distinguishing strains according to their pathogenicity. Thus, studies of the factors determining colonisation and immune-escape may be more beneficial than comparative virulence studies. Contact with house-hold pets may pose low zoonotic risk.

Summary Objectives To describe the demographics, clinical manifestations, treatment, and outcomes of patients with pulmonary alveolar proteinosis (PAP) who developed an opportunistic infection with Nocardia spp., mycobacteria or fungal pathogens. Methods A case of PAP and Nocardia spp. brain abscess is described. A comprehensive review of the English-language literature was conducted to identify all reported cases of PAP and opportunistic infections between 1950 and July, 2010. Results Seventy five cases were reviewed. Thirty two patients (43%) had nocardial infection, 28 (37%) mycobacterial infection, and 15 (20%) fungal infection. Thirty nine patients (65%) were male. Seventeen patients (23%) were immunosuppressed. Twenty patients (27%) were active smokers. PAP was the initial diagnosis in 19 patients (33%), while infection presented first in 23 patients (40%); 16 patients (27%) had a concurrent diagnosis of PAP and infection. The average interval between PAP diagnosis and an opportunistic infection was 16 months. Lungs were the most common site of infection; extra-pulmonary infection was present in 27 patients (32%). Thirty nine patients (57%) survived through the follow-up period, while 31 died. Conclusions Opportunistic infections can either precede or follow a diagnosis of PAP. PAP should be considered in apparently immunocompetent patients who present with an opportunistic infection and diffuse alveolar infiltrates.

Summary A 26-year-old woman was HIV-1 diagnosed at 11 weeks of pregnancy (CD4 = 7/mm 3 , HIV-1 RNA = 108,000 copies/mL) with immunity against toxoplasmosis ( Toxoplasma IgG = 1800 UI/mL). A fetal death was diagnosed 7 weeks after starting HAART (CD4 = 185/mm 3 , HIV-1 RNA = 391 copies/mL) with a positive Toxoplasma PCR on fetal tissues and amniotic fluid. The absence of severe toxoplasmic foetopathy, the very exaggerated and atypical placental inflammation and the immune restoration context led to the diagnosis of placental IRIS associated with Toxoplasma gondii reactivation. This outcome remains undescribed and could represent an issue in resource-limited settings where HIV-pregnant patients are often severely immunodeficient and infected with opportunistic pathogens.

Mucormycosis is a potentially fatal, rapidly destructive, opportunistic infection often seen in immunocompromsied individuals and patients with diabetes mellitus. We describe two patients with rhino-orbital mucormycosis caused by Rhizopus oryzae who received posaconazole within 7 days of diagnosis and in whom cure was achieved in conjunction with extensive surgical resection of diseased tissue. Posaconazole was well-tolerated. Our experience indicates that this new extended-spectrum azole antifungal agent can be used early in the course of zygomycete infection with good results.

Summary Objectives Pneumocystis pneumonia (PCP) is a severe opportunistic infection in immunosuppressed patients, caused by Pneumocystis jiroveci . The incidence among HIV negative patients is considered to have increased during the last decade. Methods We collected data retrospectively from the cases with PCP diagnosed at Sahlgrenska University Hospital between January 1991 and December 2001. Results 118 episodes of PCP were registered in 108 patients. The most common underlying immunosuppressions were HIV and solid organ transplantation with 29 and 26 cases, respectively. The number of PCP cases did not increase during the study period. Out of the 118 episodes of PCP 89 (75%) were in patients not infected with HIV. No clusters were found among HIV positive patients. We found 5 smaller clusters among non-HIV patients. Among the cases with proven PCP, 17% were on prophylaxis: 30% of the HIV infected patients and 13% of the non-HIV patients. Conclusions •The number of PCP cases is not increasing, •75% of the patients are HIV negative, •Only 17% of the patients were on prophylaxis before the episode of PCP, indicating that not all patients at risk are identified.

Tuberculosis is the most common opportunistic infection in HIV-infected people living in developing countries and is believed to accelerate the progression of HIV disease. This effect may be mediated by increased immune activation. We measured levels of CD4 and CD8 T-lymphocyte activation and proliferation in control subjects, patients with HIV alone, TB alone and patients with HIV and TB co-infection. Our results indicate that TB (in the absence of HIV) increases T-lymphocyte proliferation but its effects are modest in comparison with the stimulation induced by HIV infection alone.

Summary We present a rare case of hemophagocytic lymphohistiocytosis (HLH) in a 70 year-old male patient with previously well-controlled HIV infection. We could confirm HLH in different organs post mortem. Since the diagnosis of HLH was delayed, the patient died despite initiation of chemotherapy. As cause for HLH, an EBV reactivation could be confirmed. In HIV infection, HLH may be the first HIV manifestation, often triggered by an opportunistic infection or immune reconstitution syndrome, but it is uncommon in the state of a well-controlled or aviremic HIV infection.

Objective: To further describe the clinical and epidemiological characteristics of Penicillium marneffei infection in human immunodeficiency virus (HIV) infected patients in India. Methods: In continuation of our earlier report of four autochthonous cases of P. marneffei infection in HIV infected patients from Manipur, a northeastern state of India, we studied additional 46 cases of penicilliosis marneffei from the same area over a period of 19 months (April 1998–October 1999). Clinical, microbiological features, and therapeutic responses were analyzed in 36 of the 46 patients as ten patients were lost to follow-up. Results: Of the 198 HIV positive patients attending the J. N. Medical Hospital, Imphal, Manipur state during the period mentioned, 46 (25%) had P. marneffei disseminated infection. Of the 36 patients analyzed 31 (86%) were intravenous drug abusers, 1 had multiple sex partners, and 3 females acquired HIV infection from their respective spouses. A 9-year-old child acquired HIV infection by vertical transmission. The common clinical symptoms included fever (97%), weight loss (100%), weakness (86%), anemia (86%), and characteristic skin lesions (81%). Presumptive diagnosis was made by microscopic examination of Wright's-stained smears of fine needle aspirated material from skin lesions and lymph nodes showing numerous intracellular and extracellular, oval, elongated, yeast-like cells dividing by fission. The etiologic agent P. marneffei was isolated in culture from clinical materials in 10 cases when isolation was attempted. All patients were treated with oral itraconazole. All, except one patient, responded favorably to treatment within 7 days. Conclusion: Thus, the present cases further confirm the endemicity of penicilliosis marneffei in Manipur and resemble the epidemiology and clinical course of patients from other parts of south-east Asia.

To identify the sources of disseminated Mycobacterium avium complex (MAC) infection in AIDS.HIV positive subjects with CD4 counts100/mm(3) in Atlanta, Boston, New Hampshire and Finland were entered in a prospective cohort study. Subjects were interviewed about potential MAC exposures, had phlebotomy performed for determination of antibody to mycobacterial lipoarabinomannin and for culture. Patient-directed water samples were collected from places of residence, work and recreation. Patients were followed for the development of disseminated MAC. Univariate and multivariate risk factors for MAC were analyzed.Disseminated MAC was identified in 31 (9%) subjects. Significant risks in univariate analysis included prior Pneumocystis carinii pneumonia (PCP) (hazard ratio 1.821), consumption of spring water (4.909), consumption of raw seafood (34.3), gastrointestinal endoscopy (2.894), and showering outside the home (0.388). PCP, showering and endoscopy remained significant in a Cox proportional hazards model. There was no association between M. avium colonization of home water and risk of MAC. In patients with CD425, median OD antibody levels to lipoarabinomannin at baseline were 0.054 among patients who did not develop MAC and 0.021 among patients who did develop MAC (P=0.077).MAC infection results from diverse and likely undetectable environmental and nosocomial exposures. Mycobacterial infection before HIV infection may confer protection against disseminated MAC in advanced AIDS.

Patients with primary antibody deficiency (PAD) are prone to mycoplasma infection with unusual strains which may be resistant to conventional antibiotics. Mycoplasmas were isolated from the joint fluid (Ureaplasma urealyticum) of two PAD patients with arthritis and from the cerebral spinal fluid (Mycoplasma maculosum) in one with meningitis, the latter probably originating from the patient's dog. Combinations of doxycycline and quinolones or macrolides failed to clear the infections, but after demonstrating in-vitro sensitivity to the pleuromutilin, Econor, for two of the isolates, all three patients responded to oral treatment with Econor. The infection was completely eradicated in two patients, with the emergence of a resistant strain in the third. Mycoplasma infection should be considered in PAD patients with unexplained sepsis. Pleuromutilins such as Econor are powerful new anti-mycoplasmal agents which provide an additional therapeutic option when patients fail to respond to conventional antibiotics.

Objectives :To quantify the progressive impact of combination antiretroviral therapy (ART) on the incidence of AIDS-defining illnesses (ADIs) over a 9-year period. Methods : Retrospective cohort study. Eligible patients were 1538 AIDS-free, HIV-1-positive patients attending a large HIV clinic in west London who were at risk of developing AIDS because their CD4 count had declined to O350e10 6 /1 cells during the period 1 January 1990 and 31 December 1998. Incidence rates for the 12 most frequent ADIs were compared for two time periods, 1990–1995 (pre-HAART) and 1996–1998 (post-HAART), using Poisson regression methods. Multivariate Poisson regression models were used to examine the contribution of ART and HAART to any observed temporal trends in incidence rates. Results : After a median follow-up of 35 months, 450 (29%) patients had developed AIDS. Between the two time periods there was a significant decrease in the incidence of Pneumocystis carinii pneumonia (PCP) by 35% (4.11 per 100 person-years in 1990–1995 vs. 2.67 in 1996–1998; P = 0.007), Kaposi's sarcoma by 34% (3.27 vs. 2.17; P = 0.022) and cryptosporidiosis by 60% (0.76 vs. 0.31; P = 0.029). A non-significant reduction in incidence was observed for cryptococcosis by 45% (0.81 vs. 0.45; P = 0.11), oesophageal candidiasis by 29% (3.34 vs. 2.39; P = 0.053) and mycobacterium avium complex by 18% (1.58 vs. 1.29; P = 0.4), and a non-significant increase was observed for tuberculosis by 17% (0.62 vs. 0.73; P = 0.66) and non-Hodgkins lymphoma (NHL) by 51% (0.43 vs. 0.65; P = 0.31). The incidence of cerebral toxoplasmosis, cytomegalovirus, recurrent bacterial chest infections and dementia remained stable. There was a clear stepwise reduction in the incidence of PCP, Kaposi's sarcoma and cryptosporidiosis with the use of non-H AART and HAART regimens relative to no ART. In a multivariate analysis, the use of ART and HAART explained the progressive decrease in incidence of PCP and Kaposi's sarcoma. Conclusions :The incidence of most ADIs has decreased over the last 9 years. The striking reduction in the inci-dence of PCP and Kaposi's sarcoma since 1996 can be attributed to the use of combination ART and particularly HAART. The non-significant increase in the incidence of NHL and tuberculosis needs confirmation in other patient cohorts.

Objective: To assess the role of Flavobacterium spp. infection in patients with HIV disease. Methods: Clinical charts of 2412 consecutive HIV-infected patients hospitalized in a 8-year period were retrospectively reviewed, to identify all cases of Flavobacterium spp. infections, and to evaluate their occurrence and outcome according to several epidemiological, clinical, and laboratory parameters. Results: Six patients out of 2412 (0.25%,), developed Flavobacterium spp. complications: septicaeama in five cases, and pneumonia in the remaining patient, with F. meningosepticum and F. odoratum isolated in two cases and one case, respectively, and unnamed Flavobacterium spp. organisms in the remaining three cases. Flavobacterium spp. organisms were responsible for six out of 1939 overall episodes of non-mycobacterial bacterial diseases observed in our patient group (0.31%). All patients were severely immunocompromised, showing a prior diagnosis of AIDS, a mean CD4+ lymphocyte count of 64.2 (range 12–187) cells/μl, and a mean neutrophil count of 1.143 (range 700–1600) cells (range 700–1600) cells/μl. Antibiotic, corticosteriod, or cotrimoxazole treatment was carried out during the month preceding disease onset by three, two and five patients, respectively Community-acquired and nosocomial Flavobacterium spp. disease were equally frequent, but the latter occurred with a significantly lower mean neutrophil and CD4+ cell count. Antimicrobial susceptibility assays showed complete sensitivity to ciprofloxacin, and variable resistance to ureidopenicillins, ceftazidirne, imipenem, aztreonam, and aminoglycosides. An appropriate antimicrobial regimen obtained clinical and microbiological cure in all cases, in absence of related mortality or relapses. Conclusions: Since only one episode of HIV-associated F. (Sphingobacterium) multivorum complication has been described to date, our series represents the largest one dealing with Flavobacterium spp. infection in the setting of HIV disease. Our experience suggests that Flavobacterium spp. organisms may play a pathogenic role in patients with advanced HIV disease, even when some commonly recognized risk factors are lacking (i.e. indwelling catheters, instrumentation, IV drug abuse), while a very love CD4+ lymphocyte count, leukopaenia-neutropaenia, and concurrent AIDS-related infectious complications may act as important predisposing factors. In view of the infrequent occurrence of these infections, early suspicion is essential for both clinicians and microbiologists facing immunocompromised patients at risk for invasive bacterial complications. Flavobacterium spp. organisms should be taken into consideration as nosocomial- or community-acquired opportunistic pathogens, due to their relationship with advanced immunodeficiency and their elevated resistance to many antimicrobial agents commonly used against Cram-negative bacterial pathogens.

Objectives : (1) To determine the incidence and outcome of Pseudornonas aeruginosa infection in HIV-infected patients. (2) To study the antimicrobial susceptibility of P aeruginosa isolates in this particular population. (3) To identify risk factors for these infections. Patients and Methods : a retrospective case-control study performed in a 28-bed infectious-diseases unit in a 940-bed university hospital. All cases were defined as HIV-infected patients with severe infections due to P aeruginosa , including bacteriemia, lower or upper respiratory tract infections, infections related to a central venous catheter, and cutaneous/muscular infection. Each case was matched with an HIV-seropositive control not infected by P. aeruginosa and hospitalized on the same dates as the cases. Results : one thousand and thirty-five HIV-infected patients were hospitalized during the study period. A first severe P. aeruginosa infection was documented in 41 patients, giving an overall annual incidence note of 2.51 episodes per 100 admissions. Forty of the 41 case notes were available for analysis. They consisted of 17 cases of bacteraemia, four upper respiratory tract infections, 10 lower respiratory tract infections, three catheter-related infections, and six cutaneous/muscular infections. Of these 40 cases, 60% were nosocomial and the remainder were community-acquired. The overall mortality rate was 22% (47% in bacteraemic forms). Twenty five percent of patients relapsed after an average of 37 days. The case-control comparison showed that AIDS was more frequent among the cases (92% vs. 74%, P = 0.04 ), who also had a lower PN count ( P = 0.005 ), and a lower CD4 cell count (15.7 ± 18.8/mm 3 vs. 115 ± 211/mm 3 ; P = 0.0007 ). The number of days spent in hospital in the previous 3 months (29.3 ± 20.7 vs. 19.7 ± 14, P = 0.04) was significantly higher among the cases. In a multivariate analysis, examining treatments received in the previous month, only co-trimoxazole [OR = 5.5 (1.1-26.9)], penicillins [OR = 5.2 (1.1-25.3)], steroids [OR = 5.5, (1.2-25.5)] and a CD4 cell count below 50/mm 3 [OR = 13.2 (1.4-129.4)] were identified as risk factors. Conclusion : P. aeruginosa infection is a not frequent bacterial disease in highly immunodeficient HIV-infected patients. It is frequently fatal and must be borne in mind in the advanced stages of HIV disease, especially when patients have received co-trimoxazole (trianthoprim-sulphametboxazole), penicillins or steroids.

Two cases of opportunistic cerebral infections in HIV-negative cancer patients due to chemotherapy induced immunosuppression are reported. A 61-year-old patient with low grade lymphoma (immunocytoma as referred to the Kiel classification) developed stereotactical biopsy proven toxoplasmic encephalitis 6 months after initiation of fludarabine treatment. The lymphoma had been diagnosed 8 years earlier and had been treated with several different regimens. In the second case, a 55-year-old patient developed neurological symptoms while in complete remission from acute T-cell leukaemia. The patient had been treated with a multidrug chemotherapy regimen including radiotherapy of the brain and intrathecal chemotherapy. When toxoplasmic encephalitis was bioptically diagnosed the patient was on maintenance chemotherapy with methotrexate and mercaptopurine for 12 months. The patients' characteristics and outcome are reported and the potential pathogenesis is discussed.

We report a case of fungal endocarditis due to Aspergillus terreus in a leukaemia patient who received a bone marrow allograft from a matched unrelated donor. He presented with persistent fever, microangiopathic haemolytic anaemia but there was no cardiac signs and symptoms. He died despite intravenous amphotericin B. Review of the English literature showed five other patients with fungal endocarditis in the setting of bone marrow transplantation and revealed the same features of difficult diagnosis and poor outcome.

We report a hypogammaglobulinemic patient who developed chronic polyarthritis and osteomyelitis due to Ureaplasma urealyticum. He also had mitral valve endocarditis of uncertain origin. Patients with primary antibody deficiency show increased susceptibility to mycoplasma infections. Early diagnosis and treatment is very important in order to prevent potentially debilitating complications.

From December 1993 until January 1996 we observed 10 cases of invasive aspergillosis in a cohort of 140 patients with AIDS (7%). By contrast, no invasive aspergillosis was diagnosed in a cohort of 278 patients with AIDS between 1986 until 1993.Case controls were assigned randomly to each patient with invasive aspergillosis from the total pool of HIV-infected patients. Patients with invasive aspergillosis were studied retrospectively by matched-pairs analysis with respect to risk factors, radiological, microbiological and autopsy findings.Patients with aspergillosis had more AIDS-defining events (3.5 [2-5] vs. 2 [2-3], median [range], P0.05) and a longer median survival time with full-blown AIDS (31.5 [14-45] months vs. 20.5 [5-32] months, P0.005) than their case controls. Patients with invasive aspergillosis tended to have lower white blood cell counts and exhibited significantly decreased median CD4 counts (7 [0-44]/mm3 vs. 27 [8-57]/mm3, P0.05).Due to better management of opportunistic diseases and improved antiretroviral therapy, the lifespan of patients with full blown AIDS is prolonged. Patients who have survived four or more AIDS-defining events are at risk for invasive aspergillosis. This risk is associated with low white blood cell counts and CD4 cell counts.

Aims of the study a retrospective study was designed to evaluate efficacy and tolerance of trimethoprim-sulphamethoxazole (MTP-SMZ) in AIDS patients with cerebral toxoplasmosis (TE). Patients and methods we reviewed 471 patients with AIDS, and we analysed 71 AIDS patients with TE, who received intravenous therapy with TMP-SMZ (TMP: 10 mg/kg/day, SMZ: 50 mg/kg/day, SMZ: 50 mg/kg/day) for 4 weeks. Results 35 patients (49.2%) had a complete regression of clinical signs, and a complete resolution of radiological lesions was noted in 41 patients (57.7%). Improvement of clinical signs and radiological lesions were observed in 27 patients (38%), and in nine patients (12.6%), respectively. In contrast, nine patients (12.6%) did not show any clinical change, or worsened. Twenty-two patients (30.9%) suffered from adverse cutaneous reactions, whereas many patients had haematological toxicity. Conclusions TMP-SMZ seems to be an efficient therapy for TE in AIDS patients, allthough further prospective, randomized therapeutic trials are required to confirm these results.

Visceral leishmaniasis (VL) is a well recognized opportunistic infection in patients with HIV-1 infection, which may occasionally present with atypical features. We describe two patients with advanced HIV-1 infection (CD4100/ mm3) in whom visceral leishmaniasis presented with atypical features, and their response to therapy. Atypical features of visceral leishmaniasis in the two infected patients include absence of fever, dissemination to the duodenal mucosa and to the skin as xanthoma-like lesions. Therapy and secondary prophylaxis remain unsatisfactory, and studies to evaluate combinations of amphotericin B and immunotherapy are needed.

There are conflicting reports concerning the prevalence of Mycoplasma fermentans in HIV-positive patients and its association with AIDS. Serum antibodies to M. fermentans were measured by a modified immunoblotting technique in 48 HIV-positive heterosexual patients and in 30 HIV-negative heterosexual controls. Antibodies to M. fermentans were detected in 19 (40%) of HIV-positive patients and in three (10%) of the HIV-negative controls ( P =0.01). The prevalence of antibodies to Mycoplasma hominis and to Ureaplasma urealyticum was similar in both groups. In the HIV-positive group, 16/19 (84%) M. fermentans -positive patients developed AIDS, compared to eight of 29 (28%) M. fermentans -negative patients ( P =0.0004). The HIV-positive patients with antibodies to M. fermentans had a lower CD4+ cell count and a higher prevalence of antibodies to the other mycoplasma tested ( P =0.007 and P =0.03, respectively), as compared to the patients without antibodies to M. fermentans . These findings may suggest that the presence of antibodies to M. fermentans indicate an opportunistic infection. Of the 19 M. fermentans -positive patients, 11 were positive on the first examination, and eight became positive during the follow-up period. Seven out of these eight patients developed antibodies to M. fermentans before the development of AIDS. Therefore, the possibility exists that M. fermentans might influence the development of AIDS.

Cutaneous lesions attributed to Leishmania are very seldom observed in classic Kala-Azar, but recently some reports have mentioned them in patients with HIV infection. We found cutaneous lesions whose biopsy disclosed the presence of Leishmania organisms in six patients of a group of 32 HIV patients with visceral Leishmaniasis. These lesions did not present a uniform or specific appearance, even though they tended to localize symmetrically on acral zones. They consisted of erythematous papules and hypopigmented macules on the dorsa of the hands, feet, and elbows; small subcutaneous nodules on the thighs; and erythematoviolaceous, scaly plaques on the face. These lesions accompanied in every case the other symptoms and/or signs of visceral leishmaniasis, responded to anti-leishmanial treatment, and were sometimes the first indicator of recurrence. The histopathological study was non-specific, but showed in every case the presence of abundant amastigotes within the dermal histiocytes and free in the dermis or subcutaneous tissue. Data from literature review are similar to ours.

The changes in the oral streptococcal flora of twenty children undergoing allogeneic bone marrow transplant are described. Saliva was collected from each child on four separate occasions: (i) before the conditioning regimen; (ii) 7 days post-transplantation; (iii) when the neutrophil count had risen above 0.5 x 10(9)/l; (iv) 119 days post-transplantation. Indices for dental caries, plaque, gingivitis, herpetic stomatitis and mucositis were also recorded. There was a significant decrease in the total aerobic (P0.001) and anaerobic counts (P0.0002) between baseline and 7 days post-transplantation. The proportion of the 'Streptococcus oralis group' (Streptococcus mitis and S. oralis) increased significantly from baseline 12.1% to 48.4% at 7 days post-transplantation (P0.003). The plaque and gingivitis indices increased significantly from baseline to 7 days post-transplantation (P0.001). Twenty percent of the children had either positive blood cultures or Hickman line cultures for the 'S. oralis group', and it is possible that the inflamed gingival tissues are a further site of entry for these streptococci. There were no differences in the total anaerobic counts or the proportion of the 'S. oralis group' between baseline and the end of the study in the transplant children, or between the transplant and control children.

Acute inflammatory polyradiculitis represents an uncommon peripheral nerve complication during HIV infection. The case of an HIV-seropositive patient who was admitted to hospital for a cauda equina syndrome is reported. Despite early application of anticytomegalic medication, a cytomegalovrirus (CMV) infection spread out to the central nervous system (CNS), causing the patient's death. A post-mortem examination confirmed the diagnosis of CMV-encephalomyelomeningoradiculitis. To the authors' knowledge, such a progress of a CMV-related polyradiculitis to an encephalomyelomeningoradiculitis has not yet been described. The clinical features of this case will aid in the recognition of CMV-related neurological complications, and may permit earlier and perhaps more successful treatment.

We report nine cases of haemophagocytic syndrome (HS) in patients with human immunodeficiency virus infection, and review the 17 cases described to date in the literature. In 21 of 26 cases, HS developed during an advanced stage of immunodeficiency. Clinical and haematological signs are not specific in this setting, and the diagnosis relies on histological features, mainly bone marrow examination. An opportunistic infection was associated in three cases and a lymphoid malignancy in two of our nine cases. The role of the human immunodeficiency virus in the occurrence of the HS remains to be defined. The overall prognosis is poor as six of our nine patients died within 12 months of presentation.

The aim of this retrospective study was to investigate the clinical significance of cytomegalovirus (CMV) viraemia in HIV-infected subjects (with or without AIDS) who had attended this hospital during a 45 month period. They were reviewed regularly and, when clinically indicated, tested for CMV viraemia. The blood of 105 subjects was cultured for CMV and 34 had at least one episode of CMV viraemia during the review period. The viraemia was present during CMV disease in nine of the 34 positive patients and was the only detectable infection in another two. In the remaining 23 patients, CMV viraemia occurred in association with intercurrent opportunistic infection. Among these 23 patients, the viraemia resolved in 12 after treatment (or natural resolution) of the intercurrent infection and only one of these 12 developed CMV disease (mean review period: 8 months). In another seven patients, CMV viraemia persisted despite treatment (or natural resolution) of the intercurrent infection and four subsequently developed CMV disease (mean review period: 4 months) (P = 0.08, Fisher's exact test). From the remaining four patients, no specimens for CMV culture were obtained after treatment of the intercurrent infection. The CD4 count was higher in the 12 patients in whom there was resolution of the viraemia [mean CD4 60 x 10(6)/l] compared with the seven in whom the viraemia persisted [mean CD4 45 x 10(6)/l]. These findings suggest that in some HIV-positive patients, CMV viraemia was potentiated by intercurrent infection with another micro-organism and that its treatment was sufficient to mitigate the CMV disease.

Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule that is primarily involved in cell to cell adhesive interactions of the immune system. Concentrations of soluble ICAM-1 (s-ICAM-1) shed into the circulation were measured by a quantitative ELISA in HIV-infected persons without AIDS, patients with AIDS with or without evidence of acute opportunistic infection at the time of sampling, and HIV-seronegative patients with toxoplasmosis, community-acquired pneumonia, leishmaniasis and rickettsial infections. Patients were classified on the basis of clinical condition and CD4+ T-cell counts according to the 1993 revised HIV classification of the USA Centers for Disease Control. Concentrations of s-ICAM-1 in the serum of HIV-infected persons without AIDS-indicator conditions (categories A1, A2, B1 and B2) as well as in the serum of patients with AIDS (categories A3, B3, C1, C2 and C3) were significantly higher than normal (mean +/- S.E.M. 469 +/- 23, n = 60 and 780 +/- 73, n = 56, respectively, versus 329 +/- 15 ng/ml, P0.0001 and0.0001 respectively) and differed also significantly from each other (P0.0001). Raised concentrations of s-ICAM-1 in the serum of afebrile patients with AIDS but without acute opportunistic infection at the time of sampling (mean +/- S.E.M. 672 +/- 76, n = 29) did not differ from those of the remaining patients with AIDS or from those of HIV-seronegative patients with the infections studied. A steady and significant increase of serum concentrations of s-ICAM-1 with progress of disease according to clinical category (categories A--B--C, p = 0.0007) as well as with the loss of circulating CD4+ T-cells (categories 1--2--3, p = 0.009) was observed. Individual serum concentrations of s-ICAM-1 showed negative correlations with individual total lymphocyte (P = 0.004), CD4+ T-cell (P = 0.05), CD8+ T-cell counts (P = 0.03) as well as positive correlation with serum concentrations of soluble interleukin-2 receptors (P0.0001), an indirect marker of progress of HIV-related disease. Serum concentrations of s-ICAM-1 did not differ between patients with AIDS who were receiving or not receiving zidovudine at the time of sampling. A longitudinal survey is needed in order to determine whether measuring serum concentrations of s-ICAM-1, although not specific, has any predictive or prognostic value in these patients as well as whether this bioactive molecule has any pathogenetic role in the progress of disease in HIV infection.

Summary The acquired immunodeficiency syndrome (AIDS) appears to alter the course of syphilis and particularly neurosyphilis. We report the case of an HIV-positive patient with two CNS lesions due to vascular complications of neurosyphilis of the meningovascular type, 18 months after he had developed a penile chancre. On admission, CT scans were inconsistent with cerebral toxoplasmosis or CNS lymphoma. At necropsy, histopathological examination showed typical Heubner's endarteritis of the basilar and posterior cerebral arteries. In AIDS patients, superadded meningovascular syphilis must be suspected, especially when CT scanning reveals the presence of multi-focal, low density lesions with the particular characteristics of infarction.

Toxoplasmosis may cause significant damage to the developing fetus and is a life-threatening opportunistic infection in immunocompromised persons. Serological investigation is unreliable, while isolation of the parasite is time consuming and may lack sensitivity. We have developed a system for detecting Toxoplasma gondii based on the amplification of the P30 gene using sequential rounds of PCR and nested primers. The clinical value of this technique was assessed by the investigation of a range of tissues taken from pregnant women, fetuses, neonates, AIDS patients and organ graft recipients. The PCR assay produced more positive reactions than isolation of the parasite by means of cell culture or animal inoculation. Extended autoradiography was found to be more sensitive than stained agarose gels for detecting the PCR product. Systematic contamination of PCR reactions was avoided but it was not possible to exclude sporadic contamination in certain cases. Detection of specific DNA is of clinical value in the investigation of the pregnant woman in order to assess the risk of transplacental passage of infection and in the fetus and neonate to identify congenital toxoplasmosis. Even so, PCR findings must be interpreted with caution because of the risk of a sample being contaminated. PCR may be the investigation of choice when brain biopsy is performed on a patient with AIDS and when toxoplasmosis associated with bone marrow transplantation is suspected.

Objectives: To describe the bone marrow lesions in eight cases of Cryptococcus neoformans infection involving the bone marrow in HIV-infected patients. Methods: Archival bone marrow biopsies from patients with HIV-related cryptococcosis of the bone marrow were retrospectively reviewed. Cryptocococcal organisms were identified on haematoxylin- and eosin-stained slides and confirmed using mucicarmine staining. Results: Yeast cells stimulated a granulomatous response in all cases despite immunosuppression. The number of cryptococcal organisms appeared to be inversely proportional to the adequacy of the granulomatous response. All patients had a cytopenia. Conclusions: The ability to mount a tissue response in order to localize organisms is retained in patients with AIDS. Infection of the bone marrow with cryptococci may act in synergy with HIV to cause cytopenia.

Falciparum malaria can cause immune suppression sufficient to allow opportunistic infection during the recovery phase. A patient is described who died from a disseminated infection with Aspergillus flavus and Absidia corymbifera, unresponsive to treatment with amphotericin and voriconazole.

A renal transplant recipient with necrotizing fasciitis due to Pseudomonas aeruginosa is presented. Only three other cases of necrotizing fasciitis due to this organism have been found in the literature. This is the first case of P. aeruginosa necrotizing fasciitis in a renal transplant patient to be reported. Prompt diagnosis, enabling treatment with appropriate antibiotics and early surgical intervention, was the key factor in his recovery.

We report two cases of cryptococcosis in patients with Waldenstrom's macroglobulinaemia and chronic lymphocytic leukaemia that responded to prolonged therapy with systemic amphotericin and flucytosine. Cryptococcosis, although more common in those with impaired cell mediated immunity, should also be considered as a complication in patients with impaired antibody responses.

We describe what is to our knowledge the first reported case of disseminated infection due to Cylindrocarpon. The presumed source was athlete's foot, a condition with which this fungus has previously been associated. Diagnosis was made by needle aspiration of a cutaneous lesion. Radiographic evidence of pulmonary involvement was present. The infection resolved following marrow regeneration and treatment with amphotericin B. Correct identification of Cylindrocarpon may be useful in guiding antifungal therapy.

We present a patient with AIDS and toxoplasma encephalitis who was unable to tolerate established therapy with sulphadiazine or clindamycin but responded to oral azithromycin and pyrimethamine. The patient was maintained on oral azithromycin but subsequently relapsed after 8 months. The recurrence was successfully treated with intravenous azithromycin. The case illustrates that azithromycin can be used to treat patients with toxoplasma encephalitis who are unable to tolerate or fail to respond to other therapeutic agents. Failure of oral azithromycin may be due to inadequate tissue concentrations and patients may further benefit from intravenous administration.

Microsporidiosis is a common finding in HIV-infected patients who have diarrhoea. The species most commonly causing gastrointestinal disease is Enterocytozoon bieneusi. Recently Septata intestinalis has been described as a cause of diarrhoea and disseminated infection in patients with AIDS. A 44-year-old homosexual man with severe immunodeficiency (CD4 cell count 40/microliters) had a history of watery diarrhoea for 2 weeks. Microsporidian spores measuring 1.2 to 1.5 x 2.5 to 3.0 microns were found in stool samples. Electron microscopy of duodenal biopsies confirmed the diagnosis of intestinal microsporidiosis and showed parasitophorous vacuoles with the typical ultrastructure of S. intestinalis. The patient was treated with albendazole (400 mg twice daily) and became asymptomatic within 4 days. No spores could be detected in stool samples after a treatment period of 14 days. About 25 infections with S. intestinalis have been reported to date, and the case presented here is the first in a German patient.

Hypercalcaemia may complicate granulomatous diseases, such as tuberculosis and sarcoidosis, and various AIDS-related opportunistic infections and malignancies. We report here two patients with AIDS and disseminated Mycobacterium avium infection who developed symptomatic hypercalcaemia several weeks after commencing antimycobacterial chemotherapy, and in whom inappropriately elevated 1,25(OH)(2)D(3)levels were documented. Although vitamin D supplementation may have contributed, no other cause for the hypercalcaemia was found. The biochemical and clinical similarities between these cases and other hypercalcaemic granulomatous diseases suggest a common mechanism related to macrophage activation and dysregulated vitamin D production.

We describe an unusual case of bacillary angiomatosis first misdiagnosed as Kaposi's sarcoma in muscle in a patient with HIV infection.

Fibreoptic bronchoscopy was performed in 43 of 52 consecutive patients with opportunistic pneumonia in the acquired immune deficiency syndrome (AIDS). The 15 patients in whom a likely pathogen was not found by bronchoscopy (including the nine not having the procedure) were treated for Pneumocystis carinii pneumonia (PCP) alone and all responded. In 11 of these a diagnosis of AIDS was confirmed because of an alternative opportunistic infection within 6 months. PCP was confirmed in 38 of the 52 patients and cytomegalovirus (CMV) was isolated from 15 patients. The lower the partial pressure of arterial oxygen (PaO2) on admission the more likely was a pathogen to be found by bronchoscopy. The admission PaO2 while the patient was breathing room air was the single most reliable prognostic indicator. The mean PaO2 for survivors was 9.6 kPa and 6.7 kPa for non-survivors (P less than 0.01 Student's t-test), with 50% mortality for patients with a PaO2 of less than 8 kPa on admission. Temperature and pulse rate were sensitive indicators of response to treatment, obviating the need for frequent arterial gas measurements and chest radiography. Our findings suggest that although fibreoptic bronchoscopy contributed little to the treatment and final outcome of the infection, it identified the causative pathogen in most patients.