Severe pulmonary haemorrhage syndrome in leptospirosis in a returning traveller.

Clinical presentation of leptospirosis ranges from asymptomatic infection to fulminant, life-threatening disease. Pulmonary involvement in terms of severe pulmonary haemorrhage syndrome (SPHS) has recently become a more frequently reported facet of leptospirosis and correlates with high mortality rates. It has not yet been described in returning German travellers. We present a case of a healthy young man developing massive pulmonary haemorrhage and severe ARDS requiring mechanical ventilation and high-dose catecholamines after travelling to Indonesia. Leptospirosis was verified by blood PCR as well as serology and treated with high-dose, intravenous penicillin. Outcome was favourable, the patient recovered completely. Leptospirosis and SPHS should be taken into account as an emerging infectious disease in patients with fever and lung involvement.

Virological failure after 1 year of first-line ART is not associated with HIV minority drug resistance in rural Cameroon .

OBJECTIVES: The aim of this study was to describe clinical and virological outcomes in therapy-naive HIV-1-positive patients treated in a routine ART programme in rural Cameroon. METHODS: In a prospective cohort, 300 consecutive patients starting first-line ART were enrolled and followed for 12 months. Among 238 patients with available viral load data at Month 12, logistic regression was used to analyse risk factors for virological failure (≥1000 HIV RNA copies/mL) including clinical, immunological and virological parameters, as well as data on drug adherence. Population sequencing was performed to detect the presence of drug-resistance mutations in patients with virological failure at Month 12; minority drug-resistance mutations at baseline were analysed using next-generation sequencing in these patients and matched controls. RESULTS: At Month 12, 38/238 (16%) patients experienced virological failure (≥1000 HIV RNA copies/mL). Patients with virological failure were younger, had lower CD4 cell counts and were more often WHO stage 3 or 4 at baseline. Sixty-three percent of patients with virological failure developed at least one drug-resistance mutation. The M184V (n = 18) and K103N (n = 10) mutations were most common. At baseline, 6/30 patients (20%) experiencing virological failure and 6/35 (17%) matched controls had evidence of minority drug-resistance mutations using next-generation sequencing (P = 0.77). Lower CD4 count at baseline (OR per 100 cells/mm(3) lower 1.41, 95% CI 1.02-1.96, P = 0.04) and poorer adherence (OR per 1% lower 1.05, 95% CI 1.02-1.08, P < 0.001) were associated with a higher risk of virological failure. Unavailability of ART at the treatment centre was the single most common cause for incomplete adherence. CONCLUSIONS: Virological failure after 1 year of ART was not associated with minority drug resistance at baseline but with incomplete adherence. Strategies to assure adherence and uninterrupted drug supplies are pivotal factors for therapy success.

Immune activation despite suppressive highly active antiretroviral therapy is associated with higher risk of viral blips in HIV-1-infected individuals.

OBJECTIVES: Viral blips are thought to represent random biological variations around a steady state of residual HIV viraemia and to lack clinical significance. We aimed to assess the association of immune activation and the occurrence of blips. METHODS: HIV-infected patients from our out-patient cohort who developed a blip after having been on fully suppressive highly active antiretroviral therapy (HAART) for at least 180 days were matched with patients without blips according to duration of complete viral suppression (CVS), age, sex and Centers for Disease Control and Prevention (CDC) stage. Frequencies of CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(+) HLA-DR(+), CD4(+) CD45RA(+), CD16(+) CD56(+) CD3(-) and CD19(+) cells, as well as C-reactive protein (CRP) levels and clinical parameters, were included in conditional logistic regression models. Adherence to HAART was assessed by measuring prescribed nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) plasma levels in a sample of 57 patients. RESULTS: Eighty-two patients with viral blip were matched with 82 controls from the same cohort. The mean age was 47.2 years [standard deviation (SD) 12.1 years], 80.5% of patients were male and 42.7% had CDC stage C disease. Viral blips occurred after a median of 14 months [interquartile range (IQR) 8-34 months] of CVS. In the logistic regression, activated CD3(+) HLA-DR(+) lymphocytes [odds ratio (OR) 1.25 per 100 cells/µL; 95% confidence interval (CI) 1.02-1.54; P = 0.03] were significantly associated with blips and there was a trend for an association of longer time on HAART with blips (OR 1.31 per year; 95% CI 0.96-1.78; P = 0.09). No between-group difference regarding subtherapeutic drug levels was found (P = 0.46). CONCLUSIONS: The occurrence of viral blips after suppressive HAART was associated with elevated markers of T-cell activation. Blips may identify a subset of patients with higher immune activation and increased risk for HIV disease progression.

High HIV prevalence among children presenting for general consultation in rural Cameroon.

Data on the HIV-prevalence children presenting to health care facilities in sub-Saharan Africa are scant in general, and the debate about opportunities for paediatric HIV screening is ongoing. Nine hundred and eighty-one children with unknown HIV-status presenting to a large general paediatric outpatient department in rural Cameroon were tested using the Determine HIV-1/2 rapid test (Abbott), and positive results were confirmed with the Hexagon HIV rapid test (Human Diagnostics). In children younger than 18 months, HIV infection was confirmed by PCR testing. Median age was 1.3 years and 52.8% were of male gender. In 514 children below 18 months of age, 16 (3.1%) tested positive. Of those, HIV-1 PCR was available for 11 children, of whom 6 had a positive PCR result. HIV prevalence was highest in the age group 5-9 years, being 8.8%. Malnutrition (33.3 vs 5.2%, p < 0.001) was associated with HIV infection. Our study results indicate that HIV testing should be offered to all children at possible entry points to medical care, irrespective of symptoms, in order to reduce HIV-associated mortality through timely initiation of antiretroviral therapy.

High prevalence of hepatitis B and syphilis co-infections among HIV patients initiating antiretroviral therapy in the north-west region of Cameroon.

Hepatitis B virus (HBV) and syphilis co-infections contribute significantly to HIV-associated morbidity and mortality, but the burden of these diseases is not fully appreciated in sub-Saharan Africa, as prevalence data are scarce. Both infections often remain undiagnosed in resource-limited settings because routine testing is not a part of most of the national guidelines. Epidemiological studies provide important information on prevalence and risk factors for such co-infections and can provide guidance for clinical management and for the development of test strategies. We analysed data on baseline characteristics, CD4 cell counts, HBV and syphilis co-infection rates of 690 patients enrolling for antiretroviral therapy in rural Cameroon. The prevalence of both hepatitis B surface antigen (HBsAg, 12.6%, 95% CI 10.1-15.1) and treponemal antibodies (11.4%, 95% CI 8.9-13.7) was high, with significantly higher prevalences for both infections in men; detection of treponemal antibodies increased with age. Although liver enzyme elevations were common, they were not useful to identify HBsAg-positive patients. In this setting, routine serological screening for HBV and syphilis co-infection should be considered to avoid complications and ongoing transmission.

Wireless capsule endoscopy for the detection of small bowel diseases in HIV-1-infected patients.

BACKGROUND AND AIMS: In HIV-infected patients, manifestations of the disease are common in the gastrointestinal tract. The objective of our study was to evaluate the diagnostic yield of the Given(R) Video Capsule System (Given Imaging, Yoqneam, Israel) in these patients. METHODS: After the exclusion of GI-tract stenosis by anamnestic exploration, 49 patients were included into the study. Stratification: Group A (n = 19): HIV-positive, CD4 cell count < 200/microl, gastrointestinal symptoms present. Group B: HIV-positive, CD subset4 < 200/microl, without gastrointestinal symptoms (n = 19 Group) C: healthy volunteers (n = 11). RESULTS: In group A there was a total of 30 pathological findings, 15 of which had therapeutic implications. In group B, there was a total of 22 pathological findings, 5 relevant for therapy. In group C there was a total of 13 pathological findings, 3 with therapeutic relevance. In 89% (group A) vs. 26% (group B), pathological findings were detected distal to the ligament of Treitz (p = 0.001). All capsules were recovered without any complication after 12 to 96 h from the stool. CONCLUSION: Wireless capsule endoscopy of the small intestine should be considered for HIV-infected patients with marked immunosuppression and gastrointestinal symptoms.

Evaluation of safety and efficacy of rosiglitazone in the treatment of HIV-associated lipodystrophy syndrome.

BACKGROUND: HIV-associated lipodystrophy syndrome (LDS) as a long-term side effect of HAART is becoming increasingly important and negatively affects adherence to medication. Currently, an effective therapy is not available. There is some evidence that the drug class of thiazolidindiones might be effective in the treatment of LDS. PATIENTS AND METHODS: Prospective open-label study with 20 HIV-infected patients suffering from severe LDS. Patients received 4 mg rosiglitazone once daily for a 24-week study period. Efficacy was assessed by measurement of metabolic and anthropometric parameters, total body DXA scan, CT scan of the abdomen, photo documentation and self-assessment. RESULTS: Rosiglitazone treatment was well tolerated. DXA scans demonstrated a highly significant increase in adipose tissue of the limbs (2644 +/- 1334 g vs 3380 +/- 1614 g, p < or = 0.001) without any change in total fat mass. Abdominal CT-scans revealed a significant increase in subcutaneous adipose tissue (113.7 +/- 82.4 cm(2) vs 125.3 +/- 83.7 cm(2), p = 0.04). Abdominal circumference decreased significantly (94.7 +/- 8.7 cm vs 92.2 +/- 8.45 cm, p = 0.03) without any relevant change of body weight or BMI. We observed an increase in serum cholesterol (248 vs 281 mg/dl, p = 0.006) and serum triglycerides (301 vs 351 mg/dl, p = 0.1). Furthermore, no side effects of clinical relevance were observed. The insulin sensitivity index improved without reaching statistical significance. Thirteen patients (65%) reported general improvement of LDS symptoms. Evaluation of photo documentation by five HIV-experts revealed poor concordance and no relevant change of LDS. CONCLUSIONS: The results of this study suggest that rosiglitazone is safe in the treatment of HAART-associated lipodystrophy and has moderate clinical efficacy. We found a trend towards improved insulin sensitivity and as a possible limiting factor an unfavorable increase in serum cholesterol and triglycerides.

Impact of rosiglitazone treatment on the bioavailability of antiretroviral compounds in HIV-positive patients.

OBJECTIVES: The insulin-sensitizer rosiglitazone is under investigation for therapy of HIV-associated lipodystrophy syndrome (LDS). Little is known about pharmacological interactions with antiretroviral (ARV) drugs. METHODS: Therapeutic drug monitoring (TDM) of ARV drugs was performed in a prospective study before and at day 28 after start of treatment with 4 mg of rosiglitazone for combined LDS. Drug levels were measured in the morning fasting, and 0.5, 1, 2, 4, 6 and 8 h after standardized drug intake. Values were log-transformed for analysis. RESULTS: Twelve males and six females were assessed; mean age was 50.7 years and mean CD4 cell count was 496 cells/mm(3). All patients had a viral load below 50 copies/mL, and backbone ARV therapy consisted of two or three nucleoside reverse transcriptase inhibitors in all cases. After administration of rosiglitazone, no significant differences in Cmax, Cmin and AUC were found in cases treated with efavirenz (n = 10) and lopinavir (n = 4). Mean Cmax of nevirapine (n = 4) was reduced significantly [-0.44; 95% confidence interval (CI) -0.86 to -0.01]. Furthermore, there was a consistent trend to a reduction in the geometric mean ratio (GMR) of Cmax, Cmin and AUC (GMR of Cmax 0.95; 95% CI 0.9-1.0; GMR of Cmin 0.89; 95% CI 0.65-1.13; GMR of AUC 0.96; 95% CI 0.91-1.01). CONCLUSIONS: Treatment with 4 mg of rosiglitazone for HIV-associated LDS is likely to reduce the bioavailability of nevirapine. Thus, routine TDM is recommended for patients treated with rosiglitazone and nevirapine. A therapy consisting of efavirenz or lopinavir seems to be without negative impact. Further studies on the interaction of rosiglitazone with ARV drugs are necessary.

Atazanavir for treatment of HIV infection in clinical routine: efficacy, pharmacokinetics and safety.

INTRODUCTION: Atazanavir (ATV) is a novel protease inhibitor that has been recently introduced into therapy of HIV infection. Currently there is little data on ATV therapy from daily practice. METHODS: In this retrospective study, we report on ATV efficacy and safety in clinical routine. Drug monitoring was performed consisting of unscheduled single measurements and a 4-hour-profile. Trough concentration of >80 ng/ml and peak concentration of 2000-6000 ng/ml were regarded as sufficient. RESULTS: Between May 2003 and April 2004, ATV treatment was started in 42 patients, mean observation time was 32 weeks (6-53). Mean age was 45.6 years, 38% had prior AIDS, viral load was undetectable in 73%. Important side effects were minor or moderate diarrhea (27%) and fatigue (15%). ATV was discontinued in 10% due to side effects or malignant diseases. No significant influence on mean values of cholesterol, triglycerides, liver enzymes, CD4-cell-count, and HI-viral load was seen. Virologic failure occurred in 13% of patients, all of them were PI-experienced. Pharmacokinetic data are available for 32 patients, all patients had sufficient trough levels. 30% with unboosted ATV and 21% with boosted ATV had peak plasma concentrations below the level defined as sufficient. Mean trough levels, plasma profile and AUC did not differ significantly between groups with non-boosted versus boosted ATV regimes but showed a wide inter-patient variability. CONCLUSIONS: ATV treatment of HIV-infected patients with or without a RTV booster was safe and effective in clinical routine. Drug levels were sufficient in the majority of cases. The variability of pharmacokinetic results in our sample supports therapeutic drug monitoring in patients treated with ATV.

Haemodynamic crisis and reversible multiorgan failure caused by HIV post-exposure prophylaxis after needle-stick injury in a health care worker.

We report the case of a 59-year-old nurse from our HIV ward who developed a severe haemodynamic crisis with concomitant acute multiorgan failure after initiation of a post-exposure prophylaxis (PEP) with zidovudine/lamivudine (CombivirTM) and lopinavir/ritonavir (KaletraTM) after a needle-stick injury with an HIV-contaminated needle. Although serious and life-threatening adverse effects of post-exposure prophylaxis have been documented in several cases, this is the first report of a severe acute cardiovascular incident following PEP initiation.

[SARS--the facts. Transmission, diagnosis and managing suspected cases]. / SARS--die Fakten. Ubertragungswege, Diagnostik und Umgang mit Verdachtsfällen.

Severe Acute Respiratory Syndrome (SARS) is a new infectious disease that, in the short period between 1 February and 24 April 2003, has been diagnosed in more than 4000 patients. Its origin was traced to Guandong, a province in southeast China. The culprit organism was identified as a new coronavirus. The clinical presentation is unspecific and includes fever, respiratory symptoms, lymphopenia and pulmonary infiltrates on X-ray. Essential steps to prevent further dissemination of the virus are rapid identification, and treatment in an isolation unit. Despite all the international efforts and the rapid progress in the investigation of SARS coordinated by the World Health Organization (WHO), the epidemic has not yet been brought under control.

Tumor necrosis factor-alpha production in whole blood after cardiopulmonary bypass: downregulation caused by circulating cytokine-inhibitory activities.

OBJECTIVES: Cardiopulmonary bypass is associated with the release of proinflammatory cytokines (tumor necrosis factor alpha, interleukin 1beta, interleukin 6, and interleukin 8) and anti-inflammatory cytokines (interleukin 10 and transforming growth factor beta(1)). On the one hand this cytokine release is related to the postoperative systemic inflammatory response syndrome, and on the other hand it is related to deterioration of the immune system, for example in monocyte or polymorphonuclear neutrophil function, leading to an increased susceptibility to infections. To gain further insight into the alterations of immune cell reactivity and possible regulatory mechanisms, we studied lipopolysaccharide-induced tumor necrosis factor alpha synthesis in whole blood from cardiac surgical patients. METHODS: Fifteen patients undergoing elective heart surgery with cardiopulmonary bypass were included in the study. Ex vivo lipopolysaccharide-induced tumor necrosis factor alpha synthesis was measured in a whole blood assay before, during, and after bypass. Corresponding tumor necrosis factor alpha messenger RNA levels were determined by semiquantitative reverse transcriptase-polymerase chain reaction. In addition, the influence of patient serum on whole blood responsiveness and its relationship to anti-inflammatory cytokines were evaluated in vitro. RESULTS: Tumor necrosis factor alpha synthesis was significantly reduced after 30 minutes of cardiopulmonary bypass and showed the lowest values at the end of bypass (mean +/- SD 0.109 +/- 0.105 ng/10(6) white blood cells after 30 minutes of bypass and 0.050 +/- 0.065 ng/10(6) white blood cells at the end of bypass, vs 0.450 +/- 0.159 ng/10(6) white blood cells preoperatively, P <.001). As a further indication of reduced cytokine biosynthesis, diminished messenger RNA levels for tumor necrosis factor alpha were detected. Serum withdrawn from patients at the end of cardiopulmonary bypass reduced tumor necrosis factor alpha synthesis in heterologous blood from healthy volunteers highly significantly to 39.93% +/- 23.18% relative to control serum (P =.005) and preoperatively drawn serum (P =.024). This effect was dose dependent and was not specific for lipopolysaccharide-induced tumor necrosis factor alpha synthesis. Anesthesia and heparin administration did not influence tumor necrosis factor alpha production significantly. Ex vivo tumor necrosis factor alpha synthesis was negatively related to interleukin 10 serum levels, positively but weakly related to interleukin 4, and was not related to transforming growth factor beta(1) (Spearman correlation coefficients -0.565, P <.001, 0.362, P <.001, and -0.062, P =.460, respectively). However, interleukin 10 levels in patient serum after cardiopulmonary bypass were 300-fold below the quantities needed for half-maximal inhibition of tumor necrosis factor alpha synthesis in vitro. Moreover, the inhibitory activity could not be removed by immune absorption of interleukin 10. CONCLUSIONS: These results suggest that during cardiac operations cytokine-inhibitory serum activities are released or newly formed. These activities could not be explained by the actions of interleukins 4 and 10 or transforming growth factor beta(1). Although their exact nature remains undetermined, these substances may contribute to the diminished immune cell functions after cardiopulmonary bypass and thus need further characterization.

Sense of coherence and health: evidence from two cross-lagged longitudinal samples.

We explored the stability of sense of coherence (SOC) and the relationship between SOC and health in two cross-lagged longitudinal samples by using structural equation modeling. In Study 1, comprising 577 municipal male and female employees, SOC was found to be stable in both sexes. In women, SOC significantly predicted sickness absences in the 4-year follow-up period. A low SOC, but not a high SOC, was associated with health prospects. Surprisingly, SOC did not influence sickness absences among men. Study 2 further tested the relationship between SOC and health in 320 male technical designers. Although SOC was cross-sectionally associated with psychological and somatic health complaints, it did not predict later health complaints in a 5-year follow-up. Thus, the present study supports the dispositional character of SOC in both sexes and its predictive validity among women. No support was found to the salutogenic status of SOC and an unexpected gender difference was revealed.