High prevalence of diabetes-specific autoimmunity in first-degree relatives of Sardinian patients with type 1 diabetes.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) in Sardinia is among the highest in the world (44.8 cases/100,000 person-years). Recommendations of the Immunology of Diabetes Society advise evaluating autoantibody positivity in first-degree relatives (FDRs) of patients with T1DM, for their higher risk to develop the disease. The aim of this study was to determine the prevalence of beta-cell autoimmunity in FDRs of T1DM patients in Sardinia. METHODS: A total of 188 Sardinian families were recruited in collaboration between diabetes and pediatric units of university and district hospitals in Sardinia. The recruitment involved 188 patients with diagnosed T1DM and all their available FDRs (n = 447). Autoantibodies (Aabs) against GAD, IA2, insulin, and ZnT8 were measured in all subjects. Human leukocyte antigen (HLA) risk genotypes (HLA-DR and DQ loci) were analyzed in 43 Aabs-positive FDR. RESULTS: The prevalence of Aabs (any type of autoantibody, single or multiple) in FDR was 11.9% (53/447). Of those with autoantibodies, 62.3% (33/53) were positive to only 1 autoantibody, 22.6% (12/53) had 2 autoantibodies, 7.55% (4/53) had 3 autoantibodies, and 7.55% (4/53) had all 4 autoantibodies. Typing of HLA-DR and DQ loci showed that 89% of FDR carried moderate- to high-risk genotypes, with only 5 FDR with low-risk genotypes. CONCLUSIONS: The prevalence of T1DM autoantibodies in FDRs of T1DM patients was very high (11.9%) in the Sardinian population, higher than in other populations from the United States and Europe, and similar to that observed in Finland. Autoantibody positivity strongly associated with HLA risk. This study provides evidence of the high risk of T1DM in FDR of T1DM patients in Sardinia and warrants longitudinal follow-up to estimate the risk of progression to T1DM in high-risk populations.

The affordability for patients of a new universal MDR-TB coverage model in China.

BACKGROUND: China has piloted a new model of universal coverage for multidrug-resistant tuberculosis (MDR-TB), designed to rationalize hospital use of drugs and tests and move away from fee-for-service payment towards a standard package with financial protection against catastrophic health costs. OBJECTIVE: To evaluate the affordability to patients of this new model. DESIGN: This was an observational study of 243 MDR-TB cases eligible for enrolment on treatment under the project. We assessed the affordability of the project from the perspective of households, with a focus on catastrophic costs. RESULTS: Of the 243 eligible cases, 172 (71%) were enrolled on treatment; of the 71 cases not enrolled, 26 (37%) cited economic reasons. The 73 surveyed cases paid an average of RMB 5977 (US$920) out-of-pocket in search costs incurred outside the pilot model. Within the pilot, they paid another RMB 2094 (US$322) in medical fees and RMB 5230 (US$805) in direct non-medical costs. Despite 90% reimbursement of medical fees, 78% of households experienced catastrophic costs, including indirect costs. CONCLUSION: The objectives of the pilot model are aligned with health reform in China and universal health coverage globally. Enrollment would almost certainly be higher with 100% reimbursement of medical fees, but patient enablers will be required to truly eliminate catastrophic costs.

Management of HIV-infected patients with MDR- and XDR-TB in resource-limited settings.

The emergence of extensively drug-resistant tuberculosis (XDR-TB) poses a significant public health threat for human immunodeficiency virus (HIV) programmes and tuberculosis (TB) control efforts. Recent reports demonstrate high mortality rates among HIV-infected multidrug-resistant (MDR) and XDR-TB patients compared to those without HIV infection. Transmission of these highly resistant TB strains is occurring both within health facilities and in the community. We review the principles of a sound public health approach to this problem, including early diagnosis, treatment for suspected disease, patient support and adherence and sound infection control measures. In the context of drug-resistant TB, we elaborate on current World Health Organization antiretroviral guidelines addressing management issues related to timing of antiretroviral treatment (ART), drug interactions and drug toxicities among patients receiving both ART and second-line TB regimens. We highlight the important research agenda that exists at the intersection of MDR- and XDR-TB and HIV disease.

National scale-up of HIV testing and provision of HIV care to tuberculosis patients in Kenya.

SETTING: Kenya, one of the 22 tuberculosis (TB) high-burden countries, whose TB burden is fuelled by the human immunodeficiency virus (HIV). OBJECTIVE: To monitor and evaluate the implementation of HIV testing and provision of HIV care to TB patients in Kenya through the establishment of a routine TB-HIV integrated surveillance system. DESIGN: A descriptive report of the status of implementation of HIV testing and provision of HIV interventions to TB patients one year after the introduction of the revised TB case recording and reporting system. RESULTS: From July 2005 to June 2006, 88% of 112835 TB patients were reported to the National Leprosy and TB Control Programme, 98773 (87.9%) of whom were reported using a revised recording and reporting system that included TB-HIV indicators. HIV testing of TB patients increased from 31.5% at the beginning of this period to 59% at the end. Of the 46428 patients tested for HIV, 25558 (55%) were found to be HIV-positive, 85% of whom were provided with cotrimoxazole preventive treatment and 28% with antiretroviral treatment. CONCLUSION: A country-wide integrated TB-HIV surveillance system in TB patients can be implemented and provides essential data to monitor and evaluate TB-HIV related interventions.

Tuberculosis immune reconstitution inflammatory syndrome in countries with limited resources.

Mycobacterium tuberculosis infection accounts for probably one third of human immunodeficiency virus (HIV) related immune reconstitution inflammatory syndrome (IRIS) events, particularly in developing countries where HIV and tuberculosis (TB) co-infection is very common. Small cohort studies of HIV-positive patients with active TB treated with antiretroviral therapy (ART) suggest an incidence of TB IRIS varying between 11% and 45%. Risk factors for TB IRIS that have been suggested in certain studies but not in others include: starting ART within 6 weeks of starting TB treatment; extra-pulmonary or disseminated disease; a low CD4+ lymphocyte count and a high viral load at the start of ART; and a good immunological and virological response during highly active antiretroviral therapy (HAART). It is important to agree on a clinical case definition of TB IRIS that could be used in resource-limited settings. Such a case definition could be used to determine the exact incidence and consequences of TB IRIS and would be valuable worldwide in clinical trials that are needed to answer questions on how this phenomenon could be prevented and treated.

WHO clinical staging of HIV infection and disease, tuberculosis and eligibility for antiretroviral treatment: relationship to CD4 lymphocyte counts.

SETTING: Thyolo district, Malawi. OBJECTIVES: To determine in HIV-positive individuals aged over 13 years CD4 lymphocyte counts in patients classified as WHO Clinical Stage III and IV and patients with active and previous tuberculosis (TB). DESIGN: Cross-sectional study. METHODS: CD4 lymphocyte counts were determined in all consecutive HIV-positive individuals presenting to the antiretroviral clinic in WHO Stage III and IV. RESULTS: A CD4 lymphocyte count of < or = 350 cells/microl was found in 413 (90%) of 457 individuals in WHO Stage III and IV, 96% of 77 individuals with active TB, 92% of 65 individuals with a history of pulmonary TB (PTB) in the last year, 91% of 89 individuals with a previous history of PTB beyond 1 year, 81% of 32 individuals with a previous history of extra-pulmonary TB, 93% of 107 individuals with active or past TB with another HIV-related disease and 89% of 158 individuals with active or past TB without another HIV-related disease. CONCLUSIONS: In our setting, nine of 10 HIV-positive individuals presenting in WHO Stage III and IV and with active or previous TB have CD4 counts of < or = 350 cells/microl. It would thus be reasonable, in this or similar settings where CD4 counts are unavailable for clinical management, for all such patients to be considered eligible for antiretroviral therapy.

PCR in meningoencephalitis diagnosis.

Polymerase chain reaction (PCR) detection of a stretch of nucleic acid sequence of microbial origin from a clinical sample is not always diagnostic of disease unless the identified agent is a strict pathogen or its growth is documented. We describe here a case of acute meningoencephalitis in a 21-y-old man, in whom no pathogen was isolated by traditional bacterial or viral culture. Standard DNA PCR performed on the cerebrospinal fluid (CSF) identified the presence of 3 infectious agents: HHV-6, HHV-7 and Mycoplasma pneumoniae. Additional PCRs performed on CSF fractions along with gene transcript analysis proved the bystander role of the 2 herpesviruses and indicated M. pneumoniae as the relevant replicating agent, most likely playing to be a pathogenic role. Until this useful analysis becomes routine, clinicians should deal carefully with DNA PCR results, especially when assessing the aetiological role of agents, such as herpesviruses, which are known to undergo latency.

Leuconostoc species: a case-cluster hospital infection.

Leuconostoc species are members of the Streptococcacae family. They are generally regarded as non-pathogenic culture contaminants and are thought to be an uncommon cause of infection. We present a study of a case-cluster nosocomial infection due to Leuconostoc spp. Three patients were hospitalized at the time of the infection with significant underlying diseases and all had a compromised skin and mucous barriers. Two had received previous antibiotic therapy. This report highlights the importance of Leuconostoc spp. as an emerging pathogen, even though the modes of transmission and reservoirs of Leuconostoc spp. are as yet unknown.

Clinical and laboratoristic remission after cryosupernatant plasma exchange in thrombotic thrombocytopenic purpura.

We describe a case of thrombotic thrombocytopenic purpura (TTP) resistant to conventional therapy with fresh-frozen plasma (FFP)-plasma exchange (PEX) as well as to steroids, immunoglobulins, vincristine, dipyridamole, dextran and iloprost, achieving complete remission with cryosupernatant-plasma exchange. Our case shows the effectiveness of cryosupernatant PEX, when FFP-PEX and alternative therapies have failed.

Prevalence and patterns of symptomatic thromboembolism in oncohematology.

BACKGROUND AND OBJECTIVE: Approximately 15% of patients with cancer will experience a thrombotic episode at some time. Some patients are at particularly high risk depending on the histology of the malignant disease. The aim of the study was to determine the actual prevalence of thrombotic episodes in oncohematologic patients. DESIGN AND METHODS: We conducted a retrospective cohort analysis on a total of 515 patients that were admitted to the out-patients clinic (Institute of Medical Semeiotics) from January 1, 1986 to January 31, 1996. Two main groups were selected for this study: 133 patients suffering from a myeloproliferative disorder and 382 patients affected by a lymphoproliferative disorder. Follow-up lasted a median of 33 months in both groups (range 3-144 months). The difference between the observed events for each group was estimated by the odds ratio and chi square. Age and sex distribution were estimated by the Mann-Whitney test. Distribution of overall survival was estimated by the Kaplan-Meier method and compared between groups (DVT patients and non DVT patients) by the log-rank test. RESULTS: Twenty-three patients experienced a venous thrombotic disorder. The prevalence of deep vein thrombosis (DVT) in myeloproliferative and lymphoproliferative disorders was 8.27% (n = 11) and 3.14% (n = 12) respectively (odds ratio = 0.36; 95% CI = 0.14-0.90; chi-square = 4.94 p = 0.028). DVT was apparently idiopathic in 17 cases. In 4 patients another cancer was present; in the remaining 2 patients the thrombotic episode was associated with other predisposing factors. Although 7 of the 23 patients with DVT died, we cannot find any difference in the overall survival compared to oncohematologic patients who did not experience DVT. INTERPRETATION AND CONCLUSIONS: The prevalence of symptomatic DVT in the oncohematological patients is lower than reported for solid tumor. Patients affected by myeloproliferative disease have a higher risk of developing thrombosis. DVT if well-treated does not influence the survival of oncohematological patients.

Hypertriglyceridemia during long-term interferon-alpha therapy in a series of hematologic patients.

Adverse reactions to interferon-alpha (IFN-alpha) therapy include flu-like syndrome, bone marrow suppression, neurotoxic effects, and autoimmunity. A slight increase in triglyceride levels has been described less frequently during IFN-alpha administration. The incidence of IFN-alpha-induced hypertriglyceridemia seems variable, and there are no clear data on how to treat it. We report the effect of long-term (more than 12 months) IFN-alpha treatment on triglyceride levels in 43 patients suffering from hairy cell leukemia (18), multiple myeloma (10), chronic myelogenous leukemia (6), cryoglobulinemia (5), non-Hodgkin's lymphoma (3), and Sezary syndrome (1). Hypertriglyceridemia was found in 6 patients (15%). In 3 patients, gemfibrozil restored normal triglyceride values. This study suggests that hypertriglyceridemia is a minor side effect of long-term IFN-alpha therapy and that gemfibrozil might be considered the treatment of choice.