Human blood outgrowth endothelial cells improve islet survival and function when co-transplanted in a mouse model of diabetes.

AIMS/HYPOTHESIS: As current islet-transplantation protocols suffer from significant graft loss and dysfunction, strategies to sustain the long-term benefits of this therapy are required. Rapid and adequate oxygen and nutrient delivery by blood vessels improves islet engraftment and function. The present report evaluated a potentially beneficial effect of adult human blood outgrowth endothelial cells (BOEC) on islet graft vascularisation and function. METHODS: Human BOEC, 5 × 10(5), were co-transplanted with a rat marginal-islet graft under the kidney capsule of hyperglycaemic NOD severe combined immunodeficiency (SCID) mice, and the effect on metabolic outcome was evaluated. RESULTS: Although vessel density remained unaffected, co-transplantation of islets with BOEC resulted in a significant and specific improvement of glycaemia and increased plasma C-peptide. Moreover, in contrast to control mice, BOEC recipients displayed reduced beta cell death and increases in body weight, beta cell proliferation and graft-vessel and beta cell volume. In vivo cell tracing demonstrated that BOEC remain at the site of transplantation and do not expand. The potential clinical applicability was underscored by the observed metabolic benefit of co-transplanting islets with BOEC derived from a type 1 diabetes patient. CONCLUSIONS/INTERPRETATION: The present data support the use of autologous BOEC in translational studies that aim to improve current islet-transplantation protocols for the treatment of brittle type 1 diabetes.

Duration of cough, TB suspects' characteristics and service factors determine the yield of smear microscopy.

OBJECTIVE: To determine the efficiency of routine tuberculosis (TB) case detection by examining sputum smear positivity for acid-fast bacilli in relation to duration of cough, characteristics of TB suspects examined and health service factors. METHOD: We combined patient interviews with routine data from laboratory registers in 6 health care facilities in San Juan de Lurigancho district, Lima, Peru. A TB case was defined as a TB suspect with at least one positive sputum smear. We calculated adjusted odds ratios with 95% confidence intervals for the association between smear positivity and health service and patient's characteristics. RESULTS: Smear positivity was 7.3% (321/4376). Of the 4376 adults submitting sputa, 55.3% (2418) reported cough for <14 days. In this group, smear microscopy yielded 3.2% (78/2418) positive results vs. 12.4% (243/1958) in patients coughing for 14 or more days. Having cough for >2 weeks, being referred by health care staff, attending a secondary-level health care facility, male sex and age between 15 and 44 years were independent determinants of smear positivity. CONCLUSIONS: Routine case detection yields a low proportion of smear-positive cases because of the inclusion of a high proportion of patients without cough or coughing for <2 weeks. Adherence to the national TB control programme guidelines on the selection of TB suspects would have a positive impact on the smear positivity rate, reduce laboratory costs and workload and possibly improve the reading quality of smear microscopy.

Yield of fluorescence microscopy versus culture for tuberculosis at a middle-income country referral hospital.

The aim of this study was to determine the usefulness of fluorescence microscopy (FM) at a referral centre in a middle-income country. Direct Ziehl-Neelsen (ZN) and direct, as well as concentrated, smear FM were performed on 2179 suspect sputa, with Löwenstein-Jensen (LJ) culture as the gold standard. ZN, direct FM and concentration FM detected 36.0, 38.6 and 37.0%, respectively, of 272 culture-positive specimens. Patient-wise, there were 8.1% (126/1553) positives on any smear compared with 12.0% (187/1553) on any culture. ZN, direct FM and concentrated FM smear were positive in 43.3, 46.5 and 45.5%, respectively, of culture-proven cases. All differences between microscopy and culture were significant (P<0.001), but not those between microscopy techniques. Acid-fast bacilli (AFB) were not rare in 60% of 48 duplicate smears, positive in ZN or FM only. Simple LJ culture, but not FM on direct or concentrated smears, was thus significantly more sensitive than ZN smears. The considerable numbers of AFB found in positive direct smears from discordant microscopy sets suggest that repeating smears can improve microscopy sensitivity more than variations of correctly executed technique, provided that overload is avoided. Thus FM could be particularly useful, as it is time-saving and could protect against the sensitivity loss associated with high workload.

HTLV-1 infection is associated with a history of active tuberculosis among family members of HTLV-1-infected patients in Peru.

The purpose of this study was to assess the association between human T-lymphotropic virus 1 (HTLV-1) and a lifetime history of active tuberculosis (TB) among relatives of HTLV-1-infected patients. We reviewed clinical charts of all relatives of HTLV-1-infected index cases who attended our institute in Lima from 1990-2004. The data of 1233 relatives was analysed; 394 (32.0%) were HTLV-1 positive. Eighty-one subjects (6.6%) had a history of active TB, including 45/394 (11.4%) HTLV-1-positive and 36/839 (4.3%) HTLV-1-negative relatives (P<0.001). On multivariate analysis, three factors were associated with TB history: HTLV-1 infection (adjusted OR 2.5, 95% CI 1.6-3.9), age (adjusted OR 1.3, 95% CI 1.1-1.5 per 10-year age increase) and relation to the index case (adjusted OR 2.6, 95% CI 1.3-5.1, for siblings vs. spouses of index cases). In conclusion, HTLV-1 infection may increase the susceptibility to active TB. In populations where both infections are frequent, such an association could affect the dynamics of TB.

HTLV-1 infection is frequent among out-patients with pulmonary tuberculosis in northern Lima, Peru.

SETTING: Tuberculosis (TB) and human T-lymphotropic virus 1 (HTLV-1) are frequent in Peru. The prevalence of HTLV-1 among Peruvian TB patients is unknown. OBJECTIVE: To determine the prevalence of HTLV-1, HTLV-2 and the human immunodeficiency virus (HIV) in out-patients with TB and to compare HTLV-1-infected patients with seronegative patients. DESIGN: Cross-sectional study including subjects aged 18-65 years diagnosed with smear-positive pulmonary TB at health centres in northern Lima from November 2004 to August 2005. HTLV and HIV screening was performed using enzyme-linked immunosorbent assay; HTLV-1 and HTLV-2 were confirmed using line immunoassay. RESULTS: There were 311 participants with a median age of 29 years; 173 (56%) were men. HTLV-1 prevalence was 5.8% (18/311, 95%CI 3.2-8.4) and HIV prevalence was 1.3% (4/304, 95%CI 0.4-3.3). HTLV-2 was not diagnosed. In comparison with HIV- and HTLV-seronegative patients, HTLV-1-infected subjects were older (median age 44 vs. 28, P < 0.001) and were more likely to have been born in the southern Andes (OR 4.4, 95%CI 1.6-11.9). They were also more likely to report a history of TB deaths in the family (OR 5.4, 95%CI 1.7-16.8) and had more sputum smear results graded as 3+ (OR 4.1, 95%CI 1.5-11.2). CONCLUSION: HTLV-1 screening among Peruvian TB patients is important. Because 3+ sputum smears are frequent and mortality is high among relatives, families of HTLV-1/TB-positive cases merit special attention.

Proviral load and immune markers associated with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Peru.

Human T-lymphotropic virus type 1 (HTLV-1) is the aetiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The objective of this study is to identify which ex vivo and in vivo markers are associated independently with HAM/TSP in a Peruvian population. Eighty-one subjects (33 men/48 women) were enrolled: 35 presented with HAM/TSP, 33 were asymptomatic HTLV-1 carriers (ACs) and 13 were HTLV-1-seronegative controls (SCs). Ex vivo markers included T cell proliferation and Th1 [interferon (IFN)-gamma], Th2 [interleukin (IL)-4, IL-5], proinflammatory [tumour necrosis factor (TNF)-alpha] and anti-inflammatory (IL-10) cytokine production in non-stimulated peripheral blood mononuclear cell (PBMC) cultures. In vivo CD4(+) T cell count, markers of Th1 [interferon-inducible protein (IP)-10] and Th2 (sCD30) activity in plasma and HTLV-1 proviral load in PBMCs were also evaluated. In univariate analysis, several markers, including T cell proliferation, IFN-gamma, IP-10, sCD30 and proviral load were associated with HAM/TSP, but in a multiple logistic regression analysis only the proviral load remained associated significantly with disease manifestation [adjusted OR 9.10 (1.24-66.91)]. Our findings suggest that HAM/TSP is associated primarily with proviral load, whereas the observed association with some immune markers seems secondary.

Clinical characteristics of patients in Peru with human T cell lymphotropic virus type 1-associated tropical spastic paraparesis.

BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1) is associated with tropical spastic paraparesis (TSP). Peru is an area of endemicity for HTLV-1. METHODS: All patients with suspected cases of TSP referred to our institute (Institute of Tropical Medicine Alexander von Humboldt, Lima, Peru) from 1989 through 2002 were interviewed and tested for HTLV-1. All patients with positive results were evaluated by an expert physician. Disease progression was defined as "rapid" if the time between TSP onset and inability to walk unaided was <2 years. RESULTS: Among 165 patients enrolled, the symptoms and signs most frequently found were spasticity (in 97.5% of patients), hyperreflexia (95.4%), lower limb paresthesia (90.2%), pyramidal signs (82.6%), urinary complaints (82.0%), and lumbar pain (79.0%). Rapid progression was present in 21.5% of patients; mean age at TSP onset was higher among these patients than among slow progressors (P<.001). Severe spasticity, diminished vibratory sensation, and tremor were found more frequently among rapid progressors, compared with slow progressors. CONCLUSIONS: HTLV-1--associated TSP is frequently diagnosed in areas of HTLV-1-endemicity. A subgroup of patients experiences rapid disease progression.

Rheumatological complications associated with the use of indinavir and other protease inhibitors.

Several cases are reported of rheumatological pathology (temporomandibular dysfunction, frozen shoulder, Dupuytren's disease, and tendinitis) most probably related to the intake of indinavir in HIV positive patients. A survey using an anonymous questionnaire of 878 people with HIV infection treated with antiretroviral drugs suggests that other protease inhibitors may also cause arthralgia.

Impact of new developments in antiretroviral treatment on AIDS prevention and care in resource-poor countries.

Combination antiretroviral treatment (ARV) including protease inhibitors, decreased the morbidity and mortality due to AIDS in the industrialized world. Many obstacles remain before ARVs can be introduced in resource-poor countries: high treatment costs, lack of laboratories to monitor the treatment, weak healthcare systems, and many other competing healthcare needs. The introduction of ARVs in resource-poor countries should be closely monitored. The first priority for the use of ARVs in resource-poor countries is the prevention of mother-to-child transmission of HIV. News about the success of ARV treatment may lead to an increase in unsafe behaviors including a decreased use of condoms. Therefore, prevention efforts should be strengthened; especially the development of an HIV vaccine needs to become a top priority. Funds for ARV treatment cannot come from the already strained healthcare budgets of resource-poor countries. The pressure on politicians and international donor agencies to provide ARVs to resource-poor countries should be used to increase overall healthcare budgets and to improve healthcare services in general.