Community-Based Antiretroviral Therapy (ART) Delivery for Female Sex Workers in Tanzania: 6-Month ART Initiation and Adherence.

We conducted an implementation science study of a community-based ART distribution program for HIV-positive female sex workers (FSW) whereby clients received ART services through community-based mobile and home-based platforms. We compared 6-month treatment-related outcomes in the community-based ART arm (N = 256) to the standard facility-based ART delivery arm (N = 253). Those in the intervention arm were more likely to have initiated ART (100.0% vs. 71.5%; p = 0.04), be currently taking ART at the 6-month visit (100.0% vs. 95.0%; p < 0.01), and less likely to have stopped taking ART for more than 30 days continuously (0.9% vs. 5.7%; p = 0.008) or feel high levels of internalized stigma (26.6% vs. 39.9%; p = 0.001). In the adjusted regression model, internalized stigma (adjusted OR [aOR]: 0.5; 95% CI 0.28-0.83) and receiving community-based ART (aOR: 208.6; 95% CI 12.5-3479.0) were significantly associated with ART initiation. Community-based ART distribution model can improve linkage to and adherence to ART over standard facility-based ART programs for FSWs.

Which linguistic measures distinguish transient from persistent language problems in Late Talkers from 2 to 4 years? A study on Italian speaking children.

BACKGROUND: In spite of the large literature on Late Talkers (LTs) it's still unclear which factors predict outcome in children younger than 3 years old. AIMS: To identify the early language characteristics of LTs whose outcome was either a transient delay or a Developmental Language Disorder (DLD). METHODS AND PROCEDURES: 50 LTs were assessed both by indirect and direct measures of expressive and receptive language at three time points between 2 and 4 years of age. OUTCOMES AND RESULTS: At the first evaluation, all LTs had an expressive language delay; 61% also had delayed early syntactic comprehension. Three different linguistic outcomes emerged: children who caught up with their peers ("Late Bloomers") at age 3; children with slow language recovery ("Slow Learners") at age 4 and children at risk of DLD. The linguistic measures that differentiated the groups changed with age. By 28 months, impaired syntactic comprehension differentiated children at risk of DLD at 4 years of age, from the other two groups. By 36 months, the discrepancy between vocabulary size and age was larger in children with persistent language difficulties compared to both "Late Bloomers" and "Slow Learners". Expressive grammar differentiated the groups significantly by age 3 with difficulties in this domain still persisting in children with DLD at age 4. CONCLUSIONS: An early syntactic comprehension delay was a predictive index of DLD in LTs, suggesting the importance of evaluating this language component when assessing LT toddlers. IMPLICATIONS: LTs with receptive-expressive language delay around 24-30 months could benefit from an early language intervention.

Implementation of tuberculosis infection control measures at HIV care and treatment sites in sub-Saharan Africa.

SETTING: A total of 663 human immunodeficiency virus (HIV) care and treatment sites in nine tuberculosis (TB) affected African countries, serving over 900,000 persons living with HIV. OBJECTIVE: To determine the implementation of infection control (IC) measures and whether program and facility characteristics were associated with implementation of these measures. DESIGN: A survey was conducted to assess the presence of a TB IC plan, triage practices for TB suspects, location of sputum collection and availability of particulate respirators. The association of facility characteristics with IC measures was examined using bivariate and multivariate methods. RESULTS: Forty-seven per cent (range across countries [RAC] 2-77%) of sites had written TB IC plans; 60% (RAC 5-93%) practiced triage; of those with access to microscopy, 83% (RAC 59-91%) performed sputum collection outdoors and 13% (RAC 0-36%) in ventilated indoor rooms; 16% (RAC 1-87%) had particulate respirators available. Sites providing anti-tuberculosis treatment were more likely to have written IC plans (54% vs. 12%, P < 0.0001) and particulate respirators (18% vs. 8%, P = 0.0126), and to perform TB triage (65% vs. 40%, P = 0.0001) than those without anti-tuberculosis treatment services. CONCLUSIONS: To protect HIV-infected patients and health care workers, there is an urgent need to scale up IC practices at HIV care and treatment sites, particularly at sites without anti-tuberculosis treatment services.

Clustering of tuberculosis among senegalese immigrants in Italy.

OBJECTIVE: To study clustered Mycobacterium tuberculosis isolates as an indicator of recent TB transmission in a small urban setting in Italy, and to determine associated risk factors. METHODS: M. tuberculosis strains isolated between 1991 and 1997 were characterised by IS6110 restriction fragment length polymorphism (RFLP) analysis. RESULTS: One hundred and ninety-five isolates were available for RFLP analysis, which revealed 163 different patterns. Available cases were represented by 137 Italians (70%), 32 Senegalese (17%), and 26 other foreign-born cases (13%). A unique fingerprint pattern was found in 143 cases (73.3%), while 52 strains (26.7%) were grouped into 20 clusters. Nineteen cases (10%) were resident in the same quarter of Brescia with a high density of Senegalese immigrants (Area A). An increased probability of yielding clustered M. tuberculosis strains was associated with residence in Area A (OR 3.87, 95%CI 1.42-10.56; P = 0.02) and being Senegalese (OR = 5.96, 95%CI 1.48-23.97; P = 0.005). In the logistic regression analysis, being Senegalese was independently associated with yielding a clustered M. tuberculosis strain. CONCLUSIONS: Our results demonstrate a clustering of TB cases among Senegalese immigrants and suggest that RFLP analysis may be used to identify geographical areas where efforts can be targeted to interrupt TB transmission.

gammadelta T lymphocytes in the peripheral blood of patients with tuberculosis with and without HIV co-infection.

BACKGROUND: Several recent studies suggest that gammadelta T lymphocytes play an important role in immunity against Mycobacterium tuberculosis. However, the dynamics of these cells in the peripheral blood of patients with tuberculosis (TB) with and without HIV infection is not fully understood. A study was undertaken to evaluate the profile of the gammadelta T cell population in patients at the time the diagnosis of TB was established. METHODS: A cross sectional study was performed in consecutive TB patients from the Department of Infectious Diseases, Spedali Civili, Brescia. CD4+, CD8+ and Vdelta1 and Vdelta2 T cell counts were analysed. Lymphocyte surface membrane expression was evaluated with the FITC-TCRgammadelta, -Vdelta1, -Vdelta2 and PE-Vdelta1 monoclonal antibodies. Blood donors and HIV seropositive asymptomatic individuals acted as controls. RESULTS: Seventy four TB patients were evaluated, 20 of whom (27%) were co-infected with HIV. HIV seronegative TB patients (n=54) had total gammadelta T cells and Vdelta1 subsets comparable to those in blood donors (n=39). However, the percentage with the Vdelta2 subset was significantly lower in patients with TB than in controls (median 1.5 v 2.1; p=0.05). Responsiveness to PPD was not associated with predominance of a specific gammadelta T cell subset. HIV seropositive individuals had a decreased percentage of circulating Vdelta2 cells at a level similar to that in HIV seronegative TB patients, regardless of the presence of active TB. CONCLUSIONS: HIV seronegative TB patients and HIV infected individuals (with or without active TB) have a reduced number of circulating Vdelta2 T cells compared with healthy individuals. Whether TB and HIV infection share a common mechanism causing Vdelta2 T cell depletion still needs to be established.

Antioxidant and radical scavenging properties in vitro of polyphenolic extracts from red wine.

BACKGROUND & AIMS: Red wine polyphenols inhibit chemically-induced oxidative DNA damage in vivo in experimental animals through a mechanism which is still unclear. On this basis, we tried to clarify the mechanisms of inhibition of DNA oxidation in vitro by wine extracts containing monomeric and polymeric phenols (WE) and monomer-free complex polyphenols and tannins (WCPT) from red wine. METHODS: Oxidative DNA damage was induced by incubating DNA with GSH/Fe3+ or cumene hydroperoxide (CumOOH) in vitro and using 8-OH-2-deoxyguanosine (8-OHdG) levels as a measure of DNA oxidation. Levels of 8-OHdG were determined by HPLC coupled with electrochemical detector (ESA). RESULTS AND CONCLUSIONS: WCPT and WE, at microM concentrations, reduced concentration-dependently oxidative DNA damage induced by GSH/Fe3+. WCPT and WE also reduced DNA oxidation by CumOOH. In conclusion, complex polyphenols and tannin extracts from red wine, with or without small molecular phenols, prevent oxidative DNA damage through a dual mechanism, iron binding and direct free radical scavenging.

Screening for tuberculosis and latent tuberculosis infection among undocumented immigrants at an unspecialised health service unit.

SETTING: Practical or cost-effective strategies to identify undocumented immigrants with latent tuberculosis infection and to deliver treatment for latent TB infection are still unavailable. OBJECTIVES: To compare completion rates of screening procedures for TB infection and disease among undocumented immigrants at specialised (TB) and unspecialised health services in Italy. DESIGN: A TB unit (TBU) and an unspecialised health service unit for migrants (MHCU) served as recruitment sites for recent undocumented immigrants from TB endemic areas. The screening included a symptom questionnaire, a tuberculin skin test and a chest X-ray. RESULTS: Of 1318 eligible subjects, 1232 (93.4%) accepted the screening. Screening was completed by 993 (80.6%) individuals overall, 86.5% and 71.4% at the TBU and MHCU services, respectively. In a multivariate analysis model, the only variable associated with an increased probability of completing screening was being enrolled at the TBU site (OR 2.5, 95%CI 1.8-3.5; P < 0.001). Three hundred and ninety-two subjects (39.4%) had a TST test of > or = 10 mm. Eight cases of active tuberculosis were detected, with a calculated prevalence of disease of 650/100,000. CONCLUSIONS: Undocumented immigrants to Italy can be screened for TB at an unspecialised health service unit, although not as efficiently as at a specialised TB unit.

[Vertical trasmission of human immunodeficiency virus (HIV) and other sexually transmitted infections (STI)]. / Trasmissione materno-fetale di HIV e di altri agenti di malattie a trasmissione sessuale.

Infectious agents which are sexually transmitted determine considerable morbidity in women during the gestational period. Connatal and perinatal infection of the newborn, miscarriage, and low birthweight have all been described. Vertical transmission of HIV and other STD may occur via the placenta during gestation (the major mechanism for syphilis) or at birth during the passage through the cervico-vaginal channel (the major mechanism for HIV, HBV, HSV, gonorrhoea and chlamydia). High serum viral loads of HIV significantly increase the likelihood of newborn infection, while the presence of lesions in the genital tract at birth increases the odd for transmission for HSV. Breast feeding is a well described route of transmission for HIV infection, but it is irrelevant to the transmission of HBV. Cutaneous lesions of the breast and nipples carry a risk of transmission of syphilis and HSV through breast-feeding. Treatment of the etiologic agent is considered an effective means for the prevention of vertical transmission and is recommended for all STI agents except for HBV. HIV infected women on antiretroviral therapy should continue the same treatment regimen if they become pregnant (with the exception of indinavir and efavirenz, which should be replaced as soon as possible); women who did not assume antiretroviral drugs at the time they became pregnant, should start treatment as soon as they reach the second trimester of gestation. Delivery should be performed by elective cesarian section in all HIV infected women. Delivery should also be performed by cesarian section in women who develop a primary HSV infection and have cervico-vaginal lesions. Recurrent episodes of genital herpes are associated to a much lower risk of vertical transmission and do not represent a criterium for cesarian section. Women with documented cervical chlamydia infection should receive a full treatment regimen at the 36th week of gestation. Women with chronic HBV infection do not require etiologic treatment; however, their newborns should receive concomitant doses of HBV immunoglobulins and HBV vaccine soon after birth. Standard practices of prevention of vertical transmission of STI agents applies to women regardless their native country. However, the feasibility of implementation of the guidelines in poor resource countries is a matter of great concern: an unresolved debate is ongoing on optimal strategies for the prevention of vertical transmission of HIV in such countries.

Efficacy and tolerability of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected persons.

BACKGROUND: Treatment options for anogenital warts in patients with HIV-1 are unsatisfactory because they fail to eradicate latent human papillomavirus. GOAL: To determine tolerability and efficacy of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected patients. STUDY DESIGN: A randomized, placebo-controlled, single-blind, crossover pilot study of either 1% cidofovir cream or placebo applied once daily 5 days a week for 2 weeks followed by 2 weeks of observation was performed. RESULTS: Six patients were randomized to 1% cidofovir cream and six to placebo. The latter patients eventually received 1% cidofovir cream. Thus, 12 treatment rounds of cidofovir were compared with six rounds of placebo. A reduction of more than 50% in the total wart area achieved by seven cidofovir treatments (58%), as compared with no placebo regimen (P = 0.02). Local reactions occurred in 10 of the 12 patients treated with cidofovir, as compared with 0 of the 6 subjects in the placebo group (P < 0.001). CONCLUSIONS: For the initial clearance of anogenital warts in HIV-infected patients, 1% cidofovir cream is significantly more effective than vehicle cream. Local mucosal erosion is a common side effect.

Supervised preventive therapy for latent tuberculosis infection in illegal immigrants in Italy.

In a multicenter, prospective, randomized, open-label study of isoniazid-preventive therapy (IPT) for latent tuberculosis infection, illegal immigrants from countries where tuberculosis is highly endemic were enrolled at two clinical sites in Northern Italy. Of 208 eligible subjects, 82 received supervised IPT at a dose of 900 mg twice weekly for 6 mo (Regimen A), 73 received unsupervised IPT 900 mg twice weekly for 6 mo (Regimen B), and 53 received unsupervised IPT 300 mg daily for 6 mo (Regimen C). Supervised IPT was delivered at either one tuberculosis clinic or one migrant clinic. The probability of completing a 26-wk regimen was 7, 26, and 41% in Regimens A, B, and C, respectively (p < 0.005, Log- rank test calculated using Kaplan-Meier plots). The mean time to dropout was 3. 8, 6, and 6.2 wk in Regimens A, B, and C, respectively (p = 0.003 for regimen A versus either Regimens B or C). Treatment was stopped in five subjects (2.4%) because of adverse events. The rate of completion of preventive therapy for latent tuberculosis infection among illegal immigrants was low. Supervised, clinic-based administration of IPT significantly reduced adherence. Alternative strategies to implement preventive therapy in illegal immigrants are clearly required.

Inhibition of 1,2-dimethylhydrazine-induced oxidative DNA damage in rat colon mucosa by black tea complex polyphenols.

The effect of black tea polyphenols on 1,2-dimethylhydrazine (DMH)-induced oxidative DNA damage in rat colon mucosa has been investigated. Fischer 344 rats were treated orally with thearubigin (TR) or theafulvin (TFu) for 10 days (40 mg/kg), injected ip with DMH (20 mg/kg) or saline and sacrificed 24 hr after DMH administration. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured in colonic mucosa DNA and expressed as a ratio relative to 2'-deoxyguanosine (2dG). Control rat mucosa had 8-OHdG values of 1.12 +/- 0.14/10(5) dG (mean +/- SEM, n=11), whereas DMH-treated rats significantly higher values (1.52 +/- 0.14/10(5) dG, n=26, P<0.05). Pretreatment of rats with TR had significantly inhibited DMH-induced oxidative DNA damage 0.99 +/- 0.09/10(5) dG, n=10, P<0.05) and a similar, although less marked, effect was observed with TFu (1.15 +/- 0.19/10(5), n=9, P=0.06). These findings confirm that DMH causes oxidative DNA damage in the colon mucosa of rats and demonstrate that this effect is prevented by the consumption of complex polyphenols from black tea.

Levels of 8-hydroxydeoxyguanosine as a marker of DNA damage in human leukocytes.

We measured 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in human leukocytes from healthy donors to evaluate oxidative DNA damage and its correlation with smoking, physical exercise, and alcohol consumption. A significant increase in oxidative DNA damage was induced by cigarette smoke, with the mean level of 8-OHdG being significantly higher in smokers (33.1 +/- 10.6 per 10(6) 2-deoxyguanosine (dG) [mean +/- SE], n = 16) compared with nonsmokers (15.3 +/- 1.8 per 10(6) dG, n = 31) and former smokers (17.8 +/- 1.5 per 10(6) dG, n = 9). The highest values were observed after smoking more than 10 cigarettes per day (41.8 +/- 17.1 per 10(6) dG, n = 9). A large interindividual variation in 8-OHdG levels was observed in all analyzed groups. We also observed a correlation between 8-OHdG levels and age in nonsmokers and former smokers. Neither frequency of physical exercise nor alcohol drinking significantly modified 8-OHdG levels in leukocytes.

Effect of complex polyphenols and tannins from red wine (WCPT) on chemically induced oxidative DNA damage in the rat.

BACKGROUND: Flavonoids are polyphenolic antioxidants occurring in vegetables and fruits as well as beverages such as tea and wine which have been thought to influence oxidative damage. AIM OF THE STUDY: We wanted to verify whether a complex mixture of wine tannins (wine complex polyphenols and tannins, WCPT) prevent chemically-induced oxidative DNA damage in vivo. METHODS: Oxidative DNA damage was evaluated by measuring the ratio of 8-hydroxy-2'-deoxyguanosine (80HdG)/ 2-deoxyguanosine (2dG) x 10(-6) in hydrolyzed DNA using HPLC coupled with electrochemical and UV detectors. RESULTS: We treated rats with WCPT (57 mg/kg p.o.) for 14 d, a dose 10-fold higher than what a moderate wine drinker would be exposed to. WCPT administration significantly reduced the ratio of 80HdG/2dG x 10(-6) in liver DNA obtained from rats treated with 2-nitropropane (2NP) relative to controls administered 2NP only (33. 3 +/- 2.5 vs. 44.9 +/- 3.2 x 10(-6) 2dG; micro +/- SE; p<0.05). On the contrary, pretreatment with WCPT for 10 d did not protect the colon mucosa from oxidative DNA damage induced by 1, 2-dimethylhydrazine (DMH). 2NP and DMH are hepatic and colon carcinogens, respectively, capable of inducing oxidative DNA damage. CONCLUSIONS: WCPT have protective action against some types of chemically-induced oxidative DNA damage in vivo.

"Developmental dysmnesia": a case report.

We report a 9-year-old girl who presented from an early age a severe and specific verbal memory disorder, in the absence of a definite etiology. The results of an extensive neuropsychological assessment showed a dissociation between normal visuo-spatial memory abilities and a marked short-term and long-term verbal memory impairment. We argue that our case is affected by "developmental dysmnesia", a condition so far described in two cases only (De Renzi and Lucchelli, 1990, and Temple, 1997). The disorder affected episodic as well as semantic verbal memory. The long term effects on learning and cognition of a memory deficit occurring early in childhood are discussed.

Reversible pseudoatrophy of the brain and mental deterioration associated with valproate treatment.

PURPOSE: To describe an 11-year-old girl with symptomatic localization-related epilepsy and normal intelligence who developed reversible mental deterioration and pseudoatrophic brain changes while receiving valproate (VPA). METHODS: Assessment of mental function using Wechsler Intelligence Scale for Children-III (WISC) and Raven's Progressive Matrices (PM), EEG recordings while awake and asleep, and brain magnetic resonance imaging (MRI), were performed at the beginning of VPA therapy, after 2 years and 8 months of treatment and following VPA discontinuation. RESULTS: After 2 years and 6 months on VPA (< or = 26 mg/kg/day) the girl insidiously developed mental deterioration (loss of 18 IQ points and drop in age-adjusted PM score from the 95th to the 50th percentile) associated with MRI-documented pseudoatrophy of the brain. Onset of severe cognitive impairment coincided with serum VPA concentrations near 100 microg/ml. There were no other manifestations of drug toxicity or hyperammonemia. Background EEG activity was normal. Reduction of VPA dosage and subsequent discontinuation 4 months later resulted in disappearance of clinical symptoms with a 20-point improvement at IQ testing and recovery of previous PM score. Repeat MRI showed disappearance of pseudoatrophic changes. CONCLUSIONS: The striking cognitive improvement and reversal of pseudoatrophic brain changes following VPA discontinuation strongly suggest a drug-induced condition. Based on this and previous reports, the syndrome of VPA-associated mental deterioration and pseudoatrophy of the brain appears to encompass different but possibly related clinical entities, which include parkinsonism with cognitive deterioration, mental deterioration with signs of VPA-toxicity, and isolated mental deterioration, as seen in our patient. A drug-induced effect should be considered whenever cognitive deterioration and imaging findings of brain atrophy occur in VPA-treated patients.

Polycyclic aromatic hydrocarbons in Laurus nobilis leaves as a measure of air pollution in urban and rural sites of Tuscany.

The levels of 9 polycyclic aromatic hydrocarbons (PAHs) 6 of which carcinogenic were measured in the leaves of evergreen tree (Laurus nobilis) sampled in 13 locations in summer and winter in Tuscany, Italy. The carcinogenic PAH levels were correlated with the PAH air levels sampled at the same site. Samples from larger towns had higher PAH levels than those from medium and small towns. Leaves collected in the center of larger cities had higher carcinogenic PAH levels than samples from residential areas indicating that vehicular traffic is the main PAH source. Carcinogenic PAH levels in leaves collected in the winter in medium towns were considerably higher than expected, probably due to domestic heating. These findings demonstrate that air quality in terms of PAH contamination is not markedly different in towns of different size in Tuscany.

Oxidative liver DNA damage in rats treated with pesticide mixtures.

Oxidative damage was quantified in the liver of rats by measuring the levels of 8-OH-2-deoxyguanosine (8-OH-2DG) relative to 2-deoxyguanosine in DNA after treating rats for 10 days at a total dose of 1 mg/kg/day with a mixture of the 15 pesticides most commonly found in Italian foods (comprised of dithiocarbamate, benomyl, procymidone, methidathion, chlorpyrifos-ethyl, parathion-methyl, chlorpropham, parathion, vinclozolin, chlorfenvinphos, pirimiphos ethyl, thiabendazole, fenarimol, diphenylamine and chlorothalonil). We fractionated this pesticide mixture into subgroups in order to determine which molecules, if any, induced DNA oxidative damage. The administration of diphenylamine (0.09-1.4 mg/kg/day) and chlorothalonil (0.13-1 mg/kg/day) induced a dose-dependent increase in 8-OH-2DG levels in liver DNA. The other 13 pesticides of the mixture on the contrary, did not produce oxidative liver DNA damage. These results indicate that the toxicity of low doses of pesticide mixtures present in food might be further reduced by eliminating diphenylamine and chlorothalonil.

Polycyclic aromatic hydrocarbon contamination in the Italian diet.

The content of total and carcinogenic polycyclic aromatic hydrocarbons (PAHs) in Italian foods was measured. The highest levels of PAHs were found in pizza baked in wood-burning ovens and barbecued beef and pork. Relatively high levels were also found in beet greens and squash, apples and bread, fried beef, pork and rabbit, cured meats and chocolate. Conversely low levels were detected in potatoes and cooked fish, beverages and eggs. The daily intake of total and carcinogenic PAHs also was calculated by multiplying the average consumption of each food by its mean concentration of PAHs. Cereal and milk products, meat, vegetables and fruits were the highest contributors to total PAH intake, since these products are the most important dietary components in Italy. The calculated total dietary PAH intake was 3 micrograms/day per person. The calculated intake of carcinogenic PAHs was 1.4 microgram/day per person. The dietary intake of PAHs was high compared with the calculated respiratory intake (370 ng/day) owing to polluted city air in Italy. These results confirm that food is the major source of human exposure to PAHs, due in particular to the high consumption of contaminated cereal products.

Is interhemispheric transfer time related to age? A developmental study.

In simple visuomotor reaction time tasks, the difference between reaction time (RT) in the uncrossed hand/hemifield condition from RT in the crossed hand/hemifield, known as CUD (crossed-uncrossed difference), has been interpreted as reflecting interhemispheric transmission time (IHTT). Several studies in normal adults have found a CUD of a few milliseconds (3-4), while an abnormally long CUD has been reported in patients who underwent a surgical section of the corpus callosum or in congenital acallosal subjects. The corpus callosum, which is the most important structure for interhemispheric transfer of information, completes its myelination approximately by age ten. It has been hypothesized that the functional maturity of the corpus callosum coincides with the termination of the myelination cycle. No developmental study has focused on the development of IHTT, in relation to callosal maturation. The purpose of our study has been to investigate the development of interhemispheric transfer of visuomotor information in children aged seven to eleven, using a simple RT task with lateralized visual stimuli. The results indicate an age-related decrease of CUD, which we interpret as reflecting the maturation of the corpus callosum during childhood years.