Laboratory and semi-field evaluation of the efficacy of Bacillus thuringiensis var. israelensis (Bactivec®) and Bacillus sphaericus (Griselesf®) for control of mosquito vectors in northeastern Tanzania.

Bacterial larvicides Bacillus thuringiensis var. israelensis (Bti) and Bacillus sphaericus (Bs) have been used extensively for mosquito control. However, their efficacy varies greatly mainly due to factors related to target mosquitoes, larval habitat conditions, and inherent larvicide properties. We evaluated the efficacy of Bti (Bactivec®) and Bs (Griselesf®) for control of Anopheles gambiae complex, Culex quinquefasciatus and Aedes aegypti larvae under laboratory and semi-field conditions in northeastern Tanzania. Laboratory bioassays were conducted with five to six different concentrations of Bti and Bs, replicated four times and the experiment repeated on three different days. Larvae mortality was recorded at 24 or 48 h after the application of larvicide and subjected to Probit analysis. Laboratory bioassays were followed by semi-field trials to establish initial and residual activity of Bti and Bs. Semi-field trials were conducted in artificial larval habitats in the open sunlit ground and in "mosquito spheres". These artificial larval habitats were colonized with mosquito larvae, treated with Bti and Bs, and the impact of treatments on mosquito larvae was monitored daily. Lethal concentration values that caused 50% and 95% mortalities of test larvae (LC50 and LC95) showed that An. gambiae complex and Cx. quinquefasciatus tested were highly susceptible to Bti and Bs under laboratory conditions. Likewise, larvae of Ae. aegypti were highly susceptible to Bti, with LC95 value as low as 0.052 mg/l. However, Ae. aegypti larvae were not susceptible to Bs under practical doses of laboratory settings. In semi-field trials, all treatment dosages for Bti provided 91.0-100% larval mortality within 24 h whereas Bs resulted in 96.8-100% larval mortality within the same time-frame. Bs had a more prolonged residual activity, with pupal reductions range of 55.7-100% for 9 days at all application rates while the corresponding pupal reduction with Bti was 15.4-100% for 5 days. Due to the low residual activity of Bti and Bs tested, weekly application at a maximum label rate would be appropriate to reduce mosquito larvae in natural larval habitats. Based on laboratory findings, Bs product tested would not be recommended for use in the control of Ae. aegypti.

Benchmarking HIV health care: from individual patient care to health care evaluation. An example from the EuroSIDA study.

BACKGROUND: State-of-the-art care involving the utilisation of multiple health care interventions is the basis for an optimal long-term clinical prognosis for HIV-patients. We evaluated health care for HIV patients based on four key indicators. METHODS: Four indicators of health care were assessed: Compliance with current guidelines on initiation of: 1) combination antiretroviral therapy (cART); 2) chemoprophylaxis; 3) frequency of laboratory monitoring; and 4) virological response to cART (proportion of patients with HIV-RNA < 500copies/ml for >90% of time on cART). RESULTS: 7097 EuroSIDA patients were included from Northern (n = 923), Southern (n = 1059), West Central (n = 1290) East Central (n = 1366), Eastern (n = 1964) Europe, and Argentina (n = 495). Patients in Eastern Europe with a CD4 < 200cells/mm(3) were less likely to initiate cART and Pneumocystis jiroveci-chemoprophylaxis compared to patients from all other regions, and less frequently had a laboratory assessment of their disease status. The proportion of patients with virological response was highest in Northern, 89% vs. 84%, 78%, 78%, 61%, 55% in West Central, Southern, East Central Europe, Argentina and Eastern Europe, respectively (p < 0.0001). Compared to Northern, patients from other regions had significantly lower odds of virological response; the difference was most pronounced for Eastern Europe and Argentina (adjusted OR 0.16 [95%CI 0.11-0.23, p < 0.0001]; 0.20[0.14-0.28, p < 0.0001] respectively). CONCLUSIONS: This assessment of HIV health care utilization revealed pronounced regional differences in adherence to guidelines and can help to identify gaps and direct target interventions. It may serve as a tool for the assessment and benchmarking of the clinical management of HIV patients in any setting worldwide.

Five-year trends in epidemiology and prevention of mother-to-child HIV transmission, St. Petersburg, Russia: results from perinatal HIV surveillance.

BACKGROUND: The HIV epidemic in Russia has increasingly involved reproductive-aged women, which may increase perinatal HIV transmission. METHODS: Standard HIV case-reporting and enhanced perinatal HIV surveillance systems were used for prospective assessment of HIV-infected women giving birth in St. Petersburg, Russia, during 2004-2008. Trends in social, perinatal, and clinical factors influencing mother-to-child HIV transmission stratified by history of injection drug use, and rates of perinatal HIV transmission were assessed using two-sided χ2 or Cochran-Armitage tests. RESULTS: Among HIV-infected women who gave birth, the proportion of women who self-reported ever using injection drugs (IDUs) decreased from 62% in 2004 to 41% in 2008 (P<0.0001). Programmatic improvements led to increased uptake of the following clinical services from 2004 to 2008 (all P<0.01): initiation of antiretroviral prophylaxis at ≤28 weeks gestation (IDUs 44%-54%, non-IDUs 45%-72%), monitoring of immunologic (IDUs 48%-64%, non-IDUs 58%-80%) and virologic status (IDUs 8%-58%, non-IDUs 10%-75%), dual/triple antiretroviral prophylaxis (IDUs 9%-44%, non-IDUs 14%-59%). After initial increase from 5.3% (95% confidence interval [CI] 3.5%-7.8%) in 2004 to 8.5% (CI 6.1%-11.7%) in 2005 (P<0.05), perinatal HIV transmission decreased to 5.3% (CI 3.4%-8.3%) in 2006, and 3.2% (CI 1.7%-5.8%) in 2007 (P for trend<0.05). However, the proportion of women without prenatal care and without HIV testing before labor and delivery remained unchanged. CONCLUSIONS: Reduced proportion of IDUs and improved clinical services among HIV-infected women giving birth were accompanied by decreased perinatal HIV transmission, which can be further reduced by increasing outreach and HIV testing of women before and during pregnancy.

Tuberculosis among HIV-positive patients across Europe: changes over time and risk factors.

OBJECTIVE: To describe temporal changes in the incidence rate of tuberculosis (TB) (pulmonary or extrapulmonary) among HIV-positive patients in western Europe and risk factors of TB across Europe. METHODS: Poisson regression models were used to determine temporal changes in incidence rate of TB among 11,952 patients from western Europe (1994-2010), and to assess risk factors for TB among 12,673 patients from across Europe with follow-up after 2001. RESULTS: Two hundred and seventy-seven TB events occurred during 84,221 person-years of follow-up (PYFU) in western Europe. The incidence rate declined from 1.91 [95% confidence interval (CI) 1.51-2.37)] in 1994-1995 to 0.12 (0.07-0.21)/100 PYFU in 2002-2003, and remained stable thereafter. After January 2001, 159 TB events were diagnosed; 65 cases in western Europe and 94 cases in eastern Europe; resulting in incidence rates of 0.12 (0.09-0.14) and 0.65 (0.52-0.79)/100 PYFU, respectively. In multivariable analysis, incidence rate of TB was approximately four-fold higher in eastern Europe compared with western Europe [incidence rate ratio (IRR) 4.25 (2.78-6.49), P < 0.001]. There were no significant temporal changes after 2001 and risk factors did not differ significantly between eastern Europe and western Europe. Lower CD4 cell counts, higher HIV-RNA levels, male sex, intravenous drug usage and African origin were all associated with higher risk of TB. CONCLUSION: Incidence rates of TB in western Europe remained at a very low and stable level since 2001. After 2001, patients in eastern Europe were at substantially higher risk of TB than in western Europe. TB is of great concern in HIV-positive patients, especially in areas with high TB prevalence, high levels of immigration from TB-endemic regions, and with suboptimal access to combination antiretroviral therapy.

Antiretroviral prophylaxis to prevent perinatal HIV transmission in St. Petersburg, Russia: too little, too late.

BACKGROUND: We evaluated the influence of type and timing of prophylaxis on perinatal HIV transmission in St. Petersburg, Russia. METHODS: We linked surveillance data for 1498 HIV-infected mothers delivering from 2004 to 2007 with polymerase chain reaction data for 1159 infants to determine predictors of transmission. RESULTS: The overall perinatal transmission rate was 6.3% [73 of 1159, 95% confidence interval (CI) 4.9% to 7.7%]. Among the 12.8% (n = 149) of mother-infant pairs receiving full course (antenatal, intrapartum, postnatal) dual/triple antiretroviral prophylaxis, the transmission rate was 2.7%. Among the 1010 receiving less complete regimens (full course zidovudine, single-dose nevirapine, or incomplete), transmission ranged from 4.1% to 12.2%. Among the 28.9% (330) of mothers initiating antiretroviral drugs or=29 weeks (or not at all) had increased transmission odds (adjusted odds ratio: 4.9, 95% CI: 1.8 to 12.9; odds ratio: 5.1, 95% CI: 2.0 to 13.1, respectively). CONCLUSIONS: In St. Petersburg, the potential for further reductions in perinatal transmission is evident, given low transmission among women receiving early combination prophylaxis.

Mortality from HIV and TB coinfections is higher in Eastern Europe than in Western Europe and Argentina.

BACKGROUND AND OBJECTIVES: Tuberculosis (TB) is a leading cause of death in HIV-infected patients worldwide. We aimed to study clinical characteristics and outcome of 1075 consecutive patients diagnosed with HIV/TB from 2004 to 2006 in Europe and Argentina. METHODS: One-year mortality was assessed in patients stratified according to region of residence, and factors associated with death were evaluated in multivariable Cox models. RESULTS: At TB diagnosis, patients in Eastern Europe had less advanced immunodeficiency, whereas a greater proportion had a history of intravenous drug use, coinfection with hepatitis C, disseminated TB, and infection with drug-resistant TB (P < 0.0001). In Eastern Europe, fewer patients initiated TB treatment containing at least rifamycin, isoniazid, and pyrazinamide or combination antiretroviral therapy (P < 0.0001). Mortality at 1 year was 27% in Eastern Europe, compared with 7, 9 and 11% in Central/Northern Europe, Southern Europe, and Argentina, respectively (P < 0.0001). In a multivariable model, the adjusted relative hazard of death was significantly lower in each of the other regions compared with Eastern Europe: 0.34 (95% confidence interval 0.17-0.65), 0.28 (0.14-0.57), 0.34 (0.15-0.77) in Argentina, Southern Europe and Central/Northern Europe, respectively. Factors significantly associated with increased mortality were CD4 cell count less than 200 cells/microl [2.31 (1.56-3.45)], prior AIDS [1.74 (1.22-2.47)], disseminated TB [2.00 (1.38-2.85)], initiation of TB treatment not including rifamycin, isoniazid and pyrazinamide [1.68 (1.20-2.36)], and rifamycin resistance [2.10 (1.29-3.41)]. Adjusting for these known confounders did not explain the increased mortality seen in Eastern Europe. CONCLUSION: The poor outcome of patients with HIV/TB in Eastern Europe deserves further study and urgent public health attention.

Rapid HIV testing and prevention of perinatal HIV transmission in high-risk maternity hospitals in St. Petersburg, Russia.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of a human immunodeficiency virus (HIV) rapid testing (RT) program. STUDY DESIGN: From April 13, 2004, to April 13, 2005, pregnant women at 2 high-risk maternity hospitals with no or incomplete HIV testing results (negative tests at <34 weeks, none thereafter) were offered point-of-care RT, with antiretroviral prophylaxis for RT-positive women and their infants. RESULTS: Overall, 89.2% of eligible women (3671/4117) underwent RT, of whom 90.4% received results before delivery. HIV seroprevalence among all women who underwent RT was 2.7% (100/3671 women); among previously untested women, seroprevalence was 6.5% (90/1375 women); the incidence of HIV seroconversion among women with previous negative tests during pregnancy was 0.4% (10/2296 women). After adjustment, the main predictor of receiving RT results after delivery was late admission. Among HIV-exposed infants, 97.9% (92/94) received prophylaxis; 61.7% (58/94) had available follow-up data, and 8.6% (5/58) met criteria for definitive or presumptive HIV infection. CONCLUSION: The RT program achieved timely detection of HIV-infected women in labor with unknown HIV status and effectively prevented perinatal HIV transmission.

A double-blind, controlled, multicenter, randomized study comparing the antihypertensive effectiveness and tolerance of a daily dose of two nifedipine formulations: nifedipine microgranules versus nifedipine osmotic pump.

INTRODUCTION: Controlled clinical studies have clearly established the advantages of blood pressure (BP) reduction. However, optimal control of BP in the population is still not adequate. Monotherapy is ineffective in the majority of hypertensive patients, and multidrug therapy increases costs. OBJECTIVE: The objective of the study was to assess to what extent and how uniformly BP can be controlled with two different 24-hour drug-releasing formulations of nifedipine, used as monotherapy. METHODS: One hundred ninety-two patients of both genders, aged 18 to 65 years, with mild to moderate (Stage 1 and 2) essential hypertension with systolic BP <200 mm Hg and diastolic BP between 90 and 115 mm Hg were randomized in a double-blind, double-dummy fashion to receive sustained-release formulations of 30 mg nifedipine/day either as microgranules (NMG) or via osmotic pump (NOP) for 8 weeks. Office BP was measured at baseline (after 2 weeks of placebo) and after the third to fourth week of treatment. If at the third to fourth week the systolic BP/diastolic BP did not reach values of <140/<90 mm Hg, the dose was doubled to 60 mg/day. Monotherapy that did not yield these BP values at 8 weeks was considered a failure. Ambulatory monitoring of blood pressure (AMBP) was also performed after the placebo period and at the end of treatment. Smoothness index (SI) and trough/peak ratio (T/P) were calculated and their correlation was checked. RESULTS: The initial systolic/diastolic BP values were similar at baseline and decreased significantly after the third to fourth week of treatment, with no difference between the groups. The proportions of patients reaching the goal BP (<140/<90 mm Hg) were similar in the two groups: NMG, 71%, and NOP, 78% (P = 0.12). There were no changes in the heart rate in either group. There was no difference between groups in the reduction in mean arterial pressure measured by AMBP. The frequency of SI values >1.4 and T/P ratios of >0.5 was similar in both groups. An important correlation was found between the SI and T/P values. The incidence of adverse effects was low and similar in both groups. CONCLUSIONS: Target BP was reached in more than 70% of patients receiving monotherapy with either formulation. Both formulations were tolerated well.

Electrocardiographic abnormalities in patients with diphtheria: a prospective study.

PURPOSE: To determine the incidence of and risk factors for electrocardiographic (ECG) abnormalities in adults with diphtheria. METHODS: A prospective study was conducted involving 122 adult patients with respiratory tract diphtheria. Diphtheria was confirmed by isolation of a toxin-producing strain of Corynebacterium diphtheriae. Patients had serial clinical evaluations and ECGs for a minimum of 21 days. RESULTS: Cardiac involvement was detected in 25 (28%) of 88 evaluable patients, with a median time from symptom onset to an abnormal ECG of 9 days (range, 4 to 24 days). In a logistic regression analysis, age (odds ratio [OR] = 4.1; 95% confidence interval [CI]: 1.6 to 11.0), shared accommodation (OR = 2.9; 95% CI: 1.0 to 8.6), fever (OR = 4.2; 95% CI: 1.1 to 16.6), and extensive respiratory tract infection with subcutaneous edema (OR = 7.0; 95% CI: 1.2 to 42.2) were independent risk factors for cardiac involvement. CONCLUSION: Cardiac involvement is a common complication of respiratory tract infection with C. diphtheriae, and occurs more often among older patients, those with lower socioeconomic status, and those with severe respiratory tract involvement.