Do antibody responses to malaria vaccine candidates influenced by the level of malaria transmission protect from malaria?

Objectives To examine whether the humoural response to malaria vaccine candidate antigens, Plasmodium falciparum [circumsporozoite repetitive sequence (NANP)₅ GLURP fragments (R0 and R2) and MSP3] varies with the level of malaria transmission and to determine whether the antibodies (IgG) present at the beginning of the malaria transmission season protect against clinical malaria. Methods Cross‐sectional surveys were conducted to measure antibody response before, at the peak and at the end of the transmission season in children aged 6 months to 10 years in two villages with different levels of malaria transmission. A cohort study was performed to estimate the incidence of clinical malaria. Results Antibodies to these antigens showed different seasonal patterns. IgG concentrations to any of the four antigens were higher in the village with high entomological inoculation rate. Multivariate analysis of combined data from the two villages indicated that children who were classified as responders to the selected antigens were at lower risk of clinical malaria than children classified as non‐responders [(NANP)₅ (incidence rate ratio (IRR) = 0.65, 95% CI: 0.46–0.92; P = 0.016), R0 (IRR = 0.69, 95% CI: 0.48–0.97; P = 0.032), R2 (IRR = 0.73, 95% CI: 0.50–1.06; P = 0.09), MSP3 (IRR = 0.52, 95% CI: 0.32–0.85; P = 0.009)]. Fitting a model with all four antibody responses showed that MSP3 looked the best malaria vaccine candidate (IRR = 0.63; 95% CI: 0.38–1.05; P = 0.08). Conclusion Antibody levels to the four antigens are affected by the intensity of malaria transmission and associated with protection against clinical malaria. It is worthwhile investing in the development of these antigens as potential malaria vaccine candidates.     

Seasonality of the dietary dimension of household food security in urban Burkina Faso

Food insecurity is affecting an increasing number of urban poor in the developing world. Yet seasonal characteristics of food intakes have rarely been studied in West African cities. The objective of the present study was to assess the seasonality of the dietary dimension of household food security in Ouagadougou (Burkina Faso). In 2007, two sets of data were collected during the lean and post-harvest seasons, respectively, on a representative sample of 1056 households. At each season, two non-consecutive 24 h recalls were performed at the household level. Food prices were also recorded. Household food security was assessed by the household's mean adequacy ratio (MAR) for energy and eleven micronutrients. Changes in the MAR according to the season were analysed by mixed multivariate linear regression. Results showed that intakes of energy and of ten micronutrients were significantly lower during the lean season than during the post-harvest season, leading to a lower MAR in the lean season (49·61 v. 53·57, P < 0·0001). This was related to less frequent consumption and consumption of smaller amounts of vegetables and of foods prepared at home. Food security relied heavily on food expenses (P < 0·0001) and on the price of meat/fish (P = 0·026). Households with economically dependent adults (P = 0·021) and larger households (P < 0·0001) were the most vulnerable, whereas education (P = 0·030), social network (P = 0·054) and urban origin other than Ouagadougou (P = 0·040) played a positive role in food security. To achieve food security in Ouagadougou, access to micronutrient-dense foods needs to be ensured in all seasons.     

Overweight,obesity and risk of premenopausal breast cancer according to ethnicity: a systematic review and dose‐response meta‐analysis

The association of overweight and obesity with premenopausal breast cancer remained unclear, ethnicity could play a role. A MEDLINE and PUBMED search of all studies on obesity and premenopausal breast cancer published from 2000 to 2010 was conducted. Dose‐response meta‐analysis was used to determine the risk of premenopausal breast cancer associated with different anthropometric measurements in different ethnic groups. For body mass index (BMI), each 5 kg m^?2 increase was inversely associated with the risk of premenopausal breast cancer (RR = 0.95, 95% confidence interval [CI]: 0.94, 0.97). After stratification by ethnicity, the inverse association remained significant only among Africans (RR = 0.95, 95% CI: 0.91, 0.98) and Caucasians (RR = 0.93, 95% CI: 0.91, 0.95). In contrast, among Asian women, a significant positive association was observed. For waist‐to‐hip ratio (WHR), each 0.1 unit increase was positively associated with premenopausal breast cancer (RR = 1.08, 95% CI: 1.01, 1.16); the largest effect was detected in Asian women (RR = 1.19, 95% CI: 1.15, 1.24), while small effects of 5% and 6% were observed in African and Caucasian women, respectively. Our results suggest the importance of considering both fat distribution and ethnicity when studying premenopausal breast cancer.     

Inhibition of Na(+)/H(+) isoform-1 exchange protects hearts perfused after 6-hour cardioplegic cold storage.

OBJECTIVES: Cardiac ischemia-reperfusion activates Na(+)/H(+) exchange; excess Na(+) and the resulting Ca(2+) overload, through reverse Na(+)/Ca(2+) exchange, cause cellular injury and cardiac dysfunction. We postulated that inhibiting the Na(+)/H(+) isoform-1 exchanger would add to the protection of hearts after long-term cold storage in acidic cardioplegic solution. METHODS: Guinea pig hearts were isolated and perfused at 37 degrees C with Krebs-Ringer's solution (KRS) and then switched to an acidic St. Thomas solution (STS) at 25 degrees C. Perfusion was stopped at 10 degrees C, and hearts were stored for 6 hours in STS at 3.4 degrees C. On reperfusion to 25 degrees C, hearts were perfused with KRS for 60 minutes. Hearts were divided into 4 groups: sham control (SHAM); eniporide (EPR, EMD96785) IV, 1 mg/kg given IV over 15 minutes before heart isolation; EPR intracoronary, 1 micromol/liter in STS given intracoronary after heart isolation; and EPR IV and intracoronary. RESULTS: Values at 60 minutes reperfusion (the percentage of control [100%] before cold storage) are given, respectively, for EPR IV, EPR intracoronary, and EPR IV and intracoronary vs drug-free SHAM (SEM, *p < 0.05 vs SHAM): 72% +/- 3%*, 65% +/- 3%*, and 81% +/- 2%* vs 55% +/- 3% for left ventricular pressure; 94% +/- 3%*, 96% +/- 5%*, and 102% +/- 2%* vs 81% +/- 3% for coronary flow; 60% +/- 2%, 58% +/- 3%, and 74%* +/- 3% vs 58% +/- 4% for cardiac efficiency; 106% +/- 2%*, 108% +/- 3%*, and 107% +/- 2%* vs 116% +/- 4% for percentage of O(2) extraction. Infarct size as percentage of ventricular weight was 20% +/- 3%*, 31% +/- 3%, and 6% +/- 2%* vs 35% +/- 3% (SHAM) after 60 minutes of reperfusion. CONCLUSIONS: Na(+)/H(+) isoform-1 exchanger inhibition, particularly if given IV before storage and intracoronary during cooling and rewarming, adds to the protection of cardioplegic solutions.     

Attenuation of Mitochondrial Respiration by Sevoflurane in Isolated Cardiac Mitochondria Is Mediated in Part by Reactive Oxygen Species

Background: Anesthetic preconditioning protects against cardiac ischemia/reperfusion injury. Increases in reduced nicotinamide adenine dinucleotide and reactive oxygen species during sevoflurane exposure suggest attenuated mitochondrial electron transport as a trigger of anesthetic preconditioning. The authors investigated the effects of sevoflurane on respiration in isolated cardiac mitochondria.

Methods: Mitochondria were isolated from fresh guinea pig hearts, and mitochondrial oxygen consumption was measured in the presence of complex I (pyruvate) or complex II (succinate) substrates. The mitochondria were exposed to 0, 0.13, 0.39, 1.3, or 3.9 mm sevoflurane. State 3 respiration was determined after adenosine diphosphate addition. The reactive oxygen species scavengers manganese(III) tetrakis (4-benzoic acid) porphyrin chloride and N-tert-Butyl-a-(2-sulfophenyl)nitrone sodium (10 [mu]m each), or the KATP channel blockers glibenclamide (2 [mu]m) or 5-hydroxydecanoate (300 [mu]m), were given alone or before 1.3 mm sevoflurane.

Results: Sevoflurane attenuated respiration for both complex I and complex II substrates, depending on the dose. Glibenclamide and 5-hydroxydecanoate had no effect on this attenuation. Both scavengers, however, abolished the sevoflurane-induced attenuation for complex I substrates, but not for complex II substrates.     

Longitudinal assessment of HIV-1 and HSV-2 shedding in the genital tract of West African women

Forty-two HSV-2-seropositive women, of whom 22 were HIV-1 seropositive, were followed up weekly for 3 weeks for assessment of HIV-1 and HSV-2 genital shedding in Bobo Dioulasso, Burkina Faso. HSV-2 DNA and HIV-1 RNA were quantitated in cervicovaginal lavages enriched with a cervical swabbing (eCVL) using real-time polymerase chain reaction. HIV-1 RNA shedding was detected in eCVL from 19 of 22 (86.4%) of the HIV-1-seropositive women and HSV-2 DNA was detected in eCVL from 12 of 42 (28.6%) of the women. Compared with the HIV-1-seronegative women, the HIV-1-seropositive women showed more persistent HSV-2 genital shedding and higher HSV-2 DNA loads in eCVL. This study showed that eCVL is a reliable sampling method for detecting both viruses. Three measurement points (at weekly intervals in this study) seem to adequately allow detection of most HIV-1 or HSV-2 genital shedders.     

Nationwide HIV prevalence survey in general population in Niger

A national population-based survey was carried out in Niger in 2002 to assess HIV prevalence in the population aged 15-49 years. A two-stage cluster sampling was used and the blood specimens were collected on filter paper and tested according to an algorithm involving up to three diagnostic tests whenever appropriate. Testing was unlinked and anonymous. The refusal rate was 1.1% and 6056 blood samples were available for analysis. The adjusted prevalence of HIV was 0.87% (95% CI, 0.5-1.3%) and the 95% CI of the estimated number of infected individuals was 22 864-59 640. HIV-1 and HIV-2 represented, respectively, 95.6% and 2.9% of infections while dual infections represented 1.5%. HIV positivity rate was 1.0% in women and 0.7% in men. It was significantly higher among urban populations than among rural ones (respectively, 2.1% and 0.6%, P < 10(-6)). Using logistic regression, the variables significantly related to the risk of being tested positive for HIV were urban housing, increasing age and being either widowed or divorced. The estimate from the national survey was lower than the prevalence assessed from antenatal clinic data (2.8% in 2001). In the future, the representativeness of sentinel sites should be improved by increasing the representation of rural areas accounting for more than 80% of the population. Compared with other sub-Saharan countries, the HIV prevalence in Niger is still moderate. This situation represents a strong argument for enhancing prevention programmes and makes realistic the projects promoting an access to potent antiretroviral therapies for the majority.     

Malaria prevention during pregnancy: assessing the disease burden one year after implementing a program of intermittent preventive treatment in Koupela District, Burkina Faso

The World Health Organization recommends that pregnant women in malaria-endemic areas receive >or= 2 doses of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp/SP) in the second and third trimesters of pregnancy to prevent maternal anemia, placental parasitemia, and low birth weight (LBW). In 2001, a program evaluation in Koupéla District, Burkina Faso demonstrated that despite widespread use of chloroquine chemoprophylaxis, the burden of malaria during pregnancy remained high. In 2003, the Burkina Faso Ministry of Health piloted a program of IPTp/SP (three doses) and accelerated distribution of insecticide-treated nets (ITN) to pregnant women in Koupéla District. In 2004, a follow-up program evaluation was conducted. Coverage with >or= 1 doses of IPTp/SP was high among women attending antenatal clinics (ANCs) (96.2%) and delivery units (DUs) (93.5%); ITN ownership was moderately high (ANC = 53.9%, DU = 61.6%). In multivariate analysis, >or= 1 dose of IPTp/SP was associated with a significant reduction in the prevalence of peripheral parasitemia at ANCs (risk ratio [RR] = 0.49, P = 0.008), >or= 2 doses of IPTp/SP were associated with a reduction in the prevalence of placental parasitemia (RR = 0.56, P = 0.02), and three doses of IPTp/SP were associated with a reduced risk of LBW (RR = 0.51, P = 0.04). The proportions of women at ANCs with peripheral parasitemia and anemia were significantly lower in 2004 than in 2001 (RR = 0.53, P = 0.001 and RR = 0.78, P = 0.003, respectively). The proportions of women at DUs with peripheral and placental parasitemia were also significantly lower in 2004 than in 2001 (RR = 0.66, P < 0.0001 and RR = 0.71, P = 0.0002, respectively). These data suggest that a package of IPTp/SP and ITNs is effective in reducing the burden of malaria during pregnancy in Burkina Faso.