Does smallpox vaccination modify HIV disease progression among ART-naive people living with HIV in Africa?

We examined the association between a history of smallpox vaccination and immune activation (IA) in a population of antiretroviral therapy-naïve people living with HIV (PLHIV). A cross-sectional study was conducted in Senegal from July 2015 to March 2017. Smallpox vaccination was ascertained by the presence of smallpox vaccine scar and IA by the plasma level of ß-2-microglobulin (ß2m). The association was analysed using logistic regression and linear regression models. The study population comprised 101 PLHIV born before 1980 with a median age of 47 years (interquartile range (IQR) = 42-55); 57·4% were women. Smallpox vaccine scar was present in 65·3% and the median ß2m level was 2·59 mg/l (IQR = 2·06-3·86). After adjustment, the presence of smallpox vaccine scar was not associated with a ß2m level ⩾2·59 mg/l (adjusted odds ratio 0·94; 95% confidence interval 0·32-2·77). This result was confirmed by the linear regression model. Our study does not find any association between the presence of smallpox vaccine scar and the ß2m level and does not support any association between a previous smallpox vaccination and HIV disease progression. In this study, IA is not a significant determinant of the reported non-targeted effect of smallpox vaccination in PLHIV.

Results from the Survey of Antibiotic Resistance (SOAR) 2011-14 in the Democratic Republic of Congo, Ivory Coast, Republic of Senegal and Kenya.

OBJECTIVES: To assess antibiotic susceptibility of community-acquired respiratory tract isolates from Ivory Coast, Kenya, Democratic Republic of Congo (DRC) and Senegal in 2011-14. METHODS: Bacterial isolates were collected and MICs determined using Etest(®) for all antibiotics except erythromycin, for which testing was by disc diffusion. Susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. For macrolide interpretation, CLSI breakpoints were adjusted for incubation in CO2. RESULTS: Susceptibility to penicillin (using CLSI oral or EUCAST breakpoints) was low among isolates of Streptococcus pneumoniae from the DRC and Kenya (17.4% and 19%, respectively) but higher among isolates from the Ivory Coast (70%) and Senegal (85.7%). Penicillin susceptibility using CLSI iv breakpoints was higher in all countries, but still only 69.6% in the DRC. Macrolide susceptibility (based on CLSI erythromycin disc diffusion breakpoints) was also low in Kenya (∼65%) but 87%-100% elsewhere. Haemophilus influenzae were only collected in the DRC and Senegal, with ß-lactamase prevalence of 39% and 4%, respectively. Furthermore, ß-lactamase-negative ampicillin-resistant (BLNAR) isolates were found in DRC (four isolates, 17%), but only two isolates were found in Senegal (by EUCAST definition). Amoxicillin/clavulanic acid in vitro susceptibility was 73.9% in the DRC and 100% in Senegal based on CLSI breakpoints, but this reduced to 65.2% in the DRC when BLNAR rates were considered. Clarithromycin susceptibility was >95% in both countries. CONCLUSIONS: There was considerable variability in antibiotic susceptibility among the African countries participating in the surveillance programme. Thus, continued surveillance is necessary to track future changes in antibiotic resistance. Use of EUCAST versus CLSI breakpoints showed profound differences for cefaclor and ofloxacin against S. pneumoniae, with EUCAST showing lower susceptibility.

Variation in transplacental transfer of tyrosine kinase inhibitors in the human perfused cotyledon model.

BACKGROUND: The use of tyrosine kinase inhibitors (TKis) during pregnancy in humans remains rare, and little data are available on their transplacental passage. Erlotinib and gefitinib are the first-line targeted therapy in case of stage IV nonsmall-cell lung cancer with an EGFR-activating mutation. There are no data available regarding the comparative use of these TKis in pregnant patients. We aimed to compare the transplacental transfer of gefitinib, imatinib and erlotinib, using the ex vivo method of human perfused cotyledon, and to determine the placental accumulation of TKis. MATERIALS AND METHODS: Term placentas were perfused after delivery with gefitinib, imatinib and erlotinib at targeted maternal concentrations around the steady-state plasma trough concentration (i.e. 500, 1000 and 1500 ng/ml, respectively). Samples from fetal and maternal circulations were collected in order to monitor TKis concentrations. Main transfer parameters such as fetal transfer rate (FTR), clearance index (CI) and placental uptake were assessed. RESULTS: Mean FTR of gefitinib, imatinib and erlotinib were 16.8%, 10.6% and 31.4%, respectively. Mean CI of gefitinib, imatinib and erlotinib were 0.59, 0.48 and 0.93, respectively. Placental uptake in cotyledon was 0.030% %, 0.010% and 0.003% for gefitinib, imatinib and erlotinib, respectively, corresponding to a mean mass of 27.7 µg for gefitinib, 15.7 µg for imatinib and 6.8 µg for erlotinib. CONCLUSION: The results suggest that TKis cross the placenta at therapeutic level. Particularly, erlotinib crosses the placenta at a higher rate than gefitinib or imatinib. All of them have a very low placental uptake. These data may suggest that gefitinib should be preferred to erlotinib for the treatment of pregnant woman with lung cancer harboring an EGFR-activating mutation, during the second and third trimesters of pregnancy.

[Relationship between bizygomatic width and the size of maxillary anterior teeth among young Senegalese black people recruited in army]. / Corrélation entre la distance bizygomatique et la largeur des dents antéromaxillaires chez les jeunes sénégalais mélanodermes recrutés dans le service militaire.

INTRODUCTION: Prosthetic teeth size and placement must be in perfect harmony with the bucco-facial structures for a successful and esthetic removable prosthesis. This study aimed to determine among young Senegalese black people facial index estimating maxillary central incisor width and distance between canine points starting from bizygomatic width. PATIENTS AND METHODS: 621 black Senegalese participated to this transversal study. Measurements were made using anthropometric slide caliper and electronic slide caliper. The comparative analysis was carried out by the test t of Student. The correlative analysis used the chi-square test. The risk of error was fixed at 5%. RESULTS: Positive correlations were found between variables. Distance between canine points was significantly (p = 0.000) correlated to bizygomatic width and central incisor width. Using bizygomatic width, the average dividing factors to estimate central incisor width and distance between canine points were respectively 15.13 and 3.75. CONCLUSION: Distance between canine points and central incisor width can be given starting from bizygomatic width, as guide of selecting maxillary anterior prosthetic teeth width.

Analyzing the benefit of optical transmission systems based on Root Raised Cosine PS-QPSK and a flexible channel grid.

We numerically investigate the multi-channel transmission performance of Polarization Switched Quadrature Phase Shift Keying (PS-QPSK) and we compare it to the performance of Polarization-Division-Multiplexed QPSK (PDM-QPSK), using Root Raised Cosine (RRC) spectral shaping, in the context of a flexible channel grid. We point out the impact of the roll-off factor and the potential influence of different dispersion compensation scenarios. Finally, the advantage of PS-QPSK against PDM-QPSK is presented as a function of the system parameters, while we also discuss the benefit of a RRC spectral shaping against a tight filtering at the transmitter side with a 2nd order super-Gaussian-shaped filter.

[Correlations between colorimetric parameters of teeth, eyes and skin. Perspectives in the choice of tooth shade for complete denture]. / Correlations entre les parametres colorimétriques des dents, des yeux et de la peau. Perspectives dans le choix de la teinte des dents en prothèse adjointe complète.

Rehabilitation with complete denture include among other objectives, improvement of facial and dental esthetics. To these ends, the artificial teeth should mimic as far as possible, healthy and natural dentition. The main objective of this study was to investigate factors associated with tooth color among black African subjects. One hundred and two subjects (72 men and 30 women) were included in this investigation. The colorimetric parameters of their teeth as well as those of the conjunctiva of their eyes and skin were recorded from standardized photographs. Two software, Mesurim and Photoshop were used for that purpose. Univariate and linear regression analysis were run to assess the association between tooth color and the variables age, gender and colorimetric parameters of eyes and skin. It appears from the result of this study that tooth color was positively and significantly associated with age. Stepwise multiple regression analysis further revealed that tooth hue can be best predicted by a combination of skin complexion and brightness and eye lightness.

[Helicobacter pylori and gastroduodenal lesions in Dakar, Senegal]. / Helicobacter pylori et pathologie gastroduodenale a Dakar (Sénégal).

INTRODUCTION: The bacteriological characteristics of Helicobacter pylori (HP) vary in function of time and place. The aim of this study was to update histological and bacteriological feature of HP infection in patients presenting gastroduodenal lesions in Dakar, Senegal. PATIENTS AND METHOD: This prospective study included patients with gastroduodenal lesions managed over a 6-month period in a digestive endoscopy center in Dakar. In all cases gastric biopsy was performed to obtain specimens for histological diagnosis according Sydney modified classification and HP culture with antibiogram. RESULTS: A total of 158 patients were included. Mean patient age was 48.7 years and the sex-ratio was 1.2. Endoscopic lesions were ulcer in 88 cases, gastritis in 54 cases and tumors in 16. Histological examination demonstrated chronic gastritis in 100% of cases, inflammatory activity in 79.1%, metaplasia in 78.5%, gastric atrophy in 41.1%, adenocarcinoma in 7.6%, dysplasia in 5.7%, and MALT lymphoma in 2.5% with presence of HP in 72.8% of cases. Cultures were positive for HP in 65.8% of cases. Antibiograms indicated that HP was sensitive to amoxicilline in 100% of cases, clarithromycine in 96.6%, ciprofloxacine in 84.1%, and métronidazole in 29.5%. CONCLUSION: Chronic gastritis is a constant feature of gastroduodenal lesions in Dakar. Histology combined with culture showed HP infection in 78.5% of cases. The antibiotic sensitivity of HP in Dakar has changed over the past decade.

[Prescription And Delivery's Survey Of Benzodiazepines In The Occurrence Of Addictions At Mbour's District]. / Evaluation De La Prescription Et De La Delivrance Des Benzodiazepines Dans La Survenue Des Addictions Dans Le District Sanitaire De Mbour.

Impact of the prescription and delivery of benzodiazepines in the occurrence of addictions in the district of Mbour. INTRODUCTION: Benzodiazepines (BZD) are widely used nowadays and are at the origin of an addiction. OBJECTIVES: The objective was to evaluate the quality of benzodiazepine prescribing and delivery in the Mbour department of Senegal and subsequently to implement an addictovigilance strategy. Thus, we studied the prescribing habits, the quality of delivery and identified the consumption habits of these drugs. MATERIALS AND METHODS: It was a cross-sectional, prospective study with two questionnaires: addressed to patients and prescribers, conducted in pharmacies, hospitals, districts and Mbour health posts. RESULTS: 44% of BZD prescriptions were prescribed by doctors and especially general practitioner. 31.1% did not comply with the rules of prescription (marketing authorization). As for the dispensing rules, (85.3%) were dispensed without a prescription. The level of consumption was high in the 30-40 age group (43.95%) predominantly female (59%). Insomnia predominated as a reason for prescription (16.4%) on anxiety (11.94%) with (65.5%) dependence. CONCLUSION: The abuses observed in the prescription, the delivery and consumption of BZD, constitutes a real health problem. Half of the consumers become addicted, hence the need for a national addictovigilance program.

INTRODUCTION: Les benzodiazépines (BZD) sont très utilisées de nos jours et sont à l'origine d'une addiction. OBJECTIFS: L'objectif était d'évaluer la qualité de la prescription et de la délivrance des benzodiazépines dans le département de Mbour au Sénégal et ultérieurement mettre en place une stratégie d'addictovigilance. Ainsi, nous avons étudié les habitudes de prescription, la qualité de délivrance et identifié les habitudes de consommation de ces médicaments. MATÉRIELS ET MÉTHODES: Il s'agissait d'une étude transversale, prospective avec deux questionnaires : adressé aux patients et prescripteurs, menée dans des pharmacies, hôpital, district et postes de santé de Mbour. RÉSULTATS: 44% des ordonnances de BZD étaient prescrites par des médecins et particulièrement des généralistes. 31,1% ne respectaient pas les règles de prescriptions (hors AMM). Quant aux règles de délivrance, 85,3% étaient délivrées sans ordonnance. Le niveau de consommation était élevé dans la tranche d'âge 30-40 ans (43,95%) avec une prédominance féminine (59%). L'insomnie prédominait comme motif de prescription (16,4%) sur l'anxiété (11,94%) avec (65,5%) de dépendance. CONCLUSION: Les abus observés dans la prescription, la délivrance et la consommation des BZD, constitue un véritable problème de santé. La moitié des consommateurs deviennent addictes, d'où la nécessité de mettre en place un programme d'addictovigilance à l'échelon national.

Th1/Th2 Dichotomy in Obese Women with Gestational Diabetes and Their Macrosomic Babies.

The aim of the study was to assess T cell differentiation and the modulation of inflammatory cytokines in obese and gestational diabetes mellitus (GDM) women and their macrosomic newborns. Hence, immediately after delivery, blood samples were collected through the mother's arm vein and the umbilical cordon vein. Biochemical parameters measured were HbA1C, glucose, insulin, triglyceride (TG), total cholesterol (Tchol), HDL cholesterol (HDLchol), and LDL cholesterol (LDLchol). T lymphocytes were purified from the total blood with Ficoll-Paque. The mRNA expression of inflammatory markers in T cells was determined by RT-qPCR. We observed that diabetic mothers exhibited higher HbA1C, glycemia, insulinemia, TG, Tchol, HDLchol, and LDLchol levels than control mothers. Glycemia was not significantly different between macrosomic and control newborns. However, insulinemia was high in macrosomic babies. TG, Tchol, HDLchol, and LDLchol were not significantly different between macrosomic and control babies. In diabetic mothers, mRNA expression of the Th1 cell subtype was significantly increased. Th1 markers were upregulated in babies born to diabetic women than in control newborns. However, expression of two Th2 markers (GATA3 and IL-4) was not significantly different between control and GDM women and between their respective newborns. Interestingly, IL-10 mRNA expression was decreased in diabetic mothers and their offsprings. The Th1/Th2 cytokine ratio was increased in GDM obese mothers and their macrosomic newborns, suggesting a proinflammatory status in these subjects.

[Efficacy of sodium hydroxide at 2.5 %, chlorhexidine gluconate at 0.5 % and calcium hydroxide against Candida albicans]. / Étude de l'efficacité de l'hypochlorite de sodium à 2,5 %, de la chlorhexidine à 0,5 %, et de l'hydroxyde de calcium sur Candida albicans.

INTRODUCTION: Endodontic flora is dominated in the apical part of the channels by strict anaerobic and some facultative anaerobic bacteria but also by Candida yeasts, especially Candida albicans species that are involved in the maintenance and persistence of endodontic infections. Their elimination of the canal system in practice by chemo-mechanical methods of disinfection is not always guaranteed. Thus, this in vitro study was performed to determine the sensitivity of C. albicans with sodium hypochlorite (NaOCl) dosed at 2.5 %, the chlorhexidine digluconate 0.5 % and calcium hydroxide used in inter-session medication. METHODS: The diffusion method was used initially to test the sensitivity of C. albicans strains with the above products. Then a dilution technique has allowed us to determine the minimum inhibitory concentration of these active products on C. albicans. RESULTS: Strains from infected pulp teeth of patients showed a sensitivity of C. albicans to sodium hypochlorite to a minimum inhibitory concentration less than 70µg/mL and 30µg/mL for chlorhexidine. CONCLUSION: This study demonstrated a sensitivity of C. albicans to sodium hypochlorite and chlorhexidine.

Antineoplastic busulfan encapsulated in a metal organic framework nanocarrier: first in vivo results.

Nanoparticles of a mesoporous iron(iii) trimesate MIL-100 nanocarrier encapsulating high amounts of the challenging antineoplastic busulfan were administered to rats and compared with the commercial Busilvex®. Large differences in serum concentration of both busulfan and trimesate revealed the great impact of drug encapsulation both on the drug and on nanoparticle pharmacokinetics during the first 24 h of administration.

[Evaluation of the efficacy and safety of three 2-drug combinations for the treatment of uncomplicated Plasmodium falciparum malaria in Senegal: artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artemether-lumefantrine]. / Évaluation de l'efficacité et de la tolérance des combinaisons artésunate-amodiaquine, dihydroartémisinine-pipéraquine et artéméther-luméfantrine pour le traitement du paludisme à Plasmodium falciparum non compliqué au Sénégal.

BACKGROUND: Since 2006, artemisinin-based combination therapies (ACT) have been used to treat uncomplicated Plasmodium falciparum malaria in Senegal, as recommended by WHO. Recently, decreased parasite clearance with artemisinin derivatives has been reported in Cambodia and Thailand. The effectiveness of artemisinin derivatives in Africa must be monitored. This study was conducted to evaluate the efficacy and the tolerability of three ACT widely used in Senegal. METHODS: From October 2010 to February 2011, a descriptive and analytical sequential study was conducted in adults and children to evaluate these three combinations: artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DHAPQ). The study took place at the health posts of Deggo and Pikine and the health center of Guédiawaye, in the suburbs of Dakar. The primary endpoint was the PCR-corrected adequate clinical and parasitological response (ACPR) at day 28 (D28); the secondary endpoints included ACPR at D42, clearance times for parasites, fever, and gametocytes, and the incidence of adverse events. RESULTS: The study included 393 patients: 139 in the AL group, 130 in the ASAQ group, and 124 in the DHAPQ group. In the intent-to-treat population, PCR-corrected ACPR at day 28 was 92.8% in the AL, 89.2% in the ASAQ, and 91.1% in the DHAPQ (p = 0.58) groups, and in the per-protocol population, 98.4%, 98.3%, and 100% respectively (p = 0.39). At D42, ACPR was 99.2% in the AL, and 99.1% in each of the ASAQ and DHAPQ arms (p = 1). No early therapeutic failure (ETF) was observed. The combinations were well tolerated, with no serious adverse events reported during the follow-up period. CONCLUSION: These combinations are still effective and well-tolerated. Continued monitoring is nonetheless essential to detect early artemisinin resistance in Africa.

[Dehydration and malnutrition as two independent risk factors of death in a Senegalese pediatric hospital]. / Déshydratation et malnutrition : deux facteurs de risque de décès indépendants chez l'enfant sénégalais hospitalisé

UNLABELLED: Inpatient mortality is an indicator of the quality of care. We analyzed the mortality of under 5-year-old hospitalized children in the pediatric ward of Aristide Le Dantec Hospital for updating our data 10 years after our first study. METHODS: We analyzed the data of the children hospitalized between 1 January and 31 December 2012. For each child, we collected anthropometric measurements converted to a z-score related to World Health Organization growth data. Logistic regression-generating models built separately with different anthropometric parameters were used to assess the risk of mortality according to children's characteristics. RESULTS: Data from 393 children were included. The overall mortality rate was 10% (39/393). Using logistic regression, the risk factors associated with death were severe wasting (odds ratio [OR]=8.27; 95% confidence interval [95% CI]) [3.79-18], male gender (OR=2.98; 95% CI [1.25-7.1]), dehydration (OR=5.4; 95% CI [2.54-13.43]) in the model using the weight-for-height z-score; male gender (OR=2.5; 95% CI [1.11-5.63]), dehydration (OR=8.43; 95% CI [3.83-18.5]) in the model using the height-for-age z-score; male gender (OR=2.7; 95% CI [1.19-6.24]), dehydration (OR=7.5; 95% CI [3.39-16.76]), severe deficit in the weight-for-age z-score (OR=2.4; 95% CI [1.11-5.63]) in the model using the weight-for-age z-score; and male gender (OR=2.5; 95% CI [1.11-5.63]) and dehydration (OR=8.43; 94% CI [3.83-18.5]) in the last model with mid-upper arm circumference (MUAC). Dehydration and malnutrition were two independent risk factors of death. The protocols addressing dehydration and malnutrition management should be audited and performed systematically for each child's anthropometric measurements at admission.

Genetic heterogeneity of autosomal dominant cerebellar ataxia type 1: clinical and genetic analysis of 10 French families.

We performed linkage analysis between the gene responsible for spinal cerebellar ataxia 1 (SCA1) and the highly polymorphic chromosome 6 locus, D6S89, in 10 French families with autosomal dominant cerebellar ataxia (ADCA) type 1. These families were clinically indistinguishable except for one family with loss of hearing and vision. Very close linkage was observed in four families, with no evidence of recombination between SCA1 and D6S89. Linkage with D6S89 was excluded in the six others, thus demonstrating genetic heterogeneity for ADCA type 1. The D6S89 marker, which is very closely linked to the disease locus, can be used to identify SCA1 families and will lead to predictive testing.

Serologic status and measles attack rates among vaccinated and unvaccinated children in rural Senegal.

During a measles vaccine trial in a rural area of Senegal, antibody status was examined within 10 days of exposure for 228 previously vaccinated and 313 unvaccinated children more than 12 months old who were exposed to measles at home. Thirty-six percent of the children developed clinical measles, the clinical diagnosis being confirmed for 135 of the 137 children from whom 2 blood samples were collected. Vaccine efficacy was 90% (95% confidence interval, 83 to 94%). The hemagglutinin-inhibiting antibodies (HI) or plaque neutralizing antibodies (PN) assays were equally efficient in predicting susceptibility and protection against measles. Vaccinated children who had no detectable HI or PN antibodies at exposure had significant protection against measles compared with seronegative unvaccinated children (HI vaccine efficacy, 49% (95% confidence interval, 21 to 68%); PN vaccine efficacy, 43% (95% confidence interval, 12 to 62%)). The attack rate was high for children with a titer of 40 to 125 mIU) 67% (4 of 6) of those with a positive hemagglutinin-inhibiting antibody test and 36% (13 of 36) of those with a positive PN test developed measles. Attack rates among children with HI or PN titers above 125 mIU were 2% (6 of 295) and 3% (7 of 258), respectively. Because titers of < or = 120 mIU have been found to offer little protection in another study, this antibody level may be the best screening value for assessing susceptibility and protection against measles. However, it should be noted that many seronegative vaccinated children are protected against measles infection.

Detection of hepatitis B virus DNA by polymerase chain reaction in vaccinated and non-vaccinated Senegalese children.

An hepatitis B immunization programme was initiated in Senegal in 1978, and infants included in this controlled study have been followed for a period of 2-12 years after immunization. During this period HBV infections have been observed both in vaccinated and non-vaccinated infants. The polymerase chain reaction was used to search for HBV DNA sequences in the sera of 153 children with evidence of serum markers of past or present HBV replication. Amplified HBV DNA sequences were detected in 93% of the HBsAg positive individuals, in 58% of those only positive for antiHBc antibodies and in 7.8% of antiHBs and antiHBc positive infants. The results confirm the high efficiency and long-lasting effectiveness of HB vaccine.

Risk factors for negative sputum acid-fast bacilli smears in pulmonary tuberculosis: results from Dakar, Senegal, a city with low HIV seroprevalence.

SETTING: Two teaching hospitals in Dakar, Senegal, a West African country with a low prevalence of human immunodeficiency virus (HIV) infection. OBJECTIVE: To determine whether patients with HIV-associated pulmonary tuberculosis have fewer acid-fast bacilli (AFB) in their sputum as assessed by routine microscopy, and to correlate the findings with systematically obtained clinical, radiographic and laboratory variables. DESIGN: Prospective study from November 1995 to October 1996 of 450 consecutive patients diagnosed with pulmonary tuberculosis. RESULTS: Tuberculosis was diagnosed in 380 patients (84.4%) by positive bacteriology, in 61 (13.6%) by a favorable response to anti-tuberculosis chemotherapy, and in nine (2.0%) by the presence of a miliary radiographic pattern. Forty (8.9%) patients were HIV-seropositive. AFB-negative smears were found in 14/40 (35.0%) of the HIV-seropositive patients with pulmonary tuberculosis compared with 71/410 (17.3%) of the seronegative patients (risk ratio [RR] = 2.02, 95% confidence interval [CI] 1.26-3.24, P = 0.01). Multivariate analysis revealed that AFB smear negativity was associated with absence of cavitation (P = 0.002), lack of cough (P = 0.005), the presence of HIV seropositivity (P = 0.02), a CD4+ cell count above 200/mm3 (P = 0.02), and age over 40 years (P = 0.03). CONCLUSIONS: Compared with HIV-seronegative patients with pulmonary tuberculosis, seropositive patients in Dakar, Senegal, are more likely to have negative sputum-AFB smears. This phenomenon has now been observed in seven of eight sub-Saharan African countries with varying HIV seroprevalence from which reports are available.

Protective efficacy of high-titre measles vaccines administered from the age of five months: a community study in rural Senegal.

Using data on incidence and secondary attack rates, we examined the protective efficacy of high-titre Edmonston-Zagreb (EZ) and Schwarz (SW-HT) measles vaccines administered at 5 months. Control children were assigned to placebo at age 5 months and standard Schwarz (SW-std) measles vaccine at 9-10 months of age. A large proportion of measles cases was verified serologically. Though high-titre vaccines seemed to be protective before 10 months of age, a significant reduction in disease could not be demonstrated due to low incidence of measles. After 10 months of age, SW-std given at 10 months gave a vaccine efficacy of 100% and induced better protection than SW-HT (P = 0.030) and EZ-HT (P = 0.128) administered at 5 months. In studies of secondary attack rates in the compound, vaccine efficacy was 91% (75%-97%) for EZ-HT, 85% (40%-96%) for SW-HT, and 100% for SW-std. Attack rates were correlated with intensity of exposure (P = 0.0006), being much higher for children exposed in the same hut than for those living in the same compound but in a different household (relative risk = 3.36 [1.32-8.57]). The attack rate was significantly lower among vaccinated than unvaccinated children with no detectable measles antibody (relative risk = 0.41 [0.18-0.93]). In rural areas with a high coverage in the surrounding community, a single dose at 9-10 months may provide sufficient protection. Since high-titre vaccines have been associated with higher mortality than SW-std, further improvements in measles control before 9 months may require two-dose strategies with standard vaccines.

A comparison of vaccine efficacy and mortality during routine use of high-titre Edmonston-Zagreb and Schwarz standard measles vaccines in rural Senegal.

Vaccine efficacy and mortality in successive cohorts of children who routinely received either Edmonston-Zagreb high-titre (EZ-HT) or Schwarz standard (SW-STD) measles vaccines have been examined in a rural area of Senegal. The 2 vaccines were equally protective against measles infection (vaccination efficacy: EZ-HT 94%; SW-STD 93%). Children who did not attend a scheduled session to receive measles vaccine had a higher mortality rate between 9 months and 2 years of age than did children receiving either EZ-HT (mortality ratio [MR] = 1.81, 95% confidence interval [CI] 1.06-3.08) or SW-STD measles vaccine (MR = 1.74, 95% CI 0.95-3.21). Children of either sex vaccinated with EZ-HT had lower mortality than their equivalents who had not received any measles vaccine. There was no difference in overall mortality between recipients of EZ-HT and SW-STD (MR = 0.96, 95% CI 0.70-1.30). Using a Cox regression analysis to adjust for sex, age and significant background factors (season and death of mother), mortality rates tended to be lower for male recipients of EZ-HT than for boys receiving SW-STD (MR = 0.73, 95% CI 0.50-1.11) and higher for girls receiving EZ-HT than for girls receiving SW-STD (MR = 1.30, 95% CI 0.81-2.09) (test of interaction between sex and vaccine, P = 0.067). The tendency to reduced survival benefit for girls following receipt of high-titre measles vaccines substantiated observations from randomized trials in Guinea-Bissau, Senegal and Haiti. Existing data provide little support for the notion that high-titre vaccine is deleterious but it may not have the same beneficial effects as standard-titre measles vaccine.

Positron emission tomography study of brain benzodiazepine receptors in Friedreich's ataxia.

Central type benzodiazepine receptors were studied in 9 patients with Friedreich's ataxia and 12 healthy subjects using positron emission tomography (PET) and [11C]Ro 15-1788, a specific antagonist of the central type benzodiazepine receptors, as radioligand. A standard PET procedure was used in 5 patients and 8 controls to obtain brain kinetics of the total binding of the radioligand. The remaining subjects were intravenously injected with a saturating dose of unlabeled Ro 15-1788, 30 minutes after the tracer injection, to determine the nondisplaceable binding of [11C]Ro 15-1788. A semi-quantitative method was used to quantify the [11C]Ro 15-1788 data. None of the quantification indices in the cerebellar hemispheres, or in the other brain areas investigated, was significantly modified in patients with Friedreich's ataxia. These findings suggest that brain benzodiazepine receptors are unaffected in Friedreich's ataxia.