Assessment of an anti-alpha-toxin monoclonal antibody for prevention and treatment of Staphylococcus aureus-induced pneumonia.

Alpha-toxin (AT) is a major virulence factor in the disease pathogenesis of Staphylococcus aureus. We previously identified a monoclonal antibody (MAb) against AT that reduced disease severity in a mouse dermonecrosis model. Here, we evaluate the activity of an affinity-optimized variant, LC10, in a mouse model of S. aureus pneumonia. Passive immunization with LC10 increased survival and reduced bacterial numbers in the lungs and kidneys of infected mice and showed protection against diverse S. aureus clinical isolates. The lungs of S. aureus-infected mice exhibited bacterial pneumonia, including widespread inflammation, whereas the lungs of mice that received LC10 exhibited minimal inflammation and retained healthy architecture. Consistent with reduced immune cell infiltration, LC10-treated animals had significantly lower (P < 0.05) proinflammatory cytokine and chemokine levels in the bronchoalveolar lavage fluid than did those of the control animals. This reduction in inflammation and damage to the LC10-treated animals resulted in reduced vascular protein leakage and CO2 levels in the blood. LC10 was also assessed for its therapeutic activity in combination with vancomycin or linezolid. Treatment with a combination of LC10 and vancomycin or linezolid resulted in a significant increase (P < 0.05) in survival relative to the monotherapies and was deemed additive to synergistic by isobologram analysis. Consistent with improved survival, the lungs of animals treated with antibiotic plus LC10 exhibited less inflammatory tissue damage than those that received monotherapy. These data provide insight into the mechanisms of protection provided by AT inhibition and support AT as a promising target for immunoprophylaxis or adjunctive therapy against S. aureus pneumonia.

[Mitochondrial toxicity: a case of palpebral ptosis in a woman infected by HIV and treated with HAART including zidovudine]. / Toxicit mitochondriale: cas d'un ptosis palpebral de l'oeil gauche chez une patiente infectée par le VIH sous trithérapie antirétrovirale comportant de l'AZT.

The usual clinical feature of mitochondrial toxicity is proximal myopathy. We present the report case of palpebral ptosis which occurred under zidovudine therapy The symptom remission was obtained by stopping the antiretroviral therapy. This involves an important vigilance from both doctor and patient.

[The outcome of resuscitated infants. Experience at an African university maternity unit]. / Devenir des enfants réanimés. Expérience d'une maternité universitaire africaine.

The authors report a study involving 90 infants born at term or close to term and who required resuscitation at birth for per-natal fetal distress. These were 16.6 per cent early deaths (between 0 and 7 days), 11.1 per cent of infants lost to follow-up, 11.1 per cent of infants dying from various causes unrelated to their history of neonatal resuscitation and 16.6 per cent of cases considered unevaluable because of incomplete records. In a second section, they compare 40 resuscitated children (44.4 per cent of the initial sample) with 40 controls of the same age from a clinical, psychomotor and scholastic standpoint. They noted no significant difference regarding clinical and psychomotor status. Results concerning scholastic achievement, with the notable role played by socio-economic circumstances, must be interpreted with caution. At any event, results here are identical in general to those reported in other publications devoted to the same subject.

[Ultrasonics and fetal growth in Gabon]. / Ultrasons et croissance foetale au Gabon.

The authors have worked out growth curves for the 3 classical parameters (BPD, HED and Femur) for the Gabonese by studying 870 ultrasound sets of measurements carried out between the 15th and the 40th week of amenorrhoea in normal pregnancies. Comparisons between these curves that have been worked out with those in Europe and the U.S.A. show that there is no difference between them that could be explained by the ecological conditions or the eating habits among other factors.

[Malaria and pregnancy. Comparative study of Central Africa and Western Africa]. / Paludisme et grossesse. Etude comparative entre l'Afrique Centrale et l'Afrique de l'Ouest.

The transmission of malaria occurs mainly in and following the rainy season (intermittent transmission) in the Sahelian zone of Africa. On the other hand in rainy Equatorial Africa the transmission of malaria is continuous so that it is stable and can give rise to continuous antigenic stimulation in pregnant women which in turn gives rise to passive early high level immunity in the infant. 150 couples of mother and cord blood and 206 placentae were studied. We found 12.1% of carriers of blood parasites in the blood as compared with 1.6% in the cord bloods (exclusively P. falciparum). Where there were medium quantities of fluorescent antibodies in the mothers 74% could be found in the cord serum. Two methods were used to measure antimalarial antibodies as evidence of infection and also partly protective: the first method was indirect immunofluorescence, and the second was co-electrosyneresis. There was a narrow correlation between the level of precipitant antibodies in the mothers who were infected and in the fetal cord bloods. Anatomo-pathological examination of the placenta showed that 2 out of the 206 had parasites in them, 9 out of the 206 had fibrin deposits around the villi and 6.8% of the placentae showed lesions of malaria. On the other hand, in West Africa there was very little maternal morbidity as evidence by fever and anaemia, or of fetal morbidity. There was no single case of congenital malaria. The levels of the plasma indices in the towns could be explained because of prophylaxis which was both controlled and uncontrolled.

[Major drepanocytosis and fertility]. / Drépanocytose majeure et fécondité.

The authors report on 4 observations they have made in cases of full-blown sickle-cell disease who became pregnant, to demonstrate that: fertility is normal in women with sickle-cell disease, it is important to screen systematically for haemoglobinopathies in populations at risk, that the condition is relatively rare, and very high-risk pregnancies do not happen very often in cases of full-blown sickle-cell disease. They recite the difficulties in providing for an efficient form of contraception with little danger in these patients.

[Pregnancy and labor in Gabonese adolescent girls. A study of 97 cases]. / La grossesse et l'accouchement de l'adolescente gabonaise. Etude de 97 cas.

The authors report a study of pregnancy and delivery in adolescent girls, based on a series of 97 cases of young Gabonese women. The study examined this subject from two points of view: obstetrical, in which the results were essentially identical to those of other studies and in other countries, and psycho-socio-economic, which revealed the feelings of shame and the problems associated with caring for the newborn infant.

[The placenta of premature and hypotrophic Gabonese infants]. / Le placenta de l'enfant gabonais, prématuré et hypotrophique.

494 placentae coming from two different geographical parts of Gabon were studied. They were grouped into control, premature, small-for-dates and stillborn. The urban population gives rise to most mothers of about 26 years of age, who deliver normally at 38 weeks of babies weighing 3,300 g and 50 cm long, with placentae weighing 550 g, as well as premature babies and those in which there is white cell infiltration of the membranes, signs of toxaemia and normal placentae. On the eastern plateaux of Gabon there are more mothers around the age of 23, who deliver normally at 37 weeks of pregnancy of babies weighing 3,100 g and 48 cm long, with placentae weighing 450 g, with small-for-dates babies and inflammation of the placenta. Malaria is the cause of many premature deliveries and of small-for-dates and stillborn, especially in the plateaux.

[Results of a systematic study of drepanocytosis in 1,500 Gabonese using hemoglobin electrophoresis]. / Résultats de l'étude systématique de la drépanocytose par électrophorèse de l'hémoglobine chez 1 500 Gabonais.

Hemoglobin electrophoresis realised as a routine screening test on 1 500 gabonese individuals revealed the existence of a sickle cell abnormality n 24.40% cases (22.27% were AS heterozygotous and 2.1% were SS homozygotous). Bapounov and Fang ethnies appeared to be the most involved. The importance of such disturbance (I gabonese individual out of 4 is concerned) could justify the creation of Prenatal Counseling Centers mainly dealing with this genetic problem.