Aspergillus fumigatus Postoperative Fasciitis and Peritonitis.

A 67 year-old male was admitted in the ICU because of multi-organ failure due to sepsis secondary to Fournier's gangrene. He had sustained radical prostatectomy in the last 48 hours. Peritoneal fluid and fatty tissue biopsies grew Aspergillus Fumigatus without concomitant pulmonary involvement. Postoperative acquisition via exogenous and endogenous routes is discussed, as this nosocomial entity is very rarely reported apart from peritoneal dialysis, especially in non-immunosuppressed patients.

[(S)un (M)ay (A)rise on SMA : the hope of a region without spinal muscular atrophy]. / (S)un (M)ay (A)rise on SMA : l'espoir d'une région sans amyotrophie spinale.

The treatment of spinal muscular atrophy (SMA) has considerably changed over the last 3 years. Several approaches that aim to increase the deficient SMN protein have demonstrated an efficacy that is inversely correlated with disease duration. In this context, newborn screening (NBS) is increasingly considered as the next step in several countries or regions. In 2018, we initiated a pilot study for NBS of SMA in French- and German-speaking Belgium. We aim to evaluate the feasibility, the efficacy, and the cost-effectiveness of such a program. Initially covering the region of Liege, the program was recently extended to the whole Southern Belgium and currently covers about 55.000 newborns per year. On June 1st 2019, 35.000 newborns had been screened and 5 affected babies were identified and referred to neuromuscular centers for early treatment. A full evaluation of the program will take place after three years to consider the inclusion of SMA screening in the publically-funded NBS program in Southern Belgium.

La prise en charge de l'amyotrophie spinale antérieure (SMA) a considérablement évolué au cours des trois dernières années. Les différents essais visant à augmenter la production de la protéine SMN déficitaire dans la SMA ont systématiquement montré une efficacité inversement proportionnelle à la durée de la maladie. Dès lors, l'implémentation d'un programme de dépistage néonatal s'est rapidement imposée comme une évidence médico-économique dans de nombreux pays. Dans ce contexte, nous avons initié un programme de dépistage néonatal pour la SMA en Belgique francophone et germanophone. En 2018, une étude pilote de trois ans visant à évaluer la faisabilité, l'efficacité et la rentabilité du screening a été initiée au sein du centre de dépistage de Liège. L'étude a récemment été étendue à l'ensemble de la Fédération Wallonie-Bruxelles (FWB) pour couvrir environ 55.000 naissances annuelles. Au 1er juin 2019, 35.000 bébés ont été dépistés et cinq nouveau-nés atteints de SMA ont été identifiés. Tous ont été immédiatement référés pour assurer leur prise en charge dans un centre de référence pour les maladies neuromusculaires. Une évaluation complète du programme aura lieu à l'issue de la phase pilote, afin d'envisager que la SMA soit reconnue comme maladie officielle du programme de dépistage néonatal en FWB.

Sequential expression of antigens on sexual stages of Plasmodium falciparum accessible to transmission-blocking antibodies in the mosquito.

Plasmodium falciparum gametocytes contain specific antigens, some of which (Mr 230,000, 48,000, 45,000) are expressed on the surface of the newly emerged macrogamete. A different antigen (Mr 25,000) surrounds the surface of the ookinete and, although present to some extent in the developing gametocyte, is synthesized in high quantities by the macrogamete/zygote and expressed progressively on the transforming zygote surface. These antigens are targets of transmission blocking antibodies that are effective at two distinct points after gametogenesis: fertilization of the macrogamete and ookinete to oocyst development. The antigens involved in the fertilization blockade are the Mr 48 and 45 proteins, which are expressed on the macrogamete surface. The Mr 230 K coprecipitating protein probably plays no part in transmission block. mAb directed against the Mr 25 K ookinete surface protein blocked transmission without inhibiting ookinete formation, indicating that this protein has an important role in the transformation of ookinete into oocyst. A combination of mAb recognizing different epitopes on the same protein molecule acted synergistically in inhibiting oocyst formation. Using a mixture of two blocking mAb reacting against the Mr 48/45 and 25 K proteins, respectively, an additive blocking effect could be demonstrated.

The effect of changes in the respiratory metabolism upon genome activity. A correlation between induced gene activity and an increase in activity of a respiratory enzyme.

The in vitro regression of experimentally induced chromosome puffs was investigated in explanted salivary gland chromosomes of Drosophila hydei. It was observed that the regression of the puffs 2-32A, 2-36A, 2-48C, and 4-81B is accelerated if substrates for the respiratory metabolism are supplied to the cells. A similar effect can be produced by addition of KCN or oligomycin to medium in which intact salivary glands are incubated. The acceleration of puff regression by these substances occurs not only if the puff-inducing stimulus is removed but as well under conditions in which the stimulus is maintained. Regression of the puffs 2-32A, 2-36A, and 4-81B is inhibited if cycloheximide is present in the incubation medium. Chloramphenicol has no effect on puff regression. Measurements on nicotinamide adenine dinucleotide-dehydrogenase activity in homogenates of salivary glands revealed an increase in enzyme activity of 41 %. Maximum increase is attained at 30 min after the induced puffs have reached their maximum size. The increase in enzyme activity does not occur if the glands are kept in a medium containing either actinomycin D or cycloheximide. Chloramphenicol does not inhibit the increase in enzyme activity. The possible relationship between puff activity and its control as a result of changes in the respiratory metabolism is discussed.

Chronic meningococcemia presenting with recurrent painful rash and poly-arthralgia without fever.

Chronic meningococcemia is an uncommon disorder, representing a diagnostic challenge. Classically, this pathology would be considered in young adults with a history of episodes of fever, disseminated cutaneous vasculitis and arthralgia. Exact and rapid diagnosis is often further challenged by the fact that routine microbiological investigations frequently failed to identify incriminated micro-organism, Neisseria meningitidis. Here we present the case of a young man not presenting with the classical triad.

Aetiology and presentation of HIV/AIDS-associated pulmonary infections in patients presenting for bronchoscopy at a referral hospital in northern Tanzania.

OBJECTIVES: To determine the aetiological agents of pulmonary infections in HIV-infected Tanzanians and to correlate the causative agents with clinical, radiographic features, and mortality. DESIGN: A prospective study. SETTING: Kilimanjaro Christian Medical Centre (KCMC), Tanzania. SUBJECTS: Bronchoalveolar lavage fluid (BAL) were obtained from 120 HIV infected patients with pulmonary infections. BAL for causative agents was analysed and correlated with clinical and radiographic features, and one-month outcome. RESULTS: Causative agents were identified in 71 (59.2%) patients and in 16 of these patients, multiple agents were found. Common bacteria were identified in 35 (29.2%) patients, Mycobacterium tuberculosis in 28 (23.3%), Human Herpes Virus 8 (HHV8) in 12 (10%), Pneumocystis jiroveci in nine (7.5%) and fungi in five (4.2%) patients. Median CD4 T cell count of the patients with identified causes was 47 cells/microl (IQR 14-91) and in the 49 patients with undetermined aetiology was 100 cells/ microl (IQR 36-188; p = 0.01). Micronodular chest radiographic lesions were associated with presence of M. tuberculosis (p = 0.002). The one-month mortality was 20 (16.7%). The highest mortality was associated with HHV8 (41.7%) and M. tuberculosis (32.1%). Mortality in patients with undetermined aetiology was 11.3%. No death occurred in patients with PCP. CONCLUSION: In this population of severely immunosuppressed HIV-infected patients with pulmonary infection a variety of causative agents was identified. Micronodular radiographic lesions were indicative of TB. High mortality was associated with M. tuberculosis or HHV8. No death occurred in patients with P. jiroveci infection.

Pro-inflammatory cytokines in lung and blood during steroid-induced Pneumocystis carinii pneumonia in rats.

To gain more insight into the role of cytokines in Pneumocystis carinii pneumonia (PCP) we followed pro-inflammatory cytokine profiles in rats with steroid-induced PCP at 2-week intervals. The cytokines measured were immunoreactive interleukin-1beta (IL-1beta), bioactive interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). In vivo cytokine concentrations were determined in three compartments, i.e., bronchoalveolar lavage (BAL) fluid, lung homogenates, and plasma. Lipopolysaccharide (LPS) -stimulated cytokine production by alveolar cells and in whole-blood cultures was measured ex vivo. P carinii load and host inflammatory response, as determined by lung/body weight ratio and 111indium-IgG biodistribution were monitored throughout developing PCP. IL-1beta was elevated in lung homogenates (600, range <20-1260 pg/mL) and IL-6 in BAL fluid (48, range <20-115 pg/mL), whereas the pro-inflammatory cytokine concentrations were not increased in plasma. Thus in rats with PCP elevated pro-inflammatory cytokine concentrations were found to be restricted to the lung compartments. Corticosteroids did not significantly influence cytokine concentrations, but showed profound inhibitory effects on ex vivo cytokine production. The LPS-stimulated cytokine production by alveolar cells gradually decreased during the 6 weeks after the start of the steroid injections, whereas the production in whole blood cultures was immediately and completely suppressed.

Cloning and expression of the gene coding for the transmission blocking target antigen Pfs48/45 of Plasmodium falciparum.

The gene encoding the gametocyte/gamete-specific membrane protein Pfs48/45 of Plasmodium falciparum has been cloned. The Pfs48/45 gene is a non-interrupted, single copy gene that codes for a hydrophobic, non-repetitive protein of 448 amino acid residues containing a putative signal peptide at the N-terminus, a hydrophobic C-terminus and 7 potential N-glycosylation sites. Antibodies directed against a Pfs48/45-glutathione-S-transferase fusion protein reacted with both the 45-kDa and 48-kDa proteins of gametocytes. When Pfs48/45 is expressed in the baculovirus-insect cell system the recombinant Pfs48/45 protein is targeted and exposed to the insect cell surface in such a configuration that it is recognized by transmission-blocking anti-45/48-kDa monoclonal antibodies.

High frequency of antibody response to Plasmodium falciparum gametocyte antigens during acute malaria infections in Papua New Guinea highlanders.

Sera from 62 adult Papua New Guinea highlanders with suspected acute malaria were tested by competitive ELISA for the presence of antibodies capable of inhibiting binding of 8 monoclonal antibodies (Mabs) directed against epitopes on gametocytes of Plasmodium falciparum. Between 33% and 72% of the malaria cases were inhibitory, depending on the Mab. There was no difference between the proportion of persons with P. falciparum (asexuals or gametocytes) and P. vivax whose sera inhibited Mab binding, but all 3 categories had a significantly higher proportion of inhibitors than persons who were malaria negative. The amount of gametocyte antibody recognizing epitopes on Pfs 48/45 and Pfs 230 increased with increasing numbers of previous malaria episodes. The proportion of sera from these relatively nonimmune adults which had gamete antibodies was similar to the proportion seen in sera from a highly endemic area, suggesting that antibody responses to these epitopes are a part of the initial response observed after a limited number of malaria episodes.

A comparison of transmission-blocking activity with reactivity in a Plasmodium falciparum 48/45-kD molecule-specific competition enzyme-linked immunosorbent assay.

Monoclonal antibodies (MAbs) 32F1 and 32F3 react with two independent epitopes of a protein doublet with molecular weights of 48 and 45 kilodaltons (kD) expressed on the surface of Plasmodium falciparum (Pfs48/45) macrogametes and zygotes; only 32F3 blocks transmission. These MAbs were used to develop a Pfs48/45-specific competition enzyme-linked immunosorbent assay (ELISA) using 32F1 to capture antigen and labeled 32F3 for quantification and analysis of the contribution of antibodies in human serum to transmission-blocking activity. A comparison analysis was used to determine agreement of competition ELISA titers and transmission-blocking activity as observed in the bioassay in three groups of serum samples: 37 from European travelers with previous exposure to malaria, 56 from gametocyte carriers, and 66 from schoolchildren from a malaria-endemic area in Cameroon. The index of agreement between outcomes of the ELISA and transmission-blocking assay in gametocyte carriers and in travelers was specifically defined as fair-to-moderate; in schoolchildren the agreement was not significant. The combined analysis of all sera showed a significant and fair-to-moderate agreement between the results of the competition ELISA and the transmission-blocking assay, with a relative specificity of 94% (of 105 cases negative in the transmission-blocking assay, 99 were also negative in the competition ELISA) and a relative sensitivity of 44% (of 54 cases positive in the transmission-blocking assay, 24 were also positive in the competition ELISA). This study shows that a positive C48/45-ELISA is indicative for transmission-blocking activity in the mosquito assay, while a negative result does not exclude transmission-blocking activity.

The SCS/ARS/CES pesticide properties database for environmental decision-making.

The only thing all pesticides have in common is that they are used to control pests. Otherwise, they come from almost every imaginable class of chemical. Everyone associated with pesticide use--farmers, Extension, EPA, state regulatory agencies, manufacturers, and environmentalists--needs information that will allow them to distinguish between pesticides that may be a problem as pollutants in certain situations, and those which may not. There are five basic properties that, when combined with information about site and use, provide much information about the potential of a pesticide to be a pollutant. These five properties are solubility in water, volatility, soil sorption tendency, persistence, and ionization potential. We have compiled the most complete collection of these properties available, using others' compilations but verifying values from the primary literature in many cases. A complete primary literature search was not done. For each parameter we suggest a "Selected Value" which we believe to be the best available, recognizing, however, that persistence and soil sorption are sensitive to specific site conditions. These Selected Values are being incorporated into pesticide environmental-impact risk assessment procedures by state and federal agencies, and are considered to be consensus values. However, there is a serious potential for misuse of these data, particularly the error of using small differences between active ingredients to make regulatory distinctions between them. The ability to relate these data to environmental impact is an essential need and is improving, but is currently at a primitive level.

Recent developments in the immunobiology of Pneumocystis.

Available data on the immune responses to Pneumocystis are discussed leading to the general conclusion that T lymphocytes and monocytic cells are involved in host defence. Recent progress in characterization of parasite antigens is reviewed with special reference to the development of monoclonal antibodies specific for Pneumocystis.

Comparison of serological tests and bio-assay for malaria transmission blocking capacity in field sera.

Competition ELISAs have been developed for natural transmission blocking antibodies. Approximately 50% of the sera blocking in the conventional mosquito feeding experiments, gave positive results in these competition ELISAs. Attempts to adapt competition ELISAs to a field application have been partly successful.

Comparative sperm ultrastructure in Nemertea.

Although the monophyly of Nemertea is strongly supported by unique morphological characters and results of molecular phylogenetic studies, their ingroup relationships are largely unresolved. To contribute solving this problem we studied sperm ultrastructure of 12 nemertean species that belong to different subtaxa representing the commonly recognized major monophyletic groups. The study yielded a set of 26 characters with an unexpected variation among species of the same genus (Tubulanus and Procephalothrix species), whereas other species varied in metric values or only one character state (Ramphogordius). In some species, the sperm nucleus has grooves (Zygonemertes virescens, Amphiporus imparispinosus) that may be twisted and give a spiral shape to the sperm head (Paranemertes peregrina, Emplectonema gracile). To make the characters from sperm ultrastructure accessible for further phylogenetic analyses, they were coded in a character matrix. Published data for eight species turned out to be sufficiently detailed to be included. Comparative evaluation of available information on the sperm ultrastructure suggests that subtaxa of Heteronemertea and Hoplonemertea are supported as monophyletic by sperm morphology. However, the data do not provide information on the existing contradictions regarding the internal relationships of "Palaeonemertea." Nevertheless, our study provides evidence that sperm ultrastructure yields numerous potentially informative characters that will be included in upcoming phylogenetic analyses.

Wet working conditions increase brittleness of nails, but do not cause it.

The incidence of brittle nails is higher in women than in men. Repeatedly a suspected cause for the higher incidence of brittle nails in women is the frequent exposure to water. This study was aimed at clarifying whether wet working conditions increase the incidence of brittle nails in women and men in a similar degree. We determined the incidence of brittle nails in 511 persons in professions that involve frequent hand contact with water. The data were compared to those of a large, non-selected control group. 50% of the female probands showed the sign of brittle nails (control group: 30.4%, p less than 0.05). Only 13.5% of the male test persons of this study had brittle nails; the difference to the control group (13.2%) was not significant. It is discussed that in women the bridges between nail corneocytes are possibly weaker than in males as a constitutional characteristic. Accordingly, frequent alternating periods of hydration and drying increase the incidence of brittle nails particularly in women.

Antibody responses to Plasmodium falciparum gametocyte antigens during and after malaria attacks in schoolchildren from Madang, Papua New Guinea.

Sera from 49 school children in Madang, Papua New Guinea with malaria and follow-up sera from 40 of these cases were tested by competitive ELISA for antibodies capable of inhibiting binding of eight monoclonal antibodies (MoAbs) to Plasmodium falciparum gametocytes. The proportion of sera inhibiting each MoAb ranged from 31.2% to 85.7%. At follow-up, the proportion of inhibitory sera decreased for 3 MoAbs, did not change significantly for 4 MoAbs and increased for one MoAb. When sera were grouped according to whether the follow-up blood slide was positive or negative, further trends emerged for MoAbs against the gamete surface antigen Pfs 48/45. Antibody levels to the IA3-B8 epitope decreased in follow-up positive cases, but remained unchanged for follow-up negative cases. The converse was observed for the IIC5-B10 epitope with an increase of antibody in follow-up positive cases and no change in the negative cases. Amount of antibody to the 3G12/58 epitope decreased when the follow-up was negative but not when it was positive. Increase in antibody to the 3E12/58 epitope occurred at the follow-up sample irrespective of the blood slide result. Thus four distinct patterns of longitudinal antibody response were observed against four epitopes on the same molecule.

Pre-AIDS era isolates of Pneumocystis carinii f. sp. hominis: high genotype similarity with contemporary isolates.

Isolates of Pneumocystis carinii f. sp. hominis were examined from six individuals who died of P. carinii pneumonia between 1968 and 1981 and who had underlying immunodeficiencies which were not due to human immunodeficiency virus infection. DNA sequence variation was analyzed in the genes encoding the mitochondrial large subunit rRNA (mt LSU rRNA), the internal transcribed spacer (ITS) regions of the nuclear rRNA, the arom locus, and the mitochondrial small subunit rRNA. No major variations were observed when these isolates were compared to isolates from HIV-infected individuals. A small number of minor differences were detected. A new position at which variation occurred in the mt LSU rRNA was observed in one sample. Three new ITS sequence types were identified. A total of nine different ITS sequence types were found in the six samples. Mixed infection with different ITS sequence types of P. carinii f. sp. hominis was observed in four of the six samples. The ITS locus was the most informative of the four loci for distinguishing among the isolates of P. carinii f. sp. hominis. The data suggest that isolates of P. carinii f. sp. hominis from before the AIDS pandemic are genetically very similar to those currently found in HIV-infected individuals.

The in vitro cultivation of P. falciparum ookinetes, and their enrichment on Nycodenz density gradients.

Employing a simple method of growing ookinetes of Plasmodium falciparum in culture, 40% of mature gametocytes convert to macrogametes, 4% reach the retort-form ookinete stage and 0.45% become mature ookinetes. A single-step gradient centrifugation method on 12.5% Nycodenz enriches both gametocytes and ookinetes.