Search

Epidemiological studies were carried out in Yaoundé and in Ngaoundéré from 1984 to 1986, in an attempt to develop adequate methods of collecting blood from small children and of diagnosing measles appropriate to conditions in the field. Alternative methods were necessary since classical methods used in modern laboratories are unsuitable in rural regions. Each study was carried out on a representative sample of 6- to 36-months-old infected children seen at consultation. This group was chosen because it suffers the highest mortality rate. The blood was obtained by digital puncture on blotting paper because venepuncture required sterile equipment and also the establishment of a cold chain for transporting the samples to the laboratory. The first criteria examined were the relative titers of sera taken by finger prick. Four serological techniques were used: indirect immunofluorescence (IIF), indirect immunoperoxidase (IIP), hemagglutination inhibition (HAI) and ELISA. Antimeasles antibodies were detected in 12% of infected children using IIF and in 18% using IIP. When sera were examined by HAI the percentage of positives was 54% and by ELISA 75%. These results clearly indicate that ELISA is the most effective and practical technique for diagnosing measles under field conditions.

In order to demonstrate the viral specificity of IgM-containing immune complexes (IgM-CIC) detected by a C1q assay in renal allograft recipients developing a CMV infection, a technique is described allowing: 1) the dissociation of IgM-CIC by action of an acid buffer, and 2) the characterization of the viral specificity of IgM antibodies released by this treatment. This step was performed by ELISA and Western Blot. When technique was applied to the follow-up of a renal allograft recipient developing a recurrent CMV infection within 2 months post-graft, it was found that the IgM-CIC detected on the day of the graft were not CMV-specific, whereas the IgM-CIC detected during the second month after transplantation contained CMV-specific IgM antibodies. These CMV-specific IgM-CIC were detected as early as the urinary viral excretion. It was shown by Western Blot analysis that these IgM antibodies reacted with a 45-47 kDa viral polypeptide which is a viral target for specific humoral response at the early phase of CMV infection.

The acquisition of drug resistance in vivo was investigated by 7 serial passages (from P0 to P7) of herpes simplex virus (HSV-1) in rabbit cornea treated with either IUdR (idoxuridine), IDC (idoxycytidine), ACV (acyclovir), TFT (trifluridine), or Ara A (adenine arabinoside). Therapeutic failure was acquired gradually: at P3 for IUdR, at P4 for ACV and at P5 for TFT. At P7, viral thymidine kinase (TK) activity was reduced to 5.6% of the parental strain for IUdR, to 7.5% for ACV and to 4.6% for TFT treatment. No signs of clinical unresponsiveness occurred with IDC or Ara A. The in vitro determination of antiviral drug sensitivity performed by the dye-uptake assay on HSV isolates at each passage showed a correlation between the increase in the 50% effective dose (ED50) and the increase of ulcer area grade at each passage under antiviral drug (p less than 0.1). Both IUdR- and TFT-resistant HSV1 developed cross-resistances to TK dependent drugs. However ACV-resistant HSV1 did not show cross-resistance to other antiviral TK dependent drugs. The acquisition of the cross-resistances is discussed, and the practical implications in case of therapeutic failures are suggested.

We studied the biological and antigenic properties of wild strains of echovirus type 25 isolated in France between 1982 and 1987 and compared them with the JV-4 prototype strains isolated in 1957. The wild strains differed from the prototype strain in their cellular tropism. The prototype strain grew readily in five cell lines (MRC5, MA 104, Vero, BGM, and HT 29-18), while for wild strains MRC5 and HT 29-18 cells were the most sensitive and supported growth to high titres (between 4.5 and 7.4 50% tissue culture infective doses per 0.05 ml). Plaques produced by wild strains were larger (6.05 +/- 0.94 mm in diameter [mean +/- standard deviation]) than those of the prototype strain (2.3 +/- 0.97 mm in diameter) and heterogeneous, even after cloning by three terminal dilution passages, which suggested heterogeneous virus populations. Virus neutralization with polyclonal monovalent sera showed that wild strains were significantly less neutralized by two reference immune sera than the prototype strain was. Monoclonal antibodies were raised against the echovirus type 25 JV-4 prototype strain. Nine clones with neutralizing activity were identified. Heterologous neutralizations of 14 clinical isolates revealed highly conserved, moderately conserved, and poorly conserved epitopes. The natural isolates differed from the prototype strain in two to four epitopes and can be classified into four different groups. We concluded that echovirus type 25, like coxsackie- and polioviruses, consists of heterogeneous viral populations with respect to biological and antigenic properties. In term of viral diagnosis, it may become increasingly difficult to identify recently isolated strains because of their antigenic variation.

A study of antibodies to human papillomavirus (HPV) 1 is reported in a series of sera from 126 patients with papilloma lesions of different clinical types (verruca plantaris, vulgaris, plana, condyloma acuminata, laryngeal papilloma) using a sensitive solid-phase enzyme-linked immunosorbent assay (ELISA). Our findings showed a significant prevalence of specific HPV 1 IgG antibodies in patients with plantar warts (65%). This incidence was considerably lower in patients with other papilloma lesions, in which positive sera may reflect a past infection with HPV 1. The ELISA test was evaluated as nearly 100 times more sensitive than the indirect immunofluorescence test, and IgG titers to HPV 1 in patients' sera were usually low. Serum samples taken at different times during the course of HPV infection in a few patients with refractory lesions did not show any significant change in their antibody titer.

A simplified and rapid micromethod based on restriction endonuclease analysis of radiolabelled varicella-zoster virus (VZV) DNA is described and applied to strains for comparison. This procedure is cheaper and less time consuming than that requiring viral nucleocapsid purification (macromethod). The micromethod is suitable for routine DNA analysis of VZV isolates, allows differentiation of vaccine strain from wild strains, and provides evidence for variability of wild strains.

A blocking ELISA was developed to confirm the specificity of screening tests for anti-HIV-1 antibodies. A murine monoclonal antibody (McAb) raised against recombinant gp160 was used in combination with a commercial technique (ELA-VIA-1). After determining the optimal experimental conditions, the assay was applied to 92 samples presenting different reactivities by Western blot (WB) analysis. All the sera containing antibodies to gp160/gp120 (53) were positive in our assay. The six patients who sero converted showed a low positivity by ELAVIA-1 (optical density near the cutoff value) reacted by blocking-ELAVIA-1 with an McAb binding inhibition greater than 85%. By contrast, negative samples (29) and specimens that exhibited reactivity only against gag-proteins (10) were not detected (McAb binding inhibition smaller than 15%). This sensitive and specific blocking-ELAVIA-1 represents a convenient alternative to WB as a confirmatory test. The technique is time-saving and inexpensive and can easily be integrated with a screening test for diagnostic or epidemiologic studies on HIV-1 infection.

Enteroviruses were specifically detected in crude clinical specimens or in cell cultures in which the viruses were amplified by dot hybridization by using poliovirus type 1-derived, subgenomic radiolabeled cRNA probes (riboprobes). The sensitivity of this test varied from 2.5 to 33%, when clinical specimens without cell culture were examined, and was about 85% in cell culture lysates. The specificity of the test was 90 to 100%. The riboprobe corresponding to the 5'-noncoding sequence specifically detected the majority of enteroviruses (56 of 57 tested); the riboprobe derived from the VPI capsid region hybridized with the three poliovirus serotypes and with some coxsackieviruses type A and with echovirus type 7. Echovirus 22 did not hybridize with any riboprobe. In stool specimens, nasal aspirates, and cerebrospinal fluids from patients with meningitis, only one type of virus was identified in different clinical samples from the same patient by the seroneutralization test. Hybridization allowed the detection of enteroviral RNAs easily in stool specimens and nasal aspirates but with a low efficiency in cerebrospinal fluids without amplification of the viruses in cell cultures.

The relative importance of the host immune response to various antigenic and functional sites on the HN glycoprotein of Sendai (6/94) virus for protection in vivo, was evaluated in mice passively immunized with monoclonal antibodies to HN and then intranasally challenged with infectious virus. Five neutralizing monoclonal antibodies reacting with distinct antigenic sites and exhibiting different reactivity patterns were selected. All of them were able to prevent entirely the growth of virus in the lungs of experimental animals injected with appropriate dilutions of monoclonal antibody. The calculation of correlation coefficients between the reduction of virus in the lungs of immunized mice and the amount of antibody, expressed in terms of hemagglutination inhibition, hemolysis inhibition or neutralizing units, showed a high degree of correlation (r = 0.89) with neutralization and a lack of correlation (r = 0.44) with hemagglutination inhibition. In parallel a minimum threshold value for protection equivalent to 2 x 10(3) neutralizing units per mouse was determined independently of the mechanism(s) by which monoclonal antibodies mediated the neutralization of the infectivity. On the HN glycoprotein of Sendai (6/94) virus we could not individualize a critical site for successful immune recognition by antibodies although the characteristics of an "ideal protective monoclonal antibody" have also been defined.

A C1q solid-phase enzyme assay for detecting circulating immune complexes (CIC) containing immunoglobulins M was developed. IgM immune complexes (IgM-CIC) bind to purified C1q-coated microplates. The amount of bound IgM-CIC is determined by adding anti-mu-alkaline phosphatase conjugate. This assay proved IgM-CIC specific; it does not detect IgG-CIC nor free anti-CMV IgM. Furthermore Rheumatoid Factor (RF) does not interfere with this test. Then, 119 renal allograft recipients were followed-up for the presence of seric IgM-CIC. Among them, 86 patients developed a recurrent Cytomegalovirus (CMV) infection and 33 did not. In the non-infected population, IgM-CIC were detected in only 15.2% of the patients. In contrast, patients with recurrent CMV infection showed a significantly higher frequency of detectable IgM-CIC (62.8%) (p less than 0.01). These IgM-CIC were detected: (a) during the first two or three weeks after graft; (b) in the course of the second month post graft. This second peak of IgM-CIC was never observed in subjects non-infected with CMV. IgM-CIC occurred before or at the same time as the detectable anti-CMV IgM and virus excretion in urines. Presence of IgM-CIC was not influenced by graft rejection episodes. Such a marker might help in discriminating immune response to viral infection from immune graft rejection.

During the first 5 years of a poliomyelitis control programme in Yaounde, Cameroon, a maximum of 35% of children aged 12-23 months were estimated to have received three doses of trivalent oral vaccine. Despite this low immunization coverage and low seroconversion rates, which were determined concurrently, the estimated incidence of paralytic poliomyelitis decreased by 85%.A detailed study of immunized children and of children living in the same households suggests that community spread of the vaccine virus and cross-immunity may have partly been responsible for the dramatic decrease in the incidence of paralytic disease, and that competing non-polio enterovirus infection was not a cause for the low seroconversion rates. These results suggest that immunization coverage and seroconversion rates alone are not sufficient criteria for determining the effectiveness of control programmes that use oral poliovirus vaccine in tropical Africa; surveillance of the incidence of paralytic disease must also be carried out.

The frequency and severity of CMV infections in kidney, bone marrow, heart transplant recipients, in polytransfused patients, in immunodeficiencies and in newborns with congenital or peri-natal infection prompted clinical trials of immunoglobulins (Ig) with anti-CMV activity. Among the various methods for titrating Ig of plasmatic or placental origin, polyvalent or hyperimmune, ELISA would be the most sensitive assay and the neutralizing reaction might be the better reflection of a protective effect. In kidney transplantation, two non-randomized clinical trials have suggested a curative effect in association to other treatments, especially when given early. In bone marrow transplantation, three randomized studies have shown a prophylactic effect on incidence of symptomatic infections, interstitial pneumonias due to CMV, but only in seronegative patients not treated with leucocyte transfusions. No effect was observed on the time of infection, the survival of patients, the incidence of surinfections or graft versus host disease. The prophylactic effect of anti-CMV Ig in kidney and heart transplantation as well as in newborns has still to be documented in randomized trials. The possible clinical benefit for the patients and the mode of preparation of effective anti-CMV antibodies need further investigations.

A case of ocular infection due to adenovirus type 19 is reported. The patient developed a bilateral keratoconjunctivitis with preauricula nodes and a mild general malaise. The virus was isolated from both eyes; serological tests carried out on the serum of the patient were compatible with the diagnosis.

Dense particles (density 1.44 g/ml) were isolated during purification in CsCl of echovirus 11 produced in HeLa cells. The dense particles had similar antigenic properties and similar RNA and protein composition to standard (density 1.33 g/ml) echovirus 11 particles. They differed from standard particles in their higher buoyant density, lower infectivity and slightly smaller diameter. In contrast to other picornavirus dense particles, echovirus 11 dense particles were present as a major component of virus population. This high ratio of dense particles was found only in virus from HeLa cells which produced non-haemagglutinating echovirus 11. Haemagglutinating echovirus 11 from primary monkey kidney (MK) cells did not contain any detectable levels of dense particles.

A modification of the single radial haemolysis test by treatment with Cl3Cr of the virus coated red blood cells is proposed for a rapid, more sensitive and reproducible serodiagnosis of Influenza infections. The reagents "red blood cells-virus-Cl3Cr" is stable at 4 degrees C for at least 1 month: the modified test gives results within 3 hours, in measuring the H-anti-H specific reactions. The anti-influenza A immune response was studied in patients of different age, bled at different time after exposure. The IgM do not diffuse in the agarose and do not haemolyse. A clear haemolytic area is produced by IgG, partially haemolysed areas occur when there is a competition between specific IgM and IgG and in the case of reactions involving cross-reacting antigenic determinants.

By polyacrylamide gel electrophoresis, Duck/Mississippi/75 virus was shown to contain five different types of polypeptides of mol. wt. ranging from 76 X 1O(3) to 43 X 10(3), two of which were glycosylated (mol. wt. 76 X 10(3) and 57 X 10(3). A comparison of this data with similar results obtained using Yucaipa and Newcastle disease virus (NDV) revealed a similarity with NDV, concerning the number, position and mol. wt. of the polypeptides. Haemagglutinating and neuraminidase properties are associated with surface glycoproteins which represent at least 40% of the virus protein. After KCl and Triton X-100 treatment and centrifugation on linear sucrose density gradients (10 to 25%, w/w) it was possible to isolate glycoprotein VP1 of mol. wt 76 X 10(3) with which haemagglutinating and neuraminidase activities were associated.

After multiplication in the continuous human cell lines HeLa, KB, and Hep 2, echovirus 11 (prototype strain Gregory) loses its haemagglutinating (HA) activity but retains infectivity. After seven passages in Hela cells the HA activity was not restored. There was no correlation between the loss of HA activity and modification of thermosensitivity, plaque morphology, surface properties and antigenicity. HA- echovirus 11 particles did not show the properties of defective interfering (DI) particles as described for poliovirus.

A simple and reproducible method for the production of purified rubella virus is described. Purified virus was subjected to morphological and chemical analysis. The virus particles were rather pleomorphic (60 nm diameter), sometimes with one or more peripheral protrusions. The viral surface, revealed by negative staining, was composed of spikes 6 nm long, featuring enlarged ends. In SDS-urea-polyacrylamide gel electrophoresis, 4 major and 4 minor polypeptide bands were revealed. Total lipids and phospholipids were analysed on the same preparation. The viral particles were composed of RNA: 0.030 mg, and lipids: 0.245 mg, of which 0.169 mg were phospholipids for each mg of viral protein. Biologically, the purified virus preparation showed high infectivity, a high hemagglutination titre and a weak neuraminidase activity under defined conditions.

The effects of repeated topical idoxuridine (IDU) administration of HSV1 strain sensitivity were investigated during 6 serial passages (P1 to P6) in the rabbit. By comparison to placebo treated rabbits, a delay in ulcer cicatrization appeared at P2 and clinical resistance was completed at P3. Clinical cross resistance to acyclovir (ACV) was also tested and demonstrated at P7. In vitro, a plaque reduction test on Vero cells using directly the tear film HSV populations allowed the prediction of the resistance by an early rise in the effective dose 90% (ED 90) value anticipating that in ED 50%. An ED 50 determination by dye-uptake assay on P6 HSV isolate demonstrated a cross resistance to viral thymidine kinase (TK) dependent drugs without any change in Ara-A and PFA sensitivity, according to a 23% TK activity at P6. At the last passage the HSV drug resistant population had an unrestricted corneal pathogenicity. A return to IDU and ACV in vitro sensitivity was demonstrated in group control animals at P2 but not at P4 or P6.

The use of both SEM and TEM techniques in studying the alterations of the columnar ciliated epithelium of the whole respiratory tract of ferrets enables the authors to find a significant discrepancy between tracheal and nasal mucosa destructions. This discrepancy is not a function of the anatomical location of virus instillation. Theoretical and pratical meanings are discussed.

Representative isolates of the paramyxoviruses duck/Hong Kong/75 and duck/Mississippi/75 were shown to be serologically closely related by haemagglutination and neuraminidase inhibition tests. The structural polypeptides of these viruses were also shown to be similar. For each of the isolates tested, polyacrylamide gel electrophoresis in the presence of SDS revealed a similar polypeptide pattern consisting, under reducing conditions, of seven polypeptides with apparent mol. wt. ranging from 46000 to 190000. Each virus had two glycosylated polypeptides with apparent mol. wt. of 56000 and 71000 to 72000 under reducing conditions and 62000 to 63000 and 135000 to 142000 under non-reducing conditions.

Splenic lymphocytes from BALB/c mice immunized with Parainfluenza 1 virus (PIV-1), HA2 strain, were fused to the non secreting 653 and secreting P3 X 63Ag8 myeloma cell lines. Fusion products were screened for antibody synthesis using an enzyme-linked immunosorbent assay (ELISA) with purified PIV-1. Antibodies were characterized by their biologic specificity and immune fluorescence staining--6 monoclones (2HI and 4 non HI) were used to further analysis by cross reactivity panels using different PIV strains. None of the anti PIV1 monoclones showed any cross reactivity with PIV2 and PIV3 whereas with HI and non HI monoclones antigenic relationships were observed between viruses belonging to serotype 1. Monoclonal antibodies were also applied to the study of host cell related changes in PIV1 proteins.

The antiviral activity of a novel biological response modifier (murabutide MDP derivative) has been investigated in 3-week-old OF1 mice infected with influenza (A/Texas/1/77) virus. In each experimental and control group, 10 mice were infected intranasally with a viral dose producing 50% mortality in 5 days and received murabutide via the subcutaneous or intranasal route at various doses either in a simple or in daily repeated administration. All experiments were done in triplicate. Significant prophylactic or therapeutic effects were observed when murabutide was administered the same day as virus, 4 days or 2 days before virus, and 2 days later. These effects varied with the route of administration and the doses of the compound.

The authors distributed a questionnaire to 89 patients who consulted them for sterility for reply by themselves. The blame for chlamydia trachomatis infection as a cause of sterility was worked out as a level of IgG above 1/8. The risk factors for being infected with chlamydia trachomatis is above all the number of sexual partners; the odds ratio of 2,68 being significant for those who had more than one partner. The age of marriage and the age at first intercourse do not count. The prevention of the consequences of infection depends on education about the risks and screening for infection when the partner is changed.

A case-control study was conducted in Yaoundé, United Republic of Cameroon, to evaluate the hypothesis that intramuscular inoculations predisposed young children to paralysis if they were later exposed to poliomyelitis virus. Thirty-three cases with lower motor neuron disease and 66 neighbourhood controls were studied. Poliovirus was isolated from 39% of the paralytic cases but from only 18% of the comparison group. Controls were more likely to have had serological evidence of previous exposure to all three poliovirus types while most of the paralytic cases had been exposed to a poliovirus for the first time. Two-thirds of the paralytic cases but only 11% of the comparison group had been ill, visited a medical facility, and received multiple injections, primarily with quinine and penicillin, in the month prior to the onset of poliomyelitis. There was a strong temporal relationship between these injections and the onset of paralysis. The increased relative risks (15 and 32, respectively) of paralysis associated with inoculations in the two weeks immediately prior to onset of disease were felt to represent the treatment of symptoms related to poliomyelitis. However, the increased relative risks (13 and 27, respectively) three and four weeks prior to onset were felt to be consistent with the hypothesis that intramuscular injections provoked paralysis. Overestimation of this measure of the effect because of bias in the control group is discussed.

A simple, indirect enzyme immunoassay using purified enterovirus adsorbed on to nitrocellulose has been developed for screening monoclonal antibodies to enteroviruses. The sensitivity of the assay ranged from 10 ng to 1 microgram of viral protein and was 10- to 50-fold more sensitive than conventional EIA on microplates. This simple, sensitive and specific assay proved to be a useful and practical tool for detecting monoclonal antibodies which would not be found in a conventional EIA screening procedure.

59 sera of 10 immunosuppressed renal allograft recipients who experienced recurrent cytomegalovirus (CMV) infection were analyzed by enzyme-linked immunosorbent assay (ELISA) for CMV IgA antibodies and by the complement-fixation (CF) test. A significant rise of CF titer was evident 4-53 weeks post-transplantation. 9 patients produced CMV IgA in high titers at about the time of CF antibody rise was observed. 1 patient did not produce IgA antibodies to CMV. In 3 of the 9 patients, specific CMV IgA antibodies were detected before the rise if CF titer was demonstrated. CMV IgA antibodies were found to persist for as long as 6 weeks post-transplantation. The potential application of ELISA detection of CMV-specific IgA antibodies as an early indication of CMV infection in kidney transplant patients is discussed.

The feasibility of using human cytomegalovirus (CMV)-specific IgA antibody determinations as a signal for early detection of recurrent CMV infections in eight renal transplant recipients was analyzed. Solid phase radioimmunoassay (RIA), enzyme-liked immunosorbent assay (ELISA) and immunoperoxidase assay (IPA) techniques were used for IgA antibody determinations. In parallel, IgG antibodies to CMV were studied by immunoperoxidase assay. A significant rise of CMV-specific IgG antibody titre was observed in all of these patients between 5 and 53 weeks post-transplantation. CMV-specific IgA antibody production was detected close to the time a rise in CMV IgG antibody was observed in seven out of eight patients studied by RIA and ELISA, and in six out of eight patients studied by IPA. In two patients specific CMV IgA antibodies were detected by all three methods before a significant rise of CMV IgG antibody titre was demonstrated. In these patients CMV IgA was detected by RIA earlier than by ELISA and IPA. The potential application of CMV-specific IgA antibody determination for early detection of recurrent CMV infection in renal transplant patients is discussed.

A virological study of sea water was carried out at Barcelona (Spain) in June and September 1979. Three beaches were sampled in June; the September samples were taken in front of an outlet at 2, 5, 20 and 1,000 m offshore. All of the samples from the 3 beaches contained viruses, at rates varying from 0.12 to 1.72 MPNCU/l. Vaccinal poliovirus type 3 and coxsackie B5 predominated. For the offshore samples, 55% were positive with rates ranging from 0.15 to 0.36 MPNCU/l. Vaccinal poliovirus type 3 was clearly predominant. There was no significant difference in viral pollution rates between 2m and 1,000 m offshore.

A study was made on the presence of antibodies against lymphocytic choriomeningitis virus in 452 children in the Lyon area who had suffered from either a major pathological condition or a congenital malformation at birth. Of 34 cases of congenital hydrocephalus, only one could be definitely attributed to a maternal infection with the virus, occurring between the 5th and 6th months of pregnancy. Lymphocytic choriomeningitis virus should thus be added to the list of those which are potentially teratogenic for the human species.

Samples of piped water were taken from the source of the springs in ten villages in Lorraine. Usually this water has not been subjected to disinfection. The water was tested for fecal indicator bacteria, phages and animal viruses. Of the ten samples examined, seven contained no fecal indicator bacteria, phages or animal viruses, in three samples, however, Reovirus type 2 was found. Among the three positive samples only one contained fecal bacteria and phages. Consequently, the two other samples could be regarded as drinking water, despite the presence of viruses. Such an approach poses the problem of testing drinking water for viruses and suggests that viral tests should be undertaken as part of the water quality control.

The treatment of human CMV infection in transplant recipients by intravenous or intramuscular administration with high doses of hyperimmune or normal Ig showed inconsistent results. In fact, all hyperimmune Ig preparations were produced from high anti-CMV Ab titer plasma selected either by ELISA, complement fixation, or indirect hemagglutination test. These tests may not investigate the neutralizing activity of antibodies (Ab). We, therefore compared the ELISA titers with the neutralizing Ab titers in various normal Ig preparations from plasma or placenta and for intramuscular or intravenous use. Hyperimmune plasmatic Igs were also included. All the preparations were tested at a 5% dilution. We report the following data: (1) There is a poor correlation between ELISA and neutralization test. (2) The Igs of placental origin have significantly higher ELISA anti-CMV Ab titers than plasmatic normal Igs. They show the same neutralizing activity. (3) When compared with the normal intravenous Ig, normal intramuscular Igs show significantly higher titers with both techniques (P less than .0001). (4) Normal intramuscular Igs from placenta offer similar ELISA Ab titers and similar or higher neutralizing activity than hyperimmune Igs purified from plasma. It would be worth using Igs with high neutralizing activity in CMV prophylaxis in order to correlate in vitro tests and in vivo protection. In this respect, normal intramuscular Igs from placenta might be challenged in a clinical trial.

Between April 3, 1977 and June 6, 1980, 97 children with congenital cataracts and 97 evenly matched control children were examined in order to clarify the biological criteria of congenital rubella and to estimate its importance in the etiology of congenital cataracts. Although the age limit had been fixed at 60 months, the 1978 rubella outbreak accelerated the immunization in young children and resulted in difficulties in interpreting some results. All children presenting with congenital cataracts associated with clinical symptoms of rubella embryopathy displayed anti-rubella antibodies including anti-rubella IgM up to the 13th month: they represent 16% of cases with congenital cataracts in this series. The rubella etiology could not be proven in children with clinically isolated congenital cataracts.

Antigenic variation of the neuraminidase of A/H3N2 influenza viruses may be associated with modifications of the catalytic activity of this enzyme. We observed this phenomenon when studying two prototype strains: A/Hong Kong/1/68 (X31K) and A/Bangkok/2/79. For the neuraminidases of these strains, we determined their substrate specificity, initial velocity, optimum pH, optimum temperature, heat inactivation and Michaelis constants and their inactivation by chemical group-specific reagents. In order to examine the relationship between antigenic variation and enzyme activity of the influenza neuraminidases, three X31K monoclonal variants were selected using anti-neuraminidase monoclonal antibodies. Two of these (X31/NC92 and X31/NC56) were modified at a single neuraminidase epitope, and the third one (X31/NC92/NC56) at two epitopes. The neuraminidase activity of the monoclonal variants was analysed and compared to that of the prototype strains. Compared to A/Hong Kong/1/68, the A/Bangkok/2/79 strain neuraminidase was more susceptible to inactivation by physical (pH, temperature) and chemical agents [urea, dithiothreitol, 1-ethyl-3-(3-dimethylaminopropyl carbodiimide), iodoacetamide, acetic anhydride, 2,3-butanedione] and showed a twofold lower substrate affinity for N-acetylneuraminlactose. The neuraminidase activity of the monoclonal variants of X31K became more susceptible to inactivation by both physical and chemical agents than the original strain and exhibited various substrate affinities. Therefore, we conclude that the enzymic properties of the structurally conserved active sites of the neuraminidase molecule may be influenced by antigenic modifications that affect the variable areas of the neuraminidase and that the degree of this enzymic variation is related to the nature and number of the modified epitope(s). A local conformational change in the neuraminidase molecule reflected as antigenic variation could be involved in modification of enzyme activity.

The collection of data for influenza surveillance is difficult because clinical cases cannot easily be notified by practitioners and because only a few cases are studied by specific biological methods. In different countries, several indices are used such as: morbidity returns, mortality returns, absenteeism returns preferably in combination. In France, the two National Reference Centres in Paris and Lyon coordinate the activities of all diagnostic laboratories where influenza is detected by collecting and redistributing their findings and by identifying the strains they isolate. Furthermore, a collaborative network of physicians and institutions is being organised to provide a complete coverage of the country. I.N.S.E.R.M. and the National Centres have set up during the last two winters a new method of specific surveillance in school children: it combines observation of absenteeism peak in randomly selected classes and etiologic diagnosis by virus isolation. Surveillance of such a group, particularly sensitive to epidemic spread and probably partly responsible for it, was very efficient: early isolations were obtained and the presence of epidemics was detected before overt outbreaks occurred.

The incidence and the outcome of cytomegalovirus (CMV) infections were evaluated in 83 adult recipients of allogenic bone marrow transplantation. Virological and serological surveillance was performed weekly for 3 months posttransplant, and then every other week or every month until 1 year. CMV infection occurred in 45 patients, with a cumulative risk of 62% at 1 year and 66% at 2 years. In multivariate analysis, two factors significantly influenced the incidence of CMV infection: patients with pretransplant positive anti-CMV titres had a risk of infection of 72% at 1 year versus 33% for patients with negative titres. Patients with acute myeloid leukemia were also infected more frequently (85% at 1 year) than patients with acute lymphoblastic leukemia (56%), chronic granulocytic leukemia (45%), or aplastic anemia (47%). In both univariate and multivariate analysis, CMV infection was not associated with a worse prognosis. However, 5 (out of 10) cases of lethal interstitial pneumonitis were associated with CMV, and two patients died of possible CMV encephalitis. All these patients had been suffering from severe acute or chronic graft versus host disease.

Intra-nasal inoculation of 10-day-old piglets, free of specific pathogenic flora, with swine influenza virus A/H1 N1 and A/H3 N2 produces lesions of viral pneumonia without detectable clinical signs. Following indirect contamination all the strains studied were able to multiply in the respiratory tract; in those cases where no macroscopic lesion was seen, microscopic examination revealed variable modification of the pulmonary tissue depending on the virus causing infection. Influenza virus type H3 N2 are naturally found in many groups of pigs and can therefore play an important role in the respiratory pathology of the hog. Experimental results when compared to findings in the field indicate that the severity of the disease is linked to associated etiological factors as well as to the virulence of the viral strains themselves.