Respiratory syncytial virus induces indoleamine 2,3-dioxygenase activity: a potential novel role in the development of allergic disease.

BACKGROUND: Infants that develop severe bronchiolitis due to respiratory syncytial virus (RSV) are at increased risk of developing asthma later in life. We investigated a potential immunological mechanism for the association between RSV and the development of allergic inflammation. The enzyme indoleamine 2,3-dioxygenase (IDO) has been reported to induce selective apoptosis of T helper 1 (Th1) cells and contributed to Th2-biased immune responses. OBJECTIVE: To determine whether RSV infection in vitro could induce IDO expression and bioactivity in human dendritic cells, leading to a Th2-biased immune response. METHODS: Human peripheral blood monocytes from healthy adult donors were isolated, differentiated to dendritic cells (moDC), in vitro. We studied RSV infection and mechanisms of IDO activation in moDC with subsequent effect on T-bet expression. RESULTS: We found that moDC were infected by RSV and that this induced IDO activation. RSV-induced IDO activity was inhibited by palivizumab, UV inactivation, TL4R inhibition, and ribavirin. However, blocking endosomal TLR function with chloroquine did not inhibit IDO activity. Selective inhibitors suggested that RSV-induced IDO activity was dependent on the retinoic acid-inducible gene-I (RIG-I) related pathway via NF-κB and p38 MAPK. Coculture of RSV-infected moDC with activated T cells, in a transwell system, suppressed expression of T-bet (a Th1-associated factor) but not GATA3 (a Th2 regulator). Inhibition of IDO activity with the competitive inhibitor, 1-methyl tryptophan, blocked the effect on T-bet expression. CONCLUSION AND CLINICAL RELEVANCE: Our data show for the first time that RSV can induce the expression and bioactivity of IDO in human moDC, in a virus replication-dependant fashion. We suggest that RSV activation of IDO could be a potential mechanism for the development of allergic diseases.

Tryptophan catabolites regulate mucosal sensitization to ovalbumin in respiratory airways.

BACKGROUND: Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in tryptophan catabolism, is important in generating tolerance at the foetal-maternal interface. Studies using 1-methyl-tryptophan (1-MT), the specific inhibitor of IDO, showed that this enzyme is important in interferon-gamma (IFN-gamma)-dependent inhibition of allergic inflammation in the respiratory airway during immunotherapy. AIMS OF STUDY: We investigated the role of IDO in the development of allergic sensitization, leading to allergic inflammation and airway hyper-responsiveness (AHR). METHODS: We used a mouse model to generate mucosal tolerance to lipopolysaccharide-free ovalbumin (OVA) following repeated intranasal inoculation of OVA over a 3-day period. We tested the successful induction of tolerance by subsequent intraperitoneal (i.p.) sensitization followed by intranasal challenge with OVA. A slow-release pellet of 1-MT implanted into mice was used to block IDO activity prior to repeated intranasal inoculation of OVA. We measured T-cell proliferation in response to OVA, determined airway inflammation, and measured AHR to intranasal methacholine to investigate the role of IDO in sensitization to OVA. RESULTS: Repeated intranasal administration of OVA generated tolerance and prevented a subsequent sensitization to OVA via the i.p. route. This response was inhibited in mice receiving a slow-release pellet of 1-MT. However, we successfully reconstituted tolerance in mice receiving 1-MT following intra-peritoneal injection of a mixture of kynurenine and hydroxyanthranilic acid. CONCLUSION: Our data suggest that, in addition to their role in IFN-gamma-mediated inhibition of allergic airway inflammation, products of tryptophan catabolism play an important role in the prevention of sensitization to potential allergens in the respiratory airway.

Hepatitis B and C in doctors and dentists in Nigeria.

We surveyed a random sample (n = 75) of doctors and dentists at University College Hospital, Ibadan, Nigeria. They were offered anonymous testing for hepatitis B surface antigen (HBsAg), hepatitis Be antigen (HBeAG), antibodies to hepatitis B core antigen (anti-HBc) and to hepatitis C virus (anti-HCV), by enzyme immunoassay. The results suggest a high prevalence of hepatitis B virus (HBV) with a high potential of transmissibility, as well as a high prevalence of HCV infection. The majority of the doctors and dentists use universal precaution for protection against viral hepatitis on < 50% of the occasions when they carry out procedures on their patients. Infection with HBV was associated with type of specialty (surgeons, dentists) and lack of HBV vaccination (p < 0.05). After logistic regression, these factors were independently associated with HBV infection (p < 0.05). Sixty (80%) had not received prior HBV vaccination. Unvaccinated personnel were more likely to be surgeons, dentists, < 37 years of age, and have fewer years of professional activity (p < 0.05). After logistic regression, only fewer years of professional activity remained independently associated with lack of vaccination (p < 0.05). To reduce the occupational exposure of HBV, universal precautions must be rigorously adhered to when the doctors and dentists carry out procedures on their patients, and all health-care workers should be vaccinated with HBV vaccine and the HCV vaccine, when it becomes available.

Circulation of poliovirus among risk groups in Ibadan, Nigeria.

Faecal samples collected from 114 fully vaccinated pre-school children and 32 unvaccinated infants in Ibadan, Nigeria, were assayed for poliovirus in Hep-2 and RD cell cultures. 8 strains of poliovirus type 1 were isolated from 146 samples--3 from 32 unvaccinated children aged less than 40 d and 5 from 114 fully vaccinated children aged between 9 and 60 months. Studies using Sabin and wild monoclonal antibodies and the polymerase chain reaction confirmed 7 of the 8 isolates to be of the wild type, a possible source of infection among vaccinated children.

Hepatitis B and C virus and hepatocellular carcinoma.

Antibody to hepatitis C virus (anti-HCV) was detected in 18.7% of patients with hepatocellular carcinoma (HCC) and in 10.9% of controls (P < 0.001). The corresponding prevalences of hepatitis B surface antigen (HBsAg) were 59.3% and 50.0% (P < 0.001). Using patients with non-hepatic disease as controls, stepwise logistic regression analysis indicated that both anti-HCV (odds ratio 6.88%; 95% confidence interval [CI] 1.63-9.77) and HBsAg (odds ratio 6.46; 95% CI 1.68-18.13) were independent risk factors for HCC. Calculation of the incremental odds ratio indicated no interaction between hepatitis B virus (HBV) and HCV. Blood transfusion was a significant risk factor for acquiring HCV infection with odds ratios of 5.48 (95% CI 1.07-29.0) and 2.86 (95% CI 1.31-22.72) for HCC cases and controls, respectively. The mean age of HCC cases with HBsAg and anti-HCV was lower than that of HCC patients with anti-HCV alone (P < 0.01). It is concluded that there is a high rate of HBV infection, and a low rate of HCV infection, among Nigerian patients with HCC. However, HBV and HCV are independent risk factors for the development of HCC, with HBV having an effect more rapidly. Screening of blood products for transfusion might minimize the risk of HCV transmission.

Protective levels of canine distemper virus antibody in an urban dog population using plaque reduction neutralization test.

Blood samples from 50 dogs were collected at three veterinary clinics in Ibadan and Abuja, Nigeria and the serum from each sample was evaluated serologically for neutralizing antibodies against canine distemper virus (CDV) by the highly sensitive plaque reduction (PRN) neutralization assay. Thirteen dogs had plaque reduction neutralization titres of 0-100, seven had titres of 100-1,000 while 30 had titres ranging from 1,000-6,000. The PRN titres of vaccinated dogs were found to be significantly higher than unvaccinated dogs. The widespread use of the highly reproducible PRN test for the evaluation of antibody response to CDV may be very important in the generation of international CDV positive serum standards that should help to improve pre-and post-vaccination testing of dogs worldwide.

Field trial of combined yellow fever and measles vaccines among children in Nigeria.

The compared tolerance and immunogenecity of yellow fever and measles vaccines administered separately or combined were evaluated in Nigerian children aged between six to eight and nine to twelve months. The vaccines were well tolerated by both age groups of children, however pyrexia which responded to analgesic was the commonest post vaccination reaction in all the groups of the vaccinated children. Immune response to the vaccines either when given separately or combined was excellent in all the vaccinated groups. Antibody titre and seroconversion rate were always higher in the group that received the combined vaccines together. Our results confirmed that combined yellow fever and measles vaccines are safe for children aged between six to twelve months and we therefore recommend that yellow fever be incorporated into the EPI programme and be given together with measles at the age of nine months.

Prevalence and epidemiological characteristics of hepatitis B and C infections among doctors and dentists in Nigeria.

A random sample of seventy five doctors and dentists at the University College Hospital, Ibadan, Nigeria, was surveyed. They were offered anonymous testing for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), antibodies to hepatitis B core antigen (anti-HBc) and to hepatitis C virus (anti-HCV) by enzyme immunoassay. The results suggest a high prevalence of hepatitis B virus (HBV) with a high potential of transmissibility, as well as a high prevalence of HCV infection. Most of the doctors and dentists use universal precaution for protection against viral hepatitis less than 50% of the occasions when they carry out procedures on their patients. Infection with HBV was associated with type of specialty (surgeons and dentists) and lack of HBV vaccination (p < 0.05). After logistic regression, these factors were independently associated with HBV infection (p < 0.05). Sixty (80%) of these health care workers had not received prior HBV vaccination. The unvaccinated personnel were more likely to be surgeons, dentists, less than 37 years of age and have fewer years of professional activity (p < 0.05). After logistic regression, only the fewer years of professional activity remained independently associated with lack of vaccination (p < 0.05). We conclude that to reduce the occupational exposure of HBV, universal precautions must be rigorously adhered to when doctors and dentists carry out procedures on their patients. It is necessary that these health care workers are vaccinated with HBV vaccine and the currently anticipated HCV vaccination, if not immune. No recent study exists that exclusively addresses this problem in health care workers in tropical Africa.

Herd immunity to measles virus in a population of student nurses and medical students following a widespread outbreak of clinical measles in Ibadan, Nigeria.

Following an outbreak of serologically--and virologically--confirmed measles requiring large-scale hospitalisation of children in Ibadan, Nigeria, the herd immunity to measles virus among medical students and student nurses was determined. Of the 200 students tested, none lacked haemagglutination--inhibiting antibody to measles virus. The titre of HI--antibody ranged from 2(5) to 2(10). Describing a titre of 2(9) as very high, a significantly higher proportion of student nurses than medical students (P < 0.05) had very high antibody titres to measles virus. There was however no statistical difference between the sexes (P > 0.05). Using a commercial Enzyme Immuno Assay kit (EIA), anti measles IgM could not be detected from any of the students. Thus a clear evidence of recent infection with measles virus during the outbreak could not be detected among the students, a probable indication that student nurses and medical students may not participate in the maintenance of wild measles virus within the hospital environment in developing countries like Nigeria.

Hepatitis B surface antigen (HbsAg) in the sera of medical, nursing and microbiology students in Ibadan, Nigeria.

A total of 331 serum samples collected from medical students, student nurses, microbiology students, and patients presenting with Pyrexia of Unknown Origin (PUO) were tested for the presence of Hepatitis B surface Antigen (HbsAg). While only seven (14.0%) of 50 microbiology students (mean age 24.0 years) tested positive for HbsAg, six (6.7%) of 89 student nurses (mean age 21.6 years) and 13 (13.5%) of 95 medical students (mean age 24.3 years) in the clinical phase of their study were found to have HbsAg in their sera. Also, 10 (10.3%) of 97 patients with PUO (mean age 25.4 years), a group of patients from whom medical personnel are most likely to often collect blood for laboratory studies, were found to have HbsAg in their sera. No significant difference was found in the prevalence of HbsAg among the different groups examined in this study (P>0.05). The result of the study thus shows that medical and nursing students, unlike what is known for practising nurses, physicians and surgeons are not at a higher risk of HBV transmission than students of botany and microbiology. Likewise, patients with PUO do not constitute a group that is more likely to transmit HBV to medical personnel than other groups of patients. Vaccination against hepatitis B virus during the early period of medical and nursing training may therefore go a long way to reduce the high prevalence of hepatitis B virus infection previously reported among practising health personnel in Nigeria.

A critical role for vesicle-associated membrane protein-7 in exocytosis from human eosinophils and neutrophils.

BACKGROUND: Granulocyte exocytosis is proposed to be critically dependent on the interaction of soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNAREs) located on granules/vesicles (v-SNAREs) and plasma membrane (t-SNAREs). Previous studies indicated that the v-SNARE, vesicle-associated membrane protein (VAMP)-2, as well as t-SNAREs (SNAP-23, syntaxin-4 and -6) are implicated in exocytosis from human granulocytes. Vesicle-associated membrane proteins-7 and -8 have been implicated in endosome/lysosome trafficking, however, their role in granulocyte exocytosis remains obscure. OBJECTIVE: We sought to investigate the expression and functional role of SNARE isoforms in the secretion of different granule-derived mediators in human eosinophils and neutrophils. METHODS: The expression of SNAREs was determined by subcellular fractionation and flow cytometry. SNARE-specific antibodies were examined for their ability to impair mediator release from permeabilized eosinophils and neutrophils. RESULTS: Vesicle-associated membrane proteins-7 and -8 were localized to granule and membrane-enriched fractions in eosinophils and neutrophils, whereas syntaxin-6 was not detectable. In permeabilized cells, anti-VAMP-7, but not anti-VAMP-8, antibody impaired the secretion of all mediators examined (in eosinophils, eosinophil peroxidase and eosinophil-derived neurotoxin; in neutrophils, myeloperoxidase, lactoferrin and matrix metalloprotease-9) in a dose-dependent manner. In contrast, anti-VAMP-2 modestly and selectively impaired secretion from small granules and vesicles. Syntaxin-4, but not syntaxin-6, was found to interact with SNAP-23 and was partially involved in mediator secretion from multiple compartments. CONCLUSION: Our observations indicate for the first time a critical role for VAMP-7 in both eosinophil and neutrophil mediator release.

Passive immunity to measles in the breastmilk and cord blood of some nigerian subjects.

Maternal and cord blood collected from 33 Nigerian mother-child pairs were tested for measles-sepcific IgG. All 33 had protective measles antibodies at the time of delivery with a positive correlation of r = 0.87. Determination of the rate of waning of these antibodies revealed that 58 per cent of these children had lost the protective maternal antibody by the age of 4 months and only 3 per cent of the children had enough antibody to protect them between the ages of 6-9 months. Fifty-five colostrum samples from the same mothers and 347 breastmilk samples collected at various periods of breastfeeding also showed that anti-measles IgA had dropped below the protective cut-off within the first 2 weeks of birth. It is evident that the Nigerian child is born with solid anti-measles antibody but the rate of waning has left a large number unprotected before the first dose of the vaccine. There is an urgent need to review the measles vaccination programme in Nigeria to protect these susceptible infants.

The rise of the phoenix: the expanding role of the eosinophil in health and disease.

We have entered a new phase in the evolution of our understanding of the role of the eosinophil with a greater appreciation of novel potential functions that may be ascribed to this enigmatic cell type. This review not only provides an update to our current understanding of the various immunobiological roles for the eosinophil, but also attracts attention to some novel observations predicting functions beyond its putative effector role. These observations include the intriguing possibility that the eosinophil may possess the capacity to regulate the immune and inflammatory responses in diseases such as asthma.

Phylogenetic analysis of new hepatitis B virus isolates from Nigeria supports endemicity of genotype E in West Africa.

Isolates of hepatitis B viruses were collected from 20 acute and chronic hepatitis patients in a highly endemic region of Nigeria. Sequencing classified the isolates to the ayw4, as they all contained the amino acid variations characteristic for that serotype. In the pre-S2 region of five isolates, three to seven amino acids were deleted, suggesting that immune escape mutations previously associated only with chronic HBV infection may be observed also in acute disease. Phylogenetic analysis of the complete pre-S2/S (large S) genes (831 nt) demonstrated that all the viruses belonged to the same genotype E. So far, no isolates of genotype E have been found in any other region of the world, including the Americas. This may suggest a relatively recent introduction of this genotype into humans and would explain the relatively low genetic diversity of viruses belonging to this genotype. One genotype E virus had been found previously in a chimpanzee, and viruses belonging to the CHIMP genotype are related to other genotype E viruses. These findings are compatible with a transmission of genotype E viruses from chimpanzees to humans.

An outbreak of African Swine Fever in Nigeria: virus isolation and molecular characterization of the VP72 gene of a first isolate from West Africa.

The isolation of 98/ASF/NG, a strain of African Swine Fever Virus (ASFV) associated with a 1998 epizootic in Nigeria, is reported. This first isolate of the virus from West Africa was identified through a successful polymerase chain reaction (PCR) amplification and sequencing of a 280 base pair (bp) fragment of the Major Capsid Protein (VP72) gene. Further amplification and sequence analysis of a 1.9 kilobase pair (kbp) fragment encompassing the complete VP72 gene showed that the isolate has a 92.2%, 92.4%, and 97.2% homology with previously sequenced Ugandan, Dominican Republican and Spanish isolates respectively. Of the 50 nucleotide changes observed in this highly conserved gene, 45 were found to result in 40 amino acid changes clustered around the central region (position 426 to 516) of the VP 72 protein while changes at the remaining 5 positions were silent. These changes also led to the loss of two out of the seven potential N-glycosylation sites which are in this gene conserved among all isolates. The possible epizootiological implications of such mutations in a highly conserved gene of a DNA virus is discussed in relation to this outbreak.