Prevalence of insomnia symptoms in patients with sleep-disordered breathing.

OBJECTIVE: To assess the prevalence of insomnia symptoms in patients with objectively diagnosed sleep-disordered breathing (SDB). DESIGN: Retrospective medical chart review of a representative sample of patients with SDB. SETTING: University sleep-disorders clinic and laboratory. PATIENTS: Two hundred thirty-one patients with SDB were selected from a pool of approximately 2,000 patients with sleep disorders. MEASUREMENTS: Data were extracted from intake questionnaires and polysomnographic studies. RESULTS: Of 231 patients with SDB diagnoses, 115 patients reported no insomnia complaints (SDB-only patients) and 116 patients reported clinically meaningful insomnia complaints (SDB-plus patients). Compared to SDB-only patients, SDB-plus patients reported significantly worse mean sleep characteristics consistent with insomnia, including sleep latency (17 min vs 65 min), total sleep time (7.2 h vs 5.6 h), and sleep efficiency (92% vs 75%). SDB-plus patients experienced significantly more psychiatric disorders, cognitive-emotional symptoms, and physical and mental symptoms that disrupted or prevented sleep. SDB-plus patients also reported greater use of sedative and psychotropic medications and had significantly more primary complaints of insomnia, restless legs or leg jerks, and poor sleep quality despite having relatively similar referral rates for sleep apnea or complaints of loud snoring. CONCLUSIONS: Problematic insomnia symptoms were reported by 50% of a representative sample of patients with objectively diagnosed SDB. Research is needed to determine the degree to which insomnia and related symptoms and behaviors interfere with SDB treatment.

Antibody responses to Onchocerca volvulus in Ecuadorian Indians and blacks.

In Ecuador, previous epidemiological studies of onchocerciasis affecting a population consisting of Blacks of African origin and Amerindians of the Chachi tribe, have demonstrated different frequencies of clinical disease manifestations in each racial group. To explore the possibility of differential antibody responses to O. volvulus antigens in this population, a subset of sera from these two groups of Ecuadorians with onchocerciasis was analyzed for antibody to O. volvulus antigens using ELISA and Western blot techniques. Significantly higher levels of immunoglobulin against O. volvulus were demonstrated in Chachi Indians compared to native Blacks of African origin: total Ig (p = 0.049), IgG (P = 0.002) IgG4 (p = 0.019) and IgA (p = 0.035). Western blot analysis of sera from 41 persons demonstrated more intense and more frequent recognition of low molecular weight parasite antigens in the Chachi compared to a similar group of male and female Ecuadorian Blacks. These data suggest that the intensity of antibody responses to O. volvulus antigens may reflect the influence of racial factors in the pathogenesis of onchocerciasis in Ecuador.

Immunity to hepatitis B: analysis of antibody and cellular responses in recipients of a plasma-derived vaccine using synthetic peptides mimicking S and pre-S regions.

The potential of a panel of synthetic HBsAg peptides as components of a synthetic hepatitis B vaccine was assessed. Each was used in turn as probes to analyse human immune responses to a licensed plasma-derived HBV vaccine. Both humoral and cellular responses were analysed with synthetic peptides representing residues 124-147 of the surface antigen of the virus (HBsAg) and residues 126-140 of the pre-S2 region. Antibody levels and affinities were assessed in radioimmunoassays with synthetic linear and cyclical forms of surface antigen peptides 124-137 and 139-147, with the gp30p25 polypeptide complex of HBsAg and with the linear pre-S2 peptide 126-140. Levels and affinities of antibodies to the antigens increased with time during immunization. However, antibodies binding the cyclical peptide representing amino acids 139 to 147 (C139) were present at higher levels and had higher affinities than were antibodies binding the other peptides, indicating that C139 more closely approximates a domain on the native antigen than do the other peptides. No humoral responses were measured with the pre-S2 peptide. Cellular responses were assessed by in vitro stimulation of peripheral blood lymphocytes by HBsAg and by the synthetic peptides. All vaccine recipients had demonstrable lymphocyte responsiveness to HBsAg after both second and third doses of the vaccine. Of the S and pre-S peptides used, only L124 failed to induce lymphocyte stimulation in all recipients. However, there were individual variations in both the time of initial responsiveness to peptides and in the level and time of maximal stimulation. Stimulation by native HBsAg particles, which corresponded to the appearance of anti-HBs antibody, preceded that observed using synthetic peptides. In all recipients, maximum stimulation indices with HBsAg were significantly higher than those observed with the peptides. In contrast to the absence of pre-S2 antibody, the lymphocytes from all recipients showed positive stimulation in response to the peptide representing residues 126-140 of the pre-S2 region. None of these individuals had antibodies to pre-S or an HB core peptide sequence nor did their lymphocytes respond to a synthetic peptide representing an HB core sequence.

Associations between clinical disease, circulating antibodies and C1q-binding immune complexes in human onchocerciasis.

Onchocerciasis is a disease where often there are high levels of serum antibodies and high parasitic loads. The role of immune complexes in the development of the disease is investigated here by studying non-specific and Onchocerca volvulus specific immune complex levels, as well as the antibody concentrations, in the sera of 372 people living in either Southern (199) or Northern (173) Sudan; sera from Sudanese individuals (31) and Caucasians (21) living outside the onchocerciasis endemic area were also tested. The levels of non-specific immune complexes (NS-IC) in these sera were measured by a solid phase radio-immunoassay and those of O. volvulus-specific immune complexes (OV-IC) by an assay measuring antibody-excess complexes using C1q-coated plates. The concentrations of O. volvulus IgG antibodies were measured by ELISA. Immune complex and antibody levels of the serum donors were compared with regard to their clinical status due to onchocerciasis. These clinical changes were classified according to onchocercal lesions related to either the active destruction of microfilariae (acute changes), or the long term tissue alterations (chronic changes). Data was analysed using the Odds Ratio method. A negative association between microfilarial load and immune complex level was found, with the higher levels of OV-IC present in patients with the lower levels of dermal microfilariae (i.e., less than 10 mf/mg). Significant associations between immune complex levels and the severity of onchocercal disease were also found. Levels of OV-IC specific immune complexes were higher in infected individuals carrying dermal onchocercal lesions than in those without such clinical changes; there was no apparent relationship between these levels and the presence of ocular lesions. OV-IC levels varied considerably within each age group and from age to age. A weak positive association was detected between microfilarial load and parasite-specific IgG antibody concentration in the sera. On average younger individuals (less than 25 years) had the higher antibody levels with a gradual reduction in mean concentrations with age. The significance of these serological findings in terms of the pathogenesis of onchocerciasis is discussed.

Onchocerciasis in southwestern Sudan: parasitological and clinical characteristics.

Parasitological and clinical observations were made on residents of Pongo Nuer, a village in the province of Bahr El Ghazal, southwestern Sudan. Of 202 skin biopsies, 189 (94%) were positive for microfilariae of Onchocerca volvulus. Nodules were most common around the pelvic girdle and rare on the limbs or head. Microfilarial intensities, ranging up to 1,094 mf/mg of skin, were highest at the iliac crest and shoulder; they increased rapidly in childhood but then appeared to reach a plateau maintained through adult life. Nodule presence and number, especially at multiple sites, was significantly related to skin microfilarial intensity. Dermal manifestations of O. volvulus infection were widespread and severe, ranging from acute maculopapular eruptions to chronic, diffuse, and degenerative changes, even in young adults. However, high skin microfilarial intensities were found in asymptomatic individuals; conversely, lowest intensities were in those with severest maculopapular lesions, suggesting that host response was a major determinant of disease outcome. Microfilariae were detected in the cornea or anterior chamber of the eyes of one third of those examined in all age groups, but lesions of the posterior segment, including optic neuritis, chorioretinitis, and pigmentary abnormalities, were considered responsible for visual deficits in the population sample. Some pathologic changes in the anterior segment attributable to microfilariae were more common in the young than in adults but there was no preponderance of sclerosing keratitis in adults, contrary to expectations in hyperexposed individuals in a Sudan savannah zone. The best correlate of the presence of microfilariae in the eye was the intensity of infection in shoulder skin snips. Little value could be derived from data on outer canthus samples, either in terms of severity of ocular infection or disease. Microfilaremia was common (76%) but in only one case was attributed to O. volvulus; the remainder were due to Mansonella perstans.

Antigens of Onchocerca volvulus.

Most studies on immunologic responses to Onchocerca volvulus have employed extracts or antigens from related filarial parasites. Consequently, little is known about the nature of O. volvulus antigens. Potential antigen sources include in vitro cultures and physicochemical fractionation of O. volvulus extracts. IgE antibody responses to a wide range of antigens occur in patients with onchocerciasis, but there is little evidence of species specificity in serologic tests. Some potent allergens are released by microfilariae, but host serum proteins appear to contaminate the most reactive fractions obtained thus far. Antibody-mediated cell adherence to microfilariae of O. volvulus occurs in vitro, and both stage and species specificity have been demonstrated. Monoclonal antibodies to O. volvulus antigens have been prepared, but, unfortunately, all to date show cross-reactivity to antigens of other filarial nematodes. Circulating antigens have been detected in patients' sera; no data are available yet on the specificity of these components. Research needs include the need for species- and stage-specific reagents for immunodiagnostic assays and for investigations on immunopathogenic mechanisms in onchocercal disease.

Variations in host responses and the pathogenesis of human onchocerciasis.

Different immune responses to Onchocerca volvulus cause considerable variation in clinical manifestations of human onchocerciasis. Onchocercal lesions result from inflammatory reactions involving immunologic mechanisms; the role of the immune system in pathogenesis is emphasized by the phenomena accompanying accelerated worm destruction during microfilaricidal chemotherapy (e.g., eosinophilia, changes in total immunoglobulin level, and anaphylactic symptoms). Although most pathologic changes are associated with the microfilarial stage, the extent to which circulating antibodies are directed against antigens in the adult worm or its uterine constituents is unknown. Microfilarial destruction can be mediated by antibody to the surface-associated antigens of the worms and enhanced by complement; a correlation exists between the presence of these antibodies and punctate keratitis. Heterogeneous immunologic components are associated with the surface of dermal and nodular microfilariae in vivo. Preliminary findings indicate that the level of O. volvulus-specific immune complexes is inversely proportional to the microfilarial load. To monitor a patient's clinical status and immunologic response, a quantitative system dividing symptoms into those associated with active responses to the microfilariae and those representing long-term consequences of these reactions is suggested.

Circulating antigen-antibody complexes in onchocerciasis.

The presence of circulating antigen-antibody complexes in the sera of patients with onchocerciasis was investigated using the Clq and conglutinin solid-phase binding assays. Only 50% of patients' sera had demonstrable complexes, levels of complexes were unrelated to microfilarial load and specific anti-onchocercal antibody titres and results with the two tests for complexes were not correlated. Both IgM- and IgG-containing complexes were commonly involved but there was no correlation between the levels of complexes containing these isotypes. Evidence for the presence of IgE in complexes of sera from a minority of individuals was also obtained.