Rupatadine 10 mg in the treatment of immediate mosquito-bite allergy.

BACKGROUND: People frequently experience wealing and delayed papules from mosquito bites. Wealing is mediated by antisaliva IgE antibodies and histamine. Rupatadine is a new antihistamine effective in allergic rhinitis and urticaria, but the effect on mosquito-bite allergy is not known. OBJECTIVE: To determine the effectiveness of rupatadine in inmediate mosquito-bite allergy-confirmed adult patients. METHODS: A double-blind, placebo-controlled, cross-over study was performed with rupatadine 10 mg and matched placebo in 30 mosquito-bite-sensitive adults. The mean age was 37 years and the subjects had suffered from harmful mosquito bites for a mean of 15 years. Either rupatadine or placebo was taken at 08:00 am for 4 days, followed by a 5 day wash out period and then alternative treatment was given for 4 days. On day 3, in both drug periods the subjects received two Aedes aegypti mosquito-bites on the forearm. The size of lesions and intensity of pruritus [visual analogue scale (VAS)] were measured after 15 min bite reaction. RESULTS: Twenty-six subjects were analysed for efficacy. The size of the 15 min bite reaction under placebo was of 106 mm2 and under rupatadine, of 55 mm2. This is a significant decrease (48%; P=0.0003). The accompanying pruritus decreased from 60 (VAS; median) under placebo to 47.5 under rupatadine, which also is a significant (P=0.019) difference. There was no significant (P=0.263) difference in adverse events under rupatadine and placebo. CONCLUSION: The present placebo-controlled study in mosquito-bite-sensitive adults shows that rupatadine 10 mg prophylactically given is an effective treatment for the mosquito-bite wealing and skin pruritus.

A study on HIV and hepatitis C virus among commercial sex workers in Tallinn.

INTRODUCTION: Estonia is confronted by a dramatic expansion of the initially injection drug use-driven HIV epidemic. Little is known about HIV occurrence in population groups at high risk other than injection drug users. OBJECTIVE: To obtain data on the prevalence of HIV and hepatitis C virus (HCV) among female sex workers (FSW) in Tallinn. DESIGN: An unlinked, anonymous, cross-sectional survey of FSW recruited in Tallinn from October 2005 to May 2006. METHODS: 227 FSW were recruited for the survey and biological sample collection (HIV, HCV antibodies detection) using a combination of time-location, community and respondent-driven sampling. RESULTS: Among 227 women the HIV and HCV prevalences were 7.6% (95% CI 4.6% to 12.5%) and 7.9% (95% CI 4.5% to 12.6%), respectively. HIV prevalence was higher among FSW working in the street (odds ratio (OR) 6.4; 95% CI 1.1 to 35.6) and at the brothels and apartments supervised by the organised sex industry (OR 5.0; 95% CI 1.3 to 18.4). The duration of sex work was negatively associated with HIV prevalence (OR 0.78; 95% CI 0.63 to 0.97). CONCLUSIONS: Prevention needs of FSW in this area include increasing rates of HIV testing and putting in place effective programmes that can help extend HIV prevention behaviours across a range of sexual and drug use risk behaviours.

Epidemiology of Sindbis virus infections in Finland 1981-96: possible factors explaining a peculiar disease pattern.

Pogosta disease (PD), an epidemic rash-arthritis occurring in late summer is caused by Sindbis virus (SINV) and is transmitted to humans by mosquitoes. Altogether 2183 PD cases were serologically confirmed 1981-96 in Finland, with an annual incidence of 2.7/100000 (18 in the most endemic area of Northern Karelia). The annual average was 136 (varying from 1 to 1282) with epidemics occurring in August-September with a 7-year interval. Studies on 6320 patients with suspected rubella (1973-89) revealed 107 PD cases. The depth of snow cover and the temperature in May-July seemed to predict the number of cases. The morbidity was highest in 45- to 65-year-old females and lowest in children. Subclinical SINV infections were 17 times more common than the clinical ones. The SINV-antibody prevalence in fertile-age females was 0.6% in 1992; the estimated seroprevalence in Finland is about 2%. Among game animals the tetraonids (black grouse and capercaillie) had the highest seroprevalence (65%) in the epidemic year of 1981.

Analysis of HIV-1 genetic subtypes in Finland reveals good correlation between molecular and epidemiological data.

The molecular epidemiology of HIV-1 genetic subtypes was studied in a cross-sectional sample collected from HIV-infected individuals living in Finland between 1988 and 1994 and compared with independently collected epidemiological data. Subtypes were determined by sequencing and phylogenetic analysis of the gag NCp7 and the env coding regions of PBMC provirus. Finnish viruses belonging to 7 subtypes were found. Two thirds (n = 70) of the sequences could be classified as subtype B, while others belonged to subtypes A, C, D, F and G and the circulating recombinant form AE(CM240) (n = 25). There were significant differences in gender distribution and mode-of-transmission between B-type infections and infections with the other subtypes. Most subtype B strains in Finland were associated with homosexual transmission and about half of these were acquired in Finland, while most individuals harbouring non-B infections indicated heterosexual transmission and direct or indirect contact with Africa or Southeast Asia. The heterogeneity of genetic subtypes in the country was in good agreement with the epidemiological data suggesting that a significant proportion of infections were imported. HIV-1 subtype determination may prove to be a valuable tool for providing objective epidemiological data.

Loratadine in the treatment of mosquito-bite-sensitive children.

BACKGROUND: Children frequently experience harmful whealing and delayed papules from mosquito bites. Whealing is mediated by antisaliva IgE antibodies and histamine, but the effect of antihistamines on mosquito-bite symptoms has not been evaluated in children. METHODS: The effect of loratadine (0.3 mg/kg) was examined in 28 mosquito-bite-sensitive children (aged 2-11 years). The double-blind, placebo-controlled, crossover study was performed with exposure to Aedes aegypti laboratory mosquitoes. The size of the bite lesion and the intensity of pruritus (visual analog scale) were measured at 15 min and at 2, 6, and 24 h. RESULTS: Loratadine decreased the size of the wheals by 45% (P < 0.001, 25 children) and accompanying pruritus by 78% (P = 0.011, 12 children) at 15 min compared to placebo. The size of the 24-h delayed bite lesion also decreased significantly (P = 0.004), but there was no change at 2 or 6 h. Loratadine was well tolerated and no marked side-effects were recorded. CONCLUSIONS: This study in children shows that prophylactically given loratadine decreases significantly the whealing and pruritus caused by mosquito bites and also reduces the size of the 24-h bite lesions. Therefore, the therapeutic profile of loratadine extends from immediate to delayed allergic symptoms in mosquito-bite-sensitive children.

HIV-1 genetic subtype A/B recombinant strain causing an explosive epidemic in injecting drug users in Kaliningrad.

OBJECTIVES: To investigate the molecular epidemiology and genetic structure of the virus strain(s) causing an outbreak of HIV-1 infection in the Kaliningrad province of the Russian Federation and to investigate the relationship of this outbreak to some other emerging HIV-1 epidemics in the countries of the former Soviet Union. DESIGN: A molecular epidemiological investigation was conducted in the city of Kaliningrad amongst individuals recently diagnosed as HIV-1-positive. Samples were also collected from neighbouring Lithuania and from the Ukraine. METHODS: Incident and population data was collected from official health statistics in Kaliningrad. A standardized questionnaire was administered to newly diagnosed individuals to assess risk factors for HIV-1 infection. For genotyping, two regions of the virus (env C2-V3 and gag NCp7) were directly sequenced. RESULTS: The number of newly diagnosed individuals testing seropositive for HIV-1 infection in Kaliningrad rose from less than one per month to more than 100 per month during the period of July-October 1996. A total of 1335 new infections were identified between 1 July 1996 and 30 June 1997. The main reported risk factor for HIV-1 infection (80%) was injecting drug use, in particular with a locally produced opiate. Sequence analysis of patient viruses in Kaliningrad (n = 50) showed that the epidemic was caused by a highly homogenous HIV-1 strain, recombinant between the genetic subtypes A and B. Comparison with subtype A strains prevalent amongst injecting drug users (IDU) in the Ukraine showed that one of these strains was the direct subtype A parent of the epidemic A/B recombinant strain in Kaliningrad. CONCLUSIONS: The HIV-1 epidemic in Kaliningrad probably started from a single source, with rapid spread of the virus through the IDU population. The origin of the epidemic strain is a recombination event occurring between the subtype A strain virus prevalent among IDU in some southern CIS countries, and a subtype B strain of unknown origin.

Seasonal increase in human IgE and IgG4 antisaliva antibodies to Aedes mosquito bites.

BACKGROUND: Mosquito bite-sensitive subjects frequently have circulating IgE and IgG4 antibodies to Aedes mosquito saliva proteins. METHODS: In the present study we examined the antibody response during a mosquito season in 14 subjects living in Finnish Lapland. Immunoblotting was performed with Aedes communis saliva and the 22- and 36-kD antisaliva antibody bands were analyzed. RESULTS: The preseason sera showed IgE antibodies to the main saliva antigens in 12, IgG4 antibodies in all 14 and IgG1 antibodies in 12 subjects, and the postseason sera in all but 1 subject. The postseason sera showed significantly more intense IgE (p < 0.05), IgG4 (p < 0.001) and IgG1 (p < 0.01) antibody bands than the preseason sera. CONCLUSION: These results show that seasonal exposure to mosquito bites leads to an increased IgE, IgG4 and IgG1 antibody response, a phenomenon similar to that occurring e.g. in pollen allergy.

Effect of ebastine on mosquito bites.

Mosquito bites usually cause wealing and delayed bite papules. Cetirizine decreases wealing, bite papules and pruritus but the effect of other antihistamines on mosquito bites is unknown. We studied the effect of ebastine in 30 mosquito bite-sensitive adult subjects. Ebastine 10 mg or 20 mg and placebo were given for 4 days in a cross-over fashion. Aedes aegypti bites were given on forearms. The size of the bite lesions and pruritus (visual analogue score) were measured at 15 min, 2, 6, and 24 h after the bites. Twenty-five subjects were evaluable in the study. At 15 min ebastine decreased significantly the size of the bite lesion (p = 0.0017) and pruritus (p<0.0001). The effects of 10 mg and 20 mg of ebastine were similar. No significant effect was found at 2, 6 or 24 h, but when the measurements at all four time points were compiled the size of the bite lesion and pruritus score decreased significantly. Sedation occurred during ebastine treatment in 6 (21%) and during placebo treatment in 2 (7%) subjects. The present results show that prophylactically given ebastine is effective against immediate mosquito bite symptoms.

Detection of mosquito saliva-specific IgE antibodies by capture ELISA.

We developed an IgE-capture ELISA and measured mosquito saliva-specific IgE antibodies in 27 children sensitive to mosquito bites. Children with large 15-min bite wheals had significantly higher (P < 0.0005) mosquito saliva-specific IgE levels than children with small wheals. In the latter group, the saliva-specific IgE level was significantly higher (P = 0.031) than the levels of six infants never exposed to mosquitoes. A positive correlation (r = 0.65; P = 0.0002) was found between the size of the 15-min wheal and the mosquito saliva-specific IgE antibody levels. These results further support the role of mosquito saliva-specific IgE antibodies in the pathogenesis of mosquito-bite whealing. Compared to immunoblotting, IgE-capture ELISA provides a quantitative method to measure mosquito saliva-specific IgE antibodies.

Characterization of Aedes communis, Aedes aegypti and Anopheles stephensi mosquito saliva antigens by immunoblotting.

BACKGROUND: Mosquito bites cause immediate wheals and delayed bite papules in sensitized subjects having saliva-specific IgE and IgG4 antibodies. At present, mosquito saliva antigens are not well characterized. METHODS: To identify immunogenic proteins in mosquito saliva and study their cross-reactivity we immunized mice with Aedes communis, Aedes aegypti and Anopheles stephensi bites. Immune sera were used in immunoblotting and immunoblot inhibition experiments. RESULTS: The main A. communis saliva antigens were 22-, 30-, and 36-kD, A. aegypti saliva antigens 31-, 36-, 46- and 64- to 66-kD, and A. stephensi saliva antigen 46-kD proteins. Most of the saliva antigens appeared to be species-specific and only weak cross-reactivity was observed with heterologous immune sera. Distinct cross-reactivity was observed only between saliva proteins of A. communis and Aedes punctor, two taxonomically closely related species. Human IgE and IgG4 antibodies from mosquito-bite-sensitive children bound to the same saliva proteins as antibodies from the immunized animals. CONCLUSIONS: This study disclosed several immunogenic proteins in Aedes and Anopheles mosquito saliva and suggests that these proteins can also be allergenic in man.

Histamine and leukotriene C4 release in cutaneous mosquito-bite reactions.

BACKGROUND: Mosquito bites are known to sensitize persons, and the most common cutaneous reactions are immediate wheals and delayed bite papules. Anti-saliva IgE and IgG4 antibodies are common in mosquito-sensitive subjects, but mediator release in bite reactions is not known. METHODS: We used the microdialysis technique to measure in vivo histamine and leukotriene C4 release after bite challenges in six mosquito-sensitive subjects. One individual who was not sensitive to bites volunteered as a control subject. RESULTS: Three of the six mosquito-sensitive subjects had large wheals and showed clearly increased histamine concentrations 30 to 45 minutes after the bites. The histamine levels declined to baseline value within 2 hours; thereafter, one subject showed a second increase in histamine concentration. Four of the six mosquito-sensitive subjects showed increased leukotriene C4 concentrations, and this mediator seemed to be released somewhat later than histamine. CONCLUSIONS: The increased histamine and leukotriene C4 release observed in this study suggests that both mediators are involved in the early allergic response caused by mosquito bites.

Passive transfer of cutaneous mosquito-bite hypersensitivity by IgE anti-saliva antibodies.

BACKGROUND: Mosquito bites frequently cause cutaneous wheal and flare reactions, and recent immunoblotting studies have shown specific anti-saliva IgE antibodies in many persons who have such reactions. OBJECTIVE: The study was designed to show that human serum containing mosquito saliva-specific IgE antibodies can produce histamine release in vitro and whealing in vivo. METHODS: Two mosquito bite-tolerant subjects had bite challenges and Prausnitz-Küstner tests with heated and unheated serum from one patient with Aedes mosquito allergy. Immunoblotting and basophil histamine release tests were performed with the patient's and subjects' sera. RESULTS: Both mosquito bite-tolerant subjects had positive Prausnitz-Küstner reactions, which indicated a successful transfer of cutaneous mosquito hypersensitivity. The ordinary and passive basophil histamine release tests also produced positive results with Aedes communis antigens. CONCLUSION: The results of the Prausnitz-Küstner test, immunoblotting, and basophil histamine release tests are consistent with the hypothesis that mosquito bite whealing is mediated by specific anti-saliva IgE antibodies.

Frequent occurrence of IgE and IgG4 antibodies against saliva of Aedes communis and Aedes aegypti mosquitoes in children.

We examined the prevalence of IgE and IgG4 class antibodies to the saliva of Aedes communis and Aedes aegypti mosquitoes in the sera of three groups of exposed children using a sensitive immunoblot method. The frequencies of IgE antibodies to the major 36-kD A. communis and A. aegypti saliva antigens ranged from 82 to 90% in the 20 Finnish, 17 Kenyan, and 20 Mexican children. The corresponding IgG4 antibody frequencies were 85, 41, and 20%, respectively. The nonexposed 20 Icelandic children did not show IgE or IgG4 antisaliva antibodies. Several of the Finnish children showed also IgE and IgG4 antibodies to a 22-kD A. communis saliva antigen. The Finnish children abnormally sensitive to mosquito bites had frequently IgE and IgG4 antibodies to the 22-kD A. communis saliva antigen, suggesting that these antibodies play a role in the pathogenesis of immediate cutaneous mosquito bite reactions. In contrast to this, no increase was found in the A. aegypti antibody frequencies in the Kenyan and Mexican children with papular urticaria, suggesting that humoral immune response to A. aegypti saliva is not involved in the development of this disorder. The present results show that humoral IgE and IgG4 immune responses to Aedes mosquito saliva antigens is common in children living both in temperature and tropical zones. The IgE antibodies seem to be involved in the immediate mosquito bite whealing, and the occurrence of the IgG4 subclass antisaliva antibodies might be an indicator of intense mosquito bite exposure.

Are we really allergic to mosquito bites?

Most, if not all, people are sensitized to mosquito bites in childhood. Cutaneous symptoms include immediate wheal-and-flare reactions and delayed bite papules, which tend to be more severe at the onset of the mosquito season. Systemic reactions to mosquito bites are, however, very rare. Recent immunoblot studies have demonstrated IgE antibodies to Aedes communis mosquito saliva 22 and 36 kD proteins. This confirms that specific sensitization occurs in man and indicates that mosquito-bite whealing is a classic type I allergic reaction. The delayed mosquito-bite papules seem to be cutaneous late-phase reactions mediated by eosinophils or they could also represent type IV lymphocyte-mediated immune reactions. People living in heavily infested areas such as Lapland frequently acquire tolerance to mosquito bites, and seem to have negligible levels of IgE but high amounts of IgG4 antisaliva antibodies. Desensitization treatment is a theoretical possibility but prophylactically given cetirizine, an H1-blocking antihistamine, has been shown to be helpful for people suffering from mosquito bites.

Detection of mosquito saliva-specific IgE and IgG4 antibodies by immunoblotting.

IgE and IgG subclass antibodies against Aedes communis mosquito saliva were studied by immunoblotting in 12 adults with immediate and/or delayed skin reactions to mosquito bites. Four antigenic proteins, with molecular weights of 22, 30, 36, and 64 kd, were found in the mosquito saliva. Almost all subjects (11 of 12) had anti-mosquito saliva-specific IgE antibodies directed against the 36 kd protein. The IgG antibody response appeared to be restricted mostly to IgG4 (11 of 12) and IgG1 (8 of 11) subclasses against the same 36 kd antigen. Ten of the 12 subjects had both IgE and IgG4 antibodies to the 36 kd protein. No anti-mosquito antibodies were found in pooled sera of five infants never exposed to mosquito bites. These results show that most persons with immediate skin reactivity to A. communis mosquito bites have both IgE and IgG4 antibodies that recognize the 36 kd antigen present in the mosquito saliva, suggesting that anti-saliva antibodies may play a role in the pathogenesis of mosquito bite reactions.

Stability of human immunodeficiency virus (HIV) antibodies in postmortem samples.

The stability of human immunodeficiency virus (HIV) antibodies was studied for samples of sera, vitreous fluid and bile obtained from eight HIV-positive autopsy cases. The autopsy delay was on average 5 days. The samples were stored at room temperature (20 degrees C) for 51 to 314 days and tested repeatedly. In Western blotting on fresh postmortem samples, the antibodies detected most of the proteins of the virus. Antibodies against all major envelope, core and transmembrane proteins, although weakened, were also detected in stored sera. In stored vitreous fluid and bile the envelope protein gp 160, the transmembrane protein gp 41 and in half of the cases also the major core protein p 24 could still be detected. The disappearance of p 24 was associated with AIDS, but was detected in all samples from patients with early infection. Of screening tests, the enzyme-linked immunosorbent assay applying synthetic peptide as an antigen detected antibodies from all serum samples, but was less applicable to vitreous fluid or bile. Another immunoassay, applying recombinant antigen, succeeded in vitreous fluid and bile but not in sera. The rapid visually read assay detected antibodies in most samples of fresh whole blood, bile and in most of the vitreous samples, but was less useful on stored specimens.

Molecular epidemiology of HIV-1 based on phylogenetic analysis of in vivo gag p7/p9 direct sequences.

Viruses of different geographical origin are circulating in Finland. We wanted to test whether phylogenetic analysis of patient lymphocyte proviral quasispecies sequences could be used to group different strains into genetic lineages. The gag p7/p9 coding region was analyzed using solid-phase direct sequencing from 30 patients in Finland and Estonia. Proviral sequences were found to represent at least four, possibly even five, different, highly diverged major lineages. Different methods of phylogenetic analysis resulted in the same conclusion. Serial samples from the same patients, taken over a period of several years showed limited variation over time. Cases of potential patient-to-patient transmission or common source of infection were identified based on the sequence analysis. Compared to similar analyses of longer genome segments, the gag p7/p9 nucleic acid binding protein coding region produces analogous results in phylogenetic analysis. The method can be used as a rapid way of determining the genetic subtype of HIV-1 strains circulating in populations.

Treatment of mosquito bites with cetirizine.

Eighteen adult subjects sensitive to mosquito bites participated in a double-blind, placebo-controlled study with 10 mg cetirizine. The drug was given prophylactically and the subjects were then exposed to bites of Aedes communis mosquitoes in the field. Bite lesions were measured and pruritus was scored with a visual analogue scale at 15 min, 60 min, 12 hr and 24 hr. Cetirizine significantly decreased immediate wealing and pruritus and, interestingly, also had a clear effect on the delayed 12 hr and 24 hr bite papules and pruritus. The diameter of a 15 min mosquito-bite weal was 10.1 +/- 10.4 mm (mean +/- s.d.) with the placebo and 5.9 +/- 5.9 mm with cetirizine treatment (P < 0.05). The 15 min pruritus scores were 36.0 +/- 25.2 and 11.2 +/- 13.2 (P < 0.001), respectively. The diameter of the 24 hr mosquito-bite lesion was 12.6 +/- 21.9 mm with the placebo and 7.4 +/- 16.1 mm with cetirizine treatment (P < 0.01). The 24 hr pruritus scores were 18.9 +/- 25.5 and 6.6 +/- 14.8 (P < 0.01), respectively. These results indicate that, in mosquito-sensitive subjects, prophylactically administered cetirizine is an effective drug against both immediate and delayed mosquito-bite symptoms.