The utility of seroepidemiology for tracking trends in pertussis infection.

Comparing pertussis epidemiology over time and between countries is confounded by differences in diagnostic and notification practices. Standardized serological methods applied to population-based samples enhance comparability. Population prevalence of different levels of pertussis toxin IgG (PT IgG) antibody, measured by standardized methods, were compared by age group and region of Australia between 1997/1998 and 2002. The proportion of 5- to 9-year-olds with presumptive recent pertussis infection (based on IgG levels >or=62.5 ELISA units/ml) significantly decreased in 2002, consistent with notification data for the same period and improved uptake of booster vaccines following the schedule change from whole-cell to acellular vaccine. In contrast, recent presumptive infection significantly increased in adults aged 35-49 years. Population-based serosurveillance using standardized PT IgG antibody assays has the potential to aid interpretation of trends in pertussis incidence in relation to vaccine programmes and between countries.

The seroepidemiology of Helicobacter pylori infection in Australia.

BACKGROUND: Infection with Helicobacter pylori is common worldwide and a significant cause of upper gastrointestinal disease. Prevalence of this infection varies in different population groups internationally. Because of the invasiveness of specimen collection for bacteriologic diagnosis and the expense of tests such as labeled urea breath tests, serology is the most feasible means of determining the population epidemiology of H. pylori. The aim of this study was to describe the seroepidemiology of H. pylori infection in Australia. METHODS: H. pylori-specific ELISA for the presence of IgG antibodies was performed on a representative sample of 2413 sera from Australia in 2002, using validated serosurveillance methods. RESULTS: The overall seroprevalence of H. pylori infection in Australia was 15.1% in 2002, with no statistical difference between genders. Seropositivity rates increased progressively with age, ranging between 4.0% in the 1-4-year-olds and 23.3% in the 50-59-year-olds. CONCLUSIONS: The prevalence of infection with H. pylori in Australia was lower than rates reported in other developed countries, at 15.4%. This study provides important baseline measurements for future preventive measures including vaccine research and development. Further studies to determine subgroups at higher risk of infection may help target the more susceptible populations.

Standardization of measles, mumps and rubella assays to enable comparisons of seroprevalence data across 21 European countries and Australia.

The aim of the European Sero-Epidemiology Network is to establish comparability of the serological surveillance of vaccine-preventable diseases in Europe. The designated reference laboratory (RL) for measles, mumps, rubella (MMR) prepared and tested a panel of 151 sera by the reference enzyme immunoassay (rEIA). Laboratories in 21 countries tested the panel for antibodies against MMR using their usual assay (a total of 16 different EIAs) and the results were plotted against the reference results in order to obtain equations for the standardization of national serum surveys. The RL also tested the panel by the plaque neutralization test (PNT). Large differences in qualitative results were found compared to the RL. Well-fitting standardization equations with R2> or =0.8 were obtained for almost all laboratories through regression of the quantitative results against those of the RL. When compared to PNT, the rEIA had a sensitivity of 95.3%, 92.8% and 100% and a specificity of 100%, 87.1% and 92.8% for measles, mumps and rubella, respectively. The need for standardization was highlighted by substantial inter-country differences. Standardization was successful and the selected standardization equations allowed the conversion of local serological results into common units and enabled direct comparison of seroprevalence data of the participating countries.

Population-based seroprevalence of Neisseria meningitidis serogroup C capsular antibody before the introduction of conjugate vaccine, in Australia.

Neisseria meningitidis serogroup C (NMC) conjugate vaccine was introduced, in Australia, in 2003. Our aims were to determine pre-immunisation IgG NMC seroprevalence and evaluate an enzyme-linked immunosorbent assay (ELISA), previously validated against the serum bactericidal assay (SBA). 2409 sera, collected in 2002, from subjects aged 2-34 years, were tested. The geometric mean concentration (GMC) of NMC anticapsular IgG was 0.38 U/mL in subjects under 19 years and it increased to 0.67 U/mL for those aged 30-34 years. Variation in GMC correlated with reported NMC disease incidence and was higher in males than females (0.52 U/mL versus 0.41 U/mL; p=0.005). The ELISA appears suitable for serosurveillance but the IgG level that correlates with protection needs further investigation. Serosurveys will be repeated to monitor the impact of vaccination.

National serosurvey of cytomegalovirus in Australia.

In anticipation of the development of a vaccine against cytomegalovirus (CMV), we conducted a large, nationally representative serosurvey to examine the seroprevalence of CMV in Australia. Sera were collected opportunistically from laboratories around Australia. Age- and gender-representative samples were tested for CMV antibody. The population-weighted rate of CMV seropositivity in subjects between 1 and 59 years of age was 57% (95% confidence interval, 55.2 to 58.6%). An association between CMV seroprevalence and increasing age was recognized; however, little overall difference in seroprevalence between the sexes was found. The finding that high levels of CMV exposure occur in the first few years of life suggests that for a universal vaccination program to have maximal impact, the vaccine would need to be delivered to infants and have a long duration of protective efficacy. This is the first national serosurvey looking at cytomegalovirus in the Australian community. This study provides valuable information that can be used to examine the incidence of infection in the community and help focus the administration of a future CMV vaccine to appropriate target populations.

Evaluation of two enzyme immunoassays for detection of immunoglobulin G antibodies to mumps virus.

To determine suitability for national serosurveys, we compared two commercial enzyme-linked immunosorbent assays (ELISAs) for mumps antibody, Enzygnost Anti-Parotitis-Virus/IgG (which uses a whole-virus antigen) and Microimmune Mumps IgG Screen ELISA (which uses a recombinant nucleoprotein antigen), by testing 1,915 opportunistically collected sera submitted to diagnostic laboratories across Australia in 1997 to 1998. The proportion of positive results increased with age in both ELISAs but was significantly higher with the Microimmune than with the Enzygnost ELISA overall (88% versus 63%; P < 0.01) and in all age groups. However, the proportion of equivocal results was significantly higher with the Enzygnost than with the Microimmune ELISA (9% versus 4%; P < 0.01). Of the 572 sera with discrepant or equivocal results, 508 had sufficient sample remaining to perform the neutralization test (NT). A proportion with concordant results in both ELISAs were also tested by the NT. For sera with discrepant results, there was significantly better agreement between the NT and Microimmune than between the NT and Enzygnost (310/444 [70%] versus 135/348 [39%]; P < 0.01). Of 64 sera with equivocal Microimmune results, 45 (70%) were positive in the NT compared with 140 of 160 (88%) equivocal Enzygnost results (P < 0.01). Compared with the NT, the Microimmune ELISA is more sensitive (96% versus 80%) but apparently less specific (36% versus 85%) than the Enzygnost ELISA. However, this is likely to be due to the generally lower sensitivity of the NT, since the Microimmune results reflect expected seroprevalence, based on vaccine uptake in the age groups studied. We conclude that the Microimmune ELISA is a more appropriate assay than the Enzygnost ELISA for estimation of mumps seroprevalence.

Treponema pallidum western blot: comparison with the FTA-ABS test as a confirmatory test for syphilis.

We developed a Treponema pallidum Western blot and compared the results with Treponema pallidum particle agglutination (TPPA) and fluorescent treponemal antibody absorption (FTA-ABS) tests. The Western blot was deemed reactive if the serum reacted with at least three major antigenic bands (TpN47, TpN44.5, TpN17, TpN15). The sensitivities of the Western blot, TPPA and FTA-ABS, were all 100% and the specificities of the Western blot, TPPA and FTA-ABS were 100%, 100% and 94.5% respectively. In 52 problem sera, reactive in only one treponemal test, the agreement between the Western blot and TPPA (61.5%) was significantly better than between Western blot and FTA-ABS (38.5%). The individual sensitivities and specificities of TpN47, TpN44.5, TpN17, TpN15 were 100%, 100%, 96%, 100% and 20%, 96%, 100%, 100% respectively. We conclude that the Western blot is a useful additional confirmatory test or alternative to the FTA-ABS and that a more sensitive and specific criterion for the Western blot would be reactivity with TpN15 and two of the three other major antigens.

Failure of penicillin treatment of yaws on Karkar Island, Papua New Guinea.

The endemic treponematosis yaws remains a significant cause of morbidity in many tropical countries, despite mass treatment campaigns to eradicate it. An outbreak of yaws in Marup village on Karkar Island, Papua New Guinea in 1988 provided an opportunity to monitor the outcome of treatment with penicillin over an extended period. Thirty-nine children with clinical yaws (6% of 632 examined) were monitored clinically and serologically, for nearly two years after mass treatment of all villagers with the World Health Organization recommended dosages of benzathine penicillin. Lesions resolved within one month of treatment in all but four (10%) children, three of whom were initially successfully retreated. Before treatment, the Venereal Disease Research Laboratory (VDRL) test result was reactive in 67% of the children and treponema-specific IgM antibody test results were reactive in 41%. Within six months of treatment, of those reactive, the VDRL titer decreased significantly in 25 (96%) of 26 and IgM antibody test results became negative in 13 (81%) of 16 children. However, by the end of follow-up, 11 (28%) of the 39 children had developed clinical and/or serologic evidence of relapse. In these children, response to further treatment was slow and, in three, evidence of active infection persisted or recurred, despite repeated courses. Exogenous reinfection was unlikely in this isolated community, in which the occurrence of yaws was closely monitored after universal treatment. Treatment failure was most likely to have been due to reduced susceptibility to penicillin of Treponema pallidum subsp. pertenue.

Pre-admission management of acute gastroenteritis.

OBJECTIVE: Acute gastroenteritis contributes to significant morbidity and need for hospital admission. The current literature suggests outpatient management is often inappropriate. This study examines the pre-admission management of children admitted with acute gastroenteritis to a major children's hospital. METHODOLOGY: Information was obtained from parental questionnaires and the medical notes for 164 children. RESULTS: Parents were poorly informed regarding appropriate home management. Over 70% sought professional advice prior to admission, usually from their general practitioner. Although 58% received advice on fluid therapy, an oral rehydration solution was recommended for only 32%, and only 9% actually used one before admission. Advice regarding fluid requirements was usually inadequate. Inappropriate medications were prescribed for 22% of children, including antibiotics (15.4%), antidiarrhoeals (1.2%) and anti-emetics (5.5%). Hospitalized children were generally well nourished with minimal dehydration and electrolyte disturbance. CONCLUSIONS: Oral rehydration therapy is utilized rarely and medications are over-utilized in home management of gastroenteritis. Education of parents, general practitioners and hospital doctors is essential to optimize outpatient management. The impact of optimal outpatient management on hospital admission rates and morbidity requires formal assessment.

Evaluation of immunoglobulin G enzyme immunoassay for serodiagnosis of yaws.

A commercially available enzyme immunoassay (EIA), the Captia Syphilis-G immunoglobulin G (IgG) EIA, for the detection of IgG antibodies to Treponema pallidum was evaluated for use as a screening test for yaws (Treponema pallidum subsp. pertenue). The IgG EIA was compared with the fluorescent treponemal antibody absorption (FTA-ABS) test. All sera were also examined by the T. pallidum hemagglutination test and the Venereal Disease Research Laboratory test. Serum samples from 271 subjects (23 control serum samples from an area nonendemic for yaws, 58 control serum samples from an area endemic for yaws, and 190 serum samples from yaws patients and contacts) were investigated. The overall agreement between the IgG EIA and the FTA-ABS test was 90%, the sensitivity was 99%, and the specificity was 70.2%. The specificity fell as the endemicity of the disease increased: from 94.4% in the nonendemic area controls to 86.4% in the endemic area controls and to 52.3% in the yaws contacts. There was no difference in specificity between children and adults within each of the three groups. Fifteen children with clinical yaws were monitored for 9 months after treatment. The level of treponemal antibody fell consistently in 9 of the 15 children as measured by the antibody index (ratio of absorbance of the test serum to the mean absorbance of the low-titer-positive controls). Reinfection was seen in three children, with the antibody index rising with the Venereal Disease Research Laboratory test titer. The Captia Syphilis-G test is a sensitive assay for the detection of treponemal antibodies in yaws patients. However, the apparent low specificity of the test in the yaws endemic area limits its use as a screening test for yaws.

A survey of sexually transmitted diseases in five STD clinics in Papua New Guinea.

The first multicentre survey of sexually transmitted diseases (STDs) performed in Papua New Guinea was conducted in STD clinics in five towns, Port Moresby, Goroka, Rabaul, Lae and Daru, from September 1989 to May 1990. Infections with Neisseria gonorrhoeae and Chlamydia trachomatis (alone or in combination) were common. Penicillinase-producing N. gonorrhoeae (PPNG) represented 44% of all gonococcal isolates but significant intrinsic resistance to penicillin was not found. Of the other antibiotics tested, significant elevation of minimum inhibitory concentration (MIC) was common only for tetracycline, although no high-level tetracycline resistance was detected. C. trachomatis was detected by direct immunofluorescence (DIF) in 26% of 210 males and 27% of 64 females. 10% (21/210) of males and 11% (7/64) of females were both DIF positive for C. trachomatis and culture positive for N. gonorrhoeae. Of 203 males and 78 females tested, 5% and 12%, respectively, had serological evidence of current syphilis infection. Clinically, genital ulcer disease was most commonly due to syphilis, donovanosis or genital herpes, while specific vaginal infections were commonly seen in female patients attending Port Moresby and Lae STD clinics.

Modified indirect hemagglutination test for detection of treponemal antibodies in finger-prick blood.

A modified indirect hemagglutination test for the detection of treponemal antibodies was developed for use with finger-prick blood. By using paired serum and absorbed finger-prick blood from 58 patients from an area previously endemic for yaws and 12 patients without yaws, the modified hemagglutination test was compared with a hemagglutination test for Treponema pallidum and the fluorescent treponemal antibody absorption test. The modified hemagglutination test showed 100% specificity and an overall agreement of 96.5% with the hemagglutination test for T. pallidum and 94.8% with the fluorescent treponemal antibody test. The modified hemagglutination test appears to be a simple and economical test that is suitable for use in large epidemiological surveys for yaws.

Treponemal serology on Bali Island, Indonesia.

As part of a multidisciplinary study of the population of Bali, Indonesia, treponemal serology was carried out on 2452 serum samples from subjects of both sexes. Sera reactive to the Treponema pallidum immobilisation test (TPI) were found in 81 (3.3%) subjects with a male prevalence of 4% and a female prevalence of 2%. All the reactive sera were from villagers. Of 1118 students sampled in various towns, none had reactive TPI tests. The prevalence of reactive sera varied greatly from one village to another; up to 50% of the sera examined were reactive. Geographical and socioeconomic analyses of the data show a strict correlation between poor socioeconomic status and high reactivity rates to the TPI test. Fifty-seven per cent of all the reactive sera originated from subjects living in two districts where yaws had recently been reported. Only three of the 1406 subjects, aged 15-29 years, had reactive sera. The reactivity rate steadily increased in the age groups 30-44, 45-59, and 60 years and over. Biological false-positive reactions occurred in 3.8% of the sera tested.

Plasma biochemistry in the horse during 3-day event competition.

Blood samples were collected from 16 Thoroughbred horses before, during and after the second day of a 3-day event. Plasma osmolality, concentrations of sodium, potassium, chloride, urea, creatinine, glucose, bilirubin, iron, total protein, albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, creatine kinase, calcium, inorganic phosphate, uric acid, cholesterol, triglycerides and non-esterified fatty acids were measured. Significant differences from pre-event values were found in all parameters with the greatest changes being found after the cross-country phase. Most parameters showed significant rises following exercise, except calcium and chloride, which decreased. It was deduced from the changes in biochemistry that dehydration, reduced glomerular filtration rate, increased glycogenolysis and increased lipid metabolism, were a result of this form of competitive exercise.

Electrocardiography and haematology of horses competing in a three-day event.

The electrocardiograms of 22 horses competing in a 3-day event were recorded before and after the event. In addition, blood samples were taken for determination of packed cell volume and total plasma protein before, during and after the speed and endurance phases (Day 2). The electrocardiograms of 13 horses showed various abnormalities before the event, most of which were T wave changes. As a result of competition in the event, there was a significant increase in the number of leads showing T wave abnormalities when the electrocardiograms taken before and after the event were compared. At all times measurements were taken there were significant increases in packed cell volume and total plasma protein over values obtained prior to the event.

Changes in blood gas, acid-base and metabolic parameters in horses during three-day event competition.

Sixteen horses competing in a three-day event had venous blood samples collected during the speed and endurance test (day 2) to examine changes in blood gas ands acid-base balance, and the concentrations of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, alpha-ketoglutarate and cortisol. Following the roads and tracks and steeplechase phases there was a significant metabolic and respiratory alkalosis despite a rise in lactate. After completion of the cross country section, although there was a significant decrease in total base, there was no significant change in pH from pre-event values. This was because the decrease in total base was accompanied by a concomitant fall in carbon dioxide levels.

Metabolic fate of administered 1,25-dihydroxycholecalciferol in controls and in patients with hypoparathyroidism.

In four healthy controls and three patients with hypoparathyroidism serum-1,25-dihydroxycholecalciferol (1,25-D.H.C.C.) concentrations, after oral or intravenous administration, declined biphasically with a rapid-phase half-time of about 14 hours. Repeated oral doses of 1 mug 1,25-D.H.C.C. (2-4 nmol) produced serum concentrations well below the assayed normal range but were nevertheless effective in raising serum-calcium. It is suggested that orally administered 1,25-D.H.C.C. acts directly on the intestinal mucosal-cell nucleus to promote calcium absorption. 1,25-D.H.C.C. is more rapidly eliminated from the body than vitamin D, and it is predicted that any hypercalcaemia caused by 1,25-D.H.C.C. therapy should be of relatively short duration.