Performance evaluation of 70 hepatitis B virus (HBV) surface antigen (HBsAg) assays from around the world by a geographically diverse panel with an array of HBV genotypes and HBsAg subtypes.

BACKGROUND AND OBJECTIVES: This study was conducted by the International Consortium for Blood Safety (ICBS) to identify high-quality test kits for detection of hepatitis B virus (HBV) surface antigen (HBsAg) for the benefit of developing countries. MATERIALS AND METHODS: The 70 HBsAg test kits from around the world were evaluated comparatively for their clinical sensitivity, analytical sensitivity, sensitivity to HBV genotypes and HBsAg subtypes, and specificity using 394 (146 clinical, 48 analytical and 200 negative) ICBS Master Panel members of diverse geographical origin comprising the major HBV genotypes A-F and the HBsAg subtypes adw2,4, adr and ayw1-4. RESULTS: Seventeen HBsAg enzyme immunoassay (EIA) kits had high analytical sensitivity <0.13 IU/ml, showed 100% diagnostic sensitivity, and were even sensitive for the various HBV variants tested. An additional six test kits had high sensitivity (<0.13 IU/ml) but missed HBsAg mutants and/or showed reduced sensitivity to certain HBV genotypes. Twenty HBsAg EIA kits were in the sensitivity range of 0.13-1 IU/ml. The other eight EIAs and the 19 rapid assays had analytical sensitivities of 1 to >4 IU/ml. These assays were falsely negative for 1-4 clinical samples and 17 of these test kits showed genotype dependent sensitivity reduction. Analytical sensitivities for HBsAg of >1 IU/ml significantly reduce the length of the HBsAg positive period which renders them less reliable for detecting HBsAg in asymptomatic HBV infections. Reduced sensitivity for HBsAg with genetic diversity of HBV occurred with genotypes/subtypes D/ayw3, E/ayw4, F/adw4 and by S gene mutants. Specificity of the HBsAg assays was >or=99.5% in 57 test kits and 96.4-99.0% in the remaining test kits. CONCLUSION: Diagnostic efficacy of the evaluated HBsAg test kits differed substantially. Laboratories should therefore be aware of the analytical sensitivity for HBsAg and check for the relevant HBV variants circulating in the relevant population.

Development of the International Consortium for Blood Safety (ICBS) HCV panels.

To evaluate the sensitivity and specificity of assays used to screen blood for antibody to hepatitis C virus (HCV) infection, the International Consortium for Blood Safety (ICBS) established fully characterized CBS panels. lCBS collected and characterized 1007 anti-HCV-positive plasma units from geographically diverse origins by ELISA, RIBA, RT-PCR, and sequence-based genotyping, 539 of which met the definition of a true positive. Of these, 200 confirmed positive plasma units, representing the 6 major HCV genotypes, were selected to assemble the true-positive constituents of the panel. The negative panel comprises 181 plasma units collected from the USA. The panels have proved valuable for determining the performance of anti-HCV assays thus permitting national authorities, especially in resource-limited countries, to make informed decisions on selection of affordable and reliable assays.

Development of the International Consortium for Blood Safety [ICBS] HCV panels

To evaluate the sensitivity and specificity of assays used to screen blood for antibody to hepatitis C virus [HCV] infection, the International Consortium for Blood Safety [ICBS] established fully characterized ICBS panels. ICBS collected and characterized 1007 anti-HCV-positive plasma units from geographically diverse origins by ELISA, RIBA, RT-PCR, and sequence-based genotyping, 539 of which met the definition of a true positive. Of these, 200 confirmed positive plasma units, representing the 6 major HCV genotypes, were selected to assemble the true-positive constituents of the panel. The negative panel comprises 181 plasma units collected from the USA. The panels have proved valuable for determining the performance of anti-HCV assays thus permitting national authorities, especially in resource-limited countries, to make informed decisions on selection of affordable and reliable assays

Quality specifications of clinical laboratory procedures: developing country needs.

In developing countries laboratory measurements are made in specimens of populations that are usually of different genetic origin and live in a different environment, under working conditions that differ from those of industrialized countries. The setting of quality specifications of laboratory measurements must take into account such differences to improve the quality of laboratory services in these countries. Industry and professional organizations should be aware of the differences, otherwise their recommendations may counteract efforts to improve laboratory services in developing countries.

Coordination for better laboratory services.

In developing countries the organization of health laboratory services commonly leaves much to be desired. Poor coordination and the absence of clear policies often inhibit efficiency and efficacy. Ways of remedying such situations are examined in the present article.

How to combat nosocomial infection in developing countries.

Hospital-acquired infections constitute a significant problem throughout the world. Ways of dealing with them are reviewed below, with particular reference to conditions in the developing countries.

Prevalence of antibodies against measles virus in Tripoli, The Socialist People's Libyan Arab Jamahiriya.

A compulsory immunization policy against measles was introduced in the Socialist People's Libyan Arab Jamahiriya in 1972. Data are presented to show that a decreased incidence of measles followed this programme. Nevertheless, measles epidemics still occur and the serological status of the population has, therefore, been examined. In the area of Tripoli, measles haemagglutination-inhibiting (HI) antibodies were found at a titre of greater than or equal to 1:10 in 97% of the adult population, and in 78%, 100% and 97.1% of schoolchildren of primary, preparatory and secondary schools respectively. The relatively high HI titres observed, particularly in adults, imply that antigenic restimulation of antibody against measles occurs and thus that coverage by immunization remains inadequate. Increased efforts to improve immunization coverage at an early age are recommended.

Salmonella isolations from human faeces in Tripoli, Libya.

Salmonella isolation was attempted from 32,336 human faecal specimens obtained between 1975 and 1980 from cases of diarrhoea in hospitals and clinics in the area of Tripoli, Libya. 34 different Salmonella serotypes were identified, by far the most common being S. wien and S. muenchen.

Analysis of neutralizing antibody responses against poliovirus types 1, 2 and 3 in the Tripoli area of the Socialist People's Libyan Arab Jamahiriya.

Analysis of the records available show that the introduction in Libya of a compulsory immunization programme against poliomyelitis was followed by a substantial decrease in the incidence of paralytic poliomyelitis. Nevertheless, the annual incidence is still higher than in many western industrialized countries. We have conducted a survey of neutralizing poliovirus antibodies in human sera. In the group aged 19 years and upwards, i.e., those born before compulsory immunization, 65% had detectable neutralizing antibodies against the 3 viruses, and on average 73% were positive for 2 of the 3 virus serotypes and 85% for only one. The overall proportions in schoolchildren 6-18 years old were lower than in adults. In adults and schoolchildren from 6-18 years old, the highest proportion of positives was against type 2 poliovirus. For infants up to 5 years old the figures overall were higher but the type 2 serotype did not predominate. Surprisingly, the anticipated increase in proportions of positive antisera in 7 year olds, following a booster immunization at the time of school entry, was not apparent, implying inadequate coverage. The results appear to show that stricter measures to control the rate of coverage of immunization are required to reduce the relatively high incidence of paralytic poliomyelitis in Libya.

Serological survey for toxoplasmosis in Tripoli, S.P.L.A.J. Libya.

Toxoplasma antibodies were found at a titre of 1:16 or above in 51.6% of 2000 adult males, in 43.4% of 300 adult females, and in 43.7% of 1980 schoolchildren (7-18 years of age) from the area of Tripoli (Libya). However, 69.4% of a group of 1921 female patients with a history of abortion and clinically suspected of being infected with T. gondii had Toxoplasma antibodies, and 18.6% of them exhibited serological evidence of recent infection (4-fold or greater increase in antibody titre over 2-3 weeks).

Pregnancy hepatitis in Libya.

The death-rate from hepatitis in pregnant women in Libya is high. Of 922 hepatitis patients treated during 1975, 377 were males and 545 were females. The case fatality-rate was 0.53% for males and 7-67% for females. In 293 pregnant women it was 12-97% compared with 1-6% in 252 non-pregnant women. In pregnant women deaths occurred mainly in the last trimester. Although 18-4% of the male patients and 15-2% of the women were hepatitis B surface antigen (HBsAg) positive, no patient shown to be antigen-positive died. The frequency of hepatitis in the second half of the year fell both in pregnant women and in the general population, suggesting a warning hepatitis-A epidemic. The exact cause of the high mortality in pregnant women is not clear, but it may have a nutritional basis.

PIP: An outbreak of hepatitis especially virulent in pregnant women in Tripoli, Libya in 1975 is described. The case-fatality rate was 12.97% in 293 pregnant women, 1.6% in 252 nonpregnant women, and 0.53% in 377 men. Deaths in pregnant women usually occurred in 3rd trimester, often at the onset of labor. There was no evidence that pregnant women with jaundice were admitted in preference to non-pregnant women, or that age or parity was related to infection. Hepatitis B antigen was tested by counter immunoelectrophoresis and later by reverse passive hemagglutination and radioimmunoassay. The overall prevalence was 16.6%. In pregnant women it was 11.1%. None of the pregnant women who died were positive for HBsAg. Coma and an abrupt deterioration were often seen in the pregnant women who dies. The women ate a diet devoid in protein from meat, eggs or fish. The epidemic died down in the second half of the year. It was conjectured that virulent a non-A-non-B hepatitis virus caused this outbreak.