Timing of Development of Measles-Specific Immunoglobulin M and G after Primary Measles Vaccination

A standard method for diagnosing measles is to detect measles-specific immunoglobulin M (IgM) in the serum of infected persons. Interpreting a positive IgM result from a person with suspected measles can be difficult if the person has recently received a measles vaccine. We have previously demonstrated that measles-specific IgM may persist for at least 8 weeks after primary vaccination, but it is unknown how quickly IgM appears. This study determined the timing of the rise of measles-specific IgM and IgG after primary measles vaccination with Schwartz vaccine. Two hundred eighty 9-month-old children from Ethiopia presenting for routine measles vaccination were enrolled. Sera were collected before and either 1, 2, 3, or 4 weeks after vaccination and tested for measles-specific antibodies by an IgM capture enzyme immunoassay (EIA) and by an indirect IgG EIA. A total of 209 of the 224 children who returned for the second visit had prevaccination sera that were both IgM and IgG negative. The postvaccination IgM positivity rates for these 209 children were 2% at 1 week, 61% at 2 weeks, 79% at 3 weeks, and 60% at 4 weeks. The postvaccination IgG positivity rates were 0% at 1 week, 14% at 2 weeks, 81% at 3 weeks, and 85% at 4 weeks. We conclude that an IgM-positive result obtained by this antibody capture EIA is difficult to interpret if serum is collected between 8 days and 8 weeks after vaccination; in this situation, the diagnosis of measles should be based on an epidemiologic linkage to a confirmed case or on the detection of wild-type measles virus.     

Timing of development of measles-specific immunoglobulin M and G after primary measles vaccination

A standard method for diagnosing measles is to detect measles-specific immunoglobulin M (IgM) in the serum of infected persons. Interpreting a positive IgM result from a person with suspected measles can be difficult if the person has recently received a measles vaccine. We have previously demonstrated that measles-specific IgM may persist for at least 8 weeks after primary vaccination, but it is unknown how quickly IgM appears. This study determined the timing of the rise of measles-specific IgM and IgG after primary measles vaccination with Schwartz vaccine. Two hundred eighty 9-month-old children from Ethiopia presenting for routine measles vaccination were enrolled. Sera were collected before and either 1, 2, 3, or 4 weeks after vaccination and tested for measles-specific antibodies by an IgM capture enzyme immunoassay (EIA) and by an indirect IgG EIA. A total of 209 of the 224 children who returned for the second visit had prevaccination sera that were both IgM and IgG negative. The postvaccination IgM positivity rates for these 209 children were 2% at 1 week, 61% at 2 weeks, 79% at 3 weeks, and 60% at 4 weeks. The postvaccination IgG positivity rates were 0% at 1 week, 14% at 2 weeks, 81% at 3 weeks, and 85% at 4 weeks. We conclude that an IgM-positive result obtained by this antibody capture EIA is difficult to interpret if serum is collected between 8 days and 8 weeks after vaccination; in this situation, the diagnosis of measles should be based on an epidemiologic linkage to a confirmed case or on the detection of wild-type measles virus.     

Measles Virus IgG Avidity Assay for Use in Classification of Measles Vaccine Failure in Measles Elimination Settings

In regions where endemic measles virus has been eliminated, diagnostic assays are needed to assist in correctly classifying measles cases irrespective of vaccination status. A measles IgG avidity assay was configured using a commercially available measles-specific IgG enzyme immunoassay by modifying the protocol to include three 5-min washes with diethylamine (60 mM; pH 10.25) following serum incubation; serum was serially diluted, and the results were expressed as the end titer avidity index. Receiver operating characteristic analysis was used for evaluation and validation and to establish low (≤30%) and high (≥70%) end titer avidity thresholds. Analysis of 319 serum specimens expected to contain either high- or low-avidity antibodies according to clinical and epidemiological data indicated that the assay is highly accurate, with an area under the curve of 0.998 (95% confidence interval [CI], 0.978 to 1.000), sensitivity of 91.9% (95% CI, 83.2% to 97.0%), and specificity of 98.4% (95% CI, 91.6% to 100%). The assay is rapid (<2 h) and precise (standard deviation [SD], 4% to 7%). In 18 samples from an elimination setting outbreak, the assay identified 2 acute measles cases with low-avidity results; both were IgM-positive samples. Additionally, 11 patients (15 samples) with modified measles who were found to have high-avidity IgG results were classified as secondary vaccine failures; one sample with an intermediate-avidity result was not interpretable. In elimination settings, measles IgG avidity assays can complement existing diagnostic tools in confirming unvaccinated acute cases and, in conjunction with adequate clinical and epidemiologic investigation, aid in the classification of vaccine failure cases.     

Cellular and humoral immune responses to measles in immune adults re-immunized with measles vaccine

The objective of this study was to characterize the kinetics of the cellular and humoral immune responses elicited by measles vaccine given to previously immune adults. The cellular and humoral immune responses to measles were measured in seven healthy adults, before vaccination and at 1, 2, 3, and 4 weeks and 3 months after vaccination, using measles-specific T-cell proliferation and plaque reduction neutralization assays. All study subjects had detectable measles antibodies, but only six (85%) showed protective titers, defined as >1:120, before immunization. However measles-specific T-cell proliferation was not detectable before vaccination in any of the subjects. The six subjects with protective titers showed a positive stimulation index (SI) of >3.0 within the first 4 weeks after vaccination, an SI of 5 at the 4th week, and an SI of 3 at 3 months after vaccination. The subject with a low antibody titer (1:99) before vaccination developed a high SI at 3 months after vaccination. This subject was the only participant whose neutralizing antibody titers increased more than 4-fold by 3 months after vaccination. No significant increases in geometric mean titers were detected in the other six subjects during the follow-up period. These data suggest that high measles antibody titers interfere with the humoral response in subjects who receive a booster immunization, whereas the cellular response is boosted at least transiently, after revaccination.     

Seroprevalences of Specific IgG Antibodies to Measles,Mumps, and Rubella in Korean Infants

In this study, the seroprevalences of measles, mumps, and rubella antibodies in infants were determined to assess the immunization strategy and control measures for these infectious diseases. Serum samples from infants < 1 year of age and their mothers were collected to measure the concentrations of specific IgG antibodies to measles, mumps, and rubella by enzyme-linked immunosorbent assay. For selected infant serum samples, measles-specific neutralizing antibody levels were determined by using the plaque reduction neutralization test. The sera from 295 of infants and 80 of their mothers were analyzed. No infants had past measles, mumps, or rubella infections. Almost all infants < 2 months of age were positive for measles and rubella IgG antibodies. However, seroprevalence of measles and rubella antibodies decreased with age, and measles IgG and rubella IgG were barely detectable after 4 months of age. The seroprevalence of mumps antibodies was lower than that of measles and rubella antibodies in infants ≤ 4 months old, and mumps IgG was barely detectable after 2 months of age. The seropositivity of measles-specific neutralizing antibody was 63.6% in infants aged 2 months and undetectable in infants ≥ 6 months old. Because the seropositivity rates of measles, mumps, and rubella antibodies were low after the first few months of age in Korean infants, active immunization with vaccines is strongly recommended for infants aged 6–11 months when measles is epidemic. Timely administration of the first dose of measles-mumps-rubella vaccine at 12 months of age should be encouraged in non-epidemic situations.     

Comparison of immunofluorescence and enzyme immunoassay for detection of measles-specific immunoglobulin M antibody.

During a measles outbreak, 283 serum specimens from 221 suspected cases of measles were tested by immunofluorescence and enzyme immunoassay for the presence of measles-specific immunoglobulin M (IgM) antibodies by using commercially available reagents. There was 97% agreement between the two assays; thus, the choice of the method for diagnostic testing is a matter of convenience and experience. In all 62 cases of measles from which a single blood sample was available, measles IgM-specific antibodies were detectable by both methods. Fifty percent of the 62 cases were positive within 3 days after onset of the rash. This increased to 91% 10 days after onset of the rash.     

Performance of indirect immunoglobulin M (IgM) serology tests and IgM capture assays for laboratory diagnosis of measles

As progress is made toward elimination of measles, the laboratory confirmation of measles becomes increasingly important. However, both false-positive and false-negative results can occur with the routinely used indirect measles immunoglobulin M (IgM) serology tests. The measles IgM capture assay is considered to be more specific, and therefore, its use is indicated for confirmatory testing, but its relative performance has not been fully assessed. Four commercial indirect measles IgM serology test kits (the Behring, Clark, Gull, and PanBio assays) and a commercial IgM capture assay (the Light Diagnostics assay) were evaluated for their abilities to detect measles virus-specific IgM antibody with a total of 308 serum samples from patients involved in a measles outbreak and with confirmed cases of measles and 454 samples from subjects without measles. The Centers for Disease Control and Prevention (CDC) IgM capture assay was also used in a part of the evaluation. Among the indirect assays, the overall sensitivities ranged from 82.8% (Clark assay) to 88.6% (Behring assay) and specificity ranged from 86.6% (PanBio assay) to 99.6% (Gull assay). These rates were 92.2 and 86.6%, respectively, for the Light Diagnostics capture assay and 87.0 and 94.8%, respectively, for the CDC capture assay. While the Light Diagnostics capture assay had the best detection rate (80%) with the acute-phase samples compared with those for the rest of the tests (CDC capture assay, 77%; Behring assay, 70%; Gull assay, 69%; PanBio assay, 58%; and Clark assay, 57%), all tests showed a significantly improved sensitivity in the range of 92% (Clark and PanBio assays) to 97% (Light Diagnostics and CDC capture assays) with the convalescent-phase samples, as expected. The best seropositivity rates (in the range of 92 to 100%) were observed with samples collected 6 to 14 days after the onset of symptoms. The Gull assay showed the highest positive predictive value (99.6%), followed by the Behring assay (97.8%) and the CDC capture assay (96.1%). Overall, the Gull and Behring assays were found to be as good as or better than the capture assays. In conclusion, laboratory diagnosis of measles based on IgM serology varies depending on the timing of specimen collection and the test used, and the case for the use of the IgM capture assay as the confirmatory test appears to be uncertain.     

Decay of Passively Acquired Maternal Antibodies against Measles, Mumps, and Rubella Viruses

The decay of maternally derived antibodies to measles, mumps, and rubella viruses in Swiss infants was studied in order to determine the optimal time for vaccination. A total of 500 serum or plasma samples from infants up to 2 years of age were tested by enzyme-linked immunosorbent assay and fluorescent-antibody testing. The decline of antibody prevalence was slowest against the measles virus. By 9 to 12 months of age, only 5 of 58 (8.6%; 95% CI, 2.9 to 19.0) infants were antibody positive for the measles virus, and only 2 had levels above 200 mIU/ml. Mumps and rubella virus antibody seropositivity was lowest at 9 to 12 months of age with 3 of 58 (5.2%; 95% CI, 1.1 to 14.4) infants and at 12 to 15 months with 1 of 48 (2.1%; 95% CI, 0.1 to 11.1) infants, respectively. Concentrations of passively acquired antibodies decreased rapidly within the first 6 months of life. We observed no significant differences in antibody prevalence or concentration according to gender in any age group. In conclusion, MMR vaccination at 12 instead of 15 months of age could reduce the pool of susceptible subjects in infancy and support the efforts to eliminate these infections, particularly in combination with a second vaccine dose before school entry.     

Evaluation of an indirect immunofluorescence assay for detection of immunoglobulin M (IgM) and IgG antibodies against yellow fever virus

The first commercial indirect immunofluorescence assay (IFA) using Euroimmun Biochip technology was evaluated for the serodiagnosis of immunoglobulin G (IgG) and IgM antibodies against yellow fever virus (YFV) and was compared with the plaque reduction neutralization test (PRNT), which is currently the gold standard test for YFV. An overall correlation between the tests of 98.7% was established based on the analysis of 150 sera from individuals after vaccination with the 17D yellow fever vaccine. The sensitivity and specificity, calculated using the 150 sera from vaccinees and 150 sera from healthy blood donors, were 95% and 95%, respectively, for the IgG IFA and 94% and 97% for the IgM IFA. Antibody titers found in the PRNT correlated poorly with the IgM and IgG titers detected by IFA. The analysis of preexisting heterologous flaviviral immunity revealed the presence of antibodies reactive with YFV, tick-borne encephalitis virus, West Nile virus, Japanese encephalitis virus, and dengue virus serotypes 1 to 4 in 20 out of the 150 vaccinees. The indirect IFA showed that nine of these individuals with previous flaviviral exposure who received 17D vaccine failed to produce detectable IgM antibodies. Despite this preexisting immunity, all vaccinees developed protective immunity as detected by PRNT and anti-YFV IgG antibodies as detected by IFA. The high specificity and sensitivity of the IFA make it a useful tool for rapid diagnosis of yellow fever during outbreaks, for epidemiological studies, and for serosurveillance after vaccination.     

Comparative detection of measles and rubella IgM and IgG derived from filter paper blood and serum samples.

We compared the use of serum and filter paper blood spots as specimen sources for the detection of measles- and rubella-specific IgM and IgG. We collected capillary blood into microtainer tubes and onto filter paper spots from 60 children and 60 healthy adults. The blood was collected from 12-15-month-old children approximately 3 weeks after primary vaccination with measles, mumps, rubella vaccine, and the sample-pairs were tested for measles-specific IgM and IgG antibodies by using a capture antibody EIA and an indirect EIA, respectively. We tested sample-pairs from a subset of participants for rubella- specific IgM and IgG antibodies by using commercially available capture IgM (Captia) and indirect IgG (Wampole) assays. The concordance of results from serum and filter paper blood spots was high for all assays: 98% for measles IgM, 93% for measles IgG, 94% for rubella IgM, and 93% for rubella IgG, and increased to between 96-100% for all four assays when indeterminate samples were excluded. The correlation coefficients for EIA signals were 0.99 and 0.77 for measles IgM and IgG, respectively, and 0.92 and 0.94 for rubella IgM and IgG, respectively. The cut-off values used for filter paper samples were the same as those used for serum samples for all tests except for the rubella IgM assay. The use of filter paper blood spots is a promising future option for the detection of measles- and rubella-specific antibodies.     

Enzyme-linked immunosorbent assay-IgG antibody avidity test for single sample serologic evaluation of measles vaccines

A measles-specific enzyme-linked immunosorbent assay (ELISA)-IgG avidity test for serologic evaluation of the efficacy of measles vaccines with only one blood sample was evaluated after vaccination with three measles vaccine strains. Avidity indices were determined by the urea elution technique in samples presenting antibody titers ⩾100 mIU/ml. All 127 sera collected 2–8 weeks after primary vaccination with Biken-CAM70 measles vaccine had low avidity indices (LAI, when ≤29%) with a time-dependent increase in avidity. In samples collected 6–10 weeks after vaccination with Edmonston-Zagreb, LAI were also observed in all 31 sera tested (mean = 15%) and in 233/242 (96.3%) filter paper samples from primary vaccination with Schwarz vaccine (mean = 14%). There was no difference in the mean avidity among the three groups of primary vaccinees, although the Schwarz group had higher antibody titers. In contrast, only 1/36 (2.8%) serum samples from children who were seropositive at the time of measles vaccination had LAI (mean = 56%), despite the fact that they were collected early (2–5 weeks after vaccination). Of 90 serum samples from children vaccinated in the past with two doses and of 42 cord blood serum samples, none had LAI. It is concluded that this test is a good tool for evaluating serologically the efficacy of a single dose schedule of measles vaccine. With only one postvaccination sample, the test can discriminate nonresponders (antibody titers below 100 mIU/ml), primary responders (antibody titers ⩾100 mIU/ml with LAI), and those previously immunized (antibody titers ⩾100 mIU/ml with high avidity indices). The seroconversion rate can be calculated after excluding the latter. J. Med. Virol. 52:275–279, 1997. © 1997 Wiley-Liss, Inc.     

Kinetics of decline of maternal measles virus-neutralizing antibodies in sera of infants in France in 2006

The optimal age for measles vaccination is an important health issue, since maternal antibodies may neutralize the vaccine antigen before a specific immune response develops, while delaying vaccination may increase the risk of complicated diseases in infants. However, measles vaccination impacts the duration of protection afforded by transplacental transfer of maternal antibodies: vaccination-induced maternal antibodies disappear faster than disease-induced antibodies. In order to maintain protection against measles in infants, it is important to monitor the dynamics of this phenomenon in vaccinated populations. To assess the current situation in France, a multicenter, prospective seroepidemiological study was conducted in seven French hospitals between October 2005 and January 2007. Maternal measles antibody concentrations from 348 infants 0 to 15 months old were measured using the plaque reduction neutralization assay. Geometric mean concentrations and the percentage of infants with maternal measles antibody concentrations above the protection threshold (≥120 mIU/ml) were assessed according to age. Results show that after more than 20 years of routine measles vaccination in France, maternal measles-neutralizing antibodies decrease dramatically in French infants by 6 months of age, from 1,740 mIU/ml for infants 0 to 1 month old to 223 mIU/ml for infants 5 to 6 months old, and that 90% of infants are not protected against measles after 6 months of age. Infant protection against measles could be optimized both by increasing herd immunity through an increased vaccine coverage and by lowering the age of routine vaccination from 12 to 9 months.     

Measles seroprevalence in pregnant women in Soweto,South Africa: a nested cohort study

ObjectivesMeasles infection causes particularly severe disease in young children who, prior to vaccination, are dependent on maternal antibodies for protection against infection. Measles vaccination was introduced into the South African public immunization programme in 1983 and became widely available in 1992. The aim of this study was to determine measles-specific immunoglobulin G (IgG) levels in pregnant women living with and without HIV born before and after measles vaccine introduction in South Africa.MethodsMeasles IgG antibody level from blood obtained at the time of delivery was compared between women who were born before 1983 (n = 349) and since 1992 (n = 349). Serum samples were tested for measles IgG antibody using an enzyme-linked immunosorbent assay. Geometric mean titres (GMTs) and the proportion with seronegative (<200 mIU/mL) or seropositive titres (≥275 mIU/mL) were compared.ResultsWomen born since 1992 had lower GMTs [379.7 mIU/mL (95% CI 352.7–448.6)] and fewer were seropositive (55.9%, 195/349) than women born before 1983 [905.8 mIU/mL (95% CI 784.7–1045.5); 76.8%, 268/349], for both comparisons p < 0.001.ConclusionsWe found an association between measles vaccine implementation into the public immunization program in South Africa and peri-partum maternal measles immunity, where women born before vaccine introduction had higher measles IgG antibody titres and were more likely to be seropositive. These findings suggest a need to reconsider the infant measles immunization schedule in settings where women have derived immunity mainly from measles vaccine rather than wild-type virus exposure.     

2009-2013年菏泽市曹县麻疹病毒感染特征分析

目的 分析曹县麻疹病例实验室检测结果、流行病学和临床特点,为当地预防控制麻疹提供指导.方法 从国家疾病监测信息报告管理系统收集2009-2013年曹县麻疹疫情数据,以及麻疹疑似病例,开展麻疹IgM、风疹IgM检测和分析麻疹病毒分离情况、病例特点.结果 2009-2013年度共报告227例麻疹疑似病例,血清标本采集率72.69％,麻疹IgM阳性率为18.71％,12例咽拭子标本中分离出5株麻疹病毒,为H1a基因型.确诊168例麻疹病例,＜4岁年龄组的构成比为80.95％,幼托儿童、散居儿童是麻疹发病的主要人群,占89.29％;主要临床表现包括发热,超过38.5℃者占86.63％,皮疹首发部位为面部,占72.95％,有口腔黏膜斑者占72.80％,麻疹并发症前三位分别为肺炎、心肌炎、喉炎.结论 经血清学和病毒学证实,曹县当地存在麻疹病毒传播,病例以散发为主,麻疹野病毒为H1基因型,麻疹发病与年龄、性别、职业、季节有关.     

Effects of interleukin-12 and interleukin-15 on measles-specific T-cell responses in vaccinated infants

Understanding the infant host response to measles vaccination is important because of their increased mortality from measles and the need to provide effective protection during the first year of life. Measles-specific T and B-cell responses are lower in infants after measles vaccination than in adults. To define potential mechanisms, we investigated age-related differences in measles-specific T-cell proliferation, CD40-L expression, and IFN-gamma production after measles immunization, and the effects of rhIL-12 and rhIL-15 on these responses. Measles-specific T-cell proliferation and mean IFN-gamma release from infant PBMCs were significantly lower when compared with responses of vaccinated children and adults. Infant responses increased to ranges observed in children and adults when both rhIL-12 and rhIL-15 were added to PBMC cultures. Furthermore, a significant rise in T-cell proliferation and IFN-gamma release was observed when infant PBMCs were stimulated with measles antigen in the presence of rhIL-12 and rhIL-15 compared to measles antigen alone. CD40-L expression by infant and adult T cells stimulated with measles antigen was comparable, but fewer infant CD40-L(+) T cells expressed IFN-gamma. These observations suggest that lower measles-specific T-cell immune responses elicited by measles vaccine in infants may be due to diminished levels of key cytokines.     

Correlations among measles virus-specific antibody, lymphoproliferation and Th1/Th2 cytokine responses following measles-mumps-rubella-II (MMR-II) vaccination

Immunity to measles is conferred by the interplay of humoral and cellular immune responses, the latter being critical in maintaining long-term recall response. Therefore, it is important to evaluate measles-specific humoral and cellular immunity in populations several years after vaccination and understand the correlations among these measures of immunity. We examined measles-specific antibodies, lymphoproliferation and the Th1/Th2 signature cytokines, interferon (IFN)-gamma and interleukin (IL)-4, in a population-based cohort of healthy children from Olmsted County, Minnesota after two doses of measles-mumps-rubella-II (MMR-II) vaccine. We detected positive measures of measles-specific cellular and humoral immunity in the majority of our study population. However, a small proportion of subjects demonstrated an immune response skewed towards the Th2 type, characterized by the presence of either IL-4 and/or measles-specific antibodies and a lack of IFN-gamma production. Further, we observed a significant positive correlation between lymphoproliferation and secretion of IFN-gamma (r = 0.20, P = 0.0002) and IL-4 (r = 0.15, P = 0.005). Measles antibody levels were correlated with lymphoproliferation (r = 0.12, P = 0.03), but lacked correlation to either cytokine type. In conclusion, we demonstrated the presence of both long-term cellular and humoral responses after MMR-II vaccination in a significant proportion of study subjects. Further, a positive correlation between lymphoproliferation and IL-4 and IFN-gamma suggests that immunity to measles may be maintained by both Th1 and Th2 cells. We speculate that the Th2 biased response observed in a subset of our subjects may be insufficient to provide long-term immunity against measles. Further examination of the determinants of Th1 versus Th2 skewing of the immune response and long-term follow-up is needed.     

Solid-phase radioimmunoassay determination of virus-specific IgM antibody levels in a follow-up of patients with naturally acquired measles infections

The question of the exact disappearance time or possible persistence of measles-specific IgM antibodies after naturally acquired measles virus infections was studied with a sensitive solid-phase radioimmunoassay (RIA) method. A total of 30 patients were analyzed with follow-up times varying from 4.5 to 8 months; all were measles IgM positive in the first serum specimen obtained after the onset of rash. In 29 of 30 patients, the measles IgM declined to undetectable levels by approximately 90 days. The remaining patient developed postmeasles encephalitis, however, and was found to have a prolonged measles IgM antibody response. For comparison, the measles-specific IgG response was also studied and was found to develop only slightly later than the IgM response, with levels then remaining high and stable up to 8 months later. Although apparent measles IgM antibodies were found in 1 of 64 nonmatched adult controls, they were due to the presence of high levels of IgM-class rheumatoid factor. The data presented indicate that measles IgM antibodies begin to decline soon after the onset of rash and reach negative levels 1 to 3 months later; in complicated infections, however, measles IgM antibody synthesis may not terminate normally.     

Immunoglobulin G avidity testing in serum and cerebrospinal fluid for analysis of measles virus infection.

We studied a variety of patients with measles virus infection by using avidity testing for measles virus-specific immunoglobulin G (IgG) in serum and cerebrospinal fluid samples. For the avidity testing, an Enzygnost measles IgG enzyme-linked immunosorbent assay kit was used with an 8 M urea denaturing method. With this method, low-avidity IgG (acute primary infection, avidity of < 30% within 15 days of the onset of rash) and high-avidity IgG (subacute sclerosing panencephalitis, avidity of > 75%) could be clearly distinguished by using serum samples. One patient, who developed a typical course of measles despite a previous vaccination, showed a positive IgM response with an initial low titer of measles virus-specific IgG of low avidity, but a later sample revealed a high titer of IgG of intermediate (40%) avidity, suggesting previous immunological priming. Two patients with breakthrough infection (secondary vaccine failure), both having central nervous system involvement, showed a positive IgM response with initial high titers of serum IgG of high avidity. In addition, one of the patients had a detectable level of measles-specific IgG in cerebrospinal fluid. In this patient, the avidity of both serum and cerebrospinal fluid IgG decreased during the short follow-up period. This phenomenon has never before been reported. In subacute sclerosing panencephalitis patients, the avidity of cerebrospinal fluid IgG was consistently lower than that of serum IgG. The difference in avidity between cerebrospinal fluid and serum IgG may be used as a direct indicator of intrathecal production of IgG. In conclusion, the avidity testing is simple to perform, reliable, and highly informative in the analysis of measles virus infection.     

Measles virus strains circulating in Ethiopia in 1998-1999: molecular characterisation using oral fluid samples and identification of a new genotype

A measles outbreak in December 1998 in Bedelle (vaccine coverage <40%) and two sporadic cases in Addis Ababa, Ethiopia, were investigated. Paired serum and oral fluid samples were collected 2-8 days after the onset of symptoms. A total of 53 of 55 outbreak cases and both sporadic cases were positive for serum measles virus-specific IgM. Oral fluid measles-specific IgM was positive in 71% of cases collected up to 5 days after onset and in 90% collected at 6-8 days. By contrast, 100% of oral fluid samples were positive for measles virus RNA by RT-PCR, suggesting that early collection of samples favoured the detection of measles virus RNA by RT-PCR. The measles virus strain in the outbreak was identified as genotype D4. One strain from a sporadic case was also genotype D4; the strain from the other sporadic case was assigned to clade D but was distinct. The degree of divergence from recognised clade D strains suggested that, together with three strains from the United Kingdom, it represents an additional genotype of clade D (GenBank accession numbers AF280800-280807).