Demonstration Of IgM Antibodies Research Articles

Dengue in Peace Corps Volunteers, 2000-14.

Dengue is an arboviral disease estimated to cause 50-100 million infections each year in >100 tropical and subtropical countries. Urbanization, human population growth and expanded global travel have resulted in an increase in the incidence of dengue worldwide. International travellers to areas with endemic dengue are at risk of contracting dengue and US Peace Corps Volunteers are one specific group of long-term travellers who are exposed to environments where dengue can be contracted. Cases of dengue among Peace Corps Volunteers, defined as clinically apparent infections with laboratory-confirmation by a positive NS1 antigen test, demonstration of IgM antibodies or by a 4-fold increase in IgG antibodies, between 1 January 2000 and 31 December 2014, reported to the Peace Corps’ Epidemiologic Surveillance System were analyzed. Overall there were 1448 cases of dengue reported among Volunteers, with an incidence rate of 1.12 cases per 1000 Volunteer-months (95% CI 1.06-1.17). The highest rate of dengue among Volunteers was reported in the Caribbean region, with a rate of 5.51 cases per 1000 Volunteer-months (95% CI 4.97-6.10), followed by the East Asia/South Asia region (3.34, 95% CI 2.96-3.75) and Central America (2.55, 95% CI 2.32-2.79). The rate of dengue peaked in 2007, 2010 and 2013. Each peak year was followed by a trough year. Globally, there appears to be a 3-year cyclical pattern of dengue incidence among Volunteers, with differences by region. Dengue continues to be a priority health issue for travellers to endemic areas, and enhanced surveillance of dengue among international travellers may result in improved patient education and prevention efforts.

Two cases of dengue meningitis: a rare first presentation

Dengue, a mosquito-borne disease caused by a flavivirus, is recognized in over 120 countries with 3.6 billion people living in areas at risk. Neurological manifestations are infrequently reported as clinical consequences of dengue infection. Though severe dengue may be associated with meningoencephalitis, meningitis is a rare initial presentation of otherwise uncomplicated dengue fever. We report two adult patients who presented with fever, headache, and nuchal rigidity without the typical symptoms of dengue infection. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis in one and slight neutrophilic pleocytosis in the other with a normal glucose value and negative bacterial cultures. Dengue was suspected because thrombocytopenia was symptomatic in one patient and documented during the hospital course, and was confirmed by demonstration of IgM antibody in the cerebrospinal fluid samples specific for dengue in both cases. Our report demonstrates that meningitis with or without encephalitis can be the first manifestation of dengue infection. In endemic areas, dengue infection should be considered as a probable etiological agent of meningitis. Regular monitoring of platelet count can be an invaluable diagnostic screening tool. In appropriate clinical settings detection of anti-dengue IgM both in serum and in CSF may lead to correct diagnosis.

Acute respiratory tract infections in Indian children with special reference to Mycoplasma pneumoniae.

A total of 70 Indian children of either sex and under 5 years of age who were admitted to the All India Institute of Medical Sciences, New Delhi during a 1-year period (January 1994-December 1994) with complaints suggestive of acute respiratory tract infections (ARTI), were investigated for bacterial aetiology of infection with special reference to Mycoplasma pneumoniae. Microbial aetiology could be established in 44/70 (62.8 per cent) of cases of ARTI. Mycoplasma pneumoniae infection was seen in 21/70 (30 per cent), aerobic bacteria in 14/70 (20 per cent), Chlamydia pneumoniae in 2/70 (2.8 per cent), and mixed infection with mycoplasma either with bacteria and/or chlamydia in 7/70 (10 per cent). However, in 26/70 (37.1 per cent) cases no cause could be detected. Diagnosis of infection with M.pneumoniae was based on culture in 2/20 (10 per cent) cases, antigen detection in throat swab by indirect immunofluorescence assay using specific antibody in 16/70 (22.8 per cent) cases, and demonstration of IgM antibody in serum by serodia Myco II particle agglutination test in 17/70 (24.2 per cent). Streptococcus pneumoniae (9/70, 12.8 per cent) and Staphylococcus aureus (5/70, 7.1 per cent) were the aerobic isolates from blood in these patients. Results of this study indicate that M.pneumoniae plays a significant role in respiratory tract infection in an Indian paediatric population. Rapid diagnostic procedures, such as antigen detection and IgM antibody demonstration, should be used more widely to determine the infective aetiology early in the course of illness. The study also highlights the mixed aetiology in ARTI in children, which has important therapeutic implications.

COMPARISON OF POLYMERASE CHAIN REACTION FROM PLASMA AND BUFFY COAT WITH ANTIGEN DETECTION AND OCCURRENCE OF IMMUNOGLOBULIN M FOR THE DEMONSTRATION OF CYTOMEGALOVIRUS INFECTION AFTER LIVER TRANSPLANTATION

We compared the value of PCR on plasma with PCR on buffy coat leukocytes, Ag assay, and the determination of IgM antibodies by ELISA for the diagnosis and follow-up of cytomegalovirus infection. Thirty patients were followed after liver transplantation (LTX). We compared the tests to assess their clinical usefulness. Fourteen of 30 (46%) patients were both positive in plasma and buffy coat PCR and Ag test. Sixteen patients were negative in both procedures. There was a 97.2% concordance between PCRs done from plasma or buffy coat. The concordance of results of PCR and Ag test in single samples was 94.3%. Discordant results were found in 5.6% of samples. Discordance was observed in the early and the late phase of CMV infection and was due to positive PCRs preceding positive Ag tests for 1-3 weeks in one-half of the patients. IgM antibodies were first observed after a median period of 8 weeks (range, 6-11 weeks) after LTX. Positive PCRs and Ag tests preceded clinical manifestation of CMV disease by a 1 week median (range, 0-3 weeks), whereas positive IgM ELISAs occurred after a median period of 2.5 weeks (range, 0-4 weeks) after the onset of CMV disease. The sensitivity and specificity of both PCR and Ag test were identical, 100% and 76%, respectively. However, for the IgM ELISA, the sensitivity was only 66%, and the specificity was 84%. In conclusion, plasma or buffy coat PCR and Ag test are equally reliable procedures for early detection and monitoring of CMV infection. PCR can become positive earlier than the Ag test, but it is technically more demanding to perform. The demonstration of IgM antibodies is of little practical help because an antibody response occurs too late in relation to infection.

Duration of specific immunoglobulin A antibody following acute toxoplasmosis as determined by enzyme immunoassay and immunosorbent agglutination assay.

Modifications of an enzyme immunoassay (EIA) and an immunosorbent agglutination assay (ISAGA) for measuring Toxoplasma gondii-specific IgM antibody were made to enable the measurement of Toxoplasma gondii-specific IgA antibody. It was shown that specific IgA could be measured by both assays but that the ISAGA was slightly more sensitive. IgA appears about two weeks after IgM and persists for 6 to 7 months. However, the IgA response varies considerably both in degree and duration, and demonstration of IgM antibody is at present the most suitable routine test for the diagnosis of recent Toxoplasma gondii infection.

Persistent atrioventricular block in Lyme borreliosis

Cardiac manifestations are reported in 0.3%-4.0% of European patients with Borrelia burgdorferi (B.b.) infection. Usually symptoms disappear within 6 weeks. We report a case with persistent impairment of atrioventricular (AV) conduction. Diagnosis was confirmed by demonstration of IgM antibodies and increase of IgG antibody titers against B.b. in serum, by isolation of the spirochete from skin biopsy material and by the typical clinical combination of erythema migrans, Bannwarth syndrome (meningoradiculitis), and complete heart block. Despite immediate antibiotic therapy with ceftriaxone, first degree AV block and second degree block Wenckebach with atrial pacing at 100 beats/minute persisted for 2 years. We conclude, that Lyme carditis can cause long-standing or irreversible AV conduction defects despite adequate and early antimicrobial therapy.

Immunoglobulin A antibodies to Trypanosoma cruzi antigens in digestive forms of Chagas' disease.

In an attempt to find a serological marker for the diagnosis of chronic digestive forms of Chagas' disease, we compared amastigote and trypomastigote antigens obtained from immunosuppressed mice infected with Trypanosoma cruzi (Y strain) with conventional epimastigote antigens to search for immunoglobulin A (IgA) antibodies. A total of 255 serum samples from patients with acute and chronic (indeterminate, digestive, and cardiac) forms of Chagas' disease and with nonchagasic diseases and from healthy individuals were studied. Amastigote antigens proved to be the most adequate for our purpose, since IgA antibodies could be detected in 23 of 25 serum samples from patients with digestive forms, with relative indices of sensitivity, specificity, and efficiency of 0.920, 0.911, and 0.912, respectively. These antigens also showed high reactivity with IgA antibodies, with a geometric mean titer of 16,635 (12.7 log2). IgA antibodies were detected in 16 of 28 serum samples from patients with the acute form as well, but this clinical form is easily distinguished from the chronic form by the demonstration of IgM antibodies. Poor results were seen with trypomastigote and epimastigote antigens. The finding of IgA antibodies in about 20% of indeterminate forms and 20% of cardiac forms, although in low titers, requires further investigation to ascertain their role as an early signal of gastrointestinal lesions. In addition, the amastigote antigens described here seem more convenient for use in endemic areas than those obtained from cell cultures because of their lower cost.

Diagnosis of enterovirus 70 infection by demonstration of IgM antibodies.

Since outbreaks of severe acute hemorrhagic conjunctivitis occur worldwide [Hierholzer and Hatch, 1985] and the majority of the epidemics are caused by enterovirus 70 (EV-70), we developed an EV-70 IgM ELISA to simplify the diagnosis of these outbreaks. The test is based on the capture antibody technique and the use of monoclonal antibodies to EV-70. We detected EV-70 IgM antibodies in 55% of 76 convalescent-phase sera from an outbreak of acute hemorrhagic conjunctivitis in a Brazilian community. Among the 71 acute- and convalescent-phase serum pairs from this outbreak, 49 (69%) demonstrated a 4-fold or greater rise in neutralizing antibody-titer. The titer of IgM antibody began to drop by the fifth week after onset of illness. EV-70 IgM antibodies were not detected in 53 serum pairs with a 4-fold or greater rise in antibodies to other picornaviruses. The EV-70 ELISA proved to simple and relatively rapid to perform, appeared to be specific, and should be sensitive enough to diagnose outbreaks of EV-70 when multiple serum specimens can be tested.

Pathologico-anatomic findings in sudden, unexpected death in children and adults with influenza A infection

Thé following observations resulted from studies on forensic autopsy cases: In 76% of the adults and 55% of the infants the cases of unexpected sudden death without morphologically verifiable causes of death showed virologic evidence of recent influenza-A (H3N2)-infection. The pathologic findings corresponded with the findings in lethal infections with influenza-A viruses. Investigation of cases of sudden and unexpected death should always include virologic serum tests. The demonstration of IgM antibodies against influenza-A virus confirms that there was a recent infection. Death from influenza-A infections occurs also in the interepidemic periods.

Early diagnosis of tick-borne encephalitis (TBE) by demonstration of specific IgM antibodies.

The demonstration of specific IgM antibodies after separation of immunoglobulins was used for the early diagnosis of tick-borne encephalitis (TBE). The separation was done by sucrose-gradient density ultracentrifugation and IgM antibodies were demonstrated with the hemagglutination-inhibition (HI) test. IgM antibodies were found in 9/11 sera taken within 3 days after onset of clinical symptoms and in all sera (37/37) taken 4--15 days after onset of the disease. Most sera (22/24) were still IgM positive 3--6 weeks after onset of the disease. After this period of time IgM antibodies could no longer be defected. The demonstration of IgM antibodies also proved valuable in confirming the diagnosis in several cases where no antibody rise was found neither by the complement-fixation (cf), nor by the HI test.

Role of rubella in congenital malformations in India.

In the present study rubella HI antibodies were determined in cases of congenital malformation and bad obstetric history to determine the role of rubella in such cases in India, as it has been reported to be rare in Japan in contrast to Western countries. The incidence of antibodies was statistically significant in cases of congenital eye, C.N.S., visceral and miscellaneous malformations and cases of spontaneous abortion and still-birth compared with controls of matching age groups. This is further supported by the demonstration of IgM antibodies in seven cases of congenital malformations and ten cases of spontaneous abortion. Our findings show that congenital rubella is not rare in India.

IgM antibodies to Epstein-Barr virus in infectious mononucleosis.

IgM antibodies to Epstein-Barr virus (EBV) could be demonstrated by immunofluorescence in the sera of all patients with clinical infectious mononucleosis (IM) and a heterophile antibody titer of ⩾40. The EBV-IgM antibodies were found only over a period of 2 to 3 months after onset of symptoms. Demonstration of IgM antibodies in the sera of patients therefore indicates recent infection and may be useful for diagnosis. The fact that EBV-IgM antibodies can only be demonstrated during a relatively short period supports the assumption that EBV is indeed the etiologic agent of IM.

Inhibition of Antichlamydial IgM Antibody by IgG Antibody in Immunofluorescence Tests

Abstract Monkeys inoculated intramuscularly with chlamydial suspensions responded with antibody demonstrable by indirect immunofluorescence. IgM antibody was not detected in the whole sera of five of six monkeys, but antibody activity could be demonstrated in IgM fractions from these sera. Monkeys inoculated intravenously with large numbers (1011) of chlamydial particles had IgM antibody detectable in whole sera as well as in fractions. IgG antibody interfered with the demonstration of IgM antibody by immunofluorescence. It is suggested that similar interference of IgG with IgM antibody may occur in other systems.

A small outbreak of Coxsackie B5 infection with two cases of cardiac involvement and orchitis followed by testicular atrophy.

Abstract. An outbreak of Coxsackie B5 infection in a group of six male students is reported. Four of the patients had the symptoms of an uncomplicated enterovirus infection with fever, chills, muscular pains etc. In two cases there was, however, marked cardiac involvement with severe chest pains and ECG changes. In addition these two patients had orchitis with secondary testicular atrophy.Immunoglobulin separation and demonstration of IgMantibodies against Coxsackie B5 was used for the confirmation of the virological diagnosis in three of the cases. The value of this technique is discussed in the paper.

IgM ANTIBODIES IN ACUTE TOXOPLASMOSIS: I. DIAGNOSTIC SIGNIFICANCE IN CONGENITAL CASES AND A METHOD FOR THEIR RAPID DEMONSTRATION

The present study was undertaken to develop a simple technique for demonstration of IgM-toxoplasma antibodies in acute congenital toxoplasmosis. Such antibodies were demonstrable by each of the four methods used, but their sensitivities varied considerably. The underlying difficulty in interpretation of results obtained in the dye and hemagglutination tests following reductive cleavage appeared to be the high titer of IgG-toxo-plasma antibodies in all sera tested, which "hides" the effect of 2-ME on the IgM-toxoplasma antibodies. Because IgG-toxoplasma antibodies do not interfere with the demonstration of IgM-toxoplasma antibodies in fractions obtained by sucrose density gradient ultracentrifugation or with the IgM-fluorescent antibody test, these two methods proved the most sensitive for demonstration of IgM-toxoplasma antibodies in congenital cases. Whereas the former of these two methods is a laborious procedure requiring facilities rarely available in clinical laboratories, the IgM-fluorescent antibody test is easily learned and it can be performed in 2 hours. Serologic diagnosis of infection in newborns is often complicated by the presence in the infant of maternal antibodies. The difficulty in interpretation of serologic results in cases of suspect congenital toxoplasmosis is magnified by the high prevalence of toxoplasma antibodies in the normal childbearing population (and thus in their offspring). Demonstration of IgM antibodies in newborn infants (in the absence of a placental leak) appears to be diagnostic of congenital toxoplasmosis. Because of the difficulty encountered in recognition of congenital cases which do not appear to have the "classical" signs and because of the infrequency with which the diagnosis can be established, even in these latter cases, the IgM-fluorescent antibody test will hopefully prove simple enough to perform to be useful as a test for the definitive diagnosis of acute congenital toxoplasmosis.