Serological Grounds Research Articles

The enigma of the 1889 Russian flu pandemic: A coronavirus?

The “Russian flu”, which raged from 1889 to 1894, is considered as the first pandemic of the industrial era for which statistics have been collected. This planetary event started in Turkestan and hit the Russian Empire, before reaching all European countries, the United States of America, and the whole world. Contemporaries were surprised by its high contagiousness as evidenced by attack rates averaging 60% in urban populations, its rapid spread in successive waves circling the globe in a few months by rail and sea, and the tendency of the disease to relapse. Despite its low case-fatality rate (0.10%-0.28%), it is estimated to have caused one million deaths worldwide. On serological grounds, it is generally accepted that the causative agent of Russian influenza was Myxovirus influenzae, the virus identified for all influenza pandemics since the “Spanish flu” of 1918. In light of the Covid-19 pandemic, which has underscored the extraordinary epidemic potential of coronaviruses, this assumption has recently been questioned. Coronaviruses come from wild reservoirs (bats, rodents, birds, …). They induce respiratory symptoms mimicking influenza, possibly leading to respiratory distress with pneumonia. In addition to the Covid-19 pandemic, recent deadly and limited epidemics, such as SARS in 2002 and MERS in 2012, have occurred. Russian influenza presented as an influenza-like syndrome with clinical peculiarities (multivisceral and neurological involvement, skin rash, early iterative relapses), evoking some particularities of Covid-19. Four other coronaviruses circulating in the human population for decades (HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1) have been found to be responsible for 15 to 30% of seasonal colds. All of these viruses are of animal origin. Recently, phylogenetic studies have revealed the genetic proximity between a bovine coronavirus BCoV and the human virus HCoV-OC43, indicating that the latter emerged around 1890, at the time of the Russian flu, when an epizootic was raging among cattle throughout Europe. Could the current human virus be the attenuated remnant that appeared after the Russian flu in 1894? Was there a coronavirus pandemic before Covid-19 ?

O23 A series of catastrophic events

Case report - IntroductionCatastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening disease occurring in up to 1% of antiphospholipid syndrome (APS) cases. It was first defined in 1992 and remains a difficult to treat entity with a mortality rate of 37%. We describe a patient with systemic lupus erythematosus (SLE) and CAPS presenting with simultaneous multi-organ injuries who was successfully managed with ‘triple’ therapy including cyclophosphamide.Case report - Case descriptionA 42-year-old female presented to her local hospital with chest pain and worsening vision. She had a background of SLE, triple antibody-positive APS (previous DVT, pregnancy loss and strokes), hypertension, a metallic mitral valve, a previous myocardial infarction and pre-existing visual impairment due to a prior intra-cerebral bleed related to anticoagulation. Examination revealed a faint malar rash, cortical blindness and long tract neurological signs. Her ECG showed ischaemic changes and the admission troponin was significantly raised (3773ng/L). An echocardiogram showed new left ventricular dysfunction and a subsequent cardiac MRI was in keeping with coronary artery disease. Investigations showed an acute kidney injury, newly deranged liver function tests and a raised INR (>11, with no bleeding). Complement was normal with a low dsDNA titre. Urinalysis revealed proteinuria and a protein creatinine ratio measured 176mg/mmol. MRI diffusion weighted brain imaging showed acute bilateral occipital and left fronto-parietal infarcts. She had symptoms of a lupus flare with arthralgia and a butterfly facial rash. COVID-19 PCR tests were negative and she had not been recently vaccinated. She was diagnosed with CAPS and transferred to St Thomas’ hospital intensive care.On arrival, she received 1mg intravenous vitamin K followed by triple therapy for CAPS: an unfractionated heparin infusion, oral prednisolone 40mg daily, 5 days of plasma exchange and, given her background of SLE, she was treated with intravenous cyclophosphamide (according to the EUROLUPUS regimen). Intravenous methylprednisolone was avoided due to a previous hypertensive encephalopathy reaction. She responded rapidly. Her troponin fell from a peak of 5054 to 294ng/L, her creatinine settled at a new baseline (232umol/L) and her liver function normalised. She was switched back to warfarin due to her metallic valve and started on aspirin for cardiovascular secondary prevention. She required physical and occupational therapy due to her strokes but recovered well.Case report - DiscussionAccording to the 2003 criteria, CAPS can be classified as definite when there is evidence of: ≥3 organs involved, development of manifestations simultaneously or within a week, confirmation by imaging and/or histopathology of small vessel occlusion and positive antiphospholipid antibodies. Probable CAPS is when 3 out of the 4 criteria are present. In this case, three organs were confirmed to be involved with imaging showing cerebral and cardiac ischaemia. Her creatinine rose from a base of 190 to 289umol/L coupled with a high protein creatinine ratio confirming renal involvement. A Budd-Chiari syndrome was also suspected due to deranged liver function tests and INR, though imaging performed after therapy did not confirm this. A biopsy of any of these four organs was not feasible given the severity of her presentation and coagulopathy. There are no randomised controlled trials but data from the CAPS registry guides treatment and management follows a logical approach: anticoagulation to treat thrombosis, glucocorticoids for inflammation and plasma exchange (or IVIG) to remove the circulating autoantibodies. Triple therapy was associated with a reduced mortality compared to no treatment (28.6% versus 75%, respectively).Following analyses from the CAPS registry we also chose to treat with cyclophosphamide, which is associated with improved survival in patients with SLE. This decision was based on the clinical features of an SLE flare as opposed to serological grounds. There have been reports of rituximab and eculizumab being used successfully in CAPS, though generally as a last resort. As complement activation is seen in animal models of antiphospholipid syndrome thrombosis and rituximab is often used in refractory SLE, they may prove to be promising agents for refractory CAPS.Case report - Key learning pointsPrompt recognition and early treatment is vital in managing CAPSTriple therapy with anticoagulation, glucocorticoids and plasma exchange / IVIG is associated with better survival in CAPSCyclophosphamide is associated with better survival in patients with CAPS and concomitant SLE

Nasal and Lacrimal Sac Histopathology in Patients With Granulomatous Polyangiitis Undergoing Lacrimal Drainage Surgery.

To examine histological changes within nasal and lacrimal sac mucosa harvested from patients with granulomatous polyangiitis (GPA) who required lacrimal drainage surgery. As these patients were considered quiescent on clinical and serological grounds, particular attention was paid to the presence of active vasculitis. Retrospective noncomparative case series. Patients with GPA who had open lacrimal drainage surgery under the care of a single surgeon between 1991 and 2017. All patients had paired biopsies of both nasal and ipsilateral lacrimal sac mucosa. Biopsies of the nasal and lacrimal sac mucosa, taken from the operative site during either primary or revisional open dacryocystorhinostomy, were reported by experienced ophthalmic histopathologists. Outcome measures were the surgical appearance of the tissues and the proportion of each tissue showing histological evidence of active vasculitis, chronic inflammation with or without fibrosis, marked fibrosis without inflammation, or acute-on-chronic inflammatory changes. Paired tissues were available from 47 patients (25 females; 53%) who had undergone 64 procedures (57 primary, 7 revisional). All patients had systemic disease, this being known prior to surgery in 43 patients (with 41/43 on long-established systemic immunosuppression) and suspected clinically after the initial lacrimal examination in 4/47. Most lacrimal sacs and nasal spaces showed a variety of abnormalities, this commonly being extensive scarring. Despite most patients being considered to have inactive systemic GPA, active vasculitis was evident in 23/64 (36%) lacrimal sac biopsies and 32/64 (50%) nasal mucosal biopsies-suggesting that serological markers may not be reliable guide to disease activity where disease is of limited volume (as, for example, with limited sino-nasal disease). Chronic lymphocytic inflammation was present in a further 35/64 (55%) sacs-associated with marked fibrosis in 5-and a further 25/64 (41%) nasal biopsies (with fibrosis in 2). The lacrimal sac and nasal space are highly abnormal in most patients with GPA undergoing lacrimal drainage surgery. Despite having clinically and serologically inactive disease on established systemic immunotherapy, histological examination often shows unrecognized active vasculitis, which might indicate inadequate systemic immunosuppression for the underlying condition.Lacrimal sac and nasal mucosa from patients with granulomatous polyangiitis undergoing dacryocystorhinostomy usually show chronic lymphocytic inflammation with marked fibrosis, but up to half reveal active vasculitis despite long-established systemic immunosuppression and apparently "quiescent" disease.

Post chikungunya pigmentation in a segmental pattern: A rare presentation

Chikungunya is a viral infection caused by chikungunya virus belonging to family Togaviridae, transmitted by Aedes mosquitoe. It presents with acute onset of fever with debilitating arthralgia/ arthritis. A spectrum of muco-cutanous manifestations have been reported in the literature. We report a case of a 35 years old female presented with non-progressive hyperpigmented macules in a segmental pattern over the left side of the neck for the past 1 month. She had a preceding history of chikungunya diagnosed on clinical and serological grounds just 2 weeks prior to the onset of pigmentation. Histopathology showed increased melanin deposition in the basal layer of the epidermis with presence of melanophages in the upper dermis. There was no basal cell vacuolization or inflammatory infiltrates. These findings were consistent with a diagnosis of post chikungunya pigmentation. Patient responded well to treatment of topical 2% hydroquinone. This unique segmental presentation of post chikungunya pigmentation must be kept in mind when a patient presents with an acquired segmental hyperpigmentary disorder of unknown origin.

Clinico-Social and Immunological Profile of Antiretroviral Naïve Children Living With HIV In Tertiary Care Hospital, Delhi

Introduction: This study was undertaken to assess the clinical profile of children living with HIV at the time of their enrolment in an ART centre in Delhi. The study also attempts to understand association between clinical staging and immunological profile (CD4 count/percentage) in HIV infected children. The findings of this study may help policy makers to plan better health care of CLHIV in resource constrained country like India. The Objectives of the study were to assess the baseline clinico-social and immunological profile of HIV positive children before the start of Antiretroviral Therapy, to study clinicosocial and morbidity profile of HIV positive children at the time of their enrolment in ART centre and to study the association between immunodeficiency and clinical staging of CLHIV.Methodology: The present study, conducted between December 2012 and March 2013, is a retrospective case review of 83 antiretroviral naïve Children living with HIV aged 8 months to 13 years and attending paediatric ART clinic of a tertiary care hospital of Delhi. After the infection was established on serological grounds, information on socio-demographic, clinical and immunological profile was studied.Results: Majority (62.7%) of CLHIV were boys. Both parents of CLHIV were found to be positive in 63.9% while mother was found to be positive in 69.9%. The most common route of HIV infection was mother-to-child transmission (69.9%), followed by transmission though blood/blood products (12.0%). Every three out of four children (71.1%) were in WHO clinical stage III or IV. Three out of four (74.7%) children presented with fever, one in two with cough (56.6%). Diarrhoea (56.6%), pneumonia (41.0%), popular pruritic eruptions (18.1%), candidiasis (16.9%) and tuberculosis (14.5%) were the most common opportunistic infections in these children. The most common signs present were hepatomegaly (81.9%), anaemia (78.3%) and lymphadenopathy (72.3%).Conclusion: Mother to child transmission is the most common route of transmission in CLHIV. At enrolment more than half of the children were in clinical stage III&IV. Fever, cough, diarrhoea, weight loss, rashes were common morbidities of the children. Majority of the children had hepatomegaly, anaemia and lymphadenopathy.SAARC J TUBER LUNG DIS HIV/AIDS, 2016; XIII(1) p.32-38

Outcome of Kidney Transplantation in Bahrain.

Pupose: Renal transplantation is considered the optimal form of renal replacement therapy for patients with end stage renal disease. Kidney transplantation was started in Bahrain in 1995 at our unit. Methods: Between June 1995 and December 2013, 125 renal transplants in 124 patients were performed at our unit. There were 115 living related donor and 20 deceased donor transplants (DD), including 81 male and 44 female patients. Most of the recipients were Bahraini (94.1%) and 116 (92.8%) of them received their first graft. Diabetic nephropathy was responsible for 22.4% of end-stage kidney disease. Their age ranged from 3 to 66 years and the follow up period was 1 to 216 months postoperatively. Results: Dialysis before transplantation was done in 85.4% of patients. All patients received triple drug immunosuppression and induction therapy with baziliximab. There were a total of 22 (17.7%) episodes of acute rejection diagnosed clinically and/ or by graft biopsy. Most of the rejection episodes occurred within the first month post-transplantation. Seven (5.6%) grafts had primary non-function due to acute tubular necrosis (ATN), and all of them were from DD. There were 15 episodes of severe infection. Seven patients died from their infection including three due to severe respiratory tract infection. Three patients developed cytomegalovirus infection which was diagnosed on clinical and serological grounds. Three patients developed malignancy (one lymphoma, one Kaposi sarcoma and one brain tumor). There were 3 surgical and urological complications encountered in our patients. At the last follow-up visit, there are 86 patients (68.8%) have good graft function. Thirty-eight patients lost their graft, 16 of them due to death with functioning grafts. The commonest cause of graft loss was chronic rejection. Conclusions: The overall results in our center are comparable to those published from other centers in the Arab World. Our main challenge is shortage of kidney donors.

Low‐frequency human platelet antigens as triggers for neonatal alloimmune thrombocytopenia

Twenty-four low-frequency human platelet antigens (LFHPAs) have been implicated as immunogens in neonatal alloimmune thrombocytopenia (NAIT). We performed studies to define more fully how often these antigens trigger maternal immunization leading to NAIT. In a Phase 1 study, fathers of selected NAIT cases not resolved by serologic testing but thought to have a high likelihood of NAIT on clinical and serologic grounds were typed for LFHPAs by DNA sequencing. In a Phase 2 study, high-throughput methods were used to type fathers of 1067 consecutive unresolved NAIT cases for LFHPAs. Mothers of 1338 unresolved cases were also typed to assess the prevalence of LFHPAs in a population racially/ethnically similar to the fathers. In Phase 1, LFHPAs were identified in 16 of 244 fathers (6.55%). In Phase 2, LFPAs were found in only 28 of 1067 fathers (2.62%). LFHPAs were identified in 27 of 1338 maternal samples (2.01%). HPA-9bw was by far the most common LFHPA identified in the populations studied and was the only LFHPA that was significantly more common in fathers than in mothers of affected infants (p = 0.02). Maternal immunization against recognized LFHPAs accounts for only a small fraction of the cases of apparent NAIT not resolved by standard serologic testing. Typing of the fathers of such cases for LFHPAs is likely to be rewarding only when a maternal antibody specific for a paternal platelet glycoprotein is demonstrated and/or there is compelling clinical evidence for NAIT.

Tularemia in children

Tularemia, an infection caused by the coccobacilus Francisella tularensis, can be a difficult disease process to diagnose and treat. The aim of this study was to evaluate an epidemic of tularemia in Bursa. In this study, we included only pediatric cases. All the cases were diagnosed on clinical and serological grounds. During an epidemic of tularemia in a village of Bursa on December 2004, 70 people (60 adults, 10 children) fell ill. In children with tularemia, the oropharyngeal form predominated which was diagnosed 70% of cases. Most of the patients (80%) who had older than 10 years old, were treated with doxycycline. All patients recovered without complications. The epidemic was thought to be waterborne. The vehicle of the infections was inadequately treated water which was used by the patient in the village.

Chlamydial Infection Showing Migratory Pulmonary Infiltrates

A 70-year old man was admitted to our hospital because of nonproductive cough, fever and increasing dyspnea associated with alveolar opacities on chest roentgenogram, which later migrated to previously unaffected areas. The diagnosis of Chlamydial pneumonitis was made on serological grounds. Organizing pneumonia was documented by transbronchial lung biopsies and the subsequent course was satisfactory under minocycline therapy. Chlamydial infection should be considered in the differential diagnosis of migratory pulmonary infiltrates.

Repeat Borderline or Negative Platelet Factor-4 ELISA May Yield Positive Results in Patients with Clinical Suspicion of Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is mediated by antibodies to heparin-platelet factor 4 (PF4) complexes which lead to platelet activation and aggregation with or without thrombosis. HIT diagnosis relies on clinical and serologic grounds. Although the detection of PF4 antibodies alone is not diagnostic of HIT without thrombocytopenia (relative or absolute) and/or thrombosis, a negative result does not exclude the diagnosis. Thus, it is expected that initially negative ELISAs may turn positive on repeat testing. We reviewed all PF4 ELISA (GTI Diagnostics, Waukesha, WI) assay reports generated at our institution from January 2003 to May 2005 in search of patients who had more than one test performed in this time-period. Of 1,128 tests performed, 181 (16%) were positive, 95 (8%) were borderline, and 852 (76%) were negative. Borderline results were considered those with an OD405 between 0.3 and 0.4 (cutoff value for positive) or two times that of the negative control of each run. No patients were evaluated using the serotonin-release assay. Nine of 70 patients (13%) with initially negative or borderline ELISAs had a positive result upon repeat testing from 2 to 63 days later (Table). All were inpatients, and 6 of 9 were from surgical specialties, mostly cardiac (5 of 6). Five of 8 patients (62.5%) with an initial positive PF4 ELISA result had either a negative or a borderline subsequent test from 7 to 225 days later (Table). The mean platelet count of the patients that had a nondiagnostic ELISA followed by a positive result was 98 x 109/L (N = 9) at the time of the initial test compared with 137 x 109/L at subsequent testing (p = 0.43 by paired Student's t test). Of note, 2 patients had a normal platelet count when the ELISA result was positive. None had evidence of thrombosis. Borderline test results tended to be repeated sooner (mean of 16 days) than negative ones (mean of 21 days). We suspect that this difference reflects the clinicians' high index of suspicion for HIT. Our findings suggest that in patients with a high pre-test probability for HIT (status post cardiac surgery with thrombocytopenia), there should be a low threshold for repeating an initial negative or borderline ELISA assay, thereby increasing detection and minimizing complications from this potentially fatal, yet common clinical entity.Test Results of the 78 Patients With Repeat HIT ELISAs.Initial Test ResultRepeat Test ResultNumber of Patients (% of Total)Mean Number of Days Between Tests (Range)NegativePositive7 (13)17 (2–63)(N=56)Negative45 (80)26 (1–216)Borderline4 (7)22 (8–36)BorderlinePositive2 (14)21.5 (10–33)(N=14)Negative6 (43)17.5 (3–42)Borderline6 (43)9 (1–23)PositivePositive3 (37.5)34 (4–88)(N=8)Negative4 (50)26 (7–80)Borderline1 (12.5)225 (NA)Total78NA: Not applicable

US Features of Liver Surface Nodularity as a Predictor of Severe Fibrosis in Chronic Hepatitis C

Editor: We read with interest the article by Dr Colli and colleagues in the April 2003 issue of Radiology (1), in which the authors assessed the predictive power of ultrasonography (US) for liver fibrosis. They claimed that nodularity of the liver surface is an accurate predictor of severe fibrosis and cirrhosis. We compared liver biopsy findings and US features in 108 patients with chronic hepatitis C who consecutively underwent diagnostic liver biopsy between May 2003 and February 2004. US was performed by one gastroenterologist (S.V.) the day of liver biopsy after patients fasted overnight. The liver surface of both liver lobes was examined with a 5.0–10.0 linear transducer (Prosound 5500; Aloka, Tokyo, Japan). The liver surface was nodular if it appeared as a dotted or irregular line, as reported by Dr Colli and colleagues. Liver biopsy was performed by using a 16-gauge needle (Tru-Cut; Sterylab Rho, Milan, Italy) with US guidance, and samples were scored for grading and staging according to the protocol of Ishak and co-workers (2) by one pathologist (G.R.). The 55 men and 53 women who participated in the study had a median age of 53 years and had an increase in alanine aminotransferase level ranging from 1.2 to 9 times the upper normal limit. Fifty-one patients circulated genotype 1 of hepatitis C virus. Factors of liver disease other than hepatitis C virus were excluded on histologic, clinical, and serologic grounds. Most patients (71 patients) had a fibrosis score of 4 or less: 39 had a score of 1, 20 had a score of 2, four had a score of 3, and seven had a score of 4. Thirty-seven (34%) patients had a fibrosis score of more than 4: 12 had a score of 5, and 25 had a score of 6. Thus, the prevalence of severe fibrosis or cirrhosis was comparable to that reported by Dr Colli and colleagues. Nineteen (51%) patients with severe liver fibrosis or cirrhosis showed surface nodularity of the liver at US examination, compared with seven (10%) of those with fibrosis with a score less than 4 (P .001). Liver surface nodularity as a predictor of severe fibrosis had 53% sensitivity and 91% specificity with a positive and negative predictive value of 0.77 and 0.78, respectively. The positive and negative likelihood ratios were 5.8 and 0.5, respectively. Our data therefore corroborate the findings of Dr Colli and colleagues that US features of liver nodularity are reliable predictors of severe liver fibrosis in patients with chronic hepatitis C.

Atypical measles in a patient twice vaccinated against measles: transmission from an unvaccinated household contact

Described are two cases within the same household that were involved in an outbreak of measles in Niterói, RJ. Measles diagnosis was confirmed serologically by specific IgM detection in Case 1 (classic measles) who was unvaccinated, and rising measles specific IgG in the absence of IgM in Case 2 (mild modified measles) who had a history of two vaccinations with measles-containing vaccines. Measles virus was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in saliva samples from both cases. The nucleic acid amplified by RT-PCR was sequenced and showed identical measles sequence in the two cases. This study highlights the difficulty of diagnosing nonclassical measles infection on clinical and serological grounds, and the usefulness of PCR for viral RNA sequencing from noninvasive specimens for confirming epidemiologic links.

Estimation of the contact rate in a seasonal SEIR model: application to chickenpox incidence in France.

This work was an attempt at analysing the seasonal pattern of varicella epidemics in France by fitting a susceptibles-exposed-infectives-recovered (SEIR) model with a periodic contact rate function to weekly chickenpox incidence data collected over the period 1991 to 1996. The contact rate was assumed to be either a continuous, or a piecewise constant, periodic function. Both assumptions gave a reasonable fit to the data and yielded estimates of the incubation and infectious periods that were consistent with values derived on clinical or serological grounds. Seasonal fluctuation of the estimated contact rate function was likely to reflect the impact of school holidays on chickenpox diffusion among schoolchildren.

Tularemia in Bursa, Turkey: 205 cases in ten years.

Tularemia is a zoonotic disease caused by the coccobacillus F. tularensis. Small epidemics and sporadic cases were seen around Bursa since November 1988. In this study, a total of 205 cases of tularemia were observed. All the cases were diagnosed on clinical, bacteriological and serological grounds. The epidemics were thought to be waterborne. The majority of the patients were young and female. In most of the cases the disease presented itself in oropharyngeal form (83%). Analysing sera from the patients with microagglutination method demonstrated that titers were > or = 1:160 in approximately 85% of the cases, including the ones in subclinical form. Five of ten patients from who the bacteria was isolated were seronegative. Streptomycin was given to the most of the patients by combining with tetracycline, doxycycline or chloramphenicol. The early administration of these antibiotics (before the third week of disease) was found to be much more effective to resolve the infection. As a result, the main mode of transmission of F. tularensis is waterborne in our region. In our region, tularemia should be considered in differential diagnosis for the cases with fever, tonsillopharyngitis and cervical lymphadenopathy to make an early diagnosis and to design relevant treatment.

Serological screening suggests that adult coeliac disease is underdiagnosed in the UK and increases the incidence by up to 12%.

Because coeliac disease often presents atypically it is underdiagnosed. It is suggested that the detection rate may be increased by 12% if serology is used to identify cases of occult enteropathy. All adults noted incidentally to be R1 anti-reticulin antibody (ARA) positive in the course of routine autoantibody testing of 6532 sera over one year were followed. None of the eight patients with seropositive serum was suspected of having coeliac disease. All eight had high titres of IgA anti-gliadin and IgA anti-endomysial antibodies, neither of which is detected in a routine autoantibody test, in addition to IgA R1-ARA. On clinical review coeliac disease was considered probable in only one patient, but because of the strong serological evidence of gluten sensitivity, jejunal biopsy was advised in all eight. Seven agreed and all had villous atrophy and crypt hyperplasia in keeping with coeliac disease. Six of the seven presented initially with vague symptoms such as tiredness or arthralgia. These symptoms disappeared after several weeks of gluten withdrawal. Forty two sera showing reticulin staining patterns other than R1 were used as controls. Low titre IgA anti-gliadin was noted in two of 42 but none had IgA anti-endomysial antibody. These 42 cases were not recommended for biopsy. During our study 58 other new adult cases of coeliac disease were diagnosed, primarily on clinical rather than serological grounds, at the four hospitals that request autoantibody studies. Occult coeliac disease detected serologically thus increased the overall incidence of coeliac disease by 12% from 58 to 65 cases. R1-ARA, even in the absence of the expected symptoms and signs of coeliac disease, is an indication for jejunal biopsy and is a reliable indicator of occult coeliac disease.

Clinical and laboratory features of measles in hospitalized adults

purpose: Description of the epidemiology, morbidity, and mortality of hospitalized adults with typical measles. patients and methods: Restrospective case analysis of 33 adults who required acute care for complications of measles in a public hospital in Los Angeles, California. The diagnosis of measles was established on standard clinical or serologic grounds. results: Of 68 patients (age greater than 14) with signs and symptoms of measles who presented for medical care, 33 (19 males and 14 females) required hospitalization; 18 were natives of the United States. The patient age was 26.1 ± 7.3 (mean ± SD) years; four patients, all natives of the U.S., were born before 1957. The duration of hospitalization was 6.8 ± 8.8 days for all patients and 13.4 ± 14.2 days for the nine patients who required intensive care unit (ICU) care. Six of the ICU patients required mechanical ventilation for 11.0 ± 15.0 days; two deaths occurred among these patients. During the course of their illness, 7 of 25 (28%), 11 of 28 (39%), 6 of 28 (21%), and 5 of 16 patients (31%) had peak lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and creatine kinase values, respectively, that were greater than 5 times the upper limit of normal. Fifteen of 28 patients (54%) developed total serum calcium levels less than or equal to 2.0 mmol/L. Ten cases were serologically confirmed; 23 cases were diagnosed as probable measles on clinical grounds. There were no significant demographic, clinical, or laboratory differences between patients with confirmed and probable measles. No patients had characteristic manifestations of atypical measles. The sole immunocompromised patient died. conclusions: Measles in adults may result in severe, life-threatening complications that utilize substantial medical resources. Physicians need to appreciate the clinical presentations and manifestations of severe measles in adults and to provide measles vaccine to nonimmune adults during community-wide outbreaks.

Is serology of any use when searching for correlations between Chlamydia trachomatis infection and male infertility?

Evidence on Chlamydia trachomatis causing male infertility is conflicting. We therefore collected data on epidemiological and clinical correlates of chlamydial infection and male fertility in 184 males visiting our Fertility Unit. Antibodies against Chlamydia trachomatis in serum and semen were also determined. Significant correlations were demonstrated between current chlamydial urethral infection and semen immunoglobulin (Ig) A, serum IgA and serum IgG. These parameters, however, were neither related to a history of sexually transmitted disease nor to lifetime number of sexual partners. Why, in the male, serology does not correlate with chlamydial infection in a more remote past is explained. Our data support, on epidemiological as well as serological grounds, the conclusion that chlamydial infection probably does not contribute significantly to male infertility.

Theileria taurotragi in Zambia.

Theileria sp. (Bwengwa) of low virulence was isolated by feeding R. appendiculatus ticks collected from the field on a susceptible calf and subsequently transmitted between cattle by R. appendiculatus ticks- Theileria sp. (Bwengwa) was shown to be T. taurotragi on parasitological, clinical and serological grounds. T. taurotragi is the fourth Theileria sp. shown to be present in Zambia.

Theileria orientalis occurs in Central Africa

An outbreak of bovine theileriosis in Burundi was investigated and the occurrence of Theileria orientalis in Central Africa was confirmed for the first time. Its identity was established on morphological and serological grounds. The parasite was associated with clinical signs and further complicates the disease picture of bovine theileriosis in Africa. Amblyomma variegatum is suspected as being the local vector.

Human immunoglobulin allotypes: previously unrecognized determinants and alleles defined with monoclonal antibodies.

The highly polymorphic system of serologically defined genetic markers on human IgG heavy chains (Gm allotypes) is second only to the HLA complex in terms of the large number of determinants, alleles, and haplotypes that can be used for analyses of disease associations and other genetic studies. However, present typing methods are based on the use of anti-Gm antisera that are derived mainly from fortuitously immunized human donors, often requiring processing before use, and must be used in a hemagglutination-inhibition assay that cannot be used in typing for isoallotypic determinants (currently termed "non-markers"). In studies presented here, we describe an allotyping system that utilizes monoclonal antibodies in a "sandwich" modification of the solid-phase radioimmunoassay, which is capable of reliable quantitative typing of allotypic, isoallotypic, and isotypic immunoglobulin determinants. We show that these highly reproducible, easily disseminated, and essentially inexhaustible reagents can be used for rapid, sensitive, and quantitative Gm typing. Using this system we define two previously unrecognized Gm determinants, one of which, found to date only in Caucasians, is different from all known Gm markers and thus defines previously unrecognized alleles and haplotypes. The other determinant co-segregates with the conventional G3m(b1) marker but is distinct from that marker on serological grounds. The successful preparation of mouse monoclonal antibodies that detect human Gm allotypic differences and the development of an assay system capable of typing isoallotypic as well as allotypic determinants opens the way to further dissection and application of this rich genetic system.