Common variable immunodeficiency (CVID), characterized by recurrent infections, is the most prevalent symptomatic antibody deficiency. In ∼90% of CVID-affected individuals, no genetic cause of the disease has been identified. In a Dutch-Australian CVID-affected family, we identified a NFKB1 heterozygous splice-donor-site mutation (c.730+4A>G), causing in-frame skipping of exon 8. NFKB1 encodes the transcription-factor precursor p105, which is processed to p50 (canonical NF-κB pathway). The altered protein bearing an internal deletion (p.Asp191_Lys244delinsGlu; p105ΔEx8) is degraded, but is not processed to p50ΔEx8. Altered NF-κB1 proteins were also undetectable in a German CVID-affected family with a heterozygous in-frame exon 9 skipping mutation (c.835+2T>G) and in a CVID-affected family from New Zealand with a heterozygous frameshift mutation (c.465dupA) in exon 7. Given that residual p105 and p50—translated from the non-mutated alleles—were normal, and altered p50 proteins were absent, we conclude that the CVID phenotype in these families is caused by NF-κB1 p50 haploinsufficiency.

Common variable immunodeficiency disorders (CVIDs) are the most frequent symptomatic primary immune deficiency condition in adults. The genetic basis for the condition is not known and no single clinical feature or laboratory test can establish the diagnosis; it has been a diagnosis of exclusion. In areas of uncertainty, diagnostic criteria can provide valuable clinical information. Here, we compare the revised European society of immune deficiencies (ESID) registry (2014) criteria with the diagnostic criteria of Ameratunga et al. (2013) and the original ESID/pan American group for immune deficiency (ESID/PAGID 1999) criteria. The ESID/PAGID (1999) criteria either require absent isohemagglutinins or impaired vaccine responses to establish the diagnosis in patients with primary hypogammaglobulinemia. Although commonly encountered, infective and autoimmune sequelae of CVID were not part of the original ESID/PAGID (1999) criteria. Also excluded were a series of characteristic laboratory and histological abnormalities, which are useful when making the diagnosis. The diagnostic criteria of Ameratunga et al. (2013) for CVID are based on these markers. The revised ESID registry (2014) criteria for CVID require the presence of symptoms as well as laboratory abnormalities to establish the diagnosis. Once validated, criteria for CVID will improve diagnostic precision and will result in more equitable and judicious use of intravenous or subcutaneous immunoglobulin therapy.

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The literature published during 1964-72 concerned with the ecology and control of Glossina is reviewed and put into context with previously published information. Thirty species or subspecies of Glossina are recognised. Improved methods of sampling have been developed which catch many more females of the morsitans group than other methods and allow more accurate estimates of population density and structure to be made than has been possible hitherto. New concepts of the activity and behaviour patterns of G. morsitans Westwood have been developed from work carried out both in the field and in the laboratory. Detailed studies on resting sites have been followed by successful control campaigns based on the selective use of insecticides. Most large-scale control campaigns during the period under review were based on applications of insecticides from the ground; other control methods used were aerial applications of insecticides, mechanical clearing of vegetation, selective game destruction and a small-scale project using the sterile insect release method. Techniques for identifying and assessing trypanosome infections in Glossina are described and a Table is given of infection rates in various species of tsetse. Differences in observed infection rates can result according to the time and method of sampling but actual infection rates are affected by a variety of factors including the maintenance temperature of puparia and adults, the age of the fly at the time of the infective feed, the age structure of the tsetse population and the hosts on which it feeds. Genetic differences in infedibility may occur between different individuals of a single species and certainly occur between different species. CONTENTS

Introduction: Diagnostic tests play a critical role in the management of Sars-CoV-2, the virus responsible for COVID-19. There are two groups of tests, which are in widespread use to identify patients who have contracted the virus. The commonly used reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) test becomes negative once viral shedding ceases by approximately three weeks. Antibody tests directed to viral antigens become positive after the second week of infection. IgG antibody responses to the virus are muted in children, pregnant females and those with mild symptoms. IgA and IgM antibodies rapidly wane although IgG antibodies directed to the receptor-binding domain (RBD) of the spike (S) glycoprotein are more durable. Current data shows variability in the sensitivity of commercial and in-house antibody tests to SARS-CoV-2. Areas covered: The role of T cells in acute illness is uncertain but long-term protection against the virus may rely on memory T cell responses. Measuring memory T cell responses is important for retrospective confirmation of cases, who may have been infected early in the pandemic before reliable RT-qPCR tests were available and whose SARS-CoV-2 antibodies may have become undetectable. Relevant peerreviewed published references from PubMed are included up to 15 March 2021. The reader is advised to seek up-to-date information on specific aspects of COVID-19 which are changing on a daily basis. Expert opinion: After surveying the literature, the authors present the case for urgent development of diagnostic T cell assays for SARS-CoV-2 by accredited laboratories.

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Male and female Glossina morsitans morsitans Westw. which emerged from puparia produced by animal-fed and in vitro-fed colonies in England were marked distinctively with non-toxic paint and released into a natural habitat of G. morsitans and G. pallidipes Aust. in Rhodesia. Concurrently, adults of both species which emerged from locally-collected puparia were marked and released. Recaptures from artificial refuges, odour attractants and mobile baits at periods up to 59 days after release and at distances up to 1800 m from the release site indicated no clear differences between native G. morsitans and the two laboratory-reared groups in respect of body size, amount of fat present at emergence, survival, dispersal, availability to a range of baits, diet, speed of taking a first meal, wing damage and insemination rate. Although the blood-meal identifications for marked female G. morsitans were similar to those for both sexes of unmarked flies, blood-meals from marked males showed a relatively high proportion of bovid identifications. Unmarked flies caught were generally older than marked catches. The ratio of females to males in unmarked samples (1:1 for G. morsitans, 2:1 for G. pallidipes) was roughly double that in marked catches.

Common variable immunodeficiency disorders (CVID) are the most frequent symptomatic primary immune defect in adults. Within the broad spectrum of CVID, a proportion of patients present with a predominant T cell phenotype associated with increased mortality. These patients are termed late-onset combined immunodeficiency (LOCID) and are currently separated from patients suffering from CVID. Areas covered: We have recently codiscovered a new CVID-like disorder caused by mutations of the NFKB1 gene. Members of this non-consanguineous New Zealand kindred have a very diverse spectrum of phenotypes in spite of carrying the identical mutation. The proband appears to have the autoimmune variant. The proband's recently deceased sister best matched LOCID while other family members are less severely affected, including one asymptomatic adult brother, who has an affected daughter. Differences in genetics was one of the main arguments for separating these disorders in the past. Expert commentary: Given the recent advances in the understanding of the genetic basis of these conditions, we present the case that LOCID should now be considered a subset of CVID, rather than a separate disorder. At a clinical level, this distinction is less important but it is imperative these patients are carefully evaluated, the relevant complications are treated, and they are offered prognostic information.