European survey on the current surveillance practices, management guidelines, treatment pathways and heterogeneity of testing of Clostridioides difficile, 2018-2019: results from The Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI).

BACKGROUND: Awareness and compliance with international guidelines for diagnosis and clinical management of Clostridioides difficile infection (CDI) are unknown. AIM: To compare the awareness and compliance with the recommended strategies for diagnosis and clinical management of CDI across Europe in 2018-2019. METHODS: Hospital sites and their associated community practices across 12 European countries completed an online survey in 2018-2019, to report on their practices in terms of surveillance, prevention, diagnosis, and treatment of CDI. Responses were collected from 105 hospitals and 39 community general practitioners (GPs). FINDINGS: Hospital sites of 11 countries reported participation in national surveillance schemes compared with six countries for international schemes. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID)-recommended CDI testing methodologies were used by 82% (86/105) of hospitals, however countries reporting the highest incidence of CDI used non-recommended tests. Over 75% (80/105) of hospitals were aware of the most recent European CDI treatment guidelines at the time of this survey compared with only 26% (10/39) of surveyed GPs. However, up to 15% (16/105) of hospitals reported using the non-recommended metronidazole for recurrent CDI cases, sites in countries with lower awareness of CDI treatment guidelines. Only 37% (39/105) of hospitals adopted contact isolation precautions in case of suspected CDI. CONCLUSION: Good awareness of guidelines for the management of CDI was observed across the surveyed European hospital sites. However, low compliance with diagnostic testing guidelines, infection control measures for suspected CDI, and insufficient awareness of treatment guidelines continued to be reported in some countries.

Do probiotics prevent antibiotic-associated diarrhoea? Results of a multicentre randomized placebo-controlled trial.

BACKGROUND: Antibiotic-associated diarrhoea (AAD) is a side-effect of antibiotic consumption and probiotics have been shown to reduce AAD. METHODS: A multicentre, double-blind, placebo-controlled, randomized trial was conducted to evaluate the role of Lactobacillus casei DN114001 (combined as a drink with two regular yoghurt bacterial strains) in reducing AAD and Clostridioides difficile infection in patients aged over 55 years. The primary outcome was the incidence of AAD during 2 weeks of follow-up. RESULTS: A total of 1127 patients (mean age ± standard deviation: 73.6 ± 10.5) were randomized to the active group (N = 549) or placebo group (N = 577). Both groups were followed up as per protocol. The proportion of patients experiencing AAD during follow-up was 19.3% (106/549) in the probiotic group vs 17.9% (103/577) in the placebo group (unadjusted odds ratio 1.10, 95% confidence interval 0.82-1.49, P = 0.53). CONCLUSIONS: No significant evidence was found of a beneficial effect of the specific probiotic formulation in preventing AAD in this elderly population drawn from a number of different UK hospitals. However, in the UK and in many other healthcare systems there have, in recent years, been many changes in antibiotic stewardship policies, an overall decrease in incidence in C. difficile infection, as well as an increased awareness of infection prevention, and modifications in nursing practice. In light of these factors, it is impossible to conclude definitively from the current trial that the study-specific probiotic formulation has no role in preventing AAD, and it is our view that further trials may be indicated, controlling for these variables.

Is there a relationship between the presence of the binary toxin genes in Clostridium difficile strains and the severity of C. difficile infection (CDI)?

Some strains of Clostridium difficile produce a binary toxin, in addition to the main C. difficile virulence factors (toxins A and B). There have been conflicting reports regarding the role of binary toxin and its relationship to the severity of C. difficile infection (CDI). Samples, isolates and clinical data were collected as part of a prospective multicentre diagnostic study. Clostridium difficile isolates (n = 1259) were tested by polymerase chain reaction (PCR) assay to detect binary toxin genes cdtA and cdtB. The PCR binary toxin gene results were compared with clinical severity and outcome data, including 30-day all-cause mortality. The 1259 isolates corresponded to 1083 different patients (October 2010 to September 2011). The prevalence of binary toxin positive strains was significantly higher in faecal samples with detectable toxin A/B than in those without toxin but that were positive by cytotoxigenic culture (26.3% vs. 10.3%, p < 0.001). The presence of binary toxin correlated moderately with markers of CDI severity (white cell count, serum albumin concentration and serum creatinine concentration). However, the risk ratio for all-cause mortality was 1.68 for binary toxin positive patients and patients were significantly less likely to survive if they had CDI caused by a binary toxin gene positive strain, even after adjusting for age (p < 0.001). The presence of binary toxin genes does not predict the clinical severity of CDI, but it is significantly associated with the risk of all-cause mortality.

Phylogenetics of Australasian gall flies (Diptera: Fergusoninidae): Evolutionary patterns of host-shifting and gall morphology.

This study investigated host-specificity and phylogenetic relationships in Australian galling flies, Fergusonina Malloch (Diptera: Fergusoninidae), in order to assess diversity and explore the evolutionary history of host plant affiliation and gall morphology. A DNA barcoding approach using COI data from 203 Fergusonina specimens from 5gall types on 56 host plant species indicated 85 presumptive fly species. These exhibited a high degree of host specificity; of the 40 species with multiple representatives, each fed only on a single host genus, 29 (72.5%) were strictly monophagous, and 11 (27.5%) were reared from multiple closely related hosts. COI variation within species was not correlated with either sample size or geographic distance. However variation was greater within oligophagous species, consistent with expectations of the initial stages of host-associated divergence during speciation. Phylogenetic analysis using both nuclear and mitochondrial genes revealed host genus-restricted clades but also clear evidence of multiple colonizations of both host plant genus and host species. With the exception of unilocular peagalls, evolution of gall type was somewhat constrained, but to a lesser degree than host plant association. Unilocular peagalls arose more often than any other gall type, were primarily located at the tips of the phylogeny, and did not form clades comprising more than a few species. For ecological reasons, species of this gall type are predicted to harbor substantially less genetic variation than others, possibly reducing evolutionary flexibility resulting in reduced diversification in unilocular gallers.

Comparison of the Vidas C. difficile GDH Automated Enzyme-Linked Fluorescence Immunoassay (ELFA) with Another Commercial Enzyme Immunoassay (EIA) (Quik Chek-60), Two Selective Media, and a PCR Assay for gluD for Detection of Clostridium difficile in Fecal Samples.

Prevention and management of Clostridium difficile infection (CDI) can be improved by rapid and reliable diagnostics. The Vidas C. difficile glutamate dehydrogenase assay had performance comparable to that of the Quik Chek-60 assay (overall agreement, 95%) and a sensitivity of >93%; thus, it is suitable as the first test in two-stage algorithms for a CDI diagnosis.

De novo Cryoglobulinaemic Mononeuritis Multiplex during Treatment of Chronic Hepatitis C Infection: A Viral Effect or Induced by Pegylated Interferon Alpha?

Cryoglobulinaemic mononeuritis multiplex (MNM) is an extrahepatic manifestation of chronic hepatitis C virus (HCV) infection for which interferon-based antiviral therapy is currently the treatment of choice. Rarely MNM can be associated with HCV treatment though generally in the setting of pre-existing cryoglobulinaemia and detectable HCV viraemia. We report an unusual case of de novo MNM occurring late during the course of pegylated interferon and ribavirin therapy for chronic HCV infection, following a prolonged period of viral suppression. The patient had no evidence of cryoglobulinaemia prior to HCV treatment and undetectable HCV RNA levels at the time of presentation with MNM. The case raises the possibility that MNM could develop as an adverse immunomodulatory effect of pegylated interferon therapy.

Insecure attachment style is associated with chronic widespread pain.

Individuals with "insecure" adult attachment styles have been shown to experience more pain than people with secure attachment, though results of previous studies have been inconsistent. We performed a cross-sectional study on a large population-based sample to investigate whether, compared to pain free individuals, subjects with chronic widespread pain were more likely to report insecure adult attachment style. Subjects in a population-based cross-sectional study completed a self-rated assessment of adult attachment style. Attachment style was categorised as secure (i.e., normal attachment style); or preoccupied, dismissing or fearful (insecure attachment styles). Subjects completed a pain questionnaire from which three groups were identified: pain free; chronic widespread pain; and other pain. Subjects rated their pain intensity and pain-related disability on an 11 point Likert scale. Subjects (2509) returned a completed questionnaire (median age 49.9 years (IQR 41.2-50.0); 59.2% female). Subjects with CWP were more likely to report a preoccupied (RRR 2.6; 95%CI 1.8-3.7), dismissing (RRR 1.9; 95%CI 1.2-3.1) or fearful attachment style (RRR 1.4; 95%CI 1.1-1.8) than those free of pain. Among CWP subjects, insecure attachment style was associated with number of pain sites (Dismissing: RRR 2.8; 95%CI 1.2-2.3, Preoccupied: RRR=1.8, 95%CI 0.98-3.5) and degree of pain-related disability (Preoccupied: RRR=2.1, 95%CI 1.0-4.1), but not pain intensity. These findings suggest that treatment strategies based on knowledge of attachment style, possibly using support and education, may alleviate distress and disability in people at risk of, or affected by, chronic widespread pain.

Premorbid psychosocial factors are associated with poor health-related quality of life in subjects with new onset of chronic widespread pain - results from the EPIFUND study.

Chronic widespread pain (CWP) is associated with poor health-related quality of life (HRQoL). It is unclear whether pain itself is the cause of poor HRQoL or other factors play a role. We hypothesised that new onset of CWP was associated with poor physical and mental HRQoL but that psychosocial risk markers for CWP onset would explain this relationship. A prospective population-based survey measured pain and psychosocial status at baseline. Subjects free of CWP at baseline were followed up 15 months later, when pain status, threatening life events and HRQoL (SF-12) were assessed. The risk associated with the new onset of CWP and reporting poor SF12-MCS and SF12-PCS was quantified using multinomial logistic regression (relative risk ratios (RRRs) with 95% confidence intervals (95% CI)), adjusted for age and gender. 3000 subjects (77%) free of CWP at baseline participated at follow-up. 2650 subjects (88%) provided full SF-12 and pain data and formed the cohort for this analysis. 9.4% of subjects (n=248) reported new CWP. New CWP was associated with an increased risk of having the poorest SF12-MCS (RRR=2.3; 95% CI 1.6-3.2) and SF12-PCS (RRR=8.0; 95% CI 5.4-11.8) scores. After adjusting for baseline psychosocial status, the relationship between CWP onset and SF12-MCS was attenuated (RRR=1.2; 95% CI 0.8-1.8), although the association with SF12-PCS remained (RRR=4.8% CI 3.1-7.47). New onset of CWP is associated with poor mental and physical HRQoL. However, the relationship with mental HRQoL is explained by psychosocial risk markers.

Restorative sleep predicts the resolution of chronic widespread pain: results from the EPIFUND study.

OBJECTIVES: Poor sleep is associated with chronic widespread pain (CWP). Conversely, good-quality sleep may play a role in the resolution of pain symptoms. Sleep is a multidimensional construct, comprising a number of diverse components. The aims of the current study were to examine the hypotheses that: (i) good sleep quality would predict the resolution of CWP, (ii) restorative sleep would predict the resolution of CWP and (iii) that these relationships would be independent of confounding psychological factors. METHODS: Subjects in a population-based prospective study completed a pain questionnaire at baseline from which subjects with CWP were identified. Baseline sleep was measured using the Estimation of Sleep Problems Scale which measures sleep onset, maintenance, early wakening and restorative sleep. The questionnaire also contained scales examining psychosocial status. Subjects were followed up 15 months later and pain status was assessed. RESULTS: A total of 1061 subjects reported CWP at baseline of whom 679 (75% of eligible subjects) responded at follow-up. Of those, a total of 300 (44%) no longer satisfied criteria for CWP. Univariate analysis revealed that three of the four sleep components were associated with the resolution of CWP: rapid sleep onset, odds ratio (OR) = 1.7, 95% CI 1.2, 2.5; absence of early wakening, OR = 1.6, 95% CI 1.1, 2.4; and restorative sleep, OR = 2.7, 95% CI 1.5, 4.8. After adjusting for the effect of psychosocial factors, which may have confounded the relationship, only restorative sleep (OR = 2.0, 95% CI 1.02, 3.8) was associated. CONCLUSIONS: Self-reported restorative sleep was independently associated with the resolution of CWP and return to musculoskeletal health.

Peritoneal mesothelioma: an unusual cause of an acute phase response presenting to the rheumatologist.

The presence of an acute phase response may pre-date the eventual diagnosis of malignant disease by months or even years. We describe two patients referred to the rheumatology clinic, in which extensive investigation failed to identify an underlying cause to account for the presenting symptoms and an associated acute phase response. Several months later, repeated abdominal CT scans revealed an abnormality and subsequent laparoscopic biopsy confirmed a diagnosis of peritoneal mesothelioma.

Both Fcgamma and complement receptors mediate transfer of immune complexes from erythrocytes to human macrophages under physiological flow conditions in vitro.

Abnormal clearance by the mononuclear phagocytic system of immune complexes (IC) is important in the pathogenesis of systemic lupus erythematosus (SLE). We have developed an in vitro model to investigate the cellular mechanisms involved in the transfer of soluble IC from erythrocytes to human macrophages under physiological flow conditions. In this assay, erythrocytes bearing fluorescently labelled IC are perfused over monolayers of human monocytes or monocyte-derived macrophages in a parallel-plate flow chamber, and transfer quantified using confocal microscopy and flow cytometry. Using aggregated human IgG as a model IC, we have been able to demonstrate transfer of IC from erythrocytes to macrophages. Blocking studies with specific neutralizing antibodies have shown that both complement and Fcgamma receptors are required for IC transfer. Blockade of CR4 (alpha(x)beta(2) integrin), FcgammaRIIa or FcgammaRIII reduced transfer, while anti-CR3 (alpha(m)beta(2) integrin) had no effect. Blockade of CR3, FcgammaRIIa or FcgammaRIII also reduced the number of adhesive interactions between fluorescently labelled IC-bearing erythrocytes and macrophage monolayers. Taken together with the transfer data, this suggests differing roles for these receptors in the human IC transfer reaction that includes an adhesive function which facilitates IC processing by mononuclear phagocytes. Finally, a functional effect of the FcgammaRIIa R131/H131 polymorphism, important in susceptibility to SLE, has also been demonstrated using this model. Uptake of IgG(2) but not IgG(1)-containing soluble IC was reduced by macrophages from individuals homozygous for the R131 allelic variant of the receptor.

Takayasu's arteritis: a cause of prolonged arterial stiffness.

OBJECTIVES: Cardiovascular disease is a major cause of mortality and morbidity in patients with Takayasu's arteritis (TA). Increased arterial stiffness is an independent risk factor and predictor of cardiovascular mortality in a variety of diseases. Pulse wave velocity (PWV) and the augmentation index (AI) are used as clinical measurements of arterial stiffness. METHODS: Data are presented from 10 patients with TA and 11 normal controls obtained between 2000 and 2004. Arterial compliance was assessed non-invasively by measurement of PWV, using the Complior system, and calculation of the aortic AI. RESULTS: TA patients (mean age 40.8+/-13.2 yr) were compared with a control group of healthy women from a parallel study (mean age 32.3+/-5.5 yr). The mean carotid-femoral PWV (PWV-CF) was higher in TA patients (P = 0.03). In addition, both aortic AI derived from the radial artery (P = 0.002) and carotid AI (P = 0.03) were higher in TA patients compared with controls. PWV-CF did not correlate with CRP (r = - 0.23, P = 0.23) or ESR (r = - 0.19, P = 0.27). Similar results were obtained for the correlation of carotid-radial PWV with CRP (r = 0.15, P = 0.32) and ESR (r = 0.33, P = 0.14). CONCLUSIONS: Our data show that TA is associated with elevated arterial stiffness in the central aorta, which may persist when the disease is quiescent. These data suggest that PWV represents a means by which cardiovascular risk can be detected and monitored in TA, and highlights the importance of effective management of cardiovascular risk factors in these patients.

Clinical significance of IgA anticardiolipin and anti-beta2-GP1 antibodies in patients with systemic lupus erythematosus and primary antiphospholipid syndrome.

The objectives of this study were to estimate the prevalence of IgA anticardiolipin antibodies (aCL) and anti-beta(2)-glycoprotein 1 antibodies (abeta(2)-GP1) in a large number of patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (PAPS) and to examine possible associations between the clinical manifestations of the APS and the levels of IgA aCL and abeta(2)-GP1. We also assessed the operative characteristics of IgA aCL and abeta(2)-GP1. We retrospectively studied 130 patients with SLE and 35 patients with PAPS. In all patients we measured IgG, IgM, and IgA aCL and abeta(2)-GP1 and recorded any of the clinical manifestations of the APS. IgA aCL were positive in 8.5% of patients with SLE and in 40% of patients with PAPS. Positive IgA abeta(2)-GP1 were found in 17.7% of patients with SLE and in 25.7% of patients with PAPS. IgA aCL were associated with a history of venous thrombosis, thrombocytopenia, and recurrent fetal loss. In contrast, we could not establish significant associations between IgA abeta(2)-GP1 and any of the clinical manifestations of the APS. Measurement of the IgA in addition to IgG and IgM aCL hardly changed the operative characteristics of aCL testing, while measurement of the IgA in addition to IgG and IgM abeta(2)-GP1 increased sensitivity but with a greater loss in specificity. IgA aCL is significantly associated with more than one of the clinical manifestations of the APS in contrast to the IgA abeta(2)-GP1. Routine measurement of the IgA isotype of both aCL and abeta(2)-GP1 does not improve the operative characteristics of aCL and abeta(2)-GP1 and therefore is not recommended at present.

Non-invasive imaging in the diagnosis and management of Takayasu's arteritis.

OBJECTIVES: Takayasu's arteritis (TA) is a rare disease, in which early diagnosis and assessment of treatment efficacy remain a problem. Signs and symptoms may be non-specific and conventional blood tests unreliable, with vascular inflammation often persisting in the face of a normal acute phase response. The current "gold standard" investigation, x ray angiography, is invasive and only identifies late, structural changes in vessels. Recently, non-invasive imaging methods have shown promise in the assessment of patients with TA. METHODS: The invasive and non-invasive imaging performed on all patients in the rheumatology department at the Hammersmith Hospital between May 1996 and May 2002 who fulfilled the ACR criteria for TA were reviewed. All patients were clinically active at diagnosis and were treated with high dose oral prednisolone and additional oral or intravenous immunosuppression. RESULTS: Non-invasive imaging methods ([(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) and magnetic resonance imaging (MRI)) provided important additional information about disease activity ([(18)F]FDG-PET) and progression of vessel wall thickening (MRI) when compared with x ray angiography. CONCLUSIONS: Non-invasive imaging methods provide useful additional information towards the diagnosis and management of TA. Such techniques may allow earlier diagnosis and more accurate assessment of response to treatment than conventional clinical assessment and/or angiography. Non-invasive imaging is likely to be useful in the management of other large vessel vasculitides.

Expression of Fcgamma and complement receptors on peripheral blood monocytes in systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVES: Fcagamma and complement receptors play an important role in the interaction between immune complexes (IC) and monocytes/macrophages. Recent work has demonstrated that their relative expression on these cells may be modified by cytokines, including TNF-alpha and IL-4. Furthermore, cytokines may alter the expression of adhesion molecules such as ICAM-1. However, little data exist on the in vivo expression of specific Fcgamma and complement receptors in systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), two diseases in which IC are important in pathogenesis. METHODS: Venous blood was obtained from 30 patients with SLE, 25 with RA and 25 healthy controls. Monocyte phenotype was determined by flow cytometric analysis of whole blood samples, with selective gating using forward and side scatter signals. Surface expression of Fcgamma receptors RI (CD64), RII (CD32) and RIII (CD16), complement receptors CR1 (CD35) and CR3 (CD11b/CD18), and adhesion molecules ICAM-1 (CD54) and CD11a (LFA-1) was determined. The effects of disease activity and corticosteroid therapy on the expression of these molecules were also examined. RESULTS: The expression of FcgammaRII was reduced on monocytes from patients with SLE compared with healthy controls and patients with RA (P = 0.002). This did not correlate with disease activity using conventional indices [SLEDAI (SLE disease activity index), C3/C4 levels and anti-double-stranded DNA antibody titres], and was independent of prednisolone therapy. There was no significant difference in FcgammaRI or RIII expression on SLE monocytes compared with healthy controls. In contrast, the expression of FcgammaRIII was increased on RA monocytes (P = 0.01), this being highest in patients with active disease. The proportion of FcgammaRIII-positive monocytes was also increased in RA, and prednisolone therapy was associated with a lower proportion of FcgammaRIII-positive cells. An increase in CR3 expression was seen on RA monocytes (P = 0.002), whilst CR1 was increased on monocytes from patients with active SLE or active RA. ICAM-1 expression was reduced on monocytes from patients with SLE (P = 0.002), although high-dose prednisolone therapy was associated with the lowest level of surface ICAM-1 on monocytes. CONCLUSIONS: Peripheral blood monocytes from patients with SLE or RA display significantly altered phenotypes compared with those from healthy controls. The observed reduction in SLE of FcgammaRII may represent a mechanism by which monocytes are protected from IC-mediated activation. Prednisolone therapy and disease activity had little effect on phagocytic receptor expression. The observed changes may reflect the different cytokine profiles seen in SLE and RA.

Histological comparisons of fergusobia/fergusonina-induced galls on different myrtaceous hosts.

The putative mutualism between different host-specific Fergusobia nematodes and Fergusonina flies is manifested in a variety of gall types involving shoot or inflorescence buds, individual flower buds, stems, or young leaves in the plant family Myrtaceae. Different types of galls in the early-to-middle stages of development, with host-specific species of Fergusobia/Fergusonina, were collected from Australian members of the subfamily Leptospermoideae (six species of Eucalyptus, two species of Corymbia, and seven species of broad-leaved Melaleuca). Galls were sectioned and histologically examined to assess morphological changes induced by nematode/fly mutualism. The different gall forms were characterized into four broad categories: (i) individual flower bud, (ii) terminal and axial bud, (iii) 'basal rosette' stem, and (iv) flat leaf. Gall morphology in all four types appeared to result from species-specific selection of the oviposition site and timing and number of eggs deposited in a particular plant host. In all cases, early parasitism by Fergusobia/Fergusonina involved several layers of uninucleate, hypertrophied cells lining the lumen of each locule (gall chamber where each fly larva and accompanying nematodes develop). Hypertrophied cells in galls were larger than normal epidermal cells, and each had an enlarged nucleus, nucleolus, and granular cytoplasm that resembled shoot bud gall cells induced by nematodes in the Anguinidae.

Antibody-mediated glomerulonephritis in mice: the role of endotoxin, complement and genetic background.

Antibody-mediated glomerulonephritis in man may be exacerbated by infection and this effect may be mediated by bacterial endotoxin. There is evidence supporting a role for endotoxin in heterologous nephrotoxic nephritis in rats, but the role of endotoxin in this model in mice has not previously been explored. Previous data in mice on the role of complement in this model are conflicting and this may be due to the mixed genetic background of mice used in these studies. We used the model of heterologous nephrotoxic nephritis in mice and explored the role of endotoxin, complement and genetic background. In this study we show a synergy between antibody and endotoxin in causing a neutrophil influx. We also show that C1q-deficient mice have an increased susceptibility to glomerular inflammation but this is seen only on a mixed 129/Sv x C57BL/6 genetic background. On a C57BL/6 background we did not find any differences in disease susceptibility when wildtype, C1q, factor B or factor B/C2 deficient mice were compared. We also demonstrate that C57BL/6 mice are more susceptible to glomerular inflammation than 129/Sv mice. These results show that endotoxin is required in this model in mice, and that complement does not play a major role in glomerular inflammation in C57BL/6 mice. C1q may play a protective role in mixed-strain 129/Sv x C57BL/6 mice, but the data may also be explained by systematic bias in background genes, as there is a large difference in disease susceptibility between C57BL/6 and 129/Sv mice.

Complement components and their autoantibodies.

The purpose of the immune system is to defend the host from constantly changing microbial pathogens. Autoimmune diseases develop as a consequence of the production of antibodies and/or cells that react with self-antigens, and may recruit other effector mechanisms that result in tissue damage. Thus, in this context, autoimmunity represents an immune response to self-antigens that is sufficient to cause disease. This article is specifically devoted to autoantibodies directed against complement components.

Evolution of Parasitism in Insect-transmitted Plant Nematodes.

Nematode-insect associations have evolved many times in the phylum Nematoda, but these lineages involve plant parasitism only in the Secernentean orders Aphelenchida and Tylenchida. In the Aphelenchida (Aphelenchoidoidea), Bursaphelenchus xylophilus (Pine wood nematode), B. cocophilus (Red ring or Coconut palm nematode) (Parasitaphelenchidae), and the many potential host-specific species of Schistonchus (fig nematodes) (Aphelenchoididae) nematode-insect interactions probably evolved independently from dauer-forming, mycophagous ancestors that were phoretically transmitted to breeding sites of their insect hosts in plants. Mycophagy probably gave rise to facultative or obligate plant-parasitism because of opportunities due to insect host switches or peculiarities in host behavior. In the Tylenchida, there is one significant radiation of insect-associated plant parasites involving Fergusobia nematodes (Fergusobiinae: Neotylenchidae) and Fergusonina (Fergusoninidae) flies as mutualists that gall myrtaceous plant buds or leaves. These dicyclic nematodes have different phases that are parasitic in either the insect or the plant hosts. The evolutionary origin of this association is unclear.