Brief Report: Determinants of Potential Sexual Activity Reduction in the Face of the Mpox Epidemic.

BACKGROUND: The current mpox epidemic is most prevalent among men-who-have-sex-with-men (MSM). Vaccination programs are being rolled-out to curb the epidemic. Behavioural measures have been called for as well, for example, by the WHO and national public health authorities to reduce the number of sexual partners and sexual activity. We investigated intentions and determinants among Dutch MSM to follow such behavioural measures. METHODS: Early in July 2022, in the context of a dynamic ongoing epidemic, 394 MSM answered an online questionnaire investigating concepts such as perceived mpox risk, vaccination and behavioural change intentions and collecting socio-demographic and sexual behaviour information. RESULTS: The overall intentions to reduce number of partners and sexual activity were high, but only a minority had developed definite intentions. Determinant analysis revealed that dating/open relationship status was a positive predictor; vaccination intentions did not predict sexual behaviour change; those not on PrEP were more likely to change their sexual behaviour. Mpox infection concern was the main predictor for behaviour change intentions. CONCLUSIONS: Our results show that behavioural measures to avoid an mpox infection are present in majority of participants in our survey, but high intentions are held by a minority. Taking the historic complexity of behavioural change pleas among MSM into account sensitive, additional public health measures are necessary to reach and to inform MSM about potential benefits of sexual behaviour change.

Perceived Monkeypox Concern and Risk among Men Who Have Sex with Men: Evidence and Perspectives from The Netherlands.

The current monkeypox epidemic is most prevalent among men who have sex with men (MSM). PrEP users and MSM with HIV (MSMHIV) are considered at highest risk of monkeypox infection in The Netherlands, and are being targeted for monkeypox vaccination. Together with the epidemiological evidence, perceived concern and risk are also relevant for decision making about health behaviour, e.g., vaccination uptake. It is thus timely to examine which subpopulations among MSM consider themselves to be most at risk and are most concerned about monkeypox. This study aimed to help determine if the current measures to curb the epidemic are successfully targeted or not in The Netherlands. We conducted an online survey among 394 MSM living in The Netherlands. We first calculated the prevalence and standardised prevalence ratio (SPR) of high perceived monkeypox concern/risk by PrEP-use and HIV status. We then conducted two multivariable logistic regression analyses to investigate perceived monkeypox concern/risk and their potential socio-demographic/behavioural/health/psycho-social determinants. Among the included MSM, 52% showed high perceived concern about and 30% showed high perceived risk of monkeypox infection. PrEP users (SPR = 0.83) showed a significantly lower chance of perceived concern; in addition, MSMHIV (SPR = 2.09) were found to have a significantly higher chance of perceiving high risk of monkeypox infection. In the multivariable logistic analyses, non-PrEP users (aOR = 2.55) were more likely to perceive higher concern, while MSM who were retired (aOR = 0.23) and who had had chemsex recently (aOR = 0.63) were less likely to perceive higher concern. MSMHIV (aOR = 4.29) and MSM who had an unknown/undisclosed HIV status (aOR = 6.07), who had attended private sex parties (aOR = 2.10), and who knew people who have/had monkeypox (aOR = 2.10) were more likely to perceive a higher risk for monkeypox infection. We found that high perceived risk (aOR = 2.97) and high perceived concern (aOR = 3.13) were correlated with each other. In sum, only one-third of MSM living in The Netherlands considered themselves at high risk of monkeypox infection, and only half of them reported high concern. We identified a potential discrepancy between "actual risk" and perceived risk of and concern about monkeypox among MSM in this early stage of the monkeypox epidemic in The Netherlands, especially among PrEP users and MSMHIV. More refined public health communication strategies may be needed to improve the understanding and knowledge of the "actual risk" of monkeypox infections among MSM sub-populations, to facilitate health behaviour uptake.

Monkeypox self-diagnosis abilities, determinants of vaccination and self-isolation intention after diagnosis among MSM, the Netherlands, July 2022.

Monkeypox is a zoonotic disease and leads to a smallpox-like disease in humans. The current epidemic in European countries requires informed responses. We investigated the ability to self-diagnose a potential infection, and determinants of vaccination and self-isolation intention after diagnosis among 394 MSM in the Netherlands. We found that about half were able to self-diagnose monkeypox, that 70% had a high intention to get vaccinated and 44% to self-isolate after monkeypox diagnosis. Determinants went beyond mere risk behaviour criteria.

Vitamin A is excreted in the urine during acute infection.

Episodes of acute infection are thought to deplete body stores of vitamin A. The mechanism by which this might occur is not known, but increased metabolic requirements are presumed to play a role. We have found, however, that significant amounts of retinol and retinol-binding protein (RBP) were excreted in the urine during serious infections, whereas only trace amounts were found in the urine of healthy control subjects. The geometric mean excretion rate in 29 subjects with pneumonia and sepsis was 0.78 mumol retinol/d. Subjects with fever (temperature > or = 38.3 degrees C) excreted significantly more retinol (geometric mean = 1.67 mumol/d) than did those without fever (0.18 mumol/d; t = 3.53, P < 0.0015). Aminoglycoside administration and low glomerular filtration rates (< 35 mL/min) were also associated with higher rates of urinary retinol excretion. Thirty-four percent of patients excreted > 1.75 mumol retinol/d, equivalent to 50% of the US recommended dietary allowance. These data show that vitamin A requirements are substantially increased during serious infections because of excretion of retinol in the urine, and suggest that these losses are due to pathologic changes associated with the febrile response.

Alteration of cellular cytosolic calcium and chemotactic peptide binding by an inhibitor of neutrophil function.

The lung is frequently exposed to particulate material that can potentially stimulate release of factors that attract polymorphonuclear neutrophils (PMN). However, few PMN are noted in the airways of normal subjects, suggesting there is some mechanism to dampen influx of these cells. We have isolated from bronchial lavage a peptide that inhibits PMN chemotaxis to formyl-methionyl-leucyl-phenylalanine (FMLP). In the present study we examined effects of this molecule on 1) chemotaxis to other agonists, 2) FMLP-stimulated PMN superoxide production, 3) PMN calcium fluxes, and 4) binding of FMLP. Our results show that purified inhibitor attenuates PMN chemotaxis to C5a and leukotriene B4. This molecule also inhibits PMN superoxide release in response to FMLP. Exposure to this inhibitor causes an abrupt rise in cytosolic calcium concentration due to a pertussis toxin-sensitive shift of intracellular calcium and attenuates subsequent influx of extracellular calcium in response to FMLP. Binding studies demonstrate the inhibitor induces increased FMLP binding at 37 degrees C but has no effects at 4 degrees C. Inhibition of chemotaxis and increased FMLP binding mediated by this molecule are attenuated by buffering PMN calcium transients. These studies suggest an inhibitor of neutrophil function present in the bronchial environment alters PMN through effects on calcium homeostasis.

Bronchiolitis obliterans organizing pneumonia associated with systemic lupus erythematosus.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a pathologic entity characterized by the formation of plugs of fibrous tissue in bronchioles and alveolar ducts. It has been described in association with several connective tissue diseases including rheumatoid arthritis, polymyositis-dermatomyositis, and mixed connective tissue disease. Well-documented reports of BOOP in patients with systemic lupus erythematosus (SLE) are limited. We report two patients with SLE who presented with subacute respiratory illnesses due to BOOP, adding further strength to the association of this entity with SLE.

Clinical aspects of amiodarone pulmonary toxicity.

Amiodarone pulmonary toxicity is a major clinical problem limiting the utility of this powerful therapeutic agent. The clinical manifestations of amiodarone lung toxicity are protean, but the most common presentation is that of an indolent illness characterized by dyspnea and often associated with cough and/or fever. Diffuse radiographic abnormalities are common, but localized infiltrates can be seen as well. The typical physiologic changes are the development of diffusing impairment and a restrictive ventilatory defect. In the absence of a 15% decline in DLCO from the pretreatment value, significant amiodarone toxicity appears to be unlikely. The diagnosis is made by the careful exclusion of other causes for the observed illness and the finding of clinical, radiographic, physiologic, and pathologic abnormalities compatible with amiodarone toxicity. Although the pathologic findings of amiodarone lung can be distinctive, the histologic demonstration of foam cells and ultrastructural lamellar inclusions alone does not distinguish toxic from nontoxic patients receiving amiodarone. If reasonable alternative antiarrhythmic therapy is available, amiodarone should be withdrawn. If the severity of illness warrants, a trial of corticosteroid therapy is reasonable. Some patients can be maintained on continued therapy despite toxicity, if the drug is deemed to be absolutely essential and clinical deterioration does not continue. The prognosis of patients who develop amiodarone pulmonary toxicity seems to be poor, but may be largely determined by the underlying cardiac disease.

Dietary fish oil inhibits bleomycin-induced pulmonary fibrosis in the rat.

Intratracheal bleomycin induces pulmonary fibrosis in experimental animals, but the mechanisms involved are poorly understood. Since altered levels of fatty acid metabolites are associated with bleomycin-induced lung injury, we examined the effects of a change in dietary fat on bleomycin-induced fibrosis. Previously we have shown that an essential fatty acid-deficient diet can reduce the severity of bleomycin-induced pulmonary fibrosis. The present study examined the effect of replacement of usual dietary fat with menhaden oil, rich in eicosapentaenoic acid, on the development of pulmonary fibrosis. Weanling rats were raised on a standard laboratory diet or a diet consisting of a fat-free powder to which was added 25% (w/w) of menhaden oil. After 8 weeks of feeding, the animals received either 1.5 units of bleomycin or an equivalent volume of saline intratracheally. In animals receiving the laboratory diet, bleomycin treatment produced a 44% increase in total lung protein content when compared to saline-treated controls (p less than 0.001) and a 77% increase in total lung hydroxyproline content (p less than 0.01). In contrast, bleomycin-treated animals receiving the menhaden oil diet had only small increases, which did not reach statistical significance, in protein and hydroxyproline content in the lung. Bronchoalveolar lavage cellularity did not differ among the treatment groups, but the percentage of lavage macrophages was slightly diminished in bleomycin-treated animals receiving the laboratory diet. Cellular differentials of lavage fluid did not differ significantly between bleomycin- and saline-treated animals receiving the menhaden oil diet. Bleomycin-induced histologic changes, quantitated by morphometric analysis, were significantly reduced with the menhaden oil diet. We conclude that a diet rich in eicosapentaenoic acid can significantly ameliorate bleomycin-induced pulmonary fibrosis, possibly via alterations in eicosanoid metabolism.

Effect of iron deficiency on bleomycin-induced lung fibrosis in the hamster.

Bleomycin produces a dose- and time-dependent interstitial pulmonary fibrosis in humans, and is widely used to produce an animal model for the study of interstitial pulmonary fibrosis. The mechanism(s) for bleomycin-induced pulmonary fibrosis is (are) unknown, but the production of oxygen radicals by a ferrous ion-molecular oxygen pathway might be related to the fibrosis. Therefore, we studied the effect of iron deficiency on the biochemical, inflammatory, and morphologic parameters of bleomycin-induced pulmonary fibrosis in the hamster. Mild iron deficiency was induced in hamsters by bleeding via the retro-orbital sinus and maintenance on an iron-deplete diet. After intratracheal administration of bleomycin (1 U), there was no accumulation of lung collagen in the iron-deficient bleomycin-treated animals. In comparison, iron-replete animals treated with bleomycin exhibited a significant (p less than 0.01) increase in lung collagen. In addition, bleomycin-treated iron-replete animals had increased lung lipid peroxidation (p less than 0.05), whereas bleomycin-treated iron-deficient animals did not (p greater than 0.05). Lung DNA and morphometric estimates of the lesion severity were significantly increased in both iron-replete and iron-deficient bleomycin-treated animals. These data indicate that iron deficiency is associated with a reduction in the severity of bleomycin-induced pulmonary fibrosis, possibly by the prevention of iron-catalyzed oxygen-radical formation and lipid peroxidation.

Amiodarone lung: pathologic findings in clinically toxic patients.

Lung biopsy and autopsy specimens of 12 patients with amiodarone pulmonary toxicity were studied to better characterize the pathology of amiodarone lung. For comparison, the autopsy specimens of five patients taking amiodarone without pulmonary side effects also were examined. Interstitial pneumonia was the most common manifestation of amiodarone lung and was characterized by interstitial inflammation, fibrosis, and hyperplasia of type II pneumocytes. Hyaline membranes were present in two cases. Foamy alveolar macrophages were present in all but one patient, and in four associated organizing pneumonia was present. Foamy alveolar macrophages also were present in three of five clinically nontoxic patients. Electron microscopy demonstrated membrane-bound lamellar inclusions in all of the three cases of amiodarone lung examined. Inclusions also were present in two of five patients who died of other causes. The authors conclude that amiodarone lung is primarily an interstitial pneumonia. Foamy alveolar macrophages and cytoplasmic lamellar inclusions are characteristic, but neither is specific, and their presence alone does not distinguish toxic from nontoxic patients.

Amiodarone pulmonary toxicity. Clinical, radiologic, and pathologic correlations.

We have studied 15 patients with amiodarone pulmonary toxicity and compared them with five amiodarone patients without evidence of toxic effect. Six of 15 patients who had toxic reactions presented with an acute illness that resembled an infectious disease. While diffuse interstitial disease was frequent on chest roentgenogram, seven of 15 had airspace opacities, and five had well-localized infiltrates. Physiologic changes were not uniformly found. An interstitial pneumonia with foamy alveolar macrophages was the most common pathologic finding. Foamy macrophages were also present in three of five nontoxic patients. Three of three patients who had toxic reactions, and two of five patients without toxic reactions had lamellated inclusion bodies by electron microscopy. We conclude that all features of amiodarone toxicity are protean, and it may mimic infectious diseases. While pathologic changes are often characteristic, neither foamy alveolar macrophages nor lamellated cytoplasmic inclusions reliably distinguish toxic from nontoxic patients.

Effects of dietary fats on bleomycin-induced pulmonary fibrosis.

Bleomycin treatment has been used for the experimental induction of pulmonary fibrosis, but the mechanisms involved are poorly understood. Since alterations in the levels of certain fatty acid metabolites have been associated with bleomycin-induced lung injury, we examined the effects of different dietary fats on the development of bleomycin-induced pulmonary fibrosis. Weanling rats were raised on standard laboratory feed or a diet consisting of a fat-free powder to which was added either coconut oil or beef tallow (25% w/w). After 8 weeks of feeding, animals received either 1.5 units bleomycin or an equivalent volume of saline intratracheally. Bleomycin treatment resulted in significant increases in total lung hydroxyproline content in the groups fed the standard lab diet (p less than 0.001) and beef tallow diet (p less than 0.001), but not in the group receiving the coconut oil diet. Furthermore, the lung hydroxyproline content in bleomycin-treated animals was less with the beef tallow diet compared with standard lab feed (p less than 0.05). Bleomycin treatment resulted in an increase in thiobarbituric acid-reactive products, an index of lipid peroxidation, in lungs from animals fed the standard lab diet, but not in the other diet groups. The percentage of diseased lung, as determined by morphometric analysis, was increased in bleomycin-treated animals from all diet groups (p less than 0.05). We conclude that alterations in dietary fats can reduce the severity of pulmonary fibrosis resulting from bleomycin treatment. Possible mechanisms for this effect include alterations in eicosanoid metabolism or changes in immune or effector cell function.

Studies of membrane receptors, phagocytosis, and morphology of subpopulations of rat lung interstitial macrophages.

Recent data suggest that pulmonary macrophages may be heterogeneous. Several studies have demonstrated that alveolar macrophages are functionally and biochemically heterogeneous. In addition, interstitial macrophages, which are believed to be the precursors to alveolar macrophages, have been suggested to be heterogeneous. Therefore, this study was undertaken to determine if density-defined interstitial macrophages (DD-IM) are heterogeneous with respect to receptors for zymosan, immunoglobulin, and complement as well as morphologically. Furthermore, avidity for IgG was defined by opsonizing sheep red blood cells (SRBC) with different amounts of IgG. Interstitial macrophages were harvested and separated into 18 DD-IM subpopulations by centrifugation through a continuous iso-osmotic gradient of colloidal silica. Interstitial macrophages showed marked heterogeneity in cellular volume. Furthermore, macrophages of density 1.046 to 1.075 g/ml exhibited higher receptor activity capability of attaching and phagocytizing SRBC opsonized with small amounts of IgG and towards zymosan. All DD-IM exhibited similar abilities to attach complement-coated SRBC. These results demonstrate the functional heterogeneity of interstitial macrophages with respect to IgG and zymosan.

Effects of central administation of probenecid on fevers produced by leukocytic pyrogen and PGE2 in the rabbit.

1. Single intracerebroventricular (I.C.V.) injections of probenecid (PBCD, 0.125--0.5 mg) enhanced and prolonged fever caused by I.V. administration of leukocytic pyrogen (LP) in rabbits resting in neutral (23 degrees C), cold (10 degrees C) and hot (30 degrees C) environments. Similar effects were produced by single I.C.V. injections of PBCD given before PGE2 (0.5 microgram) was injected I.C.V. in the three ambient temperatures. 2. Fever produced by IV. LP was also prolonged by infusion and by multiple injections of PBCD. 3. PBCD given I.P. (100 mg/kg) enhanced and prolonged fever caused by I.V. injection of Salmonella typhosa endotoxin. 4. Hyperthermia produced by I.C.V. PGE2 was not augmented by subsequent PBCD infusion. However, pre-treatment with PBCD followed by PGE2 injection and PBCD infusion caused hyperthermia that was very high and prolonged, and, in some cases, lethal. 5. Acetaminophen (2 mg, I.C.V.) and indomethacin (10 mg/kg, I.V.) lowered body temperature when given during fever induced by LP and prolonged by PBCD infusion. 6. The concentration of PGE in cerebrospinal fluid (c.s.f.) samples taken from the third or lateral ventricles rose or stabilized during PBCD infusions made during LP fever. However, similar changes in PGE concentration also occurred during control infusions when body temperature was low. 7. We conclude that termination of the actions of both central endogenous pyrogen and centrally administered PGE2, and the subsequent reduction of fevers produced by them, require a PBCD-sensitive facilitated transport system. The reduction of PBCD-prolonged PL fevers by antipyretics which block PGE synthesis suggests that prolongation by PBCD of LP fever is not due to blockade of PGE transport in a subsequent step in fever mediation per se, but is due to inhibition of transport of LP itself, or of other mediators associated with it.

Central thermosensitivity during fever produced by intra-PO/AH and intravenous injections of pyrogen.

Squirrel monkeys with thermodes implanted in the preoptic/anterior hypothalamic (PO/AH) region and the medulla oblongata were used to examine three questions about central thermoresponsiveness in fever: Does thermoresponsiveness of the PO/AH region and medulla change during fevers caused by injection of bacterial endotoxin IV or directly into the PO/AH region? Does thermosensitivity of these brain regions determine the upper fever limit? Is thermoresponsiveness of the PO/AH region affected by local injections of salicylate? Changes in rectal temperature and oxygen consumption in response to heating and cooling the PO/AH region were reduced during fever caused by intra-PO/AH injections of bacterial endotoxin compared with changes produced during afebrile periods. PO/AH thermosensitivity was also reduced during fever caused by IV administration of bacterial pyrogen. Prolonged cooling of the PO/AH region or the medulla oblongata during fever produced by peripheral and central pyrogen injections did not cause rectal temperature (Tre) to rise above 41.1 degrees C although local heating reduced Tre or limited the fever maximum. From the latter result it is concluded that both pools of central thermoreceptors can limit maximal fever by reacting to local high temperature but that lowered temperature in neither region can raise Tre above a level determined by antagonistic input from thermoreceptors in other parts of the body. Injections of sodium salicylate into the PO/AH region had no effect on thermoresponsiveness of the region. This finding reinforces the idea that salicylates do not produce antipyresis by acting directly on thermosensitive cells of the central temperature control system.