Field sting reactions in patients receiving Hymenoptera venom immunotherapy: real-life experience.

BACKGROUND: Hymenoptera stings can cause systemic allergic reactions (SARs) that are prevented by venom immunotherapy (VIT). Sting challenge tests or field stings are used to evaluate the outcome of VIT. OBJECTIVE: The aim of the study was to investigate the consequences of field stings in patients during or after completion of VIT, and to identify patients at higher risk. METHODS: Patients treated with VIT between 1995 and 2018 were retrospectively evaluated. Contacted patients were invited to the clinic and a questionnaire was conducted regarding the history of field stings. RESULTS: A total of 115 patients (F/M: 45/70, mean age: 38.5 ± 12 years) treated with VIT were included; 74/115 were contacted and asked about field stings after VIT cessation. A history of 73 field stings was reported in 38 patients, 25 of whom were treated with honeybee venom and 13 with common wasp venom. Eighteen of the reactions were SARs [8 with honeybees (1 grade-I, 6 grade-II, 1 grade-III) and 10 with common wasps (1 grade-I, 5 grade-II, 4 grade-III)]. There was no association between the severity of index reactions and field stings with either the honeybee or common wasp. The median duration of VIT was longer in patients showing no reaction than in patients with an SAR. Of the 7 patients on ACE inhibitors or beta-blockers, 1 asthmatic patient developed grade-II SAR due to field stings in the first year of VIT. CONCLUSIONS: This study confirms that VIT lasting at least 3 years is effective in preventing SARs after field stings.

Simplified binomial estimation of human malaria transmission exposure distributions based on hard classification of where and when mosquitoes are caught: statistical applications with off-the-shelf tools.

The impacts and limitations of personal protection measures against exposure to vectors of malaria and other mosquito-borne pathogens depend on behavioural interactions between humans and mosquitoes. Therefore, understanding where and when they overlap in time and space is critical. Commonly used approaches for calculating behaviour-adjusted estimates of human exposure distribution deliberately use soft classification of where and when people spend their time, to yield nuanced and representative distributions of mean exposure to mosquito bites across entire human populations or population groups. However, these weighted averages rely on aggregating individual-level data to obtain mean human population distributions across the relevant behavioural classes for each time increment, so they cannot be used to test for variation between individuals. Also, these summary outcomes are quite complex functions of the disaggregated data, so they do not match the standard binomial or count distributions to which routine off-the-shelf statistical tools may be confidently applied. Fortunately, the proportions of exposure to mosquito bites that occur while indoors or asleep can also be estimated in a simple binomial fashion, based on hard classification of human location over a given time increment, as being either completely indoors or completely outdoors. This simplified binomial approach allows convenient analysis with standard off-the-shelf logistic regression tools, to statistically assess variations between individual humans, human population subsets or vector species. Such simplified binomial estimates of behavioural interactions between humans and mosquitoes should be more widely used for estimating confidence intervals around means of these indicators, comparing different vector populations and human population groups, and assessing the influence of individual behaviour on exposure patterns and infection risk. Also, standard sample size estimation techniques may be readily used to estimate necessary minimum experimental scales and data collection targets for field studies recording these indicators as key outcomes. Sample size calculations for field studies should allow for natural geographic variation and seasonality, taking advantage of rolling cross-sectional designs to survey and re-survey large numbers of separate study locations in a logistically feasible manner.

Mediator-Related Symptoms and Anaphylaxis in Children with Mastocytosis.

Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier's sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.

An Investigation of Human-Mosquito Contact Using Surveys and Its Application in Assessing Dengue Viral Transmission Risk.

Aedes-borne viral diseases such as dengue fever are surging in incidence in recent years. To investigate viral transmission risks, the availability of local transmission parameters is essential. One of the most important factors directly determining infection risk is human-mosquito contact. Yet the contact rate is not often characterized, compared with other risk metrics such as vector density, because of the limited research tool options. In this study, human-mosquito contact was assessed in two study sites in the Southern United States using self-administered standardized survey instruments. The fraction of mosquito bites attributed to important vector species was estimated by human landing sampling. The survey participants reported a significantly higher outdoor mosquito bite exposure than indoor. The reported bite number was positively correlated with outdoor time during at-risk periods. There was also a significant effect of the study site on outdoor bite exposure, possibly due to the differing vector density. Thus, the levels of human-mosquito contact in this study were influenced both by the mosquito density and human behaviors. A dengue virus transmission model demonstrated that the observed difference in the contact rates results in differential virus transmission risks. Our findings highlight the practicality of using surveys to investigate human-mosquito contact in a setting where bite exposure levels differ substantially, and serve as a basis for further evaluations. This study underscores a new avenue that can be used in combination with other field methods to understand how changes in human behavior may influence mosquito bite exposure which drives mosquito-borne virus transmission.

Circadian Regulation of Light-Evoked Attraction and Avoidance Behaviors in Daytime- versus Nighttime-Biting Mosquitoes.

Mosquitoes pose widespread threats to humans and other animals as disease vectors [1]. Day- versus night-biting mosquitoes occupy distinct time-of-day niches [2, 3]. Here, we explore day- versus night-biting female and male mosquitoes' innate temporal attraction/avoidance behavioral responses to light and their regulation by circadian circuit and molecular mechanisms. Day-biting mosquitoes Aedes aegypti, particularly females, are attracted to light during the day regardless of spectra. In contrast, night-biting mosquitoes, Anopheles coluzzii, specifically avoid ultraviolet (UV) and blue light during the day. Behavioral attraction to/avoidance of light in both species change with time of day and show distinct sex and circadian neural circuit differences. Males of both diurnal and nocturnal mosquito species show reduced UV light avoidance in anticipation of evening onset relative to females. The circadian neural circuits of diurnal/day- and nocturnal/night-biting mosquitoes based on PERIOD (PER) and pigment-dispersing factor (PDF) expression show similar but distinct circuit organizations between species. The basis of diurnal versus nocturnal behaviors is driven by molecular clock timing, which cycles in anti-phase between day- versus night-biting mosquitoes. Observed differences at the neural circuit and protein levels provide insight into the fundamental basis underlying diurnality versus nocturnality. Molecular disruption of the circadian clock severely interferes with light-evoked attraction/avoidance behaviors in mosquitoes. In summary, attraction/avoidance behaviors show marked differences between day- versus night-biting mosquitoes, but both classes of mosquitoes are circadian and light regulated, which may be applied toward species-specific control of harmful mosquitoes.

Impact of vector control interventions on malaria transmission intensity, outdoor vector biting rates and Anopheles mosquito species composition in Tororo, Uganda.

BACKGROUND: Long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) are widely recommended for the prevention of malaria in endemic regions. Data from human landing catches provide information on the impact of vector control on vector populations. Here, malaria transmission indoors and outdoors, before and after mass deployment of LLINs and IRS in Uganda was compared. METHODS: The study took place in Tororo district, a historically high transmission area where universal LLIN distribution was conducted in November 2013 and May 2017 and 6 rounds of IRS implemented from December 2014 to July 2018. Human landing catches were performed in 8 houses monthly from October 2011 to September 2012 (pre-intervention period) and every 4 weeks from November 2017 to October 2018 (post-intervention period). Mosquitoes were collected outdoors from 18:00 to 22:00 h and indoors from 18:00 to 06:00 h. Female Anopheles were tested for the presence of Plasmodium falciparum sporozoites and species identification performed using gross dissection and polymerase chain reaction (PCR). RESULTS: The interventions were associated with a decline in human biting rate from 19.6 to 2.3 female Anopheles mosquitoes per house per night (p < 0.001) and annual entomological inoculation rate from 129 to 0 infective bites per person per year (p < 0.001). The proportion of mosquitoes collected outdoors increased from 11.6 to 49.4% (p < 0.001). Prior to the interventions the predominant species was Anopheles gambiae sensu stricto (s.s.), which comprised an estimated 76.7% of mosquitoes. Following the interventions, the predominant species was Anopheles arabiensis, which comprised 99.5% of mosquitoes, with almost complete elimination of An. gambiae s.s. (0.5%). CONCLUSIONS: Mass distribution of LLINs and 6 rounds of IRS dramatically decreased vector density and sporozoite rate resulting in a marked reduction in malaria transmission intensity in a historically high transmission site in Uganda. These changes were accompanied by a shift in vector species from An. gambiae s.s. to An. arabiensis and a relative increase in outdoor biting.

Host Associations Of Biting Midges (Diptera: Ceratopogonidae: Culicoides) Near Sentinel Chicken Surveillance Locations In Florida, USA.

Quantifying host use is important for understanding transmission of vector-borne pathogens. Despite the importance of biting midges (Diptera: Ceratopogonidae) in pathogen transmission, the vector-host relationships of most Culicoides species are poorly documented, even in locations where active arbovirus surveillance is conducted. Polymerase chain reaction-based blood-meal analysis was performed on 663 blood-engorged Culicoides females collected by 7 Florida mosquito control districts at 24 sentinel chicken arbovirus surveillance sites in 2017. A total of 638 blood meals were successfully analyzed to determine host species source, representing 11 Culicoides species. The most commonly bitten host was domestic chicken (Gallus gallus) (presumably sentinel chickens), constituting 565 of 638 (88.6%) the total blood meals. Other common hosts included humans (5.8%), white-tailed deer (Odoocoileus virginianus) (2.5%), and brown basilisk (Basiliscus vittatus) (1.6%). Significant differences in distribution of mammal and avian blood meals were found for a number of Culicoides species, and these patterns did not vary across locations. These results indicate that sentinel chickens are exposed to bites by Culicoides, potentially exposing them to Culicoides-borne pathogens. The findings that vertebrate host use was consistent across locations suggests that each Culicoides species has affinity for one or more specific animal groups, and does not feed randomly upon available animals.

Fire Ant Punctate Keratopathy: A Novel Diagnosis Based on Clinical and Anterior Segment Optical Coherence Tomography Findings.

PURPOSE: To describe the ocular findings and the long-term outcomes of patients diagnosed with corneal injury due to little fire ants (LFAs). METHODS: This is a retrospective case series of patients evaluated with corneal injury due to LFAs from October 2015 to January 2018 at the Cornea Clinic in Meir Medical Center. Patients underwent anterior segment optical coherence tomography (AS-OCT) imaging during the follow-up. RESULTS: Four patients reported ocular contact with LFAs and presented to our department with unilateral, scattered, small, dense, round, bright white opacities in the anterior corneal stroma, which remained unchanged in appearance over time, despite topical antibiotic and steroid treatment. No inflammatory signs were noted in the anterior chamber. Follow-up was performed clinically using AS-OCT for periods of 9 to 26 months after the incidents. AS-OCT findings demonstrated small, subepithelial, hyperreflective foci at the level of the anterior stroma to a depth of 145 to 250 µm, with posterior shadowing that remained unchanged over time. These findings were well-correlated with biomicroscopy findings. CONCLUSIONS: LFA bites can cause long-lasting corneal injury in humans with characteristic clinical biomicroscopic findings. The corneal lesions do not respond to conventional topical treatment. AS-OCT imaging can be a useful modality for diagnosis and follow-up. Awareness by both patients and ophthalmologists of this clinical entity may be helpful in diagnosis and management.

Common causes of emergency department visits for anaphylaxis in Korean community hospitals: A cross-sectional study.

Anaphylaxis can cause death and requires immediate management. For prevention and education programs for anaphylaxis, it is important to be aware of the common triggering factors. We investigated the triggers of anaphylaxis in the emergency departments (EDs) of community hospitals in Korea.Patients who visited the EDs of 7 community hospitals for anaphylaxis from January 1, 2012 to December 31, 2016 were enrolled. Anaphylaxis was defined according to the World Allergy Organization criteria and identified via a thorough review of the medical records of patients who were diagnosed with anaphylaxis (ICD-10 codes: T780, T782, T805, and T886) at the ED or administered epinephrine in the ED. Triggers of anaphylaxis were also evaluated by a review of the medical records.We identified 1021 ED visits for anaphylaxis. The incidence of anaphylaxis ED visits was 0.08%. The triggers of ED visits for anaphylaxis were bee venom (55.0%), foods (21.3%), and drugs (13.2%); 9.6% of cases were idiopathic. However, food was the most common trigger among the patients aged <20 years old. The frequency of ED visits for anaphylaxis was highest in summer (47.9%), followed by autumn (28.2%), spring (12.3%), and winter (11.6%). The incidence of anaphylaxis ED visits was highest in August, during which bee venom was the trigger for 80% of anaphylaxis cases. For the 55 patients with repeat ED visits for anaphylaxis, Bee venom was also the most common trigger.The number of ED visits for anaphylaxis showed marked seasonal variation, peaking in summer. Bee venom was the most common trigger for adults and the main reason for seasonal variations of anaphylaxis ED visits in Korean community hospitals.

Understanding toxicological implications of accidents with caterpillars Megalopyge lanata and Podalia orsilochus (Lepidoptera: Megalopygidae).

Megalopygids Megalopyge lanata and Podalia orsilochus are common causative agents of accidents in agricultural workers. These accidents are provoked by dermal contact at their larval stage and are characterized by cutaneous reactions, such as burning pain, edema and erythema, typically mild and self-limited. There is very little information about their venoms and their toxicological implications on human health. Thus, we employed proteomic techniques and biological assays to characterize venoms (bristle extracts) from caterpillars of both species collected from Misiones, Argentina. The electrophoretic profiles of both venoms were substantially different, and they presented proteins related to toxicity, such as serinepeptidases, serpins and lectins. P. orsilochus venom exhibited higher caseinolytic activity than M. lanata venom, agreeing with the fact that only P. orsilochus venom hydrolyzed human fibrin(ogen). In addition, the latter shortened the clotting time triggered by calcium. While the venom of M. lanata induced a mild inflammatory lesion in mouse skin, P. orsilochus venom caused prominent necrosis, inflammatory infiltration and hemorrhage at the site of venom injection. On the other hand, P. orsilochus venom was better recognized by Lonomia obliqua antivenom, although many of its proteins could not be cross-reacted, what may explain the difference in the clinical manifestations between accidents by Podalia and those by Lonomia. Altogether, this study provides relevant information about the pathophysiological mechanisms whereby both caterpillars can induce toxicity on human beings, and paves the way for novel discovery of naturally occurring bioactive compounds.

Management of severe pain after dermal contact with caterpillars (erucism): a prospective case series.

CONTEXT: Erucism, envenomation caused by dermal contact with larval forms of moths, may result in intense local pain, mainly after contact with puss caterpillars (family Megalopygidae). OBJECTIVE: To evaluate the response to different treatments for controlling severe pain in a case series of erucism in Campinas, southeastern Brazil. PATIENTS AND METHODS: Prospective cohort study. A Numeric Pain Rating Scale (NPRS 0-10) was used to assess pain intensity in the Emergency Department (ED). Pain was considered as severe upon ED admission (T0) when the NPRS was ≥8. INCLUSION CRITERIA: age ≥8 years old, severe pain at T0, with continuous assessment of pain intensity in all patients using the NPRS during the ED stay (T5, T15, T30, T60 min and at discharge). RESULTS: Fifty-five patients fulfilled the inclusion criteria and were divided into three groups according to the initial treatment at T0: local anesthesia alone with 2% lidocaine (group 1, n = 15), local anesthesia and analgesics (group 2, n = 26) and analgesics without local anesthesia (group 3, n = 14). Most patients were admitted within 2 h after dermal contact with the stinging bristles of caterpillars (median =90 min, IQR: 40-125 min). In 22 cases (40%), the caterpillar was brought for identification (Podalia spp., n = 18; Megalopyge spp., n = 4). There was a significant decrease in pain from T5 onwards with all of the treatments. When the short-term response (T5 and T15) was considered, analgesia was more effective in groups 1 and 2 compared to group 3 (p < .01). Additional analgesia (from T5 until discharge) was frequently required (n = 25/55), mainly in group 1 (n = 11/15). The median length of stay in the ED was 120 min (IQR: 80-173 min). CONCLUSIONS: The association of local anesthesia with analgesics was apparently a good combination for the rapid management of severe pain in the ED.

The allergic response mediated by fire ant venom proteins.

Fire ants are widely studied, invasive and venomous arthropod pests. There is significant biomedical interest in immunotherapy against fire ant stings. However, mainly due to practical reasons, the physiological effects of envenomation has remained poorly characterized. The present study takes advantage of a recently-described venom protein extract to delineate the immunological pathways underlying the allergic reaction to fire ant venom toxins. Mice were injected with controlled doses of venom protein extract. Following sensitization and a second exposure, a marked footpad swelling was observed. Based on eosinophil recruitment and production of Th2 cytokines, we hereby establish that fire ant proteins per se can lead to an allergic response, which casts a new light into the mechanism of action of these toxins.

Megalopyge opercularis Caterpillar Stings Reported to Texas Poison Centers.

INTRODUCTION: The Megalopyge opercularis caterpillar is covered with spines that break off and release venom on contact, resulting in severe pain, erythema, rash, and other adverse effects. In Texas, these caterpillars are abundant and of potential health threat. This study describes M opercularis caterpillar stings reported to Texas poison centers. METHODS: Cases were M opercularis caterpillar stings reported to Texas poison centers during 2000-2016. The distribution of stings was determined related to exposure circumstances and management. RESULTS: There were 3484 M opercularis caterpillar stings reported during 2000-2016. The annual number of stings did not consistently change over the 17-year time period. The monthly number of stings was highest in July (12%) and October to November (59%). The patients were female in 53% of cases and aged 20 years or more in 56%. The sting occurred at the patient's own residence in 91% of cases. The patients were managed outside of a healthcare facility in 89% of cases; 93% of the patients were known or expected to have no or at most minor clinical effects. Dermal clinical effects were reported in 90% of cases, the most common being irritation/pain (84%), puncture/wound (45%), erythema/flushed (29%), and edema (15%). CONCLUSIONS: M opercularis caterpillar stings reported to Texas poison centers were more frequently reported in July and October to November. Most of the patients were adults. The majority of patients were managed outside of healthcare facilities and did not have serious outcomes. Most of the adverse clinical effects were dermal in nature.

Nightly Biting Cycles of Anopheles Species in Rural Northwestern Burkina Faso.

The biting behavior of anophelines is an important determinant of malaria transmission. Understanding the local vector host-seeking behavior, its outdoor/ indoor biting preference, and nocturnal biting periods is essential for effectively applying and improving vector control methods, such as Long Lasting Insecticidal Nets (LLINs) and personal protective measures. To better understand the biting and host-seeking patterns of Anopheles mosquitoes in Northwestern Burkina Faso, we performed biweekly Human Landing Catches (HLC) in six villages during the period of highest mosquito abundance and malaria transmission. We applied a negative binomial regression framework to statistically analyze the host-seeking activities of Anopheles species and test for differences across hours, months, and villages, as well as for differences between indoor and outdoor capture points. Anopheles gambiae s.l. was identified as the main malaria vector in this region, representing about 90% of the total anopheline population. Biting activity was significantly different across hours and showed a peaked plateau between 2000 and 0200 hours. Differences in the pattern of biting cycles were observed between the early and late rainy season. This study shows that anopheline biting activity in Northwest Burkina Faso is high throughout the night, at indoor and outdoor posts alike. Consequently, bed nets alone may not provide sufficient protection against early biting anophelines and should be complemented with additional strategies such as indoor residual spraying (IRS) and larval source management (LSM) to meet the WHO's ambitious goals that are reflected in the global technical malaria strategy for 2030.

Nationwide insecticide resistance status and biting behaviour of malaria vector species in the Democratic Republic of Congo.

BACKGROUND: Globally, the Democratic Republic of Congo (DRC) accounted for 9% of malaria cases and 10% of malaria deaths in 2015. As part of control efforts, more than 40 million long-lasting insecticidal nets (LLINs) were distributed between 2008 and 2013, resulting in 70% of households owning one or more LLINs in 2014. To optimize vector control efforts, it is critical to monitor vector behaviour and insecticide resistance trends. Entomological data was collected from eight sentinel sites throughout DRC between 2013 and 2016 in Kingasani, Mikalayi, Lodja, Kabondo, Katana, Kapolowe, Tshikaji and Kalemie. Mosquito species present, relative densities and biting times were monitored using human landing catches (HLC) conducted in eight houses, three times per year. HLC was conducted monthly in Lodja and Kapolowe during 2016 to assess seasonal dynamics. Laboratory data included resistance mechanism frequency and sporozoite rates. Insecticide susceptibility testing was conducted with commonly used insecticides including deltamethrin and permethrin. Synergist bioassays were conducted with PBO to determine the role of oxidases in permethrin resistance. RESULTS: In Lodja, monthly Anopheles gambiae s.l. biting rates were consistently high at > 10 bites/person/night indoors and outdoors. In Kapolowe, An. gambiae s.l. dominated during the rainy season, and Anopheles funestus s.l. during the dry season. In all sites, An. gambiae and An. funestus biting occurred mostly late at night. In Kapolowe, significant biting of both species started around 19:00, typically before householders use nets. Sporozoite rates were high, with a mean of 4.3% (95% CI 3.4-5.2) for An. gambiae and 3.3% (95% CI 1.3-5.3) for An. funestus. Anopheles gambiae were resistant to permethrin in six out of seven sites in 2016. In three sites, susceptibility to deltamethrin was observed despite high frequency permethrin resistance, indicating the presence of pyrethroid-specific resistance mechanisms. Pre-exposure to PBO increased absolute permethrin-associated mortality by 24%, indicating that resistance was partly due to metabolic mechanisms. The kdr-1014F mutation in An. gambiae was present at high frequency (> 70%) in three sites (Kabondo, Kingasani and Tshikaji), and lower frequency (< 20%) in two sites (Lodja and Kapolowe). CONCLUSION: The finding of widespread resistance to permethrin in DRC is concerning and alternative insecticides should be evaluated.

A Review of Sclerodermus Latreille, 1809 (Hymenoptera: Bethylidae) Infestations and Report of the First Case in North America North of Mexico.

Sclerodermus Latreille, 1809 (Hymenoptera: Bethylidae), are parasitoids of wood-boring beetle larvae that can co-infest furniture and homes attacked by such larvae. This can result in the human inhabitants receiving stings from adult female wasps as they wander in search of new hosts. Herein, I report the first infestation of Sclerodermus macrogaster (Ashmead, 1887) of a home in North America and provide a review of Sclerodermus biology and clinical signs relevant to their pestiferous nature.