Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial.

BACKGROUND: Whole sporozoite immunization under chemoprophylaxis (CPS regime) induces long-lasting sterile homologous protection in the controlled human malaria infection model using Plasmodium falciparum strain NF54. The relative proficiency of liver-stage parasite development may be an important factor determining immunization efficacy. Previous studies show that Plasmodium falciparum strain NF135 produces relatively high numbers of large liver-stage schizonts in vitro. Here, we evaluate this strain for use in CPS immunization regimes. METHODS: In a partially randomized, open-label study conducted at the Radboudumc, Nijmegen, the Netherlands, healthy, malaria-naïve adults were immunized by three rounds of fifteen or five NF135-infected mosquito bites under mefloquine prophylaxis (cohort A) or fifteen NF135-infected mosquito bites and presumptive treatment with artemether/lumefantrine (cohort B). Cohort A participants were exposed to a homologous challenge 19 weeks after immunization. The primary objective of the study was to evaluate the safety and tolerability of CPS immunizations with NF135. RESULTS: Relatively high liver-to-blood inocula were observed during immunization with NF135 in both cohorts. Eighteen of 30 (60%) high-dose participants and 3/10 (30%) low-dose participants experienced grade 3 adverse events 7 to 21 days following their first immunization. All cohort A participants and two participants in cohort B developed breakthrough blood-stage malaria infections during immunizations requiring rescue treatment. The resulting compromised immunizations induced modest sterile protection against homologous challenge in cohort A (5/17; 29%). CONCLUSIONS: These CPS regimes using NF135 were relatively poorly tolerated and frequently required rescue treatment, thereby compromising immunization efficiency and protective efficacy. Consequently, the full potential of NF135 sporozoites for induction of immune protection remains inconclusive. Nonetheless, the high liver-stage burden achieved by this strain highlights it as an interesting potential candidate for novel whole sporozoite immunization approaches. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov under identifier NCT03813108.

Systems analysis of immune responses to attenuated P. falciparum malaria sporozoite vaccination reveals excessive inflammatory signatures correlating with impaired immunity.

Immunization with radiation-attenuated sporozoites (RAS) can confer sterilizing protection against malaria, although the mechanisms behind this protection are incompletely understood. We performed a systems biology analysis of samples from the Immunization by Mosquito with Radiation Attenuated Sporozoites (IMRAS) trial, which comprised P. falciparum RAS-immunized (PfRAS), malaria-naive participants whose protection from malaria infection was subsequently assessed by controlled human malaria infection (CHMI). Blood samples collected after initial PfRAS immunization were analyzed to compare immune responses between protected and non-protected volunteers leveraging integrative analysis of whole blood RNA-seq, high parameter flow cytometry, and single cell CITEseq of PBMCs. This analysis revealed differences in early innate immune responses indicating divergent paths associated with protection. In particular, elevated levels of inflammatory responses early after the initial immunization were detrimental for the development of protective adaptive immunity. Specifically, non-classical monocytes and early type I interferon responses induced within 1 day of PfRAS vaccination correlated with impaired immunity. Non-protected individuals also showed an increase in Th2 polarized T cell responses whereas we observed a trend towards increased Th1 and T-bet+ CD8 T cell responses in protected individuals. Temporal differences in genes associated with natural killer cells suggest an important role in immune regulation by these cells. These findings give insight into the immune responses that confer protection against malaria and may guide further malaria vaccine development. Trial registration: ClinicalTrials.gov NCT01994525.

[Urticaria associated with COVID-19 in allergic patients. A case series]. / Urticaria asociada a COVID-19 en pacientes alérgicos. Serie de casos.

INTRODUCTION: In December 2019, a new coronavirus was identified as the causal agent of the 2019 coronavirus disease (COVID-19) with a wide clinical spectrum that goes from asymptomatic cases to critical and fatal cases. Its usual manifestations are fever, cough, and fatigue; although some cases present skin lesions. CASES REPORT: The first case was a 30-year-old woman with a history of controlled solar urticaria who presented erythematous and pruritic wheals in malar and cervical regions and extremities; associated with general malaise, headaches, and nausea, in whom the presence of COVID-19 was confirmed; her condition improved with a quadruple dose of antihistamines. The second case was a 47-year-old woman with a history of wasp sting anaphylaxis, without mastocytosis, who presented nasal congestion, headaches, and hypogeusia associated with generalized, erythematous, and pruritic wheals, with confirmation of COVID-19; her condition improved with quadruple doses of antihistamines. CONCLUSIONS: Cutaneous manifestations associated with COVID-19 are frequent and can be classified as inflammatory and vascular. Among them, urticarial lesions occupy the fourth place, and although there could be some predominance of these in patients with a history of allergies, more studies are required to define an association.

Introducción: En diciembre de 2019 fue identificado un nuevo coronavirus como agente causal de la enfermedad por coronavirus del 2019 con un amplio espectro clínico, desde casos asintomáticos hasta críticos y fatales. Generalmente se manifiesta con fiebre, tos y fatiga, aunque algunos casos se presentan con lesiones cutáneas. Reporte de casos: El primer caso es una mujer de 30 años con antecedente de urticaria solar controlada quien presentó habones eritematosos y pruriginosos en región malar, cervical y extremidades, asociado a malestar general, cefalea y náuseas, en quien se confirmó la presencia de COVID-19, y mejoró con antihistamínicos a dosis cuádruple. El segundo caso es una mujer de 47 años con antecedente de anafilaxia por picadura de avispa, sin mastocitosis, quien presentó congestión nasal, cefalea e hipogeusia asociado a habones generalizados, eritematosos y pruriginosos, con confirmación de COVID-19, y mejoría con dosis cuadruple de antihistamínicos. Conclusiones: Las manifestaciones cutáneas asociadas a COVID-19 son frecuentes y se pueden clasificar en inflamatorias y vasculares. Dentro de ellas, las lesiones urticariales ocupan el cuarto lugar, y aunque podría existir algún predominio de estas en pacientes con antecedentes de alergias, se necesitan más estudios para definir una asociación.

Fighting mosquito bite during a crisis: capabilities of Florida mosquito control districts during the COVID-19 pandemic.

BACKGROUND: The stay-at-home orders imposed in early April 2020 due to the COVID-19 pandemic in various states complicated mosquito control activities across the United States (US), and Florida was no exception. Mosquito control programs are the first line of defense against mosquito-borne pathogens. The purpose of this study was to examine the capabilities of Florida mosquito programs to implement key mosquito measures during the COVID-19 pandemic lockdown. METHODS: Using a self-administered online survey, we examined the capabilities of all Florida mosquito control programs (both state-approved mosquito districts, N = 63; and open programs, N = 27) at a time when the state of Florida was still under heightened awareness of, stay-at-home orders and planning a phase 1 reopening over the COVID-19 pandemic (June to July 2020). The final sample included mosquito control programs structured as the Board of County Commissioners (BOCC) (n = 42), independent tax district (n = 16), municipal (n = 10), and health or emergency department (n = 5). We used descriptive statistics to summarize information about the characteristics of responding programs, their implemented mosquito control and surveillance activities.  wWe used bivariate analysis to compare the characteristics of responding programs and the self-reported mosquito measures. RESULTS: Of the recruited mosquito control programs, 73 completed the survey (81.1% response rate; 73/90). Of these, 57.5% (n = 42) were Board of County Commissioners (BOCC) mosquito control programs, 21.9% (n = 16) were independent tax district programs, 13.7% (n = 10) were municipal mosquito control programs, and only 6.8% (n = 5) were either health or emergency department mosquito control programs. Except for arbovirus surveillance, most programs either fully or partially performed larval (61.8%) and adult (78.9%) surveillance; most programs conducted species-specific control for Aedes aegypti (85.2%, n = 54), Aedes albopictus (87.3%, n = 55), Culex quinquefasciatus (92.1%, n = 58), and Culex nigripalpus (91.9%, n = 57). CONCLUSIONS: Findings underscore the importance of ongoing mosquito control activities, and suggest that Florida mosquito control programs are vigilant and have significant capability to handle potential mosquito-borne disease threats, but arbovirus surveillance systems (laboratory testing of mosquito pools and testing of human and nonhuman specimens for arboviruses) are needed during pandemics as well.

Etiological and predictive factors of pediatric urticaria in an emergency context.

BACKGROUND: Urticaria is common in pediatric population and is caused by various etiologies which usually differ among different age groups. The different etiologies require different management strategies. Thus, understanding detailed of the etiologies of urticaria in children would help pediatricians to perform appropriate initial treatment. METHODS: A cross-sectional epidemiological study of all patients aged under 18-year-old with the diagnosis of urticaria from any causes entered in the emergency department during January 1st, 2016 to December 31st, 2019 by collecting the data from the Health Object Program®, an authorized electronic medical records program, at the Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand. RESULTS: There were total of 515 urticaria patients aged under 18 years old at the emergency department. The ages of patients ranged from 8 months to 18 years with a median age of 7 years (IQR 3.17-12.08). The majority of the patients were in the preschool-aged group (40.97%), followed by the school-aged (28.16%), adolescent (22.14%), and infant (8.74%). Six major etiologic categories were identified in the present study. The most common cause of urticaria was infection (51.26%), followed by idiopathic urticaria (34.37%), inhalants (6.99%), drugs (4.08%), foods (2.52%), and insect stings (0.78%). CONCLUSIONS: Having underlying allergic diseases had a strong association with all identified causes of urticaria in the study population, of which, food and inhalation etiologies had a significant difference when compared to the other identified causes. The present study has found that infection was the most common cause of acute urticaria in children. This etiology (infection-induced urticaria) usually presents concurrent with fever, however, non-febrile symptoms were also presented. Therefore, in the pediatric population, pediatricians should always look for infection as the cause of urticaria even in patients without pyrexia.

Beekeepers who tolerate bee stings are not protected against SARS-CoV-2 infections.

A survey on 5115 beekeepers and 121 patients treated with bee venom by an apitherapy clinic in the Hubei province, the epicenter of COVID-19 in China, reported that none of the beekeepers developed symptoms associated with COVID-19, the new and devastating pandemic. The hypothesis that immunity to bee venom could have a preventive effect was expressed and the authors of the Chinese survey suggested that the next step should be animal experiments on monkeys. We believed that before starting such studies, a second independent survey should verify the findings and define the hypothesis more clearly. Thus we asked all German beekeepers to complete an assessment form which would summarize their experiences with COVID-19. In contrast to the Chinese study we found that two beekeepers had died from a SARS-CoV-2 infection and forty-five were affected. The reaction to bee stings (none; mild swelling; severe swelling) correlated with the perceived severity of the SARS-CoV-2-infection-associated symptoms - exhaustion and sore throat. Beekeepers comorbidity correlated with problems with breathing at rest, fever, and diarrhea. Our results did not confirm the findings of the Chinese study. However, since the antiviral effects of bee venom have been found in several studies, we cannot exclude that there could be a direct preventive or alleviating effect when bee venom is administered during the infection.