Plasmodium knowlesi malaria in a traveller returning from the Philippines to Italy, 2016.

Plasmodium knowlesi is a simian parasite responsible for most human cases of malaria in Malaysian Borneo. A timely recognition of infection is crucial because of the risk of severe disease due to the rapid increase in parasitemia. We report a case of P. knowlesi infection in a traveller who developed fever and thrombocytopenia after returning from the Philippines in 2016. Rapid antigen test was negative, microscopy examination showed parasites similar to Plasmodium malariae, with a parasite count of 10,000 parasites per µL blood, while molecular testing identified P. knowlesi infection. Treatment with atovaquone-proguanil led to resolution of fever and restoration of platelet count in two days. P. knowlesi infection should be suspected in febrile travellers returning from South East Asia. Due to the low sensitivity of rapid antigen tests and the low specificity of microscopy, confirmation by molecular tests is recommended.

Effects of the age of vaccination on the humoral responses to a human papillomavirus vaccine.

Adult vaccination programs are receiving increasing attention however, little is known regarding the impact of age on the maintenance of the immune response. We investigated this issue in the context of a human papillomavirus (HPV) vaccination program collecting real-world data on the durability of humoral immunity in 315 female subjects stratified according to vaccination age (adolescents and adults) and sampled at early or late time points after the last vaccine dose. HPV-specific IgGs, but not memory B cells, were induced and maintained at higher levels in subjects vaccinated during adolescence. Nonetheless, antibody functions waned over time to a similar degree in adolescents and adults. To shed light on this phenomena, we analyzed quantitative and qualitative properties of lymphocytes. Similar biochemical features were observed between B-cell subsets from individuals belonging to the two age groups. Long term humoral responses toward vaccines administered at an earlier age were comparably maintained between adolescents and adults. The percentages of naïve B and CD4+ T cells were significantly higher in adolescents, and the latter directly correlated with IgG titers against 3 out of 4 HPV types. Our results indicate that age-specific HPV vaccine responsiveness is mostly due to quantitative differences of immune cell precursors rather than qualitative defects in B cells. In addition, our results indicate that adults also have a good humoral immunogenic profile, suggesting that their inclusion in catch-up programmes is desirable.

Characterization of Intra-Type Variants of Oncogenic Human Papillomaviruses by Next-Generation Deep Sequencing of the E6/E7 Region.

Different human papillomavirus (HPV) types are characterized by differences in tissue tropism and ability to promote cell proliferation and transformation. In addition, clinical and experimental studies have shown that some genetic variants/lineages of high-risk HPV (HR-HPV) types are characterized by increased oncogenic activity and probability to induce cancer. In this study, we designed and validated a new method based on multiplex PCR-deep sequencing of the E6/E7 region of HR-HPV types to characterize HPV intra-type variants in clinical specimens. Validation experiments demonstrated that this method allowed reliable identification of the different lineages of oncogenic HPV types. Advantages of this method over other published methods were represented by its ability to detect variants of all HR-HPV types in a single reaction, to detect variants of HR-HPV types in clinical specimens with multiple infections, and, being based on sequencing of the full E6/E7 region, to detect amino acid changes in these oncogenes potentially associated with increased transforming activity.

Neutralizing and cross-neutralizing antibody titres induced by bivalent and quadrivalent human papillomavirus vaccines in the target population of organized vaccination programmes.

Aim of this investigator-initiated study was to evaluate and compare the titres of neutralizing and cross-neutralizing antibodies (NAbs) induced by the bivalent (Cervarix(®)) and quadrivalent (Gardasil(®)) HPV vaccines in a cohort of girls aged 11-13 years from organized vaccination programmes. To this aim, HPV16 and HPV18 NAbs were measured by pseudovirion-based neutralization assays in serum collected at 1-6 months after the third vaccine dose in 107 girls vaccinated with Cervarix(®) and 126 vaccinated with Gardasil(®), while HPV31 and HPV45 cross-NAbs were tested in the first 50 consecutive girls of both vaccine groups. The results of this study demonstrated that all vaccinated girls developed HPV16 and HPV18 NAbs, with the exception of two Gardasil(®) vaccinees with undetectable HPV18 NAbs. Geometric mean titres (GMTs) of both HPV16 and HPV18 NAbs were significantly higher in Cervarix(®) than in Gardasil(®) vaccinees [HPV16 NAb GMT 22,136 (95% CI, 18,811-26,073) vs 5092 (4230-6151), respectively; P<0.0001; HPV18 NAb GMT 11,962 (9536-14,363) vs 1804 (1574-2110), respectively; P<0.0001]. Cross-NAbs to HPV31 and HPV45 were detected more frequently Cervarix(®) (HPV31 NAb positivity rates 92.7% and 36%, respectively; P<0.05) than in Gardasil(®) vaccinees (HPV45 NAb positivity rates 56% and 6%, respectively; P<0.0001). The titres of cross-NAbs against HPV31 and HPV45 were also significantly higher in Cervarix(®) than in Gardasil(®) vaccinees [HPV31 NAb GMT 157.2 (95% CI, 92-269) vs 13.0 (6.5-25.8), respectively; P<0.0001; HPV45 NAb GMT 4.7 (2.1-10.2) vs 1.3 (0.3-3.1), respectively; P<0.01]. In conclusion, in adolescent girls vaccinated within organized vaccination programmes, HPV vaccines drive the generation not only of NAbs to HPV vaccine types, but also of cross-NAbs. The bivalent vaccine induced significantly higher HPV16 and HPV18 NAb titres and more frequently and at higher titre HPV31 and HPV45 cross-NAbs than the quadrivalent vaccine.

Validation of the UEBE Visomat Double Comfort upper arm blood pressure monitor, in oscillometric mode, for clinic use and self-measurement in a general population according to the European Society of Hypertension International Protocol, revision 2010.

OBJECTIVE: To validate the UEBE Visomat Double Comfort, an upper arm blood pressure monitor designed for self-measurement of blood pressure and for clinical use in a general population according to the European Society of Hypertension International Protocol revision 2010. METHODS: The device is provided with two operational modalities, a microphonic mode and an oscillometric mode. In this study, the oscillometric modality was tested. Device evaluation was performed in 33 participants with a mean ± standard deviation age of 56.3 ± 20.0 years (range, 25-85 years). Their systolic blood pressure was 140.4 ± 27.7 mmHg, diastolic blood pressure was 86.8 ± 17.2 mmHg, and arm circumference was 29.3 ± 3.9 cm. RESULTS: The protocol requirements were followed precisely. The device passed all of the requirements fulfilling the standards of the protocol. Mean blood pressure differences between device and observer were -0.9 ± 4.1 mmHg for systolic blood pressure and -0.1 ± 3.3 mmHg for diastolic blood pressure. CONCLUSION: As the Visomat Double Comfort in the oscillometric modality has achieved the required standards, it is recommended for clinical use in an adult population.

Accuracy of Microlife WatchBP Office ABI monitor assessed according to the 2002 European Society of Hypertension protocol and the British Hypertension Society protocol.

OBJECTIVE: To determine the accuracy of the WatchBP Office ABI monitor for blood pressure measurement developed by the Microlife Company. METHODS: The device accuracy was tested in 85 subjects with a mean age of 54 ± 19 years. Their systolic and diastolic blood pressure (SBP/DBP) at entry was 141 ± 30/86 ± 19 mmHg, and upper arm circumference was 28 ± 5 cm. Initially, the data from 33 participants were examined according to the 2002 version of the European Society of Hypertension (ESH) protocol. An additional 52 subjects were then enrolled to fulfill the requirements of the British Hypertension Society (BHS) protocol. In all participants, sequential same arm measurements were performed by two trained observers. RESULTS: The device passed all three phases of the ESH protocol for SBP and DBP. For the BHS protocol the device was graded A for both SBP and DBP. The A/A grade was achieved in the low blood pressure category (< 130/80 mmHg), the B/A grade in the medium category (130-160/80-100 mmHg) and the A/A grade in the high category (> 160/100 mmHg). Mean blood pressure difference between device and observers in the first 33 subjects was -0.9 ± 5.5 mmHg for SBP and -2.2 ± 4.5 mmHg for DBP and in the 85 participants it was -1.2 ± 6.5 mmHg and -2.3 ± 5.1, respectively. CONCLUSION: These data show that the Microlife WatchBP Office ABI monitor satisfied the recommended ESH accuracy levels and achieved A/A grade of the BHS protocol across a wide range of BP.

Accuracy of the Microlife large-extra large-sized cuff (32-52 cm) coupled to an automatic oscillometric device.

To determine the accuracy of the large-extra large-sized (L-XL) cuff (32-52 cm) coupled to a Microlife WatchBP Office ABI blood pressure measuring device tested according to the requirements of the International Protocol of the European Society of Hypertension. The L-XL cuff tested in this study is designed to provide accurate blood pressure measurements in patients with large arms (arm circumference≥32 cm) over a wide range of arm circumferences using a single 145±1×320±1 mm bladder. The evaluation was made in 33 patients with a mean±standard deviation age of 53±17 years (range: 30-96 years). Their systolic blood pressure (SBP) was 142±21 mmHg (range: 110-180 mmHg), diastolic blood pressure (DBP) was 87±14 mmHg (range: 62-106 mmHg) and arm circumference was 36±5 cm (range: 32-50 cm). Blood pressure measurements were made in the sitting position. The L-XL cuff coupled to the WatchBP Office ABI passed all three phases of the European Society of Hypertension protocol for SBP and DBP. Mean blood pressure differences between device and observer were -1.3±5.1 mmHg for SBP and -1.8±5.8 mmHg for DBP. Similar device-observer differences were observed in patients divided into two subgroups according to whether their arm circumference was above or below the median in the group. These results indicate that the L-XL cuff coupled to the WatchBP Office ABI monitor provides accurate blood pressure readings in patients with large arms over a wide range of arm circumferences.

Effects of hypnotic focused analgesia on dental pain threshold.

The rate, intensity, and selectivity of hypnotic focused analgesia (HFA) were tested with dental pulp stimulation. Thirty-one healthy subjects were hypnotized, and hypnotic suggestions were given for anesthesia of the right mandibular arch. A posthypnotic suggestion of persisting analgesia was also given. The pain threshold of the first premolar was bilaterally measured before, during, and after hypnosis using a pulp tester. During hypnosis, the pain threshold increased significantly (p < .0001) for both sides. The posthypnotic right pain threshold was also significantly (p < .0015) higher than in the basal condition.