Acceptance and timeliness of post-exposure vaccination against mpox in high-risk contacts, Amsterdam, the Netherlands, May-July 2022.

BACKGROUND: May 2022, several countries reported mpox outbreaks among men-who-have-sex-with-men. In the Netherlands, high-risk contacts were offered the third-generation smallpox vaccine as post-exposure-prophylaxis (PEP) within 4 but maximum 14 days after exposure. We investigated their PEP acceptance, timeliness of uptake and development of mpox for the region of the Public Health Service (PHS) Amsterdam. METHODS: High-risk contacts identified during 20 May-22 July 2022 were included. Contacts were followed-up 21 days after exposure and classified as: no patient (no mpox symptoms or orthopoxvirus PCR-negative) or mpox patient (clinically suspected mpox or orthopoxvirus PCR-positive). We calculated time intervals between date of last exposure and first PHS consultation, PEP administration, and symptom onset. RESULTS: Two-hundred-ninety contacts were at high-risk of mpox predominantly due to sexual and/or direct skin-skin contact (212/290, 73 %). First PHS consultation was a median of 5 (IQR 3, 7) days after exposure, at which point 26/290 (9 %) contacts were ineligible for PEP. 84 % (223/264) of contacts eligible for PEP, received PEP within a median of 6 (IQR 3, 8) days after exposure. Of 282 contacts (missing outcome n = 8) 38 (14 %) developed mpox a median of 7 (IQR 5, 12) days after exposure, of whom 50 % (19/38) developed mpox before their first PHS consultation. Among contacts eligible for PEP, 2/38 (5 %) unvaccinated and 16/218 (7 %) vaccinated contact developed mpox. CONCLUSIONS: PEP acceptance among contacts of mpox patients was high. However, PEP timeliness was inadequate. Half of contacts received PEP 6 or more days after exposure, and half of contacts who developed mpox had an onset prior to their first PHS consultation. Estimating PEP vaccine effectiveness is problematic due to the timeliness of PEP and the time it takes to generate vaccine-induced immunity. It is important to assess how PEP timeliness may improve and to promote pre-exposure vaccination to control mpox outbreaks.

[Hydroxychloroquine and chloroquine for COVID-19: no evidence of effectiveness]. / Hydroxychloroquine en chloroquine bij COVID-19.

On 3 March 2020, the document 'Drug treatment options for patients with COVID-19 (infections with SARS-CoV-2)' was published on the website of the Dutch Working Party on Antibiotic Policy (StichtingWerkgroepAntibioticabeleid, SWAB). Based on a 7-step analysis of the literature, hydroxychloroquine (HCQ) and chloroquine (CQ) were initially included in the SWAB document as possible drug treatments for hospitalised adult COVID-19 patients. However, recent weeks have seen the publication of the results of various studies into the effectiveness of treatment with HCQ and CQ in patients with COVID-19. On the basis of these results, we conclude that there is insufficient evidence to consider HCQ and CQ as meaningful treatment options in patients with COVID-19. Clinically relevant QTc prolongation occurs in at least 1 in 10 COVID-19 patients treated with HCQ or HQ.

[Influenza vaccination of patients with solid tumours during chemotherapy: efficacy and safety]. / Griepvaccinatie tijdens chemotherapie bij patiënten met solide tumoren.

- Adult patients with solid tumours receiving chemotherapy have reduced immunity against infections and are at increased risk of influenza infection and its complications. However, many of said patients are not vaccinated for influenza.- Limited observational research in this patient group has given some indication of the protective effects of the influenza vaccine on clinical outcome measures.- Serological studies have shown that the antibody response following influenza vaccination is often less pronounced in patients with solid tumours compared to healthy individuals. Nonetheless, in most cases a timely protective antibody response can be achieved.- The inactivated influenza vaccine is safe in immunosuppressed patients, irrespective of the moment at which it is administered. Side-effects are similar, both in nature and number, to those seen in healthy individuals.- Influenza vaccination can be offered to all adult patients with solid tumours, preferably before chemotherapy is commenced. Vaccination during chemotherapy, however, usually also generates sufficient vaccination response and can reduce the risk of influenza-related complications. Therefore, chemotherapy should not preclude patients from being administered the influenza vaccine.

Prognostic value of pro-adrenomedullin, procalcitonin and C-reactive protein in predicting outcome of febrile urinary tract infection.

Bacterial infections such as febrile urinary tract infection (fUTI) may run a complicated course that is difficult to foretell on clinical evaluation only. Because the conventional biomarkers erythrocyte sedimentation rate (ESR), leucocyte count, C-reactive protein (CRP) and procalcitonin (PCT) have a limited role in the prediction of a complicated course of disease, a new biomarker-plasma midregional pro-adrenomedullin (MR-proADM)-was evaluated in patients with f UTI. We conducted a prospective multicentre cohort study including consecutive patients with f UTI at 35 primary-care centres and eight emergency departments. Clinical and microbiological data were collected and plasma biomarker levels were measured at presentation to the physician. Survival was assessed after 30 days. Of 494 fUTI patients, median age was 67 (interquartile range 49-78) years, 40% were male; two-thirds of them had significant co-existing medical conditions. Median MR-proADM level was 1.42 (interquartile range 0.67-1.57) nM; significantly elevated MR-proADM levels were measured in patients with bacteraemia, those admitted to the intensive care unit, and in 30-day and 90-day non-survivors, compared with patients without these characteristics. The diagnostic accuracy for predicting 30-day mortality in fUTI, reflected by the area-under-the-curve of receiver operating characteristics were: MR-proADM 0.83 (95% CI 0.71-0.94), PCT 0.71 (95% CI 0.56-0.85); whereas CRP, ESR and leucocyte count lacked diagnostic value in this respect. This study shows that MR-proADM assessed on first contact predicts a complicated course of disease and 30-day mortality in patients with fUTI and in this respect has a higher discriminating accuracy than the currently available biomarkers ESR, CRP, PCT and leucocyte count.

PARK2/PACRG polymorphisms and susceptibility to typhoid and paratyphoid fever.

Host genetic factors may contribute to susceptibility to and outcome in infectious diseases. Recently polymorphisms in PARK2/PACRG, a gene cluster linked to ubiquitination and proteasome-mediated protein degradation, were found to be associated with manifest infection by M. leprae. Here, we address whether these polymorphisms are associated with susceptibility to infection with Salmonella typhi and S. paratyphi A, intracellular pathogens that upon infection of humans share with mycobacteria aspects of the hosts' immune response. The polymorphisms of PARK_e01(-697), PARK2_e01(-2599), rs1333955 and rs1040079 were analysed by polymerase chain reaction and restriction fragment length polymorphism in a case-control study of typhoid and paratyphoid fever patients in an endemic area in Jakarta, Indonesia. For this study, samples were obtained from patients with blood culture-confirmed typhoid fever (n=90), paratyphoid fever (n=26) and fever controls (n=337) in a passive, community-based surveillance and compared to those of randomly selected community controls (n=322) from the same city area. The PARK2_e01(-2599) allele T was significantly associated with typhoid and paratyphoid fever (OR: 1.51, 95%CI: 1.02-2.23) but the other polymorphisms, PARK2_e01(-697), rs1333955 and rs1040079, were not associated. Although within the PARK2/PACRG gene cluster the PARK2_e01(-2599) allele T was most strongly associated with leprosy (OR approximately 3-5), the association with typhoid is much less strong. Our findings suggest that this polymorphism in PARK2/PACRG plays a small but significant role in susceptibility to the intracellular pathogens S. typhi and S. paratyphi.

Helicobacter pylori infection and typhoid fever in Jakarta, Indonesia.

We evaluated the association between typhoid fever and Helicobacter pylori infection, as the latter microorganism may influence gastric acid secretion and consequently increase susceptibility to Salmonella typhi infection. Anti-H. pylori IgG and IgA antibody titres (ELISA) and gastrin concentration (RIA) were determined in the plasma of 87 blood culture-confirmed typhoid fever cases (collected after clinical recovery) and 232 random healthy controls without a history of typhoid fever, in the Jatinegara district, Jakarta. Patients with typhoid fever more often than controls were seropositive for H. pylori IgG (67% vs. 50%, P<0.008), when antibody titres were dichotomized around median titres observed in controls. H. pylori IgA seropositivity was not associated with typhoid fever. Plasma gastrin concentrations indicative of hypochlorhydria (i.e. gastrin > or =25 or > or =100 ng/l) were not significantly elevated in typhoid fever cases compared to controls (P=0.54 and P=0.27 respectively). In a multivariate analysis, typhoid fever was independently associated with young age (<33 years, median age of the controls) [odds ratio (OR) 7.93, 95% confidence interval (CI) 3.90-16.10], and H. pylori IgG seropositivity (OR 1.93, 95% CI 1.10-3.40). Typhoid fever was independently associated with H. pylori IgG seropositivity, but not with elevated gastrin concentration. Therefore, the association suggests a common risk of environmental exposure to both bacteria, e.g. poor hygiene, rather than a causal relationship via reduced gastric acid production.

Risk factors for transmission of foodborne illness in restaurants and street vendors in Jakarta, Indonesia.

In a previous risk factor study in Jakarta we identified purchasing street food as an independent risk factor for paratyphoid. Eating from restaurants, however, was not associated with disease. To explain these findings we compared 128 street food-vendors with 74 food handlers from restaurants in a cross-sectional study in the same study area. Poor hand-washing hygiene and direct hand contact with foods, male sex and low educational level were independent characteristics of street vendors in a logistic regression analysis. Faecal contamination of drinking water (in 65 % of samples), dishwater (in 91 %) and ice cubes (in 100 %) was frequent. Directly transmittable pathogens including S. typhi (n = 1) and non-typhoidal Salmonella spp. (n = 6) were isolated in faecal samples in 13 (7 %) vendors; the groups did not differ, however, in contamination rates of drinking water and Salmonella isolation rates in stools. Poor hygiene of street vendors compared to restaurant vendors, in combination with faecal carriage of enteric pathogens including S. typhi, may help explain the association found between purchasing street food and foodborne illness, in particular Salmonella infections. Public health interventions to reduce transmission of foodborne illness should focus on general hygienic measures in street food trade, i.e. hand washing with soap, adequate food-handling hygiene, and frequent renewal of dishwater.