Can dengue virus be sexually transmitted?

It has been well documented that Zika virus (ZIKV) can be sexually transmitted. Dengue virus (DENV) shows many similarities with ZIKV; both belong to the genus Flavivirus and share the same main vector route of transmission. Moreover, they share overall architectural features on a molecular level, with a highly similar structure and distinctive insertions, deletions and mutations of their respective E proteins, and it has been suggested that they use a common pathophysiological pathway. In view of similarities with other sexually transmissible viruses, the question arises as to whether DENV could also be sexually transmissible. Limited animal model data do not suggest otherwise. The presence of dengue virus in - and human-to-human, non-vector transmission from - various bodily fluids other than semen or vaginal secretions has been documented anecdotally. Several anecdotal reports described prolonged presence of DENV in semen, urine and vaginal secretions. In 2019, two cases of likely sexual transmission were reported from Spain and South Korea, respectively. We discuss the evidence for and against a relevant DENV sexual transmission potential, highlight controversies and propose a future research agenda on this issue

A Prospective Study on the Impact and Out-of-Pocket Costs of Dengue Illness in International Travelers.

Although the costs of dengue illness to patients and households have been extensively studied in endemic populations, international travelers have not been the focus of costing studies. As globalization and human travel activities intensify, travelers are increasingly at risk for emerging and reemerging infectious diseases, such as dengue. This exploratory study aims to investigate the impact and out-of-pocket costs of dengue illness among travelers. We conducted a prospective study in adult travelers with laboratory-confirmed dengue and recruited patients at travel medicine clinics in eight different countries from December 2013 to December 2015. Using a structured questionnaire, we collected information on patients and their health-care utilization and out-of-pocket expenditures, as well as income and other financial losses they incurred because of dengue illness. A total of 90 patients participated in the study, most of whom traveled for tourism (74%) and visited countries in Asia (82%). Although 22% reported hospitalization and 32% receiving ambulatory care while traveling, these percentages were higher at 39% and 71%, respectively, after returning home. The out-of-pocket direct and indirect costs of dengue illness were US$421 (SD 744) and US$571 (SD 1,913) per episode, respectively, averaging to a total out-of-pocket cost of US$992 (SD 2,052) per episode. The study findings suggest that international travelers incur important direct and indirect costs because of dengue-related illness. This study is the first to date to investigate the impact and out-of-pocket costs of travel-related dengue illness from the patient's perspective and paves the way for future economic burden studies in this population

Rabies Antibody Response After Booster Immunization: A Systematic Review and Meta-analysis

Although fatal once symptomatic, rabies is preventable by administration of pre- and post-exposure vaccines. International guidelines suggest lifelong protection by a pre-exposure vaccination scheme followed by timely post-exposure vaccines. Rapidity and magnitude of the antibody recall response after booster inoculation are essential, as many people have been previously immunized a long time ago. The objective of this study was therefore to systematically review the evidence on the boostability of rabies immunization to date. We included 36 studies, of which 19 studies were suitable for meta-analysis. Reduced antibody levels were found after intradermal primary schedules as compared to intramuscular schedules. However, responses after booster immunization were adequate for both routes. Although studies showed that antibody levels decline over time, adequate booster responses were still retained over long time intervals indicating that post-exposure treatment is effective without extra measures after long periods of time

Comparison of equivalent fractional vaccine doses delivered by intradermal and intramuscular or subcutaneous routes: A systematic review

Background: For certain vaccines, dosing can be reduced by intradermal (ID) immunization without loss of immunogenicity, as an alternative to standard routes of administration. However, a certain level of dose-sparing might also be achieved by reducing doses of intramuscular (IM) or subcutaneous (SC) vaccines. Method: We conducted a systematic review comparing identical reduced amounts of antigen delivered by either ID, or IM/SC routes (PROSPERO registration no. CRD42020151725). Results: Of 6015 articles identified, we included 26 articles, covering eight different vaccines. Equivalent immune responses were demonstrated in 19/26 studies, and 7/26 studies suggested inferior immune responses after IM/SC immunization. Conclusions: We conclude that fractional dosed IM/SC vaccination is at best as immunogenic, but potentially inferior to ID vaccination. The safety profiles were at large comparable, although minor local adverse events were more common after ID delivery. Future vaccine trials, depending on the platform used, should add a fractional dose IM/SC arm, besides a fractional dose ID arm

Fractional dose of intradermal compared to intramuscular and subcutaneous vaccination - A systematic review and meta-analysis

Background: Vaccine supply shortages are of global concern. We hypothesise that intradermal (ID) immunisation as an alternative to standard routes might augment vaccine supply utilisation without loss of vaccine immunogenicity and efficacy. Methods: We conducted a systematic review and meta-analysis searching Medline, Embase and Web of Science databases. Studies were included if: licensed, currently available vaccines were used; fractional dose of ID was compared to IM or SC immunisation; primary immunisation schedules were evaluated; immunogenicity, safety data and/or cost were reported. We calculated risk differences (RD). Studies were included in meta-analysis if: a pre-defined immune correlate of protection was assessed; WHO-recommend schedules and antigen doses were used in the control group; the same schedule was applied to both ID and control groups (PROSPERO registration no. CRD42020151725). Results: The primary search yielded 5,873 articles, of which 156 articles were included; covering 12 vaccines. Non-inferiority of immunogenicity with 20–60% of antigen used with ID vaccines was demonstrated for influenza (H1N1: RD -0·01; 95% CI -0·02, 0·01; I2 = 55%, H2N3: RD 0·00; 95% CI -0·01, 0·01; I2 = 0%, B: RD -0·00; 95% CI -0·02, 0·01; I2 = 72%), rabies (RD 0·00; 95% CI -0·02, 0·02; I2 = 0%), and hepatitis B vaccines (RD -0·01; 95% CI -0·04, 0·02; I2 = 20%). Clinical trials on the remaining vaccines yielded promising results, but are scarce. Conclusions: There is potential for inoculum/antigen dose-reduction by using ID immunisation as compared to standard routes of administration for some vaccines (e.g. influenza, rabies). When suitable, vaccine trials should include an ID arm

Immunogenicity and 1-year boostability of a three-dose intramuscular rabies pre-exposure prophylaxis schedule in adults receiving immunosuppressive monotherapy: a prospective single-centre clinical trial

BACKGROUND: For immunocompromised patients (ICPs), administration of rabies immunoglobulins (RIG) after exposure is still recommended regardless of prior vaccination, due to a lack of data. We aimed to assess the 1-year boostability of a three-dose rabies pre-exposure prophylaxis (PrEP) schedule in individuals using immunosuppressive monotherapy. METHODS: In this prospective study, individuals on immunosuppressive monotherapy with a conventional immunomodulator (cIM) or a TNF-alpha inhibitor (TNFi) for a chronic inflammatory disease received a three-dose intramuscular PrEP schedule (days 0,7,21-28) with 1 mL Rabipur®, followed by a two-dose simulated post-exposure prophylaxis (PEP) schedule (days 0,3) after 12 months. Rabies neutralizing antibodies were assessed at baseline, on day 21-28 (before the third PrEP dose), day 60, month 12 and month 12 + 7 days. The primary outcome was 1-year boostability, defined as the proportion of patients with a neutralizing antibody titre of ≥ 0.5 IU/mL at month 12 + 7 days. Secondary outcomes were geometric mean titres (GMTs) and factors associated with the primary endpoint. RESULTS: We included 56 individuals, of whom 52 completed the study. The 1-year boostability was 90% (47/52) with a GMT of 6.16 (95% CI 3.83-9.91). All participants seroconverted at some point in the study. Early response to PrEP (at day 21-28) was significantly associated with 100% boostability (Odds Ratio 51; 95% confidence interval [5.0-6956], P < 0.01). The vaccination schedule was safe and well tolerated. No vaccine-related serious adverse events occurred. CONCLUSION: In patients using immunosuppressive monotherapy, a three-dose rabies PrEP schedule followed by a two-dose PEP schedule is immunogenic, with all patients seroconverting at some point in the study. Although boostability 7 days after PEP was not 100%, nobody would wrongly be denied RIG when only administered to those who responded early to PrEP while reducing the administration of RIG by 73%

Boostability after single-visit pre-exposure prophylaxis with rabies vaccine:a randomised controlled non-inferiority trial

Background: After rabies pre-exposure prophylaxis (PrEP) vaccination, scarcely available rabies immunoglobulins are not required for post-exposure prophylaxis (PEP). However, PrEP is not sufficiently accessible as it is cost-intensive and time-intensive. This study investigates whether rabies PrEP schedules can be shortened to one visit, removing some of these barriers. Methods: In a block-randomised (2:2:2:1) controlled, multicentre non-inferiority trial, healthy adult travellers (aged 18–50 years and &gt;50 years) were randomly assigned to (A) single-visit intramuscular (1·0 mL); (B) single-visit intradermal (0·2 mL); (C) standard two-visit intramuscular (1·0 mL; day 0 and 7) PrEP; or (D) no rabies vaccination. 6 months later, participants received simulated intramuscular rabies PEP (1·0 mL; day 0 and 3). Rabies virus neutralising antibody (RVNA) concentrations were measured repeatedly. The primary outcome was the fold increase in geometric mean RVNA concentrations between day 0 and 7 after simulated PEP for all participants. The two main comparisons of this primary outcome are between the standard two-visit schedule and the one-visit intramuscular schedule, and between the standard two-visit schedule and the one-visit intradermal schedule. The non-inferiority margin was 0·67. This study is registered with EudraCT, 2017-000089-31. Findings: Between May 16, 2018, and March 26, 2020, 288 healthy adult travellers were randomly assigned and 214 participants were evaluated for the primary outcome. Single-visit intramuscular rabies PrEP induced an anamnestic antibody response non-inferior compared with the two-visit intramuscular schedule; single-visit intradermal PrEP did not. The fold increases in the single-visit intramuscular and the single-visit intradermal schedule were 2·32 (95% CI [1·43–3·77]) and 1·11 (0·66–1·87) times as high as the fold increase in the standard schedule, respectively. No vaccine-related serious adverse events were observed. Adverse events related to vaccination were mostly mild. Interpretation: Single intramuscular rabies vaccination can effectively prime travellers (aged 18–50 years), and potentially other populations, and could replace current standard two-visit rabies vaccination as PrEP.</p