Zika circulation, congenital syndrome, and current guidelines: making sense of it all for the traveller Purpose of review Zika virus (ZIKV) swept through the Americas and led to recognition of its neurotropism. Zika circulation elsewhere in the world, nonvector transmission including maternal–fetal/sexual/transfusion routes, and additional reports on congenital Zika syndrome (CZS) and Guillain–Barré syndrome (GBS) have been published. Recent findings In 2018–2019, ZIKV transmission occurred in Cuba, India, and is suspected to appear sporadically in other countries. Maternal–fetal ZIKV transmission appears to occur in about 26% of ZIKV-infected pregnant women. The US ZIKV Pregnancy and Infant Registry identified 6% of live births to have at least one ZIKV-associated birth defect; 9% had at least one neurodevelopmental abnormality; 1% had both. Infectious virus was rarely isolated from semen of ZIKV-infected male patients beyond day 38 after symptom onset. Brazilian blood donations had low ZIKV prevalence in 2015–2016; in the United States, screening donations was cost-effective only in the high mosquito season in Puerto Rico. Summary ZIKV transmission continues; many countries with competent mosquitoes are at risk. Transmission can occur without detection where surveillance is poor and laboratory capacity limited. Travelers are important sentinels. Variations exist among ZIKV strains and Aedes mosquitoes that influence competence for transmission. Maternal–fetal transmission results in significant rates of abnormality. Identification of infectious virus in semen clarifies sexual transmission risk, with updated recommendations for preconception planning. ZIKV neurotropism requires further research and long-term follow-up.

Fractional-dose yellow fever vaccination: how much more can we do with less? Purpose of review Climate change, deforestation, urbanization, and increased population mobility have made the risk of large outbreaks of yellow fever more likely than ever. Yellow fever vaccine production barely meets demands. In this review, we address the causes of the recent yellow fever outbreaks, why fractional dose yellow fever vaccination works, the role of virus neutralizing antibodies in the protection against yellow fever, and the need for revaccination. Recent findings Human activities have profoundly changed the epidemiology of yellow fever. The excess of infectious viral particles in routine yellow fever vaccine batches allows for off-label use of fractional dose yellow fever vaccination in response to emergency situations. Two studies have confirmed long-term protection after fractional dose yellow fever vaccination. The need for the presence of virus neutralizing antibodies (VNA) to protect an individual against yellow fever depends on the epidemiological setting. In case of sylvatic transmission, population immunity is irrelevant for individual protection, as mosquitoes are transmitting the virus from infected nonhuman primates to human. Summary With the growing connectivity through air travel, countries with high densities of nonimmune populations and of the urban mosquito vector, Aedes aegypti, should ensure that their citizens are properly vaccinated against yellow fever before traveling to a yellow fever endemic country. In the situation of sylvatic transmission, the presence of protective levels of VNA will determine the outcome and may require revaccination at some point in time.

The first licensed dengue vaccine: can it be used in travelers? Purpose of review The first dengue vaccine (Dengvaxia) was endorsed by the European Medicine Agency and the US Food and Drug Administration. Given the excess risk of severe dengue in seronegative vaccinees, use is restricted to seropositive individuals. Dengvaxia confers high protection against severe dengue in seropositive vaccinees. Recent findings With increasing global travel, the probability of travelers being seropositive increases. Such seropositive travelers may be at increased risk of severe dengue as a result of a second dengue infection during repeat travel. Nevertheless, the use of Dengvaxia in travelers requires a careful analysis of all the factors. Seropositive travelers only present a minority of all travelers. A validated rapid diagnostic test to screen for dengue serostatus is not yet available. Such a test should be highly specific to avoid inadvertent vaccination of seronegative individuals. The three-dose regimen precludes the use in most travelers who tend to present at travel clinics less than 6 weeks prior to departure. Furthermore, questions about potential sub-optimal immunogenicity in seropositives in nonendemic settings, and the need and timing of boosters remain unanswered. Summary Although there could potentially be substantial protection against severe dengue in seropositive travelers, Dengvaxia is far from an ideal travel vaccine.

WHO's new rabies recommendations: implications for high incidence countries Purpose of review Rabies is virtually always fatal; however, it is nearly 100% preventable with timely and appropriate prophylactic immunization. This review summarizes the recently revised WHO guidelines for rabies prophylaxis published in 2018, following a scientific review by a strategic advisory group of experts on immunization. The scientific basis for the major changes and its implications for countries with high disease burden are also discussed. Recent findings The key changes in the updated WHO 2018 guidelines for rabies prophylaxis include abbreviated vaccination regimens for pre and postexposure prophylaxis. These cost and dose-sparing regimens allow equitable sharing of vaccines, necessitate fewer clinic visits and thus can enhance patient compliance. The recommendations on rabies immunoglobulin administration permit prioritization and optimal use of this life-saving biologic, especially in areas with scarcity. However, there is a need for additional evidence to support the abridgment of some regimens and need for data on the safety and immunogenicity of these regimens in special groups such as infants and the immunocompromised. Summary National health authorities in high incidence countries need to develop consensus for effective implementation of simplified, cost-effective, and logistically feasible regimens for rabies prophylaxis, on the basis of the revised WHO guidelines.

Tafenoquine: the new kid on the block Purpose of review This is a review of tafenoquine, a new antimalarial drug. Here we examine the recent literature supporting the use of tafenoquine and summarize the opportunities and challenges for its well tolerated use worldwide. Recent findings Tafenoquine was recently approved by the US Food and Drug Administration for the treatment of dormant liver stage (hypnozoite) in Plasmodium vivax and for malaria prophylaxis. Single-dose tafenoquine provides equivalent efficacy to 14 days of primaquine for radical cure in P. vivax, and it can be dosed weekly to prevent malaria. However, tafenoquine can only be used in patients with normal G6PD activity and is contraindicated in children and during pregnancy or in lactating mothers with infants of deficient or unknown G6PD status. Summary Tafenoquine's long half-life allows a single dose to achieve radical cure, and weekly dosing for chemoprophylaxis to provide an exciting therapeutic option for patient care and as a new weapon for malaria control/eradication programs. Global implementation of tafenoquine will require the development and validation of a robust, low-cost diagnostic to reliably identify G6PD-deficient individuals. In addition, studies on tafenoquine safety in children are needed.

Severe malaria: update on pathophysiology and treatment Purpose of review Malaria threatens the lives of over 200 million individuals with the disease each year. Plasmodium falciparum is the predominant cause of severe malaria which may be lethal and result in neurocognitive sequelae despite appropriate treatment. We review recent advances regarding the pathophysiology of severe malaria and treatment recommendations for severe disease in the United States. Recent findings Infected red blood cell (iRBC) sequestration in microvascular beds is a critical factor in the development of severe malaria syndromes. Interactions between iRBC variant adhesive peptides and the endothelial protein C receptor (EPCR) result in perturbations of coagulation and cytopreservation pathways. Alterations in the protein C/EPCR axis are implicated in cerebral malaria, respiratory distress, and anemia. Brain MRIs reveal the posterior reversible encephalopathy syndrome in cerebral malaria patients. Transcriptomic analysis reveals commonalities in disease pathogenesis in children and adults despite differences in clinical presentation. US guidelines for severe malaria treatment currently recommend intravenous artesunate including in pregnant women and children. Summary Despite advances in our understanding of malarial pathogenesis much remains unknown. Antimalarial agents eradicate parasites but no treatments are available to prevent or ameliorate severe malaria or prevent disease sequelae. Further study is needed to develop effective adjunctive therapies.

Cutaneous leishmaniasis in the 21st century: from the laboratory to the bedside Purpose of review Despite modern advances in molecular diagnostic tools and a better understanding of its complex pathophysiology, cutaneous leishmaniasis, a neglected tropical disease, remains a major global health problem. Laboratory methods to inform prognosis and treatment are not widely available, the therapeutic options are limited and have significant adverse effects, and emergence of drug resistance is a further complication. New advances in the understanding of the role of Leishmania RNA virus (LRV) as a prognostic factor, speciation methods and antimicrobial resistance testing and their limitations will be discussed. Recent findings LRV, an intracytoplasmic endosymbiont found mostly in Leishmania spp. associated with more severe disease, appears to play a role in modulating the host immune response and has been associated with treatment failure in some Viannia subgenus species. Proper speciation is an important guide to management. However, recent findings have demonstrated significant heterogeneity of results related to differences in genotyping methods. Summary Recognition of the role of LRV in immune modulation and response to treatment along with more accessible tools for its detection to guide management at the bedside should allow a better individualized approach. Improving accessibility and standardization of speciation methods and antimicrobial susceptibility testing should be major goals to improve cutaneous leishmaniasis management in the 21st century.

Approach to ocular toxoplasmosis including pregnant women Purpose of review To discuss available information on the effectiveness of anti-toxoplasma therapy for ocular toxoplasmosis and to provide clinicians with a practical approach to the disease. Recent findings Only eleven randomized studies were identified. In the three studies for acute retinitis, there was a clear trend in favor of treatment. In the two studies for the prevention of recurrences, trimethoprim–sulfamethoxazole prophylaxis was superior to placebo. In the six studies comparing different regimens, there was no statistically significant difference between the regimens. In the setting of acute posterior uveitis suspected to be caused by toxoplasma, serological testing should always be obtained, and anti-toxoplasma drug treatment, and corticosteroids should be instituted for at least 6 weeks. Toxoplasmic chorioretinitis during pregnancy represents a particular challenge. Summary Treatment with at least two drugs and corticosteroids should be offered to patients with active toxoplasmic chorioretinitis. Pregnant women with confirmed acute infection and concomitant acute retinitis should be treated for the ocular lesion(s) and to prevent vertical transmission. Pregnant women with chronic Toxoplasma infection acquired prior to gestation and concomitant retinitis by reactivation should be treated for the retinitis and monitored for vertical transmission.

Current and new rotavirus vaccines Purpose of review As of 2019, four rotavirus vaccines have been prequalified by the WHO for use worldwide. This review highlights current knowledge regarding rotavirus vaccines available, and provides a brief summary of the rotavirus vaccine pipeline. Recent findings Data generated from use of currently available products supports their effectiveness and impact in diverse settings. Rotavirus vaccines have a favorable risk–benefit profile, but previous associations of rotavirus vaccination with intussusception necessitate continued monitoring for this rare but serious adverse event. Implementation of rotavirus vaccines was jeopardized in late 2018 and 2019 by a shortage of vaccine supply. Fortunately, with the prequalification of two additional vaccines in 2018, countries have increased choice in products with different characteristics, pricing, and implementation strategies. Other vaccines currently in development may open up further immunization strategies, such as neonatal vaccination schedules or parenteral administration. Summary Rotavirus vaccines have demonstrated impact in reducing diarrheal morbidity and mortality worldwide. As countries begin to introduce the newly prequalified vaccines, additional data will become available on the safety and effectiveness of those products. Products in the pipeline have distinct profiles and could be an essential part of the expansion of rotavirus vaccine use worldwide.