Recent years have seen unprecedented investment in research and development for countermeasures for high-threat pathogens, including specific and ambitious objectives for development of diagnostics, therapeutics, and vaccines. The inadequate availability of biological reference materials for these pathogens poses a genuine obstacle in pursuit of these objectives, and the lack of a comprehensive and equitable framework for developing reference materials is a weakness. We outline the need for internationally standardized biological materials for high-threat pathogens as a core element of global health security. We also outline the key components of a framework for addressing this deficiency.

We report a case of atypical cowpox virus infection in France in 2016. The patient sought care for thoracic lesions after injury from the sharp end of a metallic guardrail previously stored in the ground. We isolated a cowpox virus from the lesions and sequenced its whole genome. The patient reported that he had been previously vaccinated against smallpox. We describe an alternative route of cowpox virus infection and raise questions about the immunological status of smallpox-vaccinated patients for circulating orthopoxviruses.

Madagascar is more seriously affected by plague, a zoonosis caused by Yersinia pestis, than any other country. The Plague National Control Program was established in 1993 and includes human surveillance. During 1998–2016, a total of 13,234 suspected cases were recorded, mainly from the central highlands; 27% were confirmed cases, and 17% were presumptive cases. Patients with bubonic plague (median age 13 years) represented 93% of confirmed and presumptive cases, and patients with pneumonic plague (median age 29 years) represented 7%. Deaths were associated with delay of consultation, pneumonic form, contact with other cases, occurrence after 2009, and not reporting dead rats. A seasonal pattern was observed with recrudescence during September–March. Annual cases peaked in 2004 and decreased to the lowest incidence in 2016. This overall reduction occurred primarily for suspected cases and might be caused by improved adherence to case criteria during widespread implementation of the F1 rapid diagnostic test in 2002.

Lassa virus is a rodentborne arenavirus responsible for human cases of Lassa fever, a viral hemorrhagic fever, in West Africa and in travelers arriving to non–Lassa-endemic countries from West Africa. We describe a retrospective review performed through literature search of clinical and epidemiologic characteristics of all imported Lassa fever cases worldwide during 1969–2016. Our findings demonstrate that approximately half of imported cases had distinctive clinical features (defined as fever and >1 of the following: pharyngitis, sore throat, tonsillitis, conjunctivitis, oropharyngeal ulcers, or proteinuria). Delays in clinical suspicion of this diagnosis were common. In addition, no secondary transmission of Lassa fever to contacts of patients with low-risk exposures occurred, and infection of high-risk contacts was rare. Future public health investigations of such cases should focus on timely recognition of distinctive clinical features, earlier treatment of patients, and targeted public health responses focused on high-risk contacts.

Ebola virus (EBOV) can persist in immunologically protected body sites in survivors of Ebola virus disease, creating the potential to initiate new chains of transmission. From the outbreak in West Africa during 2014–2016, we identified 13 possible events of viral persistence–derived transmission of EBOV (VPDTe) and applied predefined criteria to classify transmission events based on the strength of evidence for VPDTe and source and route of transmission. For 8 events, a recipient case was identified; possible source cases were identified for 5 of these 8. For 5 events, a recipient case or chain of transmission could not be confidently determined. Five events met our criteria for sexual transmission (male-to-female). One VPDTe event led to at least 4 generations of cases; transmission was limited after the other events. VPDTe has increased the importance of Ebola survivor services and sustained surveillance and response capacity in regions with previously widespread transmission.

Zika virus infection during pregnancy may result in birth defects and pregnancy complications. We describe the Zika virus outbreak in pregnant women in the Dominican Republic during 2016–2017. We conducted multinomial logistic regression to identify factors associated with fetal losses and preterm birth. The Ministry of Health identified 1,282 pregnant women with suspected Zika virus infection, a substantial proportion during their first trimester. Fetal loss was reported for ≈10% of the reported pregnancies, and 3 cases of fetal microcephaly were reported. Women infected during the first trimester were more likely to have early fetal loss (adjusted odds ratio 5.9, 95% CI 3.5–10.0). Experiencing fever during infection was associated with increased odds of premature birth (adjusted odds ratio 1.65, 95% CI 1.03–2.65). There was widespread morbidity during the epidemic. Our findings strengthen the evidence for a broad range of adverse pregnancy outcomes resulting from Zika virus infection.

Infection with West Nile virus (WNV) has a well-characterized acute disease process. However, long-term consequences are less understood. We searched death records for 4,142 residents of Texas, USA, infected with WNV during 2002–2012 and identified 557 (13%) deaths. We analyzed all-cause and cause-specific deaths after WNV infection by calculating standardized mortality ratios and using statewide mortality data. Acute-phase deaths (<90 days after symptom onset) occurred in 289 (7%) of case-patients; of those deaths, 289 (92%) were cases of West Nile neuroinvasive disease (WNND). Convalescent-phase deaths (>90 days after symptom onset) occurred in 268 (7%) of the remaining 3,853 case-patients; 210 (78%) of these deaths occurred in patients with WNND. Convalescent-phase WNND case-patients showed excess deaths from infectious and renal causes; case-patients <60 years of age had increased risk for all-cause death, specifically from renal, infectious, digestive, and circulatory causes. We provide population-level evidence of increased risk for death after WNV infection resulting in WNND.

Alveolar echinococcosis, the disease caused by infection with the intermediate stage of the Echinococcus multilocularis tapeworm, is typically fatal in humans and dogs when left untreated. Since 2012, alveolar echinococcosis has been diagnosed in 5 dogs, 3 lemurs, and 1 chipmunk in southern Ontario, Canada, a region previously considered free of these tapeworms. Because of human and animal health concerns, we estimated prevalence of infection in wild canids across southern Ontario. During 2015–2017, we collected fecal samples from 460 wild canids (416 coyotes, 44 foxes) during postmortem examination and analyzed them by using a semiautomated magnetic capture probe DNA extraction and real-time PCR method for E. multilocularis DNA. Surprisingly, 23% (95% CI 20%–27%) of samples tested positive. By using a spatial scan test, we identified an infection cluster (relative risk 2.26; p = 0.002) in the western-central region of the province. The cluster encompasses areas of dense human population, suggesting zoonotic transmission.

A malaria survey was conducted in Atar, the northernmost oasis city in Mauritania, during 2015–2016. All febrile patients in whom malaria was suspected were screened for malaria by using rapid diagnostic testing and microscopic examination of blood smears and later confirmed by PCR. Of 453 suspected malaria cases, 108 (23.8%) were positive by rapid diagnostic testing, 154 (34.0%) by microscopic examination, and 162 (35.7%) by PCR. Malaria cases were observed throughout the year and among all age groups. Plasmodium vivax was present in 120/162 (74.1%) cases, P. falciparum in 4/162 (2.4%), and mixed P. falciparum–P. vivax in 38/162 (23.4%). Malaria is endemic in northern Mauritania and could be spreading farther north in the Sahara, possibly because of human-driven environmental changes. Further entomologic and parasitologic studies and monitoring are needed to relate these findings to major Anopheles mosquito vectors and to design and implement strategies for malaria prevention and control.

Monkeypox, caused by a zoonotic orthopoxvirus, is endemic in Central and West Africa. Monkeypox has been sporadically reported in the Republic of the Congo. During March 22–April 5, 2017, we investigated 43 suspected human monkeypox cases. We interviewed suspected case-patients and collected dried blood strips and vesicular and crust specimens (active lesions), which we tested for orthopoxvirus antibodies by ELISA and monkeypox virus and varicella zoster virus DNA by PCR. An ecologic investigation was conducted around Manfouété, and specimens from 105 small mammals were tested for anti-orthopoxvirus antibodies or DNA. Among the suspected human cases, 22 met the confirmed, probable, and possible case definitions. Only 18 patients had available dried blood strips; 100% were IgG positive, and 88.9% (16/18) were IgM positive. Among animals, only specimens from Cricetomys giant pouched rats showed presence of orthopoxvirus antibodies, adding evidence to this species’ involvement in the transmission and maintenance of monkeypox virus in nature.

Ebola virus disease (EVD) is associated with elevated cytokine levels, and hypercytokinemia is more pronounced in fatal cases. This type of hyperinflammatory state is reminiscent of 2 rheumatologic disorders known as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, which are characterized by macrophage and T-cell activation. An evaluation of 2 cohorts of patients with EVD revealed that a marker of macrophage activation (sCD163) but not T-cell activation (sCD25) was associated with severe and fatal EVD. Furthermore, substantial immunoreactivity of host tissues to a CD163-specific antibody, predominantly in areas of extensive immunostaining for Ebola virus antigens, was observed in fatal cases. These data suggest that host macrophage activation contributes to EVD pathogenesis and that directed antiinflammatory therapies could be beneficial in the treatment of EVD.

Data on the duration of detectable Zika virus–specific IgM in infected persons are limited. Neutralizing antibody cross-reactivity occurs between Zika virus and related flaviviruses, but the degree to which this confounds diagnosis is uncertain. We tested serum specimens collected 12–19 months after illness onset from patients with confirmed Zika virus disease for Zika virus IgM and Zika virus and dengue virus neutralizing antibodies. Among 62 participants, 45 (73%) had detectable Zika virus IgM and 12 (19%) had an equivocal result. Although all patients tested had Zika virus neutralizing antibodies, 39 (63%) also had neutralizing antibodies against dengue virus; of those, 12 (19%) had <4-fold difference between Zika virus and dengue virus titers, and 5 (8%) had dengue virus titer >4-fold higher than Zika virus titer. Prolonged detection of IgM and neutralizing antibody cross-reactivity make it difficult to determine the timing of Zika virus infection and differentiate between related flaviviruses.

Louseborne relapsing fever (LBRF) was once a cosmopolitan disease, but it now occurs only in the Horn of Africa. Recent cases in refugees to Europe made LBRF topical again. Crowded boarding houses and church dwellings in Ethiopia are analogous to the crowded air-raid shelters of World War II. Thus, we might learn from experiments the London School of Tropical Hygiene and Medicine conducted during World War II. When the vector of Borrelia recurrentis (Pediculus humanus lice) was held away from the host for 10 days, 100% of nymphal and adult lice starved to death and 100% of eggs did not hatch. We hypothesize that holding infested clothes away from hosts in plastic shopping bags will kill enough lice to control LBRF in Ethiopia. Owning 2 sets of clothes might be useful; 1 set might be held in a plastic shopping bag for 10 days to kill lice and their eggs.

In seroconversion panels obtained from patients from Brazil, diagnostic testing for Zika virus infection was improved by combining multiple antibody isotypes, techniques, and antigens, but sensitivity remained suboptimal. In contrast, chikungunya virus diagnostic testing was unambiguous. Recurrent recent arbovirus infections suggested by serologic data and unspecific symptoms highlight the need for exhaustive virologic testing.

We studied the clinical manifestations and outcomes of 114 patients with culture-confirmed melioidosis treated at a tertiary hospital in southern India. Diabetes mellitus is the main risk factor, and chronic melioidosis mimicking tuberculosis was more common than acute disease. Septicemia and respiratory involvement were associated with poor outcomes.

During 2013–2016, a total of 32 patients were treated for Crimean-Congo hemorrhagic fever in Prishtina, Kosovo; 11 died. In the 11 patients who died, findings included viral loads >1 × 10^8.5/mL, lactate dehydrogenase >2,700 U/mL, bleeding, and impaired consciousness. Ribavirin therapy had no noticeable effect in this small patient sample.

Using reported case data from ArboNET and previous seroprevalence data stratified by age and sex, we conservatively estimate that ≈7 million persons in the United States have been infected with West Nile virus since its introduction in 1999. Our data support the need for public health interventions and improved surveillance.

Analysis of surveillance data for 2010–2016 in eastern Ontario, Canada, demonstrates the rapid northward spread of Ixodes scapularis ticks and Borrelia burgdorferi, followed by increasing human Lyme disease incidence. Most spread occurred during 2011–2013. Continued monitoring is essential to identify emerging risk areas in this region.

Screening of 533 bats for influenza A viruses showed subtype HL18NL11 in intestines of 2 great fruit-eating bats (Artibeus lituratus). High concentrations suggested fecal shedding. Genomic characterizations revealed conservation of viral genes across different host species, countries, and sampling years, suggesting a conserved cellular receptor and wide-ranging occurrence of bat influenza A viruses.

Phylogenetic analysis of Rift Valley fever virus partial genomic sequences from a patient infected in South Africa in May 2018 suggests reemergence of an endemic lineage different from that of the epidemic in South Africa during 2010–2011. Surveillance during interepidemic periods should be intensified to better predict future epidemics.

To increase knowledge of tick-borne encephalitis virus (TBEV) circulation in the Netherlands, we conducted serosurveillance in roe deer (Capreolus capreolus) during 2017 and compared results with those obtained during 2010. Results corroborate a more widespread occurrence of the virus in 2017. Additional precautionary public health measures have been taken.

We assessed the vector competence of Aedes caspius and Aedes albopictus mosquitoes in Spain for the transmission of Zika virus. Whereas Ae. albopictus mosquitoes were a competent vector, Ae. caspius mosquitoes were unable to transmit Zika virus. We also identified high levels of vertical transmission of Zika virus in Ae. albopictus mosquitoes.

In a screening program, we detected submicroscopic malaria in 8.9% of recent migrants to Spain from sub-Saharan Africa. Hemoglobinopathies and filarial infection occurred more frequently in newly arrived migrants with submicroscopic malaria than in those without. Our findings could justify systematic screening in immigrants and recent travelers from malaria-endemic areas.

We performed a molecular survey for Cytauxzoon felis infection in 311 domestic cats in Yunnan Province, China, in 2016 and found a prevalence of 21.5%. C. felis infection in domestic and wild cats in other provinces should be investigated to determine parasite prevalence and genetic diversity among cats throughout China.

In southeastern Venezuela, malaria cases have increased since 2013. We found that 46% of 352 blood samples from symptomatic patients in 1 municipality tested positive for Plasmodium spp. In addition, the number of cases increased by 10 times in 4 years (2014–2017) and by 3 times in 1 year (2016–2017).

We estimated the seroprevalence of Heartland virus antibodies to be 0.9% (95% CI 0.4%–4.2%) in a convenience sample of blood donors from northwestern Missouri, USA, where human cases and infected ticks have been identified. Although these findings suggest that some past human infections were undetected, the estimated prevalence is low.

High infection rates of Leishmania donovani and L. tropica were detected in Phlebotomus spp. sand flies collected from refugee camps in Greece, indicating increased risk of infection among local populations. Detection and treatment of leishmaniasis, community education, and vector control are essential measures to prevent pathogen transmission and protect public health.

Schistosomiasis is frequently detected in persons entering Europe. In 2017, we detected a Schistosoma mansoni–Schistosoma haematobium hybrid parasite infection in a migrant boy from Côte d’Ivoire entering France. Because such parasites might be established in Europe, as illustrated by an outbreak on Corsica Island, vectors of these parasites should be investigated.

West Nile virus (WNV) is an arthropod-transmitted flavivirus that causes West Nile fever and may infrequently cause neuroinvasive disease in humans. We present 2 cases of confirmed WNV infection, 1 of severe encephalitis and 1 of mild febrile illness, in a couple returning to the United Kingdom from South Africa.

In 2017, an unprecedented increase in febrile illness was observed in Dhaka, Bangladesh. Real-time reverse transcription PCR confirmed that 603 (40.2%) of 1,500 cases were chikungunya fever. Phylogenetic analysis revealed circulation of the non-A226V East/Central/South African genotype of chikungunya virus in Bangladesh.

We report biomolecular evidence of dolphin morbillivirus in 4 wild Eurasian otters (Lutra lutra) from southern Italy; 2 animals showed simultaneous immunohistochemical reactivity against morbilliviral antigen. These cases add further concern and support to the progressively expanding host range of dolphin morbillivirus in the western Mediterranean Sea.

We tested a sample of 234 wild long-tailed macaques (Macaca fascicularis) trapped in Peninsular Malaysia in 2009, 2010, and 2016 for Zika virus RNA and antibodies. None were positive for RNA, and only 1.3% were seropositive for neutralizing antibodies. Long-tailed macaques are unlikely to be reservoirs for Zika virus in Malaysia.

Of 103 serum samples collected from dogs in South Korea, 3 (2.9%) were positive for severe fever with thrombocytopenia syndrome virus (SFTSV) and 22 (21.4%) were positive for antibodies against SFTSV. A dog-derived isolate of SFTSV clustered with many South Korea SFTSV strains in the Japanese clade.

Pin-site myiasis is an underreported complication of surgical interventions. We present a case of myiasis caused by the New World screwworm fly (Cochliomyia hominivorax) in a pin site of a chronic nonhealed wound 12 years after the intervention. This infection apparently was the result of poor perfusion of the leg.

Oropouche fever is a neglected arthropodborne disease and zoonosis responsible for several outbreaks of a febrile disease in Central and South America. We present a clinical case of aseptic meningoencephalitis in an immunocompetent patient that resulted from Oropouche virus acquired in northern Brazil but diagnosed in a nonendemic region.

Human metapneumovirus is an emerging pathogen that causes upper and lower respiratory illness. Nursing home outbreaks of infection with this virus can cause severe illness and lead to poor patient outcomes. We report an outbreak investigation in a nursing home during 2018 and infection control guidelines to assist in disease control.

Leishmania infantum causes potentially life-threatening disease in humans. To determine the extent of the animal reservoir for this pathogen in Bosnia and Herzegovina, we tested dogs and cats. We found that a large proportion of dogs were exposed to or infected with L. infantum, indicating endemicity in dogs and zoonotic risk for humans.

Although Seoul orthohantavirus is the only globally spread hantavirus pathogen, few confirmed human infections with this virus have been reported in Western countries, suggesting lower medical awareness of the milder, transient, and often chameleon-like symptoms of this zoonosis. We describe lesser known clinical and laboratory characteristics to help improve underreporting of this virus.

Influenza virus infections are a major public health threat. Vaccination is available, but unpredictable antigenic changes in circulating strains require annual modification of seasonal influenza vaccines. Vaccine effectiveness has proven limited, particularly in certain groups, such as the elderly. Moreover, preparedness for upcoming pandemics is challenging because we can predict neither the strain that will cause the next pandemic nor the severity of the pandemic. The European Union fosters research and innovation to develop novel vaccines that evoke broadly protective and long-lasting immune responses against both seasonal and pandemic influenza, underpinned by a political commitment to global public health.