Hitoshi Oshitani

Infectious diseases following natural disasters: prevention and control measures

Natural disasters may lead to infectious disease outbreaks when they result in substantial population displacement and exacerbate synergic risk factors (change in the environment, in human conditions and in the vulnerability to existing pathogens) for disease transmission. We reviewed risk factors and potential infectious diseases resulting from prolonged secondary effects of major natural disasters that occurred from 2000 to 2011. Natural disasters including floods, tsunamis, earthquakes, tropical cyclones (e.g., hurricanes and typhoons) and tornadoes have been secondarily described with the following infectious diseases including diarrheal diseases, acute respiratory infections, malaria, leptospirosis, measles, dengue fever, viral hepatitis, typhoid fever, meningitis, as well as tetanus and cutaneous mucormycosis. Risk assessment is essential in post-disaster situations and the rapid implementation of control measures through re-establishment and improvement of primary healthcare delivery should be given high priority, especially in the absence of pre-disaster surveillance data.

Major Issues and Challenges of Influenza Pandemic Preparedness in Developing Countries

Summary line: A pandemic is a global issue, and pandemic preparedness should be considered from a global perspective.

Enterovirus 68 among Children with Severe Acute Respiratory Infection, the Philippines

TOC summary: Enterovirus 68 was found in 21 children with severe pneumonia.

Origin of measles virus: divergence from rinderpest virus between the 11th and 12th centuries

Measles, caused by measles virus (MeV), is a common infection in children. MeV is a member of the genus Morbillivirus and is most closely related to rinderpest virus (RPV), which is a pathogen of cattle. MeV is thought to have evolved in an environment where cattle and humans lived in close proximity. Understanding the evolutionary history of MeV could answer questions related to divergence times of MeV and RPV.We investigated divergence times using relaxed clock Bayesian phylogenetics. Our estimates reveal that MeV had an evolutionary rate of 6.0 - 6.5 × 10-4 substitutions/site/year. It was concluded that the divergence time of the most recent common ancestor of current MeV was the early 20th century. And, divergence between MeV and RPV occurred around the 11th to 12th centuries. The result was unexpected because emergence of MeV was previously considered to have occurred in the prehistoric age.MeV may have originated from virus of non-human species and caused emerging infectious diseases around the 11th to 12th centuries. In such cases, investigating measles would give important information about the course of emerging infectious diseases.

Evolution of the M gene of the influenza A virus in different host species: large-scale sequence analysis.

BackgroundInfluenza A virus infects not only humans, but also other species including avian and swine. If a novel influenza A subtype acquires the ability to spread between humans efficiently, it could cause the next pandemic. Therefore it is necessary to understand the evolutionary processes of influenza A viruses in various hosts in order to gain better knowledge about the emergence of pandemic virus. The virus has segmented RNA genome and 7th segment, M gene, encodes 2 proteins. M1 is a matrix protein and M2 is a membrane protein. The M gene may be involved in determining host tropism. Besides, novel vaccines targeting M1 or M2 protein to confer cross subtype protection have been under development. We conducted the present study to investigate the evolution of the M gene by analyzing its sequence in different species.ResultsPhylogenetic tree revealed host-specific lineages and evolution rates were different among species. Selective pressure on M2 was stronger than that on M1. Selective pressure on M1 for human influenza was stronger than that for avian influenza, as well as M2. Site-by-site analyses identified one site (amino acid position 219) in M1 as positively selected in human. Positions 115 and 121 in M1, at which consensus amino acids were different between human and avian, were under negative selection in both hosts. As to M2, 10 sites were under positive selection in human. Seven sites locate in extracellular domain. That might be due to hosts immune pressure. One site (position 27) positively selected in transmembrane domain is known to be associated with drug resistance. And, two sites (positions 57 and 89) locate in cytoplasmic domain. The sites are involved in several functions.ConclusionThe M gene of influenza A virus has evolved independently, under different selective pressure on M1 and M2 among different hosts. We found potentially important sites that may be related to host tropism and immune responses. These sites may be important for evolutional process in different hosts and host adaptation.

Frequency of Amantadine-Resistant Influenza A Viruses during Two Seasons Featuring Cocirculation of H1N1 and H3N2

ABSTRACT In two influenza seasons during which H1N1 and H3N2 cocirculated, resistance was more frequent in H3N2 strains than in H1N1 strains after amantadine treatment. Predominant amino acid substitutions in M2 protein occurred at position 31 (serine to asparagine) in H3N2 strains and at position 27 (valine to alanine) in H1N1 strains.

Global reemergence of enterovirus D68 as an important pathogen for acute respiratory infections: EV-D68 in acute respiratory infections

We previously detected enterovirus D68 (EV‐D68) in children with severe acute respiratory infections in the Philippines in 2008–2009. Since then, the detection frequency of EV‐D68 has increased in different parts of the world, and EV‐D68 is now recognized as a reemerging pathogen. However, the epidemiological profile and clinical significance of EV‐D68 is yet to be defined, and the virological characteristics of EV‐D68 are not fully understood. Recent studies have revealed that EV‐D68 is detected among patients with acute respiratory infections of differing severities ranging from mild upper respiratory tract infections to severe pneumonia including fatal cases in pediatric and adult patients. In some study sites, the EV‐D68 detection rate was higher among patients with lower respiratory tract infections than among those with upper respiratory tract infections, suggesting that EV‐D68 infections are more likely to be associated with severe respiratory illnesses. EV‐D68 strains circulating in recent years have been divided into three distinct genetic lineages with different antigenicity. However, the association between genetic differences and disease severity, as well as the occurrence of large‐scale outbreaks, remains elusive. Previous studies have revealed that EV‐D68 is acid sensitive and has an optimal growth temperature of 33 °C. EV‐D68 binds to α2,6‐linked sialic acids; hence, it is assumed that it has an affinity for the upper respiratory track where these glycans are present. However, the lack of suitable animal model constrains comprehensive understanding of the pathogenesis of EV‐D68.

Epidemiological characteristics and low case fatality rate of pandemic (H1N1) 2009 in Japan.

Pandemic (H1N1) 2009 has been causing large outbreaks in Japan. Yet, the case fatality rate (CFR) remains low and only 85 deaths have been confirmed as of December 17, 2009. Surveillance data was analyzed to define epidemiological characteristics of pandemic (H1N1) 2009 in Japan. It was shown that most of the reported influenza-like illness cases and hospitalizations have occurred in those aged 5–9 years and 10–14 years, in whom CFR is extremely low. However, CFRs are higher in small children (<5 years) and adults. The transmission to these age groups may possibly have been minimized through aggressive suspension of classes in schools.

Acute respiratory infections due to enterovirus 68 in Yamagata, Japan between 2005 and 2010

To clarify the epidemiology of enterovirus 68 (EV68), which is one of the most rarely identified enteroviruses, virus isolation and molecular screening using RT‐PCR was performed on 6307 respiratory specimens collected at pediatric clinics in Yamagata, Japan between 2005 and 2010. In the years 2005–2009, 10, 1, 2, 0, and 2 (40) EV68‐positive cases, respectively, were identified by RT‐PCR. In 2010, 40 cases were identified altogether: 2 by isolation only, 26 by RT‐PCR only, and 12 by both isolation and RT‐PCR. Phylogenetic analysis indicated that plural genetically distinct clusters co‐circulated. These results suggest that that difficulty in EV68 isolation leads to an underestimation of the prevalence of EV68 infections.

Large-Scale Sequence Analysis of M Gene of Influenza A Viruses from Different Species: Mechanisms for Emergence and Spread of Amantadine Resistance

ABSTRACT Influenza A virus infects many species, and amantadine is used as an antiviral agent. Recently, a substantial increase in amantadine-resistant strains has been reported, most of which have a substitution at amino acid position 31 in the M2 gene. Understanding the mechanism responsible for the emergence and spread of antiviral resistance is important for developing a treatment protocol for seasonal influenza and for deciding on a policy for antiviral stockpiling for pandemic influenza. The present study was conducted to identify the existence of drug pressure on the emergence and spread of amantadine-resistant influenza A viruses. We analyzed data on more than 5,000 virus sequences and constructed a phylogenetic tree to calculate selective pressures on sites in the M2 gene associated with amantadine resistance (positions 26, 27, 30, and 31) among different hosts. The phylogenetic tree revealed that the emergence and spread of the drug-resistant M gene in different hosts and subtypes were independent and not through reassortment. For human influenza virus, positive selection was detected only at position 27. Selective pressures on the sites were not always higher for human influenza virus than for viruses of other hosts. Additionally, selective pressure on position 31 did not increase after the introduction of amantadine. Although there is a possibility of drug pressure on human influenza virus, we could not find positive pressure on position 31. Because the recent rapid increase in drug-resistant virus is associated with the substitution at position 31, the resistance may not be related to drug use.