COVID-19 health system response monitor: Japan

The COVID-19 Health System Response Monitor presents findings from a systematic approach to collect and synthesise up-to-date information on Singapore’s policy response to the COVID-19 outbreak. This publication is part of the APO’s COVID-19 HSRM series which presents detailed information on country-specific responses to COVID-19, to facilitate easy comparisons of health systems and public health, and policy responses to COVID-19. It also aims to strengthen evidence on the global response to the pandemic and allow for easy comparison of activities at national and sub-national levels. The series is updated to reflect changes in the health systems and policies to the COVID-19 response.

Household transmission of influenza (H1N1-2009) in Japan: age-specificity and reduction of household transmission risk by zanamivir treatment.

This study investigated household transmission data for influenza (H1N1-2009) in Japan in order to quantify the age-specific risk of infection and estimate the impact of antiviral treatment on the risk of household transmission. Among a total of 1547 households, involving 4609 household contacts, the secondary attack ratio (SAR) was estimated to be 11.4%. School children aged 5 - 18 years dominated the index cases. Age-specific infectiousness and susceptibility were highest among 0 - 4-year olds, with SAR estimated at 19.4% and 29.6%, respectively. Zanamivir treatment within 24 and 24 - 48 h of illness onset in index cases, respectively, reduced the risk of household transmission to 0.57 (95% CI 0.44, 0.73) and 0.58 (95% CI 0.38, 0.86) times that among those receiving the same treatment at > 48 h and those not receiving treatment. The preventive performance of antiviral treatment and prophylaxis should be further examined in randomized controlled trials.

Influenza pandemic preparedness and severity assessment of pandemic (H1N1) 2009 in South-east Asia.

Pandemic (H1N1) 2009 poses a serious global health threat. However, the global impact of this new pandemic remains uncertain. Past pandemics had different impacts on mortality which varied between countries. Several countries in South-east Asia have already developed their national pandemic preparedness plans. However, these plans have focused on surveillance for and response to the highly pathogenic avian influenza (H5N1), including the rapid containment of H5N1. The newly emerged pandemic (H1N1) 2009 is different from H5N1 in terms of severity and requires different approaches. There are several factors that can potentially affect the severity of pandemic (H1N1) 2009, including a population's vulnerability and response capacity. The pattern of severity appears to be changing with the spread of pandemic (H1N1) 2009, which can be conceptualized in a step-wise manner based on observation of the current situation. The overall impact of pandemic (H1N1) 2009 remains unknown and it is difficult to assess its severity. However, there is an urgent need to assess its potential severity based on the available data so that appropriate responses can be provided in order to mitigate its impact.

Outbreak of measles and rubella in refugee transit camps.

In 2004, concurrent measles and rubella outbreaks occurred in four camps hosting 2767 Liberian refugees in Côte d'Ivoire. Sixty rash and fever cases were identified. From 19 January to 23 February 2004 (weeks 8-13), measles IgM testing showed that 61.1% were positive. The highest incidence rate (18.5%) of measles was observed in children aged <9 months. Ninety-three percent of children aged between 6 months and 15 years received a measles vaccine during week 13, but the rash and fever cases continued to occur. This prompted a systematic test for both measles and rubella IgM antibodies. Rubella IgM testing revealed 74.0% positive cases between 14 February and 25 April (weeks 11-21). The highest incidence rate (3.88%) of rubella was found in children aged between 5 and 15 years. Supplemental immunization with a measles-mumps-rubella (MMR) vaccine was conducted during week 20. This study illustrates the importance of testing for both measles and rubella in outbreaks of rash and fever in refugee settings.

Incidence of amantadine-resistant influenza A viruses in sentinel surveillance sites and nursing homes in Niigata, Japan.

We surveyed the incidence of amantadine-resistant influenza A viruses both at sentinel surveillance sites and at nursing homes, and verified their types of change by partial nucleotide sequence analysis of the M2 protein. Fifty-five influenza A viruses from 27 sentinel surveillance sites during six influenza seasons from 1993 to 1999, and 26 influenza A viruses from 5 nursing homes from 1996 to 1999 were examined for susceptibility to the drug by virus titration in the presence or absence of amantadine. While amantadine-resistant viruses were not found in sentinel surveillance sites, a high frequency of resistance (8/26, 30.8%) in nursing homes was observed. Resistant viruses can occur quickly and be transmitted when used in an outbreak situation at nursing homes, where amantadine is used either for neurologic indications or for influenza treatment. Eight resistant viruses had a single amino acid change of the M2 protein at residue 30 or 31. In vitro, all 11 sensitive viruses turned resistant after 3 or 5 passages in the presence of 2 microg/ml amantadine, and they showed an amino acid change at residue 27, 30, or 31. The predominant amino acid substitution in the M2 protein of resistant viruses is Ser-31-Asp (a change at 31, serine to asparagine). The results indicate that a monitoring system for amantadine-resistant influenza viruses should be established without delay in Japan.

Influenza vaccination levels and influenza-like illness in long-term-care facilities for elderly people in Niigata, Japan, during an influenza A (H3N2) epidemic.

Surveys on influenza vaccination and illness in long-term-care facilities in Niigata Prefecture during an influenza A (H3N2) epidemic revealed that >20% of facilities had outbreaks and >10% of residents experienced influenza. Outbreaks and number of cases were significantly reduced by vaccination, which should be strongly recommended for institutionalized elderly people.

[Incidence of amantadine-resistant influenza A (genotype Ser-31-Asn) in nursing homes in Niigata, Japan].

The antiviral agent amantadine specifically inhibit influenza A virus infection, but the emergence of drug-resistant viruses occur more readily with amantadine treatment. In human influenza viruses, single amino acid changes at 4 sites spanning the transmembrane domain of the M2 protein can confer drug resistance. Amantadine was approved for treatment of Parkinson's disease in 1975, and for the influenza A virus infection in November 1998, in Japan. Annual consumption of amantadine for influenza treatment increased suddenly after the approval. According to our previous report, the predominant genotype of resistant virus is the substitution S-31-N in M2 both in vitro and in clinical samples, as in the other reports. Based on the above findings, we focused on single amino acid change at position 31 (genotype S-31-N) and applied polymerase chain-reaction restriction fragment length polymorphism (PCR-RFLP), directly from throat swab samples, by using primers that insert a restriction site for Sca I. With this technique, we surveyed the incidence of amantadine resistant viruses in nursing homes, Niigata, Japan. Thirty-one (22.0%) of 141 PCR positive samples from 8 nursing homes in 1998-99 season showed resistant patterns, and only 6 (19.4%) of them were after the administration of amantadine for treatment. All of these 8 nursing homes used amantadine for Parkinson's disease, but only half of them used the drug for influenza A infection. The incidence of resistant viruses was not significantly different from facilities with amantadine for influenza treatment to those without, 25.5% and 14.0% respectively. The occurrence of outbreaks and sporadic illness in those facilities, with different administration status were observed, but fortunately we could not find any evidence to relate the emergence of resistant viruses to the outbreaks. This is the first report that the resistant influenza viruses already exist in nursing facilities where amantadine was used for not only influenza but also Parkinson's disease in Japan.

[Antibody induction and frequency of adverse reactions to influenza vaccines in the elderly].

A total of 1,223 elderly people in nursing homes in Niigata Prefecture, Japan, were immunized with one or two doses of commercial trivalent split vaccine formulation, against strains including A/HN, A/H3N2 and B for three seasons (1996-1999). The frequencies of adverse reactions and antibody induction were assessed. Frequent side effects of vaccination were local reactions such as redness and tenderness at the site of injection, but there were no serious reactions, suggesting that the vaccine was quite safe for the elderly. Furthermore, antibody induction by immunization was relatively high and independent of the degree of activities of daily living (ADL). Annual repeated influenza vaccination did not diminish protection against influenza. However, antibody induction against antigens was insufficient in the 1997/1998 season, and further improvement in the combination of quantities of the four included antigens may by required. A booster dose after the first dose did not enhance immune responses in the nursing staff, and the one dose method appeared to be indicated for the elderly.

[Influenza surveillance and control program of WHO].

The World Health Organization(WHO) influenza surveillance network now maintains 110 National Influenza Centers in 83 countries and four WHO Collaborating Centers(London, Atlanta, Melbourne and Tokyo). This network provides useful epidemiological and virological information to decide the recommended vaccine composition each year. Another important role of the network is to detect and analyze potential pandemic strains, since an early detection of pandemic strain is crucial to minimize the impact of the pandemic. WHO continues to improve the global surveillance particularly in China, since China has the important role for the influenza epidemiology in the world. WHO also published Influenza Pandemic Preparedness Plan in 1999.

PCR-RFLP analysis of cytomegalovirus infections associated with bone marrow transplantation in Japanese children.

In order to investigate the longitudinal molecular epidemiology of cytomegalovirus (CMV) infections associated with bone marrow transplantation (BMT) in Japanese children, we analyzed 36 CMV strains from 11 cases. Three regions (DNA polymerase, glycoprotein H, and immediate-early regions) of CMV DNA were amplified by polymerase chain reaction (PCR), and amplified products were each digested with two restriction enzymes, followed by electrophoresis. These restriction fragment length polymorphism (RFLP) analyses allowed the differentiation of 36 strains into 13 genotypes. Each patient excreted his or her own CMV with distinct genotype over the study period of up to one year. CMVs of two different genotypes were recovered during a one-month study from one recipient, who received a peripheral blood stem cell transplantation. Although the majority of patients and donors were CMV-seropositive before BMT, multiple CMV infections might not be common and the reactivation of latently infected CMV might be prominent in Japanese children receiving transplants.

Replication of clinical measles virus strains in hispid cotton rats.

An alternative model to nonhuman primates to study measles virus (MV) pathogenesis, to evaluate potential MV vaccines, or to screen for potential antivirals effective against this virus is highly desirable. The laboratory-adapted Edmonston strain of MV has been reported to replicate in the lungs of hispid cotton rats following intranasal inoculation, immunosuppress infected animals, and disseminate widely from the lungs, making these animals a candidate model. However, clinical MV strains have generally not been found to grow in these animals, limiting the utility and acceptance of this model. In the present studies we demonstrate reproducible replication of several clinical MV strains in hispid cotton rats. As with the Edmonston strain, leukocytes appear to be the primary target cells of these viruses following intranasal inoculation, and extrapulmonary dissemination is common. It is also demonstrated that prior MV infection or immunization of test animals with MV vaccine prevents pulmonary tract infection. These findings should make the MV-cotton rat model more acceptable.

[Analysis of actual coverage of the immunization program in Niigata Prefecture and development of a simple estimation of its coverage].

OBJECTIVE: We investigated measles immunization coverage and the actual situation of immunization in Niigata Pref. METHOD: We distributed questionnaires to all parents of pediatric outpatients who went to hospitals and clinics in Niigata Pref. from January 20 to 31. In the questionnaire, we asked parents about the measles immunization status of not only patients but also their sisters and brothers in each household, reasons for their immunization failure, and sources of information on immunization. We were able to collect 4,840 questionnaires from the parents who lived in Niigata Pref. and analyzable data obtained from 9,783 children. Furthermore we compared these with data from official annual reports of public health centers in Niigata Pref. RESULT: Our survey showed that around 90% of the children who had been born since 1979 to 1993 had received measles vaccine, while the official annual reports indicated low immunization coverage (around 70%). The age at which children received measles vaccine was one year old (38.2% of the vaccinated) and two years old (37.5%), and finally 93.6% of children were immunized by three years old. The primary reason for failure to receive immunization was that he or she was infected with measles before immunization (30.4%). Around 53% of these were infected with measles by 2 years old. With regard to sources of information on immunization, public announcements and letters were the greatest sources, whereas the contribution of doctors and paramedical staffs which was expected to be the main providers of the information to parents was quite low. CONCLUSIONS: 1) It was shown that there was a difference of measles immunization coverage between our results (90%) and the official record (70%), indicating that the current coverage survey method does not reflect the actual situation of immunization. Since more than 90% of children were immunized by three years old, we recommend that measles immunization coverage should be surveyed through interviews and data in maternity record book at the health examination for three year-old children which is operated by the government and has good attendance. 2) More than 50% of children who were infected with measles before immunization were infected by two years old, suggesting further promotion of measles immunization before two years old. 3) The main source of information on immunization was public announcements and publications. Further participation of doctors and paramedical staffs in disseminating information and providing education activities is desired.

Respiratory syncytial virus infection in children with acute respiratory infections in Zambia.

Epidemiological research on respiratory syncytial virus (RSV) infections in children was carried out at the Virology Laboratory, University Teaching Hospital (UTH), in Lusaka, Zambia, from January-December 1996. Specimens including 736 nasal washings and 2424 throat swabs were collected from children with acute respiratory infections (ARI) and tested for RSV by enzyme immunoassay and by virus isolation. RSV was isolated in 62 (4.1%) of 1496 throat swabs collected from March to September and was detected in 99 (16.3%) of 609 nasal washings from March to November. The average RSV isolation rate was 2.6% and the average RSV detection rate was 13.5%. The highest RSV isolation (8.1%) and detection (30.5%) rates were in June 1996. RSV antibody in the 278 serum specimens collected from Zambian children, who were hospitalized in the paediatric ward, UTH, was detected using a standard neutralization test. The antibody positive rate was 60-80% in children > 4 years. It is evident that RSV is one of the main causal agents of ARI in children in Zambia.

Characterization of VP6 subgroup, VP7 and VP4 genotype of rotavirus strains in Lusaka, Zambia.

In a previous study, rotavirus infection was determined in young children at the University Teaching Hospital in Lusaka. In this study, selected rotavirus strains were characterized by monoclonal antibody assay to the VP6 subgroup antigen present and by hybridization analysis of the VP7 and VP4 genes carried by the virus. The majority of the strains were characterized as a VP6 subgroup II, VP7 serotype G1 strain with a long electropherotype and bearing the VP4 P8 genotype. A further four minor rotavirus strains with a long RNA electropherotype and subgroup II antigen were also observed to be circulating bearing G1 or G4 VP7 genes and the VP4 P8 genotype. Two electrophoretic strains with differing short RNA electropherotypes and subgroup I antigenicity were also present. These strains hybridized to the VP7 type G2 and VP4 P4 genotype probes.

Laboratory diagnosis of acute measles infections in hospitalized children in Zambia.

Laboratory diagnosis of measles infection is rarely performed in developing countries and tends to depend on clinical symptoms alone. We evaluated detection of immunoglobulin M (IgM) antibodies for confirmation of acute measles infection in Zambia. In 149 hospitalized children with clinical diagnosis of measles, IgM antibodies were detected in 88.6% (132/149). The IgM-positive rate increased with time after onset of skin rash and all samples were positive after 4 days. In addition to IgM antibody test, virus isolations from throat swabs using B95a cells were also performed. These were positive in only 20.9% (14/67), and both IgM and virus isolation in combination increased the positive rate to 92.5% (62/67). Vaccinated children had higher neutralizing (Nt) antibody responses and, among IgM-negative patients, all 4 vaccinated children had high Nt antibodies while all 10 unvaccinated children had negative or low Nt results. The IgM antibody test was proved to be a sensitive method for laboratory confirmation of measles virus infection in developing countries.