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  1. Yusof MA, Ali HM
    Radiat Prot Dosimetry, 2011 Jul;146(1-3):38-41.
    PMID: 21729940 DOI: 10.1093/rpd/ncr102
    Planning and preparation in advance for radiological emergencies can help to minimise potential public health and environmental threats if and when an actual emergency occurs. During the planning process, emergency response organisations think through how they would respond to each type of incident and the resources that will be needed. In Malaysia, planning, preparation for and response to radiological emergencies involve many parties. In the event of a radiological emergency and if it is considered a disaster, the National Security Council, the Atomic Energy Licensing Board and the Malaysian Nuclear Agency (Nuclear Malaysia) will work together with other federal agencies, state and local governments, first responders and international organisations to monitor the situation, contain the release, and clean up the contaminated site. Throughout the response, these agencies use their protective action guidelines. This paper discusses Malaysian preparedness for, and response to, any potential radiological emergency.
  2. Johari MI, Ismail MN, Mohamad F, Yusof MA
    BMJ Case Rep, 2021 Jan 18;14(1).
    PMID: 33461997 DOI: 10.1136/bcr-2020-236420
    Primary cardiac valve tumours are rare. This is a case report of a 32-year-old non-smoker man with a history of stroke 1 year prior and no other cardiovascular risk factors. The patient was admitted to our acute stroke ward for recurrent left hemiparesis, slurring of speech, facial asymmetry and central retinal artery occlusion. Initial laboratory investigations and ECG were normal. An urgent CT brain showed a large hypodense area at the right frontal, parietal, temporal, occipital region with effaced sulci and right lateral ventricle with midline shift and cerebral oedema in keeping with acute infarction. We proceeded with CT angiography of the cerebral and carotid on the following day, which revealed no evidence of thrombosis, aneurysm or arteriovenous malformation. There were no abnormal beaded vessels to suggest vasculitis. Transthoracic echocardiography revealed a large mobile mass in the left atrium. Meanwhile, MRI cardiac confirmed a large ill-defined mobile solid mass attached to the mitral valve's inferoseptal component suggestive of mitral valve myxoma. This case report highlights the significance of considering a cardiogenic source of emboli in patients with large cerebral infarcts and other cardiac embolic phenomena. Imaging modalities such as echocardiography and cardiac MRI will help detect treatable conditions, such as valvular myxoma and prevent further complications.
  3. Suppiah J, Yusof MA, Othman KA, Saraswathy TS, Thayan R, Kasim FM, et al.
    PMID: 21323171
    The 2009 pandemic influenza A(H1N1) infection in Malaysia was first reported in May 2009 and oseltamivir was advocated for confirmed cases in postexposure prophylaxis. However, there are cases of oseltamivir-resistance reported among H1N1-positive patients in other countries. Resistance is due to substitution of histidine by tyrosine at residue 275 (H275Y) of neuraminidase (NA). In this study, we have employed Sanger sequencing method to investigate the occurrence of mutations in NA segments of 67 pandemic 2009 A(H1N1) viral isolates from Malaysian patients that could lead to probable oseltamivir resistance. The sequencing analysis did not yield mutation at residue 275 for all 67 isolates indicating that our viral isolates belong to the wild type and do not confer resistance to oseltamivir.
  4. Thayan R, Yusof MA, Saat Z, Sekaran SD, Wang SM
    Methods Mol Biol, 2016;1426:11-9.
    PMID: 27233257 DOI: 10.1007/978-1-4939-3618-2_2
    Molecular surveillance of Chikungunya virus (CHIKV) is important as it provides data on the circulating CHIKV genotypes in endemic countries and enabling activation of measures to be taken in the event of a pending outbreak. Molecular surveillance is carried out by first detecting CHIKV in susceptible humans or among field-caught mosquitoes. This is followed by sequencing a selected region of the virus which will provide evidence on the source of the virus and possible association of the virus to increased cases of Chikungunya infections.
  5. Kamaruzaman HF, Ku Abd Rahim KN, Mohamed Ghazali IM, Mohd Yusof MA
    PMID: 33745482 DOI: 10.1017/S0266462321000118
    Patient and public involvement (PPI) in health technology assessment (HTA) is widely promoted to ensure that all health-related decisions are made after taking into consideration the viewpoints of important stakeholders. In Malaysia, patients or their representatives have been involved in the development of HTA and Clinical Practice Guidelines (CPG) since 2009 and their influences have been growing steadily over the years. This paper aimed to describe the journey, achievements, challenges, and future direction of the PPI throughout all stages of the development and implementation of HTA and CPG in Malaysia. Currently, in Malaysia, patients or their representatives are mainly involved during the initial development of HTA and CPG drafts as well as during the internal and external reviews. Additionally, they are also encouraged to be involved during the implementation of HTA and CPG recommendations. Although their involvement in this aspect has slowly increased over time, challenges remain in the form of limited representativeness of selected patients or carers, uncertainty on the level of patient involvement allowed during the HTA/CPG development processes, and limited health literacy, which affect their ability to contribute meaningfully throughout the processes. Continuous improvement in these processes is important as patients or their representatives play a pivotal role in ensuring transparency, accountability, and credibility throughout the HTA/CPG development and decision-making processes.
  6. Yusof MA, Rashid TR, Thayan R, Othman KA, Hasan NA, Adnan N, et al.
    Emerg Infect Dis, 2012 May;18(5):852-4.
    PMID: 22515984 DOI: 10.3201/eid1805.110865
    In March 2011, an outbreak of acute respiratory disease was reported at the Kuala Lumpur (Malaysia) Police Training Centre. Approximately 100 trainees were hospitalized and 5 were admitted to the intensive care unit. Three of these 5 trainees died. Human adenovirus type 7 was identified as the etiologic agent.
  7. Saat Z, Abdul Rashid TR, Yusof MA, Kassim FM, Thayan R, Kuen LS, et al.
    PMID: 21329312
    From 2005 to 2009, the Institute for Medical Research (IMR), Kuala Lumpur received a total of 7,117 respiratory specimens from patients with influenza-like illness (ILI) for influenza screening. Seasonal influenza virus was isolated from 17.3% of patients with ILI in 2005, 31.6% in 2006, 12.8% in 2007, 10.2% in 2008 and 13.5% in 2009. There were one or more influenza A and B virus strains circulating in Malaysia throughout the year, with distinctly a peak in May to August. The predominant circulating strains of seasonal influenza A were A/California/7/2004-like (H3N2) in 2005, A/New Caledonia/20/99-like (H1N1) in 2006, A/ Brisbane/10/2007-like (H3N2) in 2007 and 2008, and A/Perth/16/2009-like (H3N2) virus in 2009. The predominant circulating strains of influenza B were B/Hong Kong/330/2001-like in 2005, B/Malaysia/2506/2004-like in 2006, B/Florida/4/2006-like in 2007 and 2008, and B/Brisbane/60/2008-like in 2009.
  8. Sam IC, Noraini W, Sandhu SS, Norizah I, Selvanesan S, Thayan R, et al.
    J Med Virol, 2019 03;91(3):498-502.
    PMID: 30199092 DOI: 10.1002/jmv.25313
    Influenza seasonality in equatorial countries is little understood. Seasonal and alert influenza thresholds were determined for Malaysia, using laboratory-based data obtained from the Malaysia Influenza Surveillance System and a major teaching hospital, from 2011 to 2016. Influenza was present year-round, with no clear annual seasons. Variable periods of higher transmission occurred inconsistently, in November to December, January to March, July to September, or a combination of these. These coincide with seasons in the nearby southeast Asian countries or winter seasons of the northern and southern hemispheres. Changes in the predominant circulating influenza type were only sometimes associated with increased transmission. The data can provide public health interventions such as vaccines.
  9. Mohd-Taib FS, Ishak SN, Yusof MA, Azhari NN, Md-Lasim A, Md Nor S, et al.
    Trop Biomed, 2020 Mar 01;37(1):142-154.
    PMID: 33612725
    Leptospirosis is a zoonotic disease caused by bacteria of the genus Leptospira and most often acquired through contact with environments contaminated with leptospires shed in the urine of infected mammals. In urban environment, rodents are well-known as the main carriers of this bacteria, however there were no intensive study on the population structure of these animals, and how it associated with this disease. Hence, we use a case study from an outbreak in a residential area in Selangor, Malaysia, to investigate how community structure of small mammals, associated with the prevalence of Leptospira. One hundred cage traps were placed randomly in and around these houses in five phases with two months interval for a year. Community structures (species, sex, and age) were assigned for each individual, prior to screening for pathogenic Leptospira, using a partial lipL32 gene from the kidney samples. 185 small mammals from four species were captured, Rattus norvegicus (74.5%, N=138), R. rattus (20%, N=37), Tupaia glis (5%, N=9), and Suncus murinus (0.5%, N=1). From this number, 29 individuals were found PCR positive for pathogenic Leptospira (R. norvegicus, N=20; R. rattus, N=6; T. glis, N=2; S. murinus, N=1). The study shows that Leptospira occurrence in the small mammals were significantly correlated to age category and sampling phases, with Spearman Correlation (rs) p=0.02 and p=0.04 respectively. Adult individuals were significantly more prevalent with Leptospira infection, whereby March and June were found to associate with higher Leptospira prevalent among the small mammals, potentially coincide with low rainfall and relative humidity level. This information is important in designing a specific control method for rodents in Leptospira outbreak areas. In addition, intensive sampling and regular cleaning effort were found to significantly reduce the small mammal Leptospira reservoir, thus should be implemented in intervention strategies in the urban environment.
  10. Perera D, Yusof MA, Podin Y, Ooi MH, Thao NT, Wong KK, et al.
    Arch Virol, 2007;152(6):1201-8.
    PMID: 17308978
    A phylogenetic analysis of VP1 and VP4 nucleotide sequences of 52 recent CVA16 strains demonstrated two distinct CVA16 genogroups, A and B, with the prototype strain being the only member of genogroup A. CVA16 G-10, the prototype strain, showed a nucleotide difference of 27.7-30.2% and 19.9-25.2% in VP1 and VP4, respectively, in relation to other CVA16 strains, which formed two separate lineages in genogroup B with nucleotide variation of less than 13.4% and less than 16.3% in VP1 and VP4, respectively. Lineage 1 strains circulating before 2000 were later displaced by lineage 2 strains.
  11. Saraswathy Subramaniam TS, Thayan R, Yusof MA, Suppiah J, Tg Abd Rashid TR, Zawawi ZM, et al.
    Asian Pac J Trop Med, 2016 Feb;9(2):201-3.
    PMID: 26919957 DOI: 10.1016/j.apjtm.2016.01.016
    An efficient public health preparedness and response plan for infectious disease management is important in recent times when emerging and exotic diseases that hitherto were not common have surfaced in countries with potential to spread outside borders. Stewardship from a reference laboratory is important to take the lead for the laboratory network, to proactively set up disease surveillance, provide referral diagnostic services, on-going training and mentorship and to ensure coordination of an effective laboratory response. In Malaysia, the Institute for Medical Research has provided the stewardship for the Ministry of Health's laboratory network that comprises of hospital pathology, public health and university laboratories. In this paper we share our experiences in recent infectious disease outbreak investigations as a reference laboratory within the Ministry of Health infectious disease surveillance network.
  12. Neela VK, Azhari NN, Joseph N, Mimie NP, Ramli SNA, Mustapha NF, et al.
    Eur J Clin Microbiol Infect Dis, 2019 Mar;38(3):523-528.
    PMID: 30680558 DOI: 10.1007/s10096-018-03450-6
    Here, we investigated an outbreak of leptospirosis among reserve military recruits that occurred following a survival exercise in the Hulu Perdik forest within the Hulu Langat district, Kuala Lumpur, Malaysia. Blood samples from the 12 patients that presented symptoms for febrile illness on clinical examination were subjected to laboratory investigation, comprising Lepto IgM rapid test, IgM ELISA, and microscopic agglutination test (MAT). All these patients were interviewed for possible risk factors for leptospirosis. Rodent trapping and environmental sampling for possible isolation of leptospires in the outbreak site was performed. The isolated leptospires were genetically characterized and investigated for the potential epidemiological link with human leptospirosis. Among the 12 patients, two (2/12; 16.6%) were confirmed positive for leptospirosis by microscopic agglutination test (MAT with titers 400-800; serovar autumnalis and hardjobovis). Two Leptospira species from rodents (L. interrogans and L. borgpetersenii) and two from the environment (L. kmetyi and L. wolffii) were identified. The possible epidemiological link between human serovars and animal Leptospira species indicates rodents as the potential reservoir while the environment (soil and water) serves as a transmission route. This investigation highlights the robust presence of pathogenic leptospires on Malaysian environment and rodents which may present the risk of infection, especially among high-risk individuals. Hence, occupational risk individuals are cautioned to observe appropriate preventive measures including prophylaxis and seek immediate medical attention for any illness following similar activities.
  13. Shimizu H, Utama A, Yoshii K, Yoshida H, Yoneyama T, Sinniah M, et al.
    Jpn J Infect Dis, 1999 Feb;52(1):12-5.
    PMID: 10808253
    Enterovirus 71 (EV71), one of the major causative agents for hand, foot and mouth disease (HFMD), is sometimes associated with severe central nervous system diseases. In 1997, in Malaysia and Japan, and in 1998 in Taiwan, there were HFMD epidemics involving sudden deaths among young children, and EV71 was isolated from the HFMD patients, including the fatal cases. The nucleotide sequences of each EV71 isolate were determined and compared by phylogenetical analysis. EV71 strains from previously reported epidemics belonged to genotype A-1, while those from recent epidemics could be divided into two genotypes, A-2 and B. In Malaysia, genotype A-2 was more prevalent, while in Japan and Taiwan, B genotype was more prevalent. Two isolates from fatal cases in Malaysia and one isolate from a fatal case in Japan were genotype A-2. However, all isolates from three fatal cases in Taiwan belonged to genotype B. The severity of the HFMD did not link directly to certain genotypes of EV71.
  14. Ariff MI, Yahya A, Zaki R, Sarimin R, Mohamed Ghazali IM, Gill BS, et al.
    PLoS One, 2017;12(5):e0178137.
    PMID: 28562626 DOI: 10.1371/journal.pone.0178137
    Clinical Practice Guideline (CPG) provides evidence-based guidance for the management of Dengue Infection in adult patients. A cross sectional study was conducted to evaluate awareness and utilization of CPG among doctors in public or private hospitals and clinics in Malaysia. Doctors practicing only at hospital Medical and Emergency Departments were included, while private specialist clinics were excluded in this study. A multistage proportionate random sampling according to region (Central, Northern, Southern, Eastern, Sabah and Sarawak) was performed to select study participants. The overall response rate was 74% (84% for public hospitals, 82% for private hospitals, 70% for public clinics, and 64% for private clinics). The CPG Awareness and Utilization Feedback Form were used to determine the percentage in the study. The total numbers of respondent were 634 with response rate of 74%. The mean lengths of service of the respondent were 13.98 (11.55).A higher percentages of doctors from public facilities (99%) were aware of the CPG compared to those in private facilities (84%). The percentage of doctors utilising the CPG were also higher (98%) in public facilities compared to private facilities (86%). The percentage of Medical Officer in private facilities that utilizing the CPG were 84% compares to Medical Officer in public facilities 98%. The high percentage of doctors using the CPG in both public (97%) and private (94%) hospitals were also observed. However, only 69% of doctors in private clinics utilised the CPG compared to doctors in public clinics (98%). Doctors in both public and private facilities were aware of the dengue CPG. However, most doctors in private clinic were less likely to utilise the CPG. Therefore, there is a need to increase the level of CPG utilisation especially in private clinics.
    Study site: primary care and hospital from Medical and Emergency Department, public and private health facilities in Malaysia
  15. Yusof MA, Mohd-Taib FS, Ishak SN, Md-Nor S, Md-Sah SA, Mohamed NZ, et al.
    Ecohealth, 2019 06;16(2):260-274.
    PMID: 31124020 DOI: 10.1007/s10393-019-01419-1
    Leptospirosis, a widespread zoonotic disease, is a public health problem, especially in major urban centres, and is mainly reported to be associated with rats. In Malaysia, focus has been primarily given to the Leptospira prevalence in rodents per se, but there is lack of information on the microhabitat structure of the outbreak areas. We aimed to determine the diversity of small mammal species, microhabitat types, and their prevalence of pathogenic Leptospira spp. in the outbreak areas, which were categorized as urban, semi-urban, and recreational forests. Sampling involved deploying 100 to 300 live traps at each study site. Kidney samples were extracted from selected individuals, for screening of pathogenic Leptospira spp. by PCR. Out of 537 individuals from 15 small mammal species captured, 4 species were recorded from urban, 13 from semi-urban, and 11 from recreational forest sites. From 389 individuals screened, 58 were tested positive for pathogenic Leptospira. Recreational forests recorded the highest prevalence with 19.4% (n = 93), followed by urban, 16.6% (n = 163) and semi-urban sites with 9.8% (n = 133). Seven rodent species were tested positive for pathogenic Leptospira from all areas. R. norvegicus was found to harbour the highest prevalence (66.7%) in urban, R. rattus (53.8%) in semi-urban, whereby M. whiteheadi (44.4%) in recreational forest sites. Microhabitat analysis revealed that rubbish quantity contributed especially strongly to a high prevalence of Leptospira. This study contributes to understanding of the host and microhabitat preferences of Leptospira, which is important in controlling the spread of this disease in human's landscapes.
  16. Podin Y, Gias EL, Ong F, Leong YW, Yee SF, Yusof MA, et al.
    BMC Public Health, 2006 Jul 07;6:180.
    PMID: 16827926
    BACKGROUND: A major outbreak of human enterovirus 71-associated hand, foot and mouth disease in Sarawak in 1997 marked the beginning of a series of outbreaks in the Asia Pacific region. Some of these outbreaks had unusually high numbers of fatalities and this generated much fear and anxiety in the region.

    METHODS: We established a sentinel surveillance programme for hand, foot and mouth disease in Sarawak, Malaysia, in March 1998, and the observations of the first 7 years are described here. Virus isolation, serotyping and genotyping were performed on throat, rectal, vesicle and other swabs.

    RESULTS: During this period Sarawak had two outbreaks of human enterovirus 71, in 2000 and 2003. The predominant strains circulating in the outbreaks of 1997, 2000 and 2003 were all from genogroup B, but the strains isolated during each outbreak were genetically distinct from each other. Human enterovirus 71 outbreaks occurred in a cyclical pattern every three years and Coxsackievirus A16 co-circulated with human enterovirus 71. Although vesicles were most likely to yield an isolate, this sample was not generally available from most cases and obtaining throat swabs was thus found to be the most efficient way to obtain virological information.

    CONCLUSION: Knowledge of the epidemiology of human enterovirus 71 transmission will allow public health personnel to predict when outbreaks might occur and to plan interventions in an effective manner in order to reduce the burden of disease.

  17. Tharumaraja T, Che-Ahmad A, Wong PF, Ahmad Hamid AH, Hasan MI, Bajuri MY, et al.
    Malays Fam Physician, 2021 Mar 25;16(1):103-113.
    PMID: 33948148 DOI: 10.51866/cpg0001
    Diabetic foot requires careful attention and coordinated management by a dedicated team. Screening, prevention, adequate assessment, and appropriate referral are crucial to prevent complications. Multimodal treatment and rehabilitation are recommended to ensure a better quality of life and reduction of amputation rate in people with diabetic foot.
  18. Azhari NN, Ramli SNA, Joseph N, Philip N, Mustapha NF, Ishak SN, et al.
    Acta Trop, 2018 Dec;188:68-77.
    PMID: 30145261 DOI: 10.1016/j.actatropica.2018.08.020
    Leptospirosis is caused by the spirochetal bacterium Leptospira of which rodents are considered the most important reservoir. This study aims to determine and characterize virulent Leptospira species among rodents and small mammals found in human settlements and recreational spots within the Hulu Langat and Gombak districts of Selangor, Malaysia; regions that frequently report probable human leptospirosis cases. Molecular analysis revealed an overall Leptospira detection rate of 14.3% among the 266 small mammals captured, and the human settlements were found to have the highest number of isolates (15.1%), followed by recreational sites (14.5%). The molecular characterization conducted based on the lipL32, secY genes and MLST revealed that the strains belonged to four different species, including; Leptospira interrogans (29; 76.3%; ST50, ST238, ST243), L. kirschneri (5; 13.15%; ST110), L. borgpetersenii (3; 8%; ST143) and L. weilii (1; 2.63%; ST242). The study revealed genotypes of circulating strains among small mammals in Malaysia, which include Leptospira locus ST110 L. kirschneri, ST 50 L. interrogans, ST143 L. borgpetersenii and ST242 L. weilii. Among the small mammals studied, 17/105 (16.2%) Rattus norvegicus, 7/59 (11.9%) of Rattus rattus, 5/24 (20.8%) of Maxomys whiteheadi, 4/18 (22.2%) of Sundamys muelleri, 2/22 (9%), Tupaia gliss, 2/16 (12.5%) Rattus tiomanicus and 1/4 (25%) of Suncus murinus carried pathogenic leptospires. The data from the present study may imply that, in addition to rodents, other small mammals also serve as maintenance hosts for Leptospira. Hence, much remains unknown about Leptospira maintenance hosts, and there is need for further investigation to ascertain the prevailing serovars of pathogenic Leptospira in Malaysia. This will assist in the development of efficient diagnostic assays with improved microscopic agglutination test (MAT) panels, and in the implementation of suitable prevention and control measures.
  19. Abd Rahman M, Ahmad Zaki R, Sarimin R, Ariff MI, Suli Z, Mahmud M, et al.
    PLoS One, 2017;12(11):e0184559.
    PMID: 29095822 DOI: 10.1371/journal.pone.0184559
    The Malaysian Dengue Clinical Practice Guidelines (CPG) have been developed to provide evidence-based guidance in the management of dengue infections. The use of these guidelines is essential to ensure its recommendations are being practiced. However, the adherence to the guidelines for management of dengue (revised 2nd edition) by healthcare providers still remains unknown. Therefore, the aim of this study was to evaluate the proportion among healthcare providers that adhere to this Dengue CPG. A retrospective cohort study of dengue cases registered from 1 January 2014 to 1 June 2015 was conducted in public hospitals and health clinics in Selangor, Putrajaya and Kuala Lumpur. Adherence to the CPG recommendations were recorded by reviewing patients' case notes. Overall proportion of adherence in clinical components of the recommendation were (7.1 to 100.0% versus 7.7 to 73.8%) in history taking, (6.7 to 100.0% versus 12.3 to 60.0%) in physical examinations, (18.4 to 100.0% versus 23.1 to 83.2%) in assessment of warning signs, (0.6 to 100.0% versus 12.3 to 87.7%) in assessment of haemodynamic status, (60.0 to 100.0% versus 27.7 to 40.0%) in diagnosis, (46.6 to 80.0% versus 52.3%) in case notifications, (73.2 to 100.0% versus 89.2 to 96.9%) in performing specific laboratory investigations and (7.9 to 100.0% versus 21.5%) in monitoring, for outpatient versus inpatient, respectively. Adherence trends were demonstrated to be higher in hospital settings compared to outpatient settings. Adherence to this Dengue CPG varies widely with overall good clinical outcomes observed.

    Study site: public hospitals and health clinics in Selangor, Putrajaya and Kuala Lumpur
  20. Saha S, Chadha M, Al Mamun A, Rahman M, Sturm-Ramirez K, Chittaganpitch M, et al.
    Bull World Health Organ, 2014 May 01;92(5):318-30.
    PMID: 24839321 DOI: 10.2471/BLT.13.124412
    OBJECTIVE: To characterize influenza seasonality and identify the best time of the year for vaccination against influenza in tropical and subtropical countries of southern and south-eastern Asia that lie north of the equator.

    METHODS: Weekly influenza surveillance data for 2006 to 2011 were obtained from Bangladesh, Cambodia, India, Indonesia, the Lao People's Democratic Republic, Malaysia, the Philippines, Singapore, Thailand and Viet Nam. Weekly rates of influenza activity were based on the percentage of all nasopharyngeal samples collected during the year that tested positive for influenza virus or viral nucleic acid on any given week. Monthly positivity rates were then calculated to define annual peaks of influenza activity in each country and across countries.

    FINDINGS: Influenza activity peaked between June/July and October in seven countries, three of which showed a second peak in December to February. Countries closer to the equator had year-round circulation without discrete peaks. Viral types and subtypes varied from year to year but not across countries in a given year. The cumulative proportion of specimens that tested positive from June to November was > 60% in Bangladesh, Cambodia, India, the Lao People's Democratic Republic, the Philippines, Thailand and Viet Nam. Thus, these tropical and subtropical countries exhibited earlier influenza activity peaks than temperate climate countries north of the equator.

    CONCLUSION: Most southern and south-eastern Asian countries lying north of the equator should consider vaccinating against influenza from April to June; countries near the equator without a distinct peak in influenza activity can base vaccination timing on local factors.

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