Displaying publications 21 - 40 of 162 in total

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  1. Sady H, Al-Mekhlafi HM, Mahdy MA, Lim YA, Mahmud R, Surin J
    PLoS Negl Trop Dis, 2013;7(8):e2377.
    PMID: 23991235 DOI: 10.1371/journal.pntd.0002377
    BACKGROUND: Schistosomiasis, one of the most prevalent neglected tropical diseases, is a life-threatening public health problem in Yemen especially in rural communities. This cross-sectional study aims to determine the prevalence and associated risk factors of schistosomiasis among children in rural Yemen.

    METHODS/FINDINGS: Urine and faecal samples were collected from 400 children. Urine samples were examined using filtration technique for the presence of Schistosoma haematobium eggs while faecal samples were examined using formalin-ether concentration and Kato Katz techniques for the presence of S. mansoni. Demographic, socioeconomic and environmental information were collected via a validated questionnaire. Overall, 31.8% of the participants were found to be positive for schistosomiasis; 23.8% were infected with S. haematobium and 9.3% were infected with S. mansoni. Moreover, 39.5% of the participants were anaemic whereas 9.5% had hepatosplenomegaly. The prevalence of schistosomiasis was significantly higher among children aged >10 years compared to those aged ≤ 10 years (P<0.05). Multivariate analysis confirmed that presence of other infected family member (P<0.001), low household monthly income (P = 0.003), using unsafe sources for drinking water (P = 0.003), living nearby stream/spring (P = 0.006) and living nearby pool/pond (P = 0.002) were the key factors significantly associated with schistosomiasis among these children.

    CONCLUSIONS/SIGNIFICANCE: This study reveals that schistosomiasis is still highly prevalent in Yemen. These findings support an urgent need to start an integrated, targeted and effective schistosomiasis control programme with a mission to move towards the elimination phase. Besides periodic drug distribution, health education and community mobilisation, provision of clean and safe drinking water, introduction of proper sanitation are imperative among these communities in order to curtail the transmission and morbidity caused by schistosomiasis. Screening and treating other infected family members should also be adopted by the public health authorities in combating this infection in these communities.

  2. Sam SS, Omar SF, Teoh BT, Abd-Jamil J, AbuBakar S
    PLoS Negl Trop Dis, 2013;7(5):e2194.
    PMID: 23658849 DOI: 10.1371/journal.pntd.0002194
    Dengue is a mosquito-borne viral disease endemic in many countries in the tropics and sub-tropics. The disease affects mainly children, but in recent years it is becoming more of an adult disease. Malaysia experienced a large dengue outbreak in 2006 to 2007, involving mostly adults, with a high number of deaths.
  3. Tan PC, Soe MZ, Si Lay K, Wang SM, Sekaran SD, Omar SZ
    PLoS Negl Trop Dis, 2012;6(5):e1637.
    PMID: 22590658 DOI: 10.1371/journal.pntd.0001637
    Dengue is the most prevalent mosquito borne infection worldwide. Vertical transmissions after maternal dengue infection to the fetus and pregnancy losses in relation to dengue illness have been reported. The relationship of dengue to miscarriage is not known.
  4. Haddow AD, Schuh AJ, Yasuda CY, Kasper MR, Heang V, Huy R, et al.
    PLoS Negl Trop Dis, 2012;6(2):e1477.
    PMID: 22389730 DOI: 10.1371/journal.pntd.0001477
    Zika virus (ZIKV) is a mosquito-borne flavivirus distributed throughout much of Africa and Asia. Infection with the virus may cause acute febrile illness that clinically resembles dengue fever. A recent study indicated the existence of three geographically distinct viral lineages; however this analysis utilized only a single viral gene. Although ZIKV has been known to circulate in both Africa and Asia since at least the 1950s, little is known about the genetic relationships between geographically distinct virus strains. Moreover, the geographic origin of the strains responsible for the epidemic that occurred on Yap Island, Federated States of Micronesia in 2007, and a 2010 pediatric case in Cambodia, has not been determined.
  5. Franco L, Palacios G, Martinez JA, Vázquez A, Savji N, De Ory F, et al.
    PLoS Negl Trop Dis, 2011 Aug;5(8):e1251.
    PMID: 21829739 DOI: 10.1371/journal.pntd.0001251
    Dengue virus (DENV) circulates in human and sylvatic cycles. Sylvatic strains are both ecologically and evolutionarily distinct from endemic viruses. Although sylvatic dengue cycles occur in West African countries and Malaysia, only a few cases of mild human disease caused by sylvatic strains and one single case of dengue hemorrhagic fever in Malaysia have been reported. Here we report a case of dengue hemorrhagic fever (DHF) with thrombocytopenia (13000/µl), a raised hematocrit (32% above baseline) and mucosal bleeding in a 27-year-old male returning to Spain in November 2009 after visiting his home country Guinea Bissau. Sylvatic DENV-2 West African lineage was isolated from blood and sera. This is the first case of DHF associated with sylvatic DENV-2 in Africa and the second case worldwide of DHF caused by a sylvatic strain.
  6. Li MH, Fu SH, Chen WX, Wang HY, Guo YH, Liu QY, et al.
    PLoS Negl Trop Dis, 2011 Jul;5(7):e1231.
    PMID: 21750744 DOI: 10.1371/journal.pntd.0001231
    Japanese encephalitis (JE) is a global public health issue that has spread widely to more than 20 countries in Asia and has extended its geographic range to the south Pacific region including Australia. JE has become the most important cause of viral encephalitis in the world. Japanese encephalitis viruses (JEV) are divided into five genotypes, based on the nucleotide sequence of the envelope (E) gene. The Muar strain, isolated from patient in Malaya in 1952, is the sole example of genotype V JEV. Here, the XZ0934 strain of JEV was isolated from Culex tritaeniorhynchus, collected in China. The complete nucleotide and amino acid sequence of XZ0934 strain have been determined. The nucleotide divergence ranged from 20.3% to 21.4% and amino acid divergence ranged from 8.4% to 10.0% when compared with the 62 known JEV isolates that belong to genotype I-IV. It reveals low similarity between XZ0934 and genotype I-IV JEVs. Phylogenetic analysis using both complete genome and structural gene nucleotide sequences demonstrates that XZ0934 belongs to genotype V. This, in turn, suggests that genotype V JEV is emerging in JEV endemic areas. Thus, increased surveillance and diagnosis of viral encephalitis caused by genotype V JEV is an issue of great concern to nations in which JEV is endemic.
  7. Alhoot MA, Wang SM, Sekaran SD
    PLoS Negl Trop Dis, 2011 Nov;5(11):e1410.
    PMID: 22140591 DOI: 10.1371/journal.pntd.0001410
    Dengue infection ranks as one of the most significant viral diseases of the globe. Currently, there is no specific vaccine or antiviral therapy for prevention or treatment. Monocytes/macrophages are the principal target cells for dengue virus and are responsible for disseminating the virus after its transmission. Dengue virus enters target cells via receptor-mediated endocytosis after the viral envelope protein E attaches to the cell surface receptor. This study aimed to investigate the effect of silencing the CD-14 associated molecule and clathrin-mediated endocytosis using siRNA on dengue virus entry into monocytes.
  8. Fry SR, Meyer M, Semple MG, Simmons CP, Sekaran SD, Huang JX, et al.
    PLoS Negl Trop Dis, 2011 Jun;5(6):e1199.
    PMID: 21713023 DOI: 10.1371/journal.pntd.0001199
    BACKGROUND: Serological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1) has been identified as an early marker for acute dengue, and is typically present between days 1-9 post-onset of illness but following seroconversion it can be difficult to detect in serum.
    AIMS: To evaluate the performance of a newly developed Panbio® Dengue Early Rapid test for NS1 and determine if it can improve diagnostic sensitivity when used in combination with a commercial IgM/IgG rapid test.
    METHODOLOGY: The clinical performance of the Dengue Early Rapid was evaluated in a retrospective study in Vietnam with 198 acute laboratory-confirmed positive and 100 negative samples. The performance of the Dengue Early Rapid in combination with the IgM/IgG Rapid test was also evaluated in Malaysia with 263 laboratory-confirmed positive and 30 negative samples.
    KEY RESULTS: In Vietnam the sensitivity and specificity of the test was 69.2% (95% CI: 62.8% to 75.6%) and 96% (95% CI: 92.2% to 99.8) respectively. In Malaysia the performance was similar with 68.9% sensitivity (95% CI: 61.8% to 76.1%) and 96.7% specificity (95% CI: 82.8% to 99.9%) compared to RT-PCR. Importantly, when the Dengue Early Rapid test was used in combination with the IgM/IgG test the sensitivity increased to 93.0%. When the two tests were compared at each day post-onset of illness there was clear differentiation between the antigen and antibody markers.
    CONCLUSIONS: This study highlights that using dengue NS1 antigen detection in combination with anti-glycoprotein E IgM and IgG serology can significantly increase the sensitivity of acute dengue diagnosis and extends the possible window of detection to include very early acute samples and enhances the clinical utility of rapid immunochromatographic testing for dengue.
  9. Engelthaler DM, Bowers J, Schupp JA, Pearson T, Ginther J, Hornstra HM, et al.
    PLoS Negl Trop Dis, 2011 Oct;5(10):e1347.
    PMID: 22028940 DOI: 10.1371/journal.pntd.0001347
    Melioidosis is caused by Burkholderia pseudomallei, a Gram-negative bacillus, primarily found in soils in Southeast Asia and northern Australia. A recent case of melioidosis in non-endemic Arizona was determined to be the result of locally acquired infection, as the patient had no travel history to endemic regions and no previous history of disease. Diagnosis of the case was confirmed through multiple microbiologic and molecular techniques. To enhance the epidemiological analysis, we conducted several molecular genotyping procedures, including multi-locus sequence typing, SNP-profiling, and whole genome sequence typing. Each technique has different molecular epidemiologic advantages, all of which provided evidence that the infecting strain was most similar to those found in Southeast Asia, possibly originating in, or around, Malaysia. Advancements in new typing technologies provide genotyping resolution not previously available to public health investigators, allowing for more accurate source identification.
  10. Ngui R, Ishak S, Chuen CS, Mahmud R, Lim YA
    PLoS Negl Trop Dis, 2011;5(3):e974.
    PMID: 21390157 DOI: 10.1371/journal.pntd.0000974
    Intestinal parasitic infections (IPIs) have a worldwide distribution and have been identified as one of the most significant causes of illnesses and diseases among the disadvantaged population. In Malaysia, IPIs still persist in some rural areas, and this study was conducted to determine the current epidemiological status and to identify risk factors associated with IPIs among communities residing in rural and remote areas of West Malaysia.
  11. Cardosa J, Ooi MH, Tio PH, Perera D, Holmes EC, Bibi K, et al.
    PLoS Negl Trop Dis, 2009;3(4):e423.
    PMID: 19399166 DOI: 10.1371/journal.pntd.0000423
    Dengue viruses circulate in both human and sylvatic cycles. Although dengue viruses (DENV) infecting humans can cause major epidemics and severe disease, relatively little is known about the epidemiology and etiology of sylvatic dengue viruses. A 20-year-old male developed dengue hemorrhagic fever (DHF) with thrombocytopenia (12,000/ul) and a raised hematocrit (29.5% above baseline) in January 2008 in Malaysia. Dengue virus serotype 2 was isolated from his blood on day 4 of fever. A phylogenetic analysis of the complete genome sequence revealed that this virus was a member of a sylvatic lineage of DENV-2 and most closely related to a virus isolated from a sentinel monkey in Malaysia in 1970. This is the first identification of a sylvatic DENV circulating in Asia since 1975.
  12. Tappe D, Büttner DW
    PLoS Negl Trop Dis, 2009;3(2):e320.
    PMID: 19238218 DOI: 10.1371/journal.pntd.0000320
    Visceral pentastomiasis in humans is caused by the larval stages (nymphs) of the arthropod-related tongue worms Linguatula serrata, Armillifer armillatus, A. moniliformis, A. grandis, and Porocephalus crotali. The majority of cases has been reported from Africa, Malaysia, and the Middle East, where visceral pentastomiasis may be an incidental finding in autopsies, and less often from China and Latin America. In Europe and North America, the disease is only rarely encountered in immigrants and long-term travelers, and the parasitic lesions may be confused with malignancies, leading to a delay in the correct diagnosis. Since clinical symptoms are variable and serological tests are not readily available, the diagnosis often relies on histopathological examinations. This laboratory symposium focuses on the diagnosis of this unusual parasitic disease and presents its risk factors and epidemiology.
  13. DeBuysscher BL, de Wit E, Munster VJ, Scott D, Feldmann H, Prescott J
    PLoS Negl Trop Dis, 2013;7(1):e2024.
    PMID: 23342177 DOI: 10.1371/journal.pntd.0002024
    Nipah virus is a zoonotic pathogen that causes severe disease in humans. The mechanisms of pathogenesis are not well described. The first Nipah virus outbreak occurred in Malaysia, where human disease had a strong neurological component. Subsequent outbreaks have occurred in Bangladesh and India and transmission and disease processes in these outbreaks appear to be different from those of the Malaysian outbreak. Until this point, virtually all Nipah virus studies in vitro and in vivo, including vaccine and pathogenesis studies, have utilized a virus isolate from the original Malaysian outbreak (NiV-M). To investigate potential differences between NiV-M and a Nipah virus isolate from Bangladesh (NiV-B), we compared NiV-M and NiV-B infection in vitro and in vivo. In hamster kidney cells, NiV-M-infection resulted in extensive syncytia formation and cytopathic effects, whereas NiV-B-infection resulted in little to no morphological changes. In vivo, NiV-M-infected Syrian hamsters had accelerated virus replication, pathology and death when compared to NiV-B-infected animals. NiV-M infection also resulted in the activation of host immune response genes at an earlier time point. Pathogenicity was not only a result of direct effects of virus replication, but likely also had an immunopathogenic component. The differences observed between NiV-M and NiV-B pathogeneis in hamsters may relate to differences observed in human cases. Characterization of the hamster model for NiV-B infection allows for further research of the strain of Nipah virus responsible for the more recent outbreaks in humans. This model can be used to study NiV-B pathogenesis, transmission, and countermeasures that could be used to control outbreaks.
  14. Nazari M, Lim SY, Watanabe M, Sharma RS, Cheng NA, Watanabe M
    PLoS Negl Trop Dis, 2013;7(1):e1982.
    PMID: 23301114 DOI: 10.1371/journal.pntd.0001982
    An epidemiological study of Ehrlichia canis infection in dogs in Peninsular Malaysia was carried out using molecular detection techniques. A total of 500 canine blood samples were collected from veterinary clinics and dog shelters. Molecular screening by polymerase chain reaction (PCR) was performed using genus-specific primers followed by PCR using E. canis species-specific primers. Ten out of 500 dogs were positive for E. canis. A phylogenetic analysis of the E. canis Malaysia strain showed that it was grouped tightly with other E. canis strains from different geographic regions. The present study revealed for the first time, the presence of genetically confirmed E. canis with a prevalence rate of 2.0% in naturally infected dogs in Malaysia.
  15. Undurraga EA, Halasa YA, Shepard DS
    PLoS Negl Trop Dis, 2013;7(2):e2056.
    PMID: 23437407 DOI: 10.1371/journal.pntd.0002056
    BACKGROUND: Dengue virus infection is the most common arthropod-borne disease of humans and its geographical range and infection rates are increasing. Health policy decisions require information about the disease burden, but surveillance systems usually underreport the total number of cases. These may be estimated by multiplying reported cases by an expansion factor (EF).

    METHODS AND FINDINGS: As a key step to estimate the economic and disease burden of dengue in Southeast Asia (SEA), we projected dengue cases from 2001 through 2010 using EFs. We conducted a systematic literature review (1995-2011) and identified 11 published articles reporting original, empirically derived EFs or the necessary data, and 11 additional relevant studies. To estimate EFs for total cases in countries where no empirical studies were available, we extrapolated data based on the statistically significant inverse relationship between an index of a country's health system quality and its observed reporting rate. We compiled an average 386,000 dengue episodes reported annually to surveillance systems in the region, and projected about 2.92 million dengue episodes. We conducted a probabilistic sensitivity analysis, simultaneously varying the most important parameters in 20,000 Monte Carlo simulations, and derived 95% certainty level of 2.73-3.38 million dengue episodes. We estimated an overall EF in SEA of 7.6 (95% certainty level: 7.0-8.8) dengue cases for every case reported, with an EF range of 3.8 for Malaysia to 19.0 in East Timor.

    CONCLUSION: Studies that make no adjustment for underreporting would seriously understate the burden and cost of dengue in SEA and elsewhere. As the sites of the empirical studies we identified were not randomly chosen, the exact extent of underreporting remains uncertain. Nevertheless, the results reported here, based on a systematic analysis of the available literature, show general consistency and provide a reasonable empirical basis to adjust for underreporting.

  16. William T, Rahman HA, Jelip J, Ibrahim MY, Menon J, Grigg MJ, et al.
    PLoS Negl Trop Dis, 2013;7(1):e2026.
    PMID: 23359830 DOI: 10.1371/journal.pntd.0002026
    BACKGROUND: The simian parasite Plasmodium knowlesi is a common cause of human malaria in Malaysian Borneo and threatens the prospect of malaria elimination. However, little is known about the emergence of P. knowlesi, particularly in Sabah. We reviewed Sabah Department of Health records to investigate the trend of each malaria species over time.

    METHODS: Reporting of microscopy-diagnosed malaria cases in Sabah is mandatory. We reviewed all available Department of Health malaria notification records from 1992-2011. Notifications of P. malariae and P. knowlesi were considered as a single group due to microscopic near-identity.

    RESULTS: From 1992-2011 total malaria notifications decreased dramatically, with P. falciparum peaking at 33,153 in 1994 and decreasing 55-fold to 605 in 2011, and P. vivax peaking at 15,857 in 1995 and decreasing 25-fold to 628 in 2011. Notifications of P. malariae/P. knowlesi also demonstrated a peak in the mid-1990s (614 in 1994) before decreasing to ≈ 100/year in the late 1990s/early 2000s. However, P. malariae/P. knowlesi notifications increased >10-fold between 2004 (n = 59) and 2011 (n = 703). In 1992 P. falciparum, P. vivax and P. malariae/P. knowlesi monoinfections accounted for 70%, 24% and 1% respectively of malaria notifications, compared to 30%, 31% and 35% in 2011. The increase in P. malariae/P. knowlesi notifications occurred state-wide, appearing to have begun in the southwest and progressed north-easterly.

    CONCLUSIONS: A significant recent increase has occurred in P. knowlesi notifications following reduced transmission of the human Plasmodium species, and this trend threatens malaria elimination. Determination of transmission dynamics and risk factors for knowlesi malaria is required to guide measures to control this rising incidence.

  17. Winskill P, Carvalho DO, Capurro ML, Alphey L, Donnelly CA, McKemey AR
    PLoS Negl Trop Dis, 2015 Nov;9(11):e0004156.
    PMID: 26554922 DOI: 10.1371/journal.pntd.0004156
    BACKGROUND: Aedes aegypti, the principal vector of dengue fever, have been genetically engineered for use in a sterile insect control programme. To improve our understanding of the dispersal ecology of mosquitoes and to inform appropriate release strategies of 'genetically sterile' male Aedes aegypti detailed knowledge of the dispersal ability of the released insects is needed.

    METHODOLOGY/PRINCIPAL FINDINGS: The dispersal ability of released 'genetically sterile' male Aedes aegypti at a field site in Brazil has been estimated. Dispersal kernels embedded within a generalized linear model framework were used to analyse data collected from three large scale mark release recapture studies. The methodology has been applied to previously published dispersal data to compare the dispersal ability of 'genetically sterile' male Aedes aegypti in contrasting environments. We parameterised dispersal kernels and estimated the mean distance travelled for insects in Brazil: 52.8 m (95% CI: 49.9 m, 56.8 m) and Malaysia: 58.0 m (95% CI: 51.1 m, 71.0 m).

    CONCLUSIONS/SIGNIFICANCE: Our results provide specific, detailed estimates of the dispersal characteristics of released 'genetically sterile' male Aedes aegypti in the field. The comparative analysis indicates that despite differing environments and recapture rates, key features of the insects' dispersal kernels are conserved across the two studies. The results can be used to inform both risk assessments and release programmes using 'genetically sterile' male Aedes aegypti.

  18. Wong ML, Chua TH, Leong CS, Khaw LT, Fornace K, Wan-Sulaiman WY, et al.
    PLoS Negl Trop Dis, 2015;9(10):e0004135.
    PMID: 26448052 DOI: 10.1371/journal.pntd.0004135
    BACKGROUND: The simian malaria parasite Plasmodium knowlesi is emerging as a public health problem in Southeast Asia, particularly in Malaysian Borneo where it now accounts for the greatest burden of malaria cases and deaths. Control is hindered by limited understanding of the ecology of potential vector species.

    METHODOLOGY/PRINCIPAL FINDINGS: We conducted a one year longitudinal study of P. knowlesi vectors in three sites within an endemic area of Sabah, Malaysia. All mosquitoes were captured using human landing catch. Anopheles mosquitoes were dissected to determine, oocyst, sporozoites and parous rate. Anopheles balabacensis is confirmed as the primary vector of. P. knowlesi (using nested PCR) in Sabah for the first time. Vector densities were significantly higher and more seasonally variable in the village than forest or small scale farming site. However An. balabacensis survival and P. knowlesi infection rates were highest in forest and small scale farm sites. Anopheles balabacensis mostly bites humans outdoors in the early evening between 1800 to 2000 hrs.

    CONCLUSIONS/SIGNIFICANCE: This study indicates transmission is unlikely to be prevented by bednets. This combined with its high vectorial capacity poses a threat to malaria elimination programmes within the region.

  19. Ratanabanangkoon K, Tan KY, Eursakun S, Tan CH, Simsiriwong P, Pamornsakda T, et al.
    PLoS Negl Trop Dis, 2016 Apr;10(4):e0004565.
    PMID: 27058956 DOI: 10.1371/journal.pntd.0004565
    Snakebite envenomation is a serious medical problem in many tropical developing countries and was considered by WHO as a neglected tropical disease. Antivenom (AV), the rational and most effective treatment modality, is either unaffordable and/or unavailable in many affected countries. Moreover, each AV is specific to only one (monospecific) or a few (polyspecific) snake venoms. This demands that each country to prepare AV against its local snake venoms, which is often not feasible. Preparation of a 'pan-specific' AV against many snakes over a wide geographical area in some countries/regions has not been possible. If a 'pan-specific' AV effective against a variety of snakes from many countries could be prepared, it could be produced economically in large volume for use in many countries and save many lives. The aim of this study was to produce a pan-specific antiserum effective against major medically important elapids in Asia. The strategy was to use toxin fractions (TFs) of the venoms in place of crude venoms in order to reduce the number of antigens the horses were exposed to. This enabled inclusion of a greater variety of elapid venoms in the immunogen mix, thus exposing the horse immune system to a diverse repertoire of toxin epitopes, and gave rise to antiserum with wide paraspecificity against elapid venoms. Twelve venom samples from six medically important elapid snakes (4 Naja spp. and 2 Bungarus spp.) were collected from 12 regions/countries in Asia. Nine of these 12 venoms were ultra-filtered to remove high molecular weight, non-toxic and highly immunogenic proteins. The remaining 3 venoms were not ultra-filtered due to limited amounts available. The 9 toxin fractions (TFs) together with the 3 crude venoms were emulsified in complete Freund's adjuvant and used to immunize 3 horses using a low dose, low volume, multisite immunization protocol. The horse antisera were assayed by ELISA and by in vivo lethality neutralization in mice. The findings were: a) The 9 TFs were shown to contain all of the venom toxins but were devoid of high MW proteins. When these TFs, together with the 3 crude venoms, were used as the immunogen, satisfactory ELISA antibody titers against homologous/heterologous venoms were obtained. b) The horse antiserum immunologically reacted with and neutralized the lethal effects of both the homologous and the 16 heterologous Asian/African elapid venoms tested. Thus, the use of TFs in place of crude venoms and the inclusion of a variety of elapid venoms in the immunogen mix resulted in antiserum with wide paraspecificity against elapid venoms from distant geographic areas. The antivenom prepared from this antiserum would be expected to be pan-specific and effective in treating envenomations by most elapids in many Asian countries. Due to economies of scale, the antivenom could be produced inexpensively and save many lives. This simple strategy and procedure could be readily adapted for the production of pan-specific antisera against elapids of other continents.
  20. NikNadia N, Sam IC, Rampal S, WanNorAmalina W, NurAtifah G, Verasahib K, et al.
    PLoS Negl Trop Dis, 2016 Mar;10(3):e0004562.
    PMID: 27010319 DOI: 10.1371/journal.pntd.0004562
    Enterovirus A71 (EV-A71) is an important emerging pathogen causing large epidemics of hand, foot and mouth disease (HFMD) in children. In Malaysia, since the first EV-A71 epidemic in 1997, recurrent cyclical epidemics have occurred every 2-3 years for reasons that remain unclear. We hypothesize that this cyclical pattern is due to changes in population immunity in children (measured as seroprevalence). Neutralizing antibody titers against EV-A71 were measured in 2,141 residual serum samples collected from children ≤12 years old between 1995 and 2012 to determine the seroprevalence of EV-A71. Reported national HFMD incidence was highest in children <2 years, and decreased with age; in support of this, EV-A71 seroprevalence was significantly associated with age, indicating greater susceptibility in younger children. EV-A71 epidemics are also characterized by peaks of increased genetic diversity, often with genotype changes. Cross-sectional time series analysis was used to model the association between EV-A71 epidemic periods and EV-A71 seroprevalence adjusting for age and climatic variables (temperature, rainfall, rain days and ultraviolet radiance). A 10% increase in absolute monthly EV-A71 seroprevalence was associated with a 45% higher odds of an epidemic (adjusted odds ratio, aOR1.45; 95% CI 1.24-1.69; P<0.001). Every 10% decrease in seroprevalence between preceding and current months was associated with a 16% higher odds of an epidemic (aOR = 1.16; CI 1.01-1.34 P<0.034). In summary, the 2-3 year cyclical pattern of EV-A71 epidemics in Malaysia is mainly due to the fall of population immunity accompanying the accumulation of susceptible children between epidemics. This study will impact the future planning, timing and target populations for vaccine programs.
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