Displaying publications 1 - 20 of 47 in total

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  1. Mustapha Kamil Y, Al-Rekabi SH, Yaacob MH, Syahir A, Chee HY, Mahdi MA, et al.
    Sci Rep, 2019 09 17;9(1):13483.
    PMID: 31530893 DOI: 10.1038/s41598-019-49891-7
    The exponential escalation of dengue cases has indeed become a global health crisis. This work elaborates on the development of a biofunctionalized tapered optical fiber (TOF) based sensor with the integration of polyamidoamine (PAMAM) dendrimer for the detection of dengue E protein. The dimension of the TOF generated an evanescent field that was sensitive to any changes in the external medium while the integration of PAMAM promoted more adhesion of bio-recognition molecules; anti-DENV II E protein antibodies; that were complementary to the targeted protein. This in return created more active sites for the absorption of DENV II E proteins onto the tapered region. The resolution and detection limit of the sensor are 19.53 nm/nM and 1 pM, respectively with Kd = 1.02 × 10-10 M.
  2. Chee HY, AbuBakar S
    Biochem Biophys Res Commun, 2004 Jul 16;320(1):11-7.
    PMID: 15207695
    Binding of dengue virus 2 (DENV-2) to C6/36 mosquito cells protein was investigated. A 48 kDa DENV-2-binding C6/36 cells protein (D2BP) was detected in a virus overlay protein-binding assay. The binding occurred only to the C6/36 cells cytosolic protein fraction and it was inhibited by free D2BP. D2BP was shown to bind to DENV-2 E in the far-Western-binding studies and using mass spectrometry (MS) and MS/MS, peptide masses of the D2BP that matched to beta-tubulin and alpha-tubulin chains were identified. These findings suggest that DENV-2 through DENV-2 E binds directly to a 48 kDa tubulin or tubulin-like protein of C6/36 mosquito cells.
  3. Ghani NA, Shohaimi S, Hee AK, Chee HY, Emmanuel O, Alaba Ajibola LS
    Trop Med Infect Dis, 2019 Feb 15;4(1).
    PMID: 30781369 DOI: 10.3390/tropicalmed4010037
    BACKGROUND: Dengue has affected more than one-third of the world population and Malaysia has recorded an increase in the number of dengue cases since 2012. Selangor state recorded the highest number of dengue cases in Malaysia. Most of the dengue infections occur among people living in hotspot areas of dengue. This study aims to compare Knowledge, Attitude, and Practice among communities living in hotspot and non-hotspot dengue areas.

    METHOD: Communities living in 20 hotspot and 20 non-hotspot areas in Selangor were chosen in this study where 406 participants were randomly selected to answer questionnaires distributed at their housing areas. Total marks of each categories were compared using t-test.

    RESULT: Results show that there were significant mean differences in marks in Knowledge (p value: 0.003; 15.41 vs. 14.55) and Attitude (p value: < 0.001; 11.41 vs. 10.33), but not Practice (p value 0.101; 10.83 vs. 10.47) categories between communities of non-hotspot and hotspot areas. After considering two confounding variables which are education level and household income, different mean marks are found to be significant in Knowledge when education level acts as a covariate and Attitude when both act as covariates.

    CONCLUSION: Overall results show that people living in non-hotspot areas had better knowledge and attitude than people living in hotspot areas, but no difference was found in practice. This suggests that public health education should be done more frequently with people with a low education background and low household income, especially in hotspot areas to fight dengue outbreak and make dengue cases decrease effectively.

  4. Low CF, Shamsudin MN, Abdullah M, Chee HY, Aliyu-Paiko M
    J Fish Dis, 2015 Jan;38(1):17-25.
    PMID: 24397626 DOI: 10.1111/jfd.12195
    The mechanisms through which brown-marbled grouper accomplishes resistance to infection, particularly against Vibrios, are not yet fully understood. In this study, brown-marbled grouper fingerlings were experimentally infected with Vibrio parahaemolyticus, to identify disease resistance grouper, and the serum proteome profiles were compared between resistant and susceptible candidates, via two-dimensional gel electrophoresis (2-DE). The results showed that putative parvalbumin beta-2 subunit I, alpha-2-macroglobulin, nattectin and immunoglobulin light chain proteins were among proteins that significantly overexpressed in the resistant fish as compared to the susceptible group of fish, whereas apolipoprotein E and immunoglobulin light chain proteins were observed to be differentially overexpressed in the susceptible fish. Further analysis by peptide sequencing revealed that the immunoglobulin light chain proteins identified in the resistant and susceptible groups differed in amino acid composition. Taken together, the results demonstrated for the first time that putative parvalbumin beta-2 subunit I, alpha-2-macroglobulin, nattectin and immunoglobulin light chain are among important proteins participating to effect disease resistance mechanism in fish and were overexpressed to function collectively to resist V. parahaemolyticus infection. Most of these molecules are mediators of immune response.
  5. Foo KY, Chee HY
    Biomed Res Int, 2015;2015:427814.
    PMID: 26347881 DOI: 10.1155/2015/427814
    Flaviviruses are potentially human pathogens that cause major epidemics worldwide. Flavivirus interacts with host cell factors to form a favourable virus replication site. Cell cytoskeletons have been observed to have close contact with flaviviruses, which expands the understanding of cytoskeleton functions during virus replication, although many detailed mechanisms are still unclear. The interactions between the virus and host cytoskeletons such as actin filaments, microtubules, and intermediate filaments have provided insight into molecular alterations during the virus infection, such as viral entry, in-cell transport, scaffold assembly, and egress. This review article focuses on the utilization of cytoskeleton by Flavivirus and the respective functions during virus replication.
  6. Khaw YS, Chan YF, Jafar FL, Othman N, Chee HY
    Front Microbiol, 2016;7:543.
    PMID: 27199901 DOI: 10.3389/fmicb.2016.00543
    Human rhinovirus-C (HRV-C) has been implicated in more severe illnesses than HRV-A and HRV-B, however, the limited number of HRV-C complete genomes (complete 5' and 3' non-coding region and open reading frame sequences) has hindered the in-depth genetic study of this virus. This study aimed to sequence seven complete HRV-C genomes from Malaysia and compare their genetic characteristics with the 18 published HRV-Cs. Seven Malaysian HRV-C complete genomes were obtained with newly redesigned primers. The seven genomes were classified as HRV-C6, C12, C22, C23, C26, C42, and pat16 based on the VP4/VP2 and VP1 pairwise distance threshold classification. Five of the seven Malaysian isolates, namely, 3430-MY-10/C22, 8713-MY-10/C23, 8097-MY-11/C26, 1570-MY-10/C42, and 7383-MY-10/pat16 are the first newly sequenced complete HRV-C genomes. All seven Malaysian isolates genomes displayed nucleotide similarity of 63-81% among themselves and 63-96% with other HRV-Cs. Malaysian HRV-Cs had similar putative immunogenic sites, putative receptor utilization and potential antiviral sites as other HRV-Cs. The genomic features of Malaysian isolates were similar to those of other HRV-Cs. Negative selections were frequently detected in HRV-Cs complete coding sequences indicating that these sequences were under functional constraint. The present study showed that HRV-Cs from Malaysia have diverse genetic sequences but share conserved genomic features with other HRV-Cs. This genetic information could provide further aid in the understanding of HRV-C infection.
  7. Abu Bakar S, Shafee N, Chee HY
    Med J Malaysia, 1999 Sep;54(3):402-3.
    PMID: 11045072
  8. AbuBakar S, Shafee N, Chee HY
    Med J Malaysia, 1998 Sep;53(3):293-5.
    PMID: 10968171
    Infectious agent(s) causing the fatal Sarawak acute childhood viral infection (SACVI) has not been identified. In the present study, results indicating that inocula prepared from the fatal cases of SACVI induced apoptosis in Vero cell cultures are presented. These findings suggest the possible involvement of apoptotic cellular responses in SACVI.
  9. Abubakar S, Shafee N, Chee HY
    Malays J Pathol, 1998 Dec;20(2):71-81.
    PMID: 10879266
    Identification of the aetiologic agent(s) associated with an outbreak of fatal childhood viral infection in Sarawak, Malaysia, in mid 1997 remains elusive. It is reported here that African green monkey kidney (Vero) and human monocytic (U937) cells treated with inocula derived from clinical specimens of some of these fatal cases showed the presence of cellular genomic DNA degradation when the extracted DNA was separated by pulsed field gel electrophoresis (PFGE), oligonucleosomal DNA ladders characteristic of apoptotic cells when the infected cells' DNA was separated by agarose gel electrophoresis, and apoptotic cellular DNA fragmentation when cells were stained using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL). These results suggest that inocula derived from the patients' clinical specimens contain factors which stimulate apoptotic cellular responses in vitro.
  10. AbuBakar S, Azmi A, Mohamed-Saad N, Shafee N, Chee HY
    Malays J Pathol, 1997 Jun;19(1):41-51.
    PMID: 10879241
    The present study was undertaken to investigate the antibody responses of dengue fever (DF) patients to specific dengue virus proteins. Partially purified dengue 2 New Guinea C (NGC) strain virus was used as antigen. Under the present experimental protocols, it was observed that almost all DF patients' sera had detectable presence of antibodies which recognize the dengue 2 envelope (E) protein. The convalescent-phase sera especially had significant detectable IgG, IgM and IgE against the protein. In addition, IgGs specific against the NS1 dimer and PrM were also detected. Antibody against the core (C) protein, however, was not detectable in any of the DF patients' sera. The substantial presence of IgG against the PrM in the convalescent-phase sera, and the presence of IgE specific for the E, reflect the potential importance of these antibody responses in the pathogenesis of dengue.
  11. Fish-Low CY, Abubakar S, Othman F, Chee HY
    Malays J Pathol, 2019 Apr;41(1):41-46.
    PMID: 31025636
    INTRODUCTION: Dengue virus (DENV), the causative agent of dengue disease exists in sylvatic and endemic ecotypes. The cell morphological changes and viral morphogenesis of two dengue ecotypes were examined at the ultrastructural level to identify potential similarities and differences in the surrogate model of enzootic host.

    MATERIALS AND METHODS: Vero cells were inoculated with virus at a multiplicity of infection (MOI) of 0.1. Cell cultures were harvested over a time course and processed for transmission electron microscopic imaging.

    RESULTS: The filopodia protrusions on cell periphery preceded virus entry. Additionally, sylvatic DENV infection was found spreading slower than the endemic DENV. Morphogenesis of both dengue ecotypes was alike but at different level of efficiency in the permissive cells.

    CONCLUSIONS: This is the first ultrastructural study on sylvatic DENV and this comparative study revealed the similarities and differences of cellular responses and morphogenesis of two dengue ecotypes in vitro. The study revealed the weaker infectivity of sylvatic DENV in the surrogate model of enzootic host, which supposed to support better replication of enzootic DENV than endemic DENV.

  12. Maryam M, Tan SL, Crouse KA, Mohamed Tahir MI, Chee HY
    Turk J Chem, 2020;44(5):1395-1409.
    PMID: 33488239 DOI: 10.3906/kim-2006-22
    A series of Schiff bases have been successfully synthesized through the acid-catalyzed condensation of S-substituted dithiocarbazates and three enantiomerically pure monoterpenes, (1 R )-(+)-camphor, (1 S )-(-)-camphor, (1 R )-(-)-camphorquinone, (1 S )-(+)-camphorquinone, ( R )-(-)-carvone and ( S )-(+)-carvone. Spectroscopic results revealed that the Schiff bases containing camphor or carvone likely adopted an E -configuration along the characteristic imine bond while those containing camphorquinone assumed a Z -configuration. The antidengue potential of these compounds was evaluated based on DENV 2 caused cytopathic effect (CPE) reduction-based in vitro evaluation. The compounds were validated through secondary foci forming unit reduction assay (FFURA). Compounds were also tested for their cytotoxicity against Vero cells. The compounds showed variable degrees of antiviral activity with the camphor compounds displaying the highest antidengue potential. The enantiomers of the compounds behaved almost similarly during the antiviral evaluation.
  13. Fish-Low CY, Abu Bakar S, Othman F, Chee HY
    Trop Biomed, 2018 Dec 01;35(4):1154-1159.
    PMID: 33601863
    Dengue virus (DENV) is maintained and circulated in both sylvatic/enzootic and endemic/human cycles and spill over infection of sylvatic DENV into human populations has been reported. Extensive deforestation and increase human activities in forest may increase the risk of human exposure to sylvatic dengue infection and this may become a threat to human. Present study investigated the changes in cell morphology and viral morphogenesis upon infection with sylvatic and endemic ecotypes in human monocytic U-937 cells using transmission electron microscopy. Autophagy, a process that is either pro-viral or anti-viral, was observed in U-937 cells of both infections, however only the replication of endemic DENV was evidenced. An insight into the infection responses of sylvatic progenitors of DENV in susceptible host cells may provide better understanding on dengue emergence in human populations.
  14. Soo KM, Tham CL, Khalid B, Basir R, Chee HY
    Trop Biomed, 2019 Dec 01;36(4):1027-1037.
    PMID: 33597472
    Dengue is a common infection, caused by dengue virus. There are four different dengue serotypes, with different capacity to cause severe dengue infections. Besides, secondary infections with heterologous serotypes, concurrent infections of multiple dengue serotypes may alter the severity of dengue infection. This study aims to compare the severity of single infection and concurrent infections of different combinations of dengue serotypes in-vitro. Human mast cells (HMC)-1.1 were infected with single and concurrent infections of multiple dengue serotypes. The infected HMC-1.1 supernatant was then added to human umbilical cord vascular endothelial cells (HUVEC) and severity of dengue infections was measured by the percentage of transendothelial electrical resistance (TEER). Levels of IL10, CXCL10 and sTRAIL in HMC-1.1 and IL-8, IL-10 and CXCL10 in HUVEC culture supernatants were measured by the ELISA assays. The result showed that the percentage of TEER values were significantly lower in single infections (p< 0.05), compared to concurrent infections on day 2 and 3, indicating that single infection increase endothelial permeability greater than concurrent infections. IL-8 showed moderate correlation with endothelial permeability (r > 0.4), indicating that IL-8 may be suitable as an in-vitro severity biomarker. In conclusion, this in-vitro model presented few similarities with regards to the conditions in dengue patients, suggesting that it could serve as a severity model to test for severity and levels of severity biomarkers upon different dengue virus infections.
  15. Suppiah J, Chan SY, Ng MW, Khaw YS, Ching SM, Mat-Nor LA, et al.
    J Biomed Sci, 2017 Jun 28;24(1):40.
    PMID: 28659189 DOI: 10.1186/s12929-017-0344-x
    BACKGROUND: Dengue and leptospirosis infections are currently two major endemics in Malaysia. Owing to the overlapping clinical symptoms between both the diseases, frequent misdiagnosis and confusion of treatment occurs. As a solution, the present work initiated a pilot study to investigate the incidence related to co-infection of leptospirosis among dengue patients. This enables the identification of more parameters to predict the occurrence of co-infection.

    METHOD: Two hundred sixty eight serum specimens collected from patients that were diagnosed for dengue fever were confirmed for dengue virus serotyping by real-time polymerase chain reaction. Clinical, laboratory and demographic data were extracted from the hospital database to identify patients with confirmed leptospirosis infection among the dengue patients. Thus, frequency of co-infection was calculated and association of the dataset with dengue-leptospirosis co-infection was statistically determined.

    RESULTS: The frequency of dengue co-infection with leptospirosis was 4.1%. Male has higher preponderance of developing the co-infection and end result of shock as clinical symptom is more likely present among co-infected cases. It is also noteworthy that, DENV 1 is the common dengue serotype among all cases identified as dengue-leptospirosis co-infection in this study.

    CONCLUSION: The increasing incidence of leptospirosis among dengue infected patients has posed the need to precisely identify the presence of co-infection for the betterment of treatment without mistakenly ruling out either one of them. Thus, anticipating the possible clinical symptoms and laboratory results of dengue-leptospirosis co-infection is essential.

  16. Suppiah J, Ching SM, Amin-Nordin S, Mat-Nor LA, Ahmad-Najimudin NA, Low GK, et al.
    PLoS Negl Trop Dis, 2018 09;12(9):e0006817.
    PMID: 30226880 DOI: 10.1371/journal.pntd.0006817
    BACKGROUND: Malaysia experienced an unprecedented dengue outbreak from the year 2014 to 2016 that resulted in an enormous increase in the number of cases and mortality as compared to previous years. The causes that attribute to a dengue outbreak can be multifactorial. Viral factors, such as dengue serotype and genotype, are the components of interest in this study. Although only a small number of studies investigated the association between the serotype of dengue virus and clinical manifestations, none of these studies included analyses on dengue genotypes. The present study aims to investigate dengue serotype and genotype-specific clinical characteristics among dengue fever and severe dengue cases from two Malaysian tertiary hospitals between 2014 and mid-2017.

    METHODOLOGY AND PRINCIPAL FINDINGS: A total of 120 retrospective dengue serum specimens were subjected to serotyping and genotyping by Taqman Real-Time RT-PCR, sequencing and phylogenetic analysis. Subsequently, the dengue serotype and genotype data were statistically analyzed for 101 of 120 corresponding patients' clinical manifestations to generate a descriptive relation between the genetic components and clinical outcomes of dengue infected patients. During the study period, predominant dengue serotype and genotype were found to be DENV 1 genotype I. Additionally, non-severe clinical manifestations were commonly observed in patients infected with DENV 1 and DENV 3. Meanwhile, patients with DENV 2 infection showed significant warning signs and developed severe dengue (p = 0.007). Cases infected with DENV 2 were also commonly presented with persistent vomiting (p = 0.010), epigastric pain (p = 0.018), plasma leakage (p = 0.004) and shock (p = 0.038). Moreover, myalgia and arthralgia were highly prevalent among DENV 3 infection (p = 0.015; p = 0.014). The comparison of genotype-specific clinical manifestations showed that DENV 2 Cosmopolitan was significantly common among severe dengue patients. An association was also found between genotype I of DENV 3 and myalgia. In a similar vein, genotype III of DENV 3 was significantly common among patients with arthralgia.

    CONCLUSION: The current data contended that different dengue serotype and genotype had caused distinct clinical characteristics in infected patients.

  17. Lam JY, Low GK, Chee HY
    PLoS Negl Trop Dis, 2020 02;14(2):e0008074.
    PMID: 32049960 DOI: 10.1371/journal.pntd.0008074
    BACKGROUND: Leptospirosis is often difficult to diagnose because of its nonspecific symptoms. The drawbacks of direct isolation and serological tests have led to the increased development of nucleic acid-based assays, which are more rapid and accurate. A meta-analysis was performed to evaluate the diagnostic accuracy of genetic markers for the detection of Leptospira in clinical samples.

    METHODOLOGY AND PRINCIPLE FINDINGS: A literature search was performed in Scopus, PubMed, MEDLINE and non-indexed citations (via Ovid) by using suitable keyword combinations. Studies evaluating the performance of nucleic acid assays targeting leptospire genes in human or animal clinical samples against a reference test were included. Of the 1645 articles identified, 42 eligible studies involving 7414 samples were included in the analysis. The diagnostic performance of nucleic acid assays targeting the rrs, lipL32, secY and flaB genes was pooled and analyzed. Among the genetic markers analyzed, the secY gene showed the highest diagnostic accuracy measures, with a pooled sensitivity of 0.56 (95% CI: 0.50-0.63), a specificity of 0.98 (95% CI: 0.97-0.98), a diagnostic odds ratio of 46.16 (95% CI: 6.20-343.49), and an area under the curve of summary receiver operating characteristics curves of 0.94. Nevertheless, a high degree of heterogeneity was observed in this meta-analysis. Therefore, the present findings here should be interpreted with caution.

    CONCLUSION: The diagnostic accuracies of the studies examined for each genetic marker showed a significant heterogeneity. The secY gene exhibited higher diagnostic accuracy measures compared with other genetic markers, such as lipL32, flaB, and rrs, but the difference was not significant. Thus, these genetic markers had no significant difference in diagnostic accuracy for leptospirosis. Further research into these genetic markers is warranted.

  18. Aliyu IA, Ling KH, Md Hashim N, Chee HY
    Rev Med Virol, 2019 05;29(3):e2038.
    PMID: 30746844 DOI: 10.1002/rmv.2038
    Annexin A2 is a membrane scaffolding and binding protein, which mediated various cellular events. Its functions are generally affected by cellular localization. In the cytoplasm, they interacted with different phospholipid membranes in Ca2+ -dependent manner and play vital roles including actin binding, remodeling and dynamics, cytoskeletal rearrangement, and lipid-raft microdomain formation. However, upon cell exposure to certain stimuli, annexin A2 translocates to the external leaflets of the plasma membrane where annexin A2 was recently reported to serve as a virus receptor, play an important role in the formation of virus replication complex, or implicated in virus assembly and budding. Here, we review some of annexin A2 roles in virus infections and the potentiality of targeting annexin A2 in the design of novel and promising antivirus agent that may have a broader consequence in virus therapy.
  19. Suppiah J, Nadaraju S, Hamzah S, Chee HY
    Trop Biomed, 2020 Jun 01;37(2):282-287.
    PMID: 33612798
    Storage of dengue virus (DENV) culture stocks in -80°C is a common laboratory practice to maintain the viability of the virus for long-term usage. However, the efficiency of this method could still be hindered by multiple factors. In our laboratory, we observed a constant and substantial deterioration in the titer of DENV in Vero culture supernatant stored in -80°C. Such incident had badly hampered the laboratory work and prompted an investigation to determine the cause. DENV isolates representing all four serotypes were propagated and the culture supernatants were harvested and stored in aliquots of original stock and 10 fold dilutions (10-1 -10-4). DENV titer in these stocks was determined prior to storage and reassessed on the third and sixth month of storage by focus forming unit assay (FFUA). The result demonstrated a constant preservation of titer ranging from 104 ffu/ml to 105 ffu/ml in the diluted DENV virus culture stocks of 10-1, and 10-2 of DENV1-4, a minor reduction of titer from 103 ffu/ml to 102 ffu/ml at dilution 10-3 for DENV4 only and complete deterioration in undiluted culture stock and lower dilution (10-4) within 6 months of storage in -80°C for all serotypes. It is recommended that propagated DENV in Vero cells are stored in 10 fold dilutions as compared to the original form to preserve the titer for long-term usage.
  20. Soo KM, Khalid B, Ching SM, Tham CL, Basir R, Chee HY
    PeerJ, 2017;5:e3589.
    PMID: 28929009 DOI: 10.7717/peerj.3589
    BACKGROUND: Dengue viral infection is an acute infection that has the potential to have severe complications as its major sequela. Currently, there is no routine laboratory biomarker with which to predict the severity of dengue infection or monitor the effectiveness of standard management. Hence, this meta-analysis compared biomarker levels between dengue fever (DF) and severe dengue infections (SDI) to identify potential biomarkers for SDI.

    METHODS: Data concerning levels of cytokines, chemokines, and other potential biomarkers of DF, dengue hemorrhagic fever, dengue shock syndrome, and severe dengue were obtained for patients of all ages and populations using the Scopus, PubMed, and Ovid search engines. The keywords "(IL1* or IL-1*) AND (dengue*)" were used and the same process was repeated for other potential biomarkers, according to Medical Subject Headings terms suggested by PubMed and Ovid. Meta-analysis of the mean difference in plasma or serum level of biomarkers between DF and SDI patients was performed, separated by different periods of time (days) since fever onset. Subgroup analyses comparing biomarker levels of healthy plasma and sera controls, biomarker levels of primary and secondary infection samples were also performed, as well as analyses of different levels of severity and biomarker levels upon infection by different dengue serotypes.

    RESULTS: Fifty-six studies of 53 biomarkers from 3,739 dengue cases (2,021 DF and 1,728 SDI) were included in this meta-analysis. Results showed that RANTES, IL-7, IL-8, IL-10, IL-18, TGF-b, and VEGFR2 levels were significantly different between DF and SDI. IL-8, IL-10, and IL-18 levels increased during SDI (95% CI, 18.1-253.2 pg/mL, 3-13 studies, n = 177-1,909, I(2) = 98.86%-99.75%). In contrast, RANTES, IL-7, TGF-b, and VEGFR2 showed a decrease in levels during SDI (95% CI, -3238.7 to -3.2 pg/mL, 1-3 studies, n = 95-418, I(2) = 97.59%-99.99%). Levels of these biomarkers were also found to correlate with the severity of the dengue infection, in comparison to healthy controls. Furthermore, the results showed that IL-7, IL-8, IL-10, TGF-b, and VEGFR2 display peak differences between DF and SDI during or before the critical phase (day 4-5) of SDI.

    DISCUSSION: This meta-analysis suggests that IL-7, IL-8, IL-10, TGF-b, and VEGFR2 may be used as potential early laboratory biomarkers in the diagnosis of SDI. This can be used to predict the severity of dengue infection and to monitor the effectiveness of treatment. Nevertheless, methodological and reporting limitations must be overcome in future research to minimize variables that affect the results and to confirm the findings.
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