M P Mammen

Publications (8)30.06 Total impact

• Article: A human challenge model for dengue infection reveals a possible protective role for sustained interferon gamma levels during the acute phase of illness.

  V J Gunther, R Putnak, K H Eckels, M P Mammen, J M Scherer, A Lyons, M B Sztein, W Sun
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  ABSTRACT: Dengue has recently been defined by the World Health Organization as a major international public health concern. Although several vaccine candidates are in various stages of development, there is no licensed vaccine available to assist in controlling the further spread of this mosquito borne disease. The need for a reliable animal model for dengue disease increases the risk to vaccine developers as they move their vaccine candidates into large-scale phase III testing. In this paper we describe the cellular immune responses observed in a human challenge model for dengue infection; a model that has the potential to provide efficacy data for potential vaccine candidates in a controlled setting. Serum levels of sIL-2Rα and sTNF-RII were increased in volunteers who developed illness. Supernatants from in vitro stimulated PBMC were tested for cytokines associated with a T(H)1 or T(H)2 T-cell response (IL-2, TNF-α, IFN-γ, IL-4, IL-10, IL-5) and only IFN-γ was associated with protection against fever and/or viremia. Interestingly, IFN-γ levels drop to 0 pg/mL for volunteers who develop illness after challenge suggesting that some mechanism of immunosuppression may play a role in dengue illness. The human challenge model provides an opportunity to test potential vaccine candidates for efficacy prior to large-scale phase III testing, and hints at a possible mechanism for immune suppression by dengue.
  Vaccine 03/2011; 29(22):3895-904. · 3.77 Impact Factor
• Article: Molecular genotyping of dengue viruses by phylogenetic analysis of the sequences of individual genes.

  C Klungthong, R Putnak, M P Mammen, T Li, C Zhang
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  ABSTRACT: The prevalence of four serotypes of dengue virus (DENV) has risen dramatically in recent years accompanied by an increase in viral genetic diversity. The evolution of DENV has had a major impact on their virulence for humans and on the epidemiology of dengue disease around the world. In order to perform disease surveillance and understand DENV evolution and its effects on virus transmission and disease, an efficient and accurate method for genotype identification is required. Phylogenetic analysis of viral gene sequences is the method used most commonly, with envelope (E) gene the most frequently selected target. To determine which gene might be suitable targets for genotyping DENV, phylogenetic analysis was performed on 10 individual coding genes plus the 3'-non-translated region (3'NTR) for 56 geographically divergent DENV strains representing all identified genotypes. These were reflected in eleven maximum likelihood phylogenetic trees. Based on the bootstrap values (over 90%) supporting the major nodes, the best target genes were identified for each serotype: for DENV-1, the sequences of all coding genes except non-structural gene 4A (NS4A), for DENV-2, PrM/M, E, NS1, NS3, NS4A and NS5, for DENV-3, all coding genes and the 3'NTR, and for DENV-4, C, PrM/M, E, NS1, NS2A, NS2B, NS4A and NS5.
  Journal of Virological Methods 10/2008; 154(1-2):175-81. · 2.01 Impact Factor
• Source

  Available from: dtic.mil

  Article: A Phase 1/2 Trial of a Tetravalent Live-Attenuated Dengue Vaccine in Flavivirus-Naive Thai Infants

  V. Watanaveeradej, A. Kerdpanich, R. Samakoses, K. Tanakijaru, C. Aree, S. Simasathien, M. P. Mammen, A. Nisalak, S. Hengprasert, R. J. Jarman, R. V. Gibbons, B. L. Innis, Y. Hutagalung, S. Chunsuttiwat, W. Sun, T. P. Endy, S. Thomas, K. H. Eckels, R. Putnak, D. W. Vaughn
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  ABSTRACT: The Walter Reed Army Institute of Research (WRAIR) has produced a tetravalent live-attenuated dengue vaccine that has been well tolerated and immunogenic in U.S. adults and Thai children. As infants are considered by many as an important age group for vaccination in dengue-endemic countries, we evaluated the vaccine in Thai flavivirus-na ve infants who are at risk for dengue.
  10/2006;
• Source

  Available from: pnas.org

  Article: Cross-protective immunity can account for the alternating epidemic pattern of dengue virus serotypes circulating in Bangkok.

  B Adams, E C Holmes, C Zhang, M P Mammen, S Nimmannitya, S Kalayanarooj, M Boots
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  ABSTRACT: Dengue virus, the causative agent of dengue fever and its more serious manifestation dengue hemorrhagic fever, is widespread throughout tropical and subtropical regions. The virus exists as four distinct serotypes, all of which have cocirculated in Bangkok for several decades with epidemic outbreaks occurring every 8-10 years. We analyze time-series data of monthly infection incidence, revealing a distinctive pattern with epidemics of serotypes 1, 2, and 3 occurring at approximately the same time and an isolated epidemic of serotype 4 occurring in the intervening years. Phylogenetic analysis of virus samples collected over the same period shows that clade replacement events are linked to the epidemic cycle and indicates that there is an interserotypic immune reaction. Using an epidemic model with stochastic seasonal forcing showing 8- to 10-year epidemic oscillations, we demonstrate that moderate cross-protective immunity gives rise to persistent out-of-phase oscillations similar to those observed in the data, but that strong or weak cross-protection or cross-enhancement only produces in-phase patterns. This behavior suggests that the epidemic pattern observed in Bangkok is the result of cross-protective immunity and may be significantly altered by changes in the interserotypic immune reaction.
  Proceedings of the National Academy of Sciences 10/2006; 103(38):14234-9. · 9.68 Impact Factor
• Source

  Available from: ncbi.nlm.nih.gov

  Article: Randomized, placebo-controlled trial of nonpegylated and pegylated forms of recombinant human alpha interferon 2a for suppression of dengue virus viremia in rhesus monkeys.

  C Ajariyakhajorn, M P Mammen, T P Endy, M Gettayacamin, A Nisalak, S Nimmannitya, D H Libraty
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  ABSTRACT: Dengue fever and dengue hemorrhagic fever are caused by infection with any one of the four dengue viruses (DVs) and are significant public health burdens throughout the tropics. Higher viremia levels are associated with greater dengue disease severity. A therapeutic intervention to suppress viremia early in DV infection could potentially ameliorate severe disease. Recombinant alpha interferon 2a (rIFN-alpha-2a, Roferon-A) suppressed DV replication in human peripheral blood mononuclear cells in vitro. We therefore examined the effects of rIFN-alpha-2a and pegylated recombinant IFN-alpha-2a (PEG-rIFN-alpha-2a, PEGASYS) on DV serotype 2 (DV-2) viremia in rhesus monkeys. Flavivirus-naïve monkeys were inoculated with DV-2 and randomized to receive a single dose of rIFN-alpha-2a (10 million international units/m2) versus placebo or PEG-rIFN-alpha-2a (6 microg/kg) versus placebo 1 day after the onset of viremia. Serial daily viremia levels were measured, and convalescent-phase DV-2 neutralizing antibody titers were determined. Compared to placebo, a single injection of rIFN-alpha-2a temporarily suppressed DV-2 replication and delayed the time to peak viremia by a median of 3 days. However, measures of total viral burden were not different between the two groups. A single injection of PEG-rIFN-alpha-2a significantly lowered daily viremia levels and improved virus clearance, starting 48 h after administration. There were no significant differences in DV-2 neutralizing antibody titers between the treatment and placebo groups at 30 and 90 days postinfection. Based on their individual effects, future studies should investigate a combination of rIFN-alpha-2a and PEG-rIFN-alpha-2a for suppression of dengue virus viremia and as a potential therapeutic intervention.
  Antimicrobial Agents and Chemotherapy 12/2005; 49(11):4508-14. · 4.84 Impact Factor
• Source

  Available from: Kittipong Kongsomboon

  Article: Temporal trends of dengue fever/dengue hemorrhagic fever in Bangkok, Thailand from 1981 to 2000: an age-period-cohort analysis.

  K Kongsomboon, P Singhasivanon, J Kaewkungwal, S Nimmannitya, M P Mammen, A Nisalak, P Sawanpanyalert
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  ABSTRACT: The aim of this study was to examine the effects of age, time period, and birth cohorts with dengue fever/dengue hemorrhagic fever (DF/DHF) in Bangkok, Thailand over the period 1981-2000. The age group at greatest risk for DF/DHF was 5-9 years old. The period effect shows a remittent pattern, with significant increases in 1986-1990 and 1996-2000. The birth cohort group showed a significant decreasing trend from the 1961-1965 group to the 1991-1995 group (R2 = 0.7620) with a decreasing rate of 0.1. We concluded that the temporal trend of DF/DHF is decreasing; especially for DHF.
  The Southeast Asian journal of tropical medicine and public health 01/2005; 35(4):913-7. · 0.60 Impact Factor
• Article: Recurrent Helicobacter cinaedi bacteremia in a patient infected with human immunodeficiency virus: case report.

  M P Mammen, N E Aronson, W J Edenfield, T P Endy
  Clinical Infectious Diseases 11/1995; 21(4):1055. · 9.15 Impact Factor
• Article: A human challenge model for dengue infection reveals a possible protective role for sustained interferon gamma levels during the acute phase of illness

  V.J. Gunther, R. Putnak, K.H. Eckels, M.P. Mammen, J.M. Scherer, A. Lyons, M.B. Sztein, W. Sun
  [show abstract] [hide abstract]
  ABSTRACT: Dengue has recently been defined by the World Health Organization as a major international public health concern. Although several vaccine candidates are in various stages of development, there is no licensed vaccine available to assist in controlling the further spread of this mosquito borne disease. The need for a reliable animal model for dengue disease increases the risk to vaccine developers as they move their vaccine candidates into large-scale phase III testing. In this paper we describe the cellular immune responses observed in a human challenge model for dengue infection; a model that has the potential to provide efficacy data for potential vaccine candidates in a controlled setting. Serum levels of sIL-2Rα and sTNF-RII were increased in volunteers who developed illness. Supernatants from in vitro stimulated PBMC were tested for cytokines associated with a TH1 or TH2 T-cell response (IL-2, TNF-α, IFN-γ, IL-4, IL-10, IL-5) and only IFN-γ was associated with protection against fever and/or viremia. Interestingly, IFN-γ levels drop to 0 pg/mL for volunteers who develop illness after challenge suggesting that some mechanism of immunosuppression may play a role in dengue illness. The human challenge model provides an opportunity to test potential vaccine candidates for efficacy prior to large-scale phase III testing, and hints at a possible mechanism for immune suppression by dengue.
  Vaccine.