Dengue hemorrhagic fever in infants: research opportunities ignored. (Perspective).The age distribution of cases of dengue dengue
or breakbone fever or dandy fever
Infectious, disabling mosquito-borne fever. Other symptoms include extreme joint pain and stiffness, intense pain behind the eyes, a return of fever after brief pause, and a characteristic rash. hemorrhagic fever and dengue shock syndrome (DHF/DSS) in infants under the age of 1 year are reported from Bangkok, Thailand, and for the first time for Ho Chi Minh City Ho Chi Minh City, formerly Saigon, city (1997 pop. 5,250,000), on the right bank of the Saigon River, a tributary of the Dong Nai, Vietnam. , Vietnam; Yangon, Myanmar; and Surabaya, Indonesia. The four dengue viruses were isolated from Thai infants, all of whom were having a primary dengue infection. Progress studying the immunologically distinct infant DHF/DSS has been limited; most contemporary research has centered on DHF/DSS accompanying secondary dengue infections. In designing research results obtained in studies on a congruent animal model, feline infectious peritonitis Feline infectious peritonitis (FIP) is a fatal, incurable disease that affects cats. It is caused by Feline Infectious Peritonitis Virus (FIPV), which is a mutation of Feline Enteric Coronavirus (FECV/FeCoV). Experts do not always agree on the specifics of FIP. virus (FIPV FIPV
feline infectious peritonitis virus. ) infections of kittens born to FIPV-immune queens should be considered. Research challenges presented by infant DHF/DSS are discussed.
Since World War II, the four dengue viruses (formal name: Dengue virus [DENV DENV Department of Environment (Canada) ]) have progressively spread geographically throughout the tropics, resulting in a global pandemic with tens of millions of infections annually, including several hundred thousand hospitalizations for dengue hemorrhagic fever (DHF DHF dihydrofolate or dihydrofolic acid. ) and dengue shock syndrome (DSS (1) (Digital Signature Standard) A National Security Administration standard for authenticating an electronic message. See RSA and digital signature.
(2) (Digital Satellite S ) (1). The size and spread of the dengue pandemic, the unpredictability of epidemic occurrences, and the circulation of virulent and nonvirulent strains make DHF/DSS a model for an emerging infectious disease An emerging infectious disease (EID) is an infectious disease whose incidence has increased in the past 20 years and threatens to increase in the near future. EIDs include diseases caused by a newly identified microorganism or newly identified strain of a known microorganism (e.g. .
Ample evidence suggests that DHF/DSS accompanies secondary dengue infections in children older than 1 year (1-3). Less well-known are the epidemiologic and clinical studies that document an identical severe syndrome in infants during their first dengue infection (4,5). Ignoring these data, contemporary models of dengue immunopathogenesis focus on the sequential dengue viral infection phenomenon; such models suggest that severe disease results from amplified cytokine release caused by dengue infections occurring in the presence of T-cell memory (6). However, that model cannot explain DHF/DSS during a first dengue infection.
That dengue in infants is not often studied is understandable. Small subjects pose technical difficulties in obtaining samples required by research protocols, and human use protocols may be constraining. Yet infants represent 5% or more of all DHF/DSS patients (7). Uniquely, infants with DHF/DSS present an opportunity to obtain both the causative virus and the preinfection antibodies as research reagents in a hospital setting without recourse to a time-consuming and expensive prospective cohort study. The all-important preinfection antibodies can be collected from the mother, as her serum is a surrogate for cord blood (8).
Enhancement of infant infectious diseases by cord blood antibodies is not described for human infections other than dengue. However, such a phenomenon occurs naturally in infected kittens born to queens immune to feline infectious peritonitis virus (FIPV) (9-11). To refocus attention on the research opportunities afforded by this immunopathologic entity, we provide evidence that infants with DHF/DSS are regularly admitted to hospitals in four of the largest dengue-endemic countries. The age distribution of all these infant DHF/DSS patients is similar. Most of those studied serologically had had primary dengue infections. Because of FIPV's congruence to infant dengue, a short literature review is provided on that animal model.
Materials and Methods
Data on infants, ages <12 months, hospitalized with a clinical diagnosis of DHF were obtained from four hospitals: Children's Hospital No. 1, Ho Chi Minh City, Vietnam; the Queen Sirikit National Institute of Child Health, also referred to as Bangkok Children's Hospital, Bangkok, Thailand; Children's Hospital, Yangon, Myanmar; and the Department of Pediatrics, Dr. Soetomo Hospital, Surabaya, Indonesia. In this study, data for 4 consecutive years, either 1995-1998 or 1996-1999 were combined. Patients were under the routine care of one or more of the authors, each an experienced senior academic infectious diseases pediatrician. All diagnoses of DHF/DSS in infants conformed to World Health Organization case definitions. In Bangkok, serum samples from all infants and children hospitalized for DHF were sent for routine diagnostic study to the Virology virology, study of viruses and their role in disease. Many viruses, such as animal RNA viruses and viruses that infect bacteria, or bacteriophages, have become useful laboratory tools in genetic studies and in work on the cellular metabolic control of gene expression Department, Armed Forces Research Institute of Medical Sciences (AFRIMS AFRIMS Armed Forces Research Institute of Medical Sciences (US, HHS & DoD)
AFRIMS Air Force Records Information Management System
AFRIMS Air Force Restoration Information Management System ). For nearly 30 years, AFRIMS has provided such dengue diagnostic services to Bangkok Children's Hospital. Similar routine diagnostic tests were provided for infants and children admitted to Children's Hospital, Yangon, by the Virology Department, Department of Medical Research. Fiscal constraints limited the number of serologic tests performed. Individual data were disassociated from any identifiers and are presented here only in aggregate.
As described, DENV isolations were attempted from acute-phase plasma or serum samples from Thai children by inoculation into C6/36 cells or intrathoracically in mosquitoes (Toxorrhynchites splendens) (12).
DENV was identified in C6/36 cells by an antigen-specific enzyme-linked immunosorbent assay enzyme-linked immunosorbent assay
Enzyme-linked immunosorbent assay (ELISA)
A diagnostic blood test used to screen patients for AIDS or other viruses. (ELISA ELISA (e-li´sah) Enzyme-Linked Immuno-Sorbent Assay; any enzyme immunoassay using an enzyme-labeled immunoreactant and an immunosorbent.
n. ) with a panel of monoclonal antibodies against DENV (13).
The division of biological science concerned with antigen-antibody reactions in serum. It properly encompasses any of these reactions, but is often used in a limited sense to denote laboratory diagnostic tests, especially for syphilis.
Plasma or serum samples were tested for serologic evidence of acute DENV infection by immunoglobulin (Ig) M and IgG ELISA, hemagglutination hemagglutination /he·mag·glu·ti·na·tion/ (he?mah-gloo-ti-na´shun) agglutination of erythrocytes.
n. inhibition (HAI) assays, or both (14). For single specimens, [greater than or equal to] 5 days after onset of fever 40 U of IgM to DENV was considered evidence of a DENV infection. A DENV IgM-to-IgG ratio [greater than or equal to] 1.8 defined a primary infection. A ratio <1.8 defined a secondary DENV infection. With serial specimens, twofold increase in IgG to DENV with an absolute value of [greater than or equal to] 100 U indicated a secondary infection in the absence of IgM to DENV of [greater than or equal to] 40 U.
In Bangkok, HAI antibody against DENV types 1-4 and Japanese encephalitis virus were measured in all sera (15). A fourfold increase was considered positive for acute flavivirus infection. The infection was diagnosed as primary if titers [greater than or equal to] 1 week after onset of illness were <1:1,280 or as secondary if antibody titers were >1:1,280 (16).
Infants are at high risk for DHF/DSS. Figure 1 provides data from the only published study to estimate age-specific dengue hospitalization rates for the Bangkok metropolitan area The Bangkok Metropolitan Area (Thai: กรุงเทพมหานครและปริมณฑล . In 1964, 17/1,000 seven-month-old infants, more than 1% of the population that age, were hospitalized for DHF/DSS (17). This modal rate was two times higher than the 1964 modal hospitalization rate for children (age 4 years, data not shown) in Bangkok during the same year (17). In our present study, infant DHF/DSS constituted 4.9%, 4.6%, 5.0%, and 4.9% of 4,872; 14,053; 8,938; and 2,057 Thai, Vietnamese, Myanmar, and Indonesian infants and children hospitalized with DHF in 1995-1998, respectively.
[FIGURE 1 OMITTED]
During a 4-year period, 237, 652, 449, and 101 infants with presumptive DHF/DSS were admitted to hospitals in Bangkok Bangkok, Thailand has many hospitals:
[FIGURE 2 OMITTED]
The distribution by age of DHF/DSS infants in all four countries presents a similar pattern: few cases were observed in infants younger than 3 months, and the largest numbers observed were in infants 6-8 months old. Later in the first year, admissions declined nearly to baseline in Thailand and Indonesia. In Yangon, the decline in admissions reversed at age 10 months and increased. In Yangon, DHF hospitalizations continued to increase during the second year of life (Figure 3). In Ho Chi Minh City, cases in 11-month-olds declined, but not quite to the baseline.
[FIGURE 3 OMITTED]
Children hospitalized with DHF/DSS in Bangkok show the classical bimodal bi·mod·al
1. Having or exhibiting two contrasting modes or forms: "American supermarket shopping shows bimodal behavior curve: relatively few cases in children 12-24 months of age and a modal age later in life, in this case at 8 years of age (Figure 4). By contrast, this bimodal distribution is not present in Yangon. DHF/DSS occurs commonly in 12- to 24-month-old children, and the modal age at admission is 4 years (Figure 3).
[FIGURE 4 OMITTED]
The patterns of age distribution of infant DHF/DSS were similar in four large Southeast Asian countries highly endemic for all four DENV serotypes. Nearly all infants in the large Thai and most in the smaller Myanmar groups had primary DENV antibody responses. The characteristic and unique age-specific hospitalization curves are consistent with published observations that describe infant DHF/DSS occurrence during primary DENV infections. Primary and secondary DHF infections are reconciled in a long-standing explanatory hypothesis linking severe disease to actively or passively acquired antibodies (4,8,18). In our study, infants constituted approximately 5% of total DHF/DSS patients, lower than the nearly 10% reported from Bangkok Children's Hospital in the 1960s (7,17).
Differences were observed in the age distribution curves in Yangon and Ho Chi Minh City compared with Bangkok and Surabaya. In Yangon, the curve declined at 8 months but rose again at age 10 months, and no dip in cases occurred in 1-year-old children (Figures 2 and 3). In Ho Chi Minh City, infant cases declined at the end of the first year of life, but not to the baseline; by contrast, in Thailand and Indonesia by the end of the first year of life, the curve approached the baseline. These phenomena may be explained by differences in average annual rates of dengue infection. In Yangon, the modal age of hospitalization for DHF/DSS for children is 4 years (Figure 3), while in Bangkok it is 8 years (Figure 4). In Bangkok, DHF/ DSS is rarely seen in 12- to 24-month-olds, signifying that second infections are usually delayed until after a child has lived through two dengue transmission periods (Figure 4). Among serologically studied infant DHF/DSS patients in Yangon, several ages 10 months and older had secondary dengue infections. These observations are consistent with high average annual rates of dengue infection in Yangon and lower infection rates in Bangkok. These relationships have been modeled mathematically (19).
Since infant DHF/DSS was first reported in 1970 (4), only a single research study has been undertaken on this group (8). This study included 13 Bangkok infants, all with primary DENV-2 infections, who were admitted to hospital at different ages in the first year of life. During hospitalization, mother's blood was taken and tested as a surrogate for cord blood at birth. An analysis of dengue-neutralizing antibodies showed that every mother in the study had had two or more previous DENV infections (8). All infants acquired DHF/DSS during the short window of time when maternal DENV-2 neutralizing antibodies had degraded to a titer of approximately 1:10. Maternal sera enhanced DENV-2 at high dilutions. These data provide a logical explanation for the observed age distribution of infant DHF/DSS. At birth, maternal antibodies protect infants from dengue infection. As IgG antibodies are catabolized, a period of risk to enhanced infection ensues, followed in turn by the loss of enhancing antibodies and a corresponding decline in risk for DHF/DSS (Figure 5).
[FIGURE 5 OMITTED]
Data from studies on infants as well as prospective cohort studies on children demonstrate that the waning or absence of heterotypic heterotypic /het·ero·typ·ic/ (-tip´ik) pertaining to, characteristic of, or belonging to a different type.
het·er·o·typ·ic or het·er·o·typ·i·cal
adj. neutralizing antibodies permits enhanced infections to occur. Infection enhancement occurs at lower antibody concentrations than neutralization neutralization, chemical reaction, according to the Arrhenius theory of acids and bases, in which a water solution of acid is mixed with a water solution of base to form a salt and water; this reaction is complete only if the resulting solution has neither acidic nor (8,20).
Immunopathogenesis mechanisms have been more extensively studied in a remarkably similar viral infection of cats, FIPV, a highly fatal coronavirus disease of domestic and exotic cats (9-11). Most cats naturally exposed as adults to FIPV develop antibody titers without showing clinical signs. Lesions in sick cats are believed to result from immunologically mediated responses (9,10,21). Kittens receiving apparently competent neutralizing antibodies to FIPV, transferred in colostrum colostrum /co·los·trum/ (kol-os´trum) the thin, yellow, milky fluid secreted by the mammary gland a few days before or after parturition.
n. from immune queens, develop a fatal disease a few days after infection with wild-type virus (22). Passive transfer of antibody by other routes produces the same result (22,23). This phenomenon is called the early death syndrome. FIPV in antibody-negative kittens occurs less reliably and is delayed for several weeks until animals develop their own antibody response to the virus. FIPV in kittens is characterized by thrombocytopenia Thrombocytopenia Definition
Thrombocytopenia is an abnormal drop in the number of blood cells involved in forming blood clots. These cells are called platelets. and elevated ALT, AST (AST Computer, Irvine, CA) A PC manufacturer founded in 1980 by Albert Wong, Safi Quershey and Tom Yuen (A, S and T). It offered a complete line of PCs that sold through its dealer channel. , and serum bilirubin Bilirubin
The predominant orange pigment of bile. It is the major metabolic breakdown product of heme, the prosthetic group of hemoglobin in red blood cells, and other chromoproteins such as myoglobin, cytochrome, and catalase. (22).
The coronaviruses, pathogens of mammals and birds, are a large family of enveloped en·vel·op
tr.v. en·vel·oped, en·vel·op·ing, en·vel·ops
1. To enclose or encase completely with or as if with a covering: "Accompanying the darkness, a stillness envelops the city" RNA viruses with a nonsegmented, positive-stranded genome that is 27-32 kb in length (24). One of the most intriguing aspects of coronavirus replication is the occurrence of high-frequency homologous RNA RNA: see nucleic acid.
in full ribonucleic acid
One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic recombination (25). Together with porcine Transmissible transmissible /trans·mis·si·ble/ (trans-mis´i-b'l) capable of being transmitted.
Capable of being conveyed from one person to another. gastroenteritis gastroenteritis: see enteritis.
Acute infectious syndrome of the stomach lining and intestines. Symptoms include diarrhea, vomiting, and abdominal cramps. virus (TGEV), canine coronavirus, and human coronavirus 229E (HCV HCV
hepatitis C virus
HCV 1 Hepatitis C virus, see there 2. Human coronavirus. See Coronavirus. ), the feline coronaviruses form a separate cluster within, the genus Coronavirus, including Feline enteric coronavirus, and FIPV (26). Coronavirus virions possess three structural proteins, a large spike glycoprotein (S), a small integral membrane glycoprotein (M), and a nucleocapsid nucleocapsid /nu·cleo·cap·sid/ (noo?kle-o-kap´sid) a unit of viral structure, consisting of a capsid with the enclosed nucleic acid.
n. protein (N) (24). These proteins are analogous to the envelope (E), M, and nucleocapsid (C) proteins of the flaviviruses. The feline coronaviruses can be divided into two serotypes, I and II, on the basis of cross-reactivity to canine coronavirus in virus neutralization assays (26). Type I viruses grow poorly in tissue cultures and show virtually no neutralization with anti-canine coronavirus sera (27). Type II viruses grow readily in vitro (28). Analysis of gene structure suggests that type II viruses are derived from recombination of type I feline coronavirus and canine coronavirus (26). The two serotypes circulate as two pathotypes, the avirulent a·vir·u·lent
Not virulent. enteric viruses and the virulent FIPV (26). High-frequency mutations may help coronaviruses escape neutralization and promote infection enhancement in Fc receptor-bearing cells.
Antibody-dependent enhancement of FIPV has been demonstrated in vitro in feline macrophages Macrophages
White blood cells whose job is to destroy invading microorganisms. Listeria monocytogenes avoids being killed and can multiply within the macrophage. as well as in stable human and mouse macrophage macrophage /mac·ro·phage/ (mak´ro-faj) any of the large, mononuclear, highly phagocytic cells derived from monocytes that occur in the walls of blood vessels (adventitial cells) and in loose connective tissue (histiocytes, phagocytic cell lines (29). More cells are infected in the presence compared with the absence of antibody; the rates of viral entry and viral replication are similar under both conditions (30). Coronaviruses appear to enter mononuclear phagocytes by means of the plasma membrane without marked involvement of phagocytic phag·o·cyt·ic
1. Of or relating to phagocytes.
2. Of, relating to, or characterized by phagocytosis.
emanating from or pertaining to phagocytes. or endosomal pathways (28). Some researchers have surmised that, as with DENV, when antibody-virus complexes attach to Fc-receptors, viruses are brought close to cell surfaces, where they enter the cells by normal mechanisms (31,32). Enhancement is mediated by clusters of epitopes on the S protein (33,34). Results with FIPV suggest that feline IgG2a antibodies mediate both neutralization and enhancement (33). Antibody-dependent enhancement in FIPV demonstrates a bell-shaped curve with increasing dilutions; maximal enhancement occurs at subneutralizing titers (34).
Antibody-dependent enhancement is believed to be the cause of vaccine failure after immunization immunization: see immunity; vaccination. with live (35,36) or recombinant (37) vaccines. Inoculation of cats with a recombinant vaccinia virus expressing the S protein FIPV 79-1146 sensitized sensitized /sen·si·tized/ (sen´si-tizd) rendered sensitive.
see sensitization (2). cats and led to accelerated disease after FIPV challenge (37), while inoculation with recombinant vaccinia viruses expressing the M or N proteins did not (38). Immunization with vaccines made from other members of the feline coronavirus group, TGEV or canine coronavirus, also sensitizes cats to early death syndrome (39).
Flaviviridae do not appear to be subject to as high rates of homologous recombination as are the Coronaviridae; nonetheless, during evolutionary history four dengue serotypes have emerged. A phenomenon reminiscent of the feline coronaviruses is the evidence that DENV also circulate as two biotypes: DENV-2 American genotype does not cause DHF/DSS, while DENV-2 SE Asian genotype does (40). As with feline coronaviruses, the severity of disease with the two DENV biotypes may be regulated by cross-reactive antibodies (41). Focused research on viral-antibody interactions at the structural level might clarify early pathogenesis events in DHF/ DSS. Infants may provide an accessible and inexpensive model to study mechanisms controlling the severity of dengue infections. Workers actively involved in developing dengue vaccines may benefit from lessons learned in the FIPV model.
We are grateful to Mlaing Myat Thu for sharing data from serologic studies performed at the Department of Medical Research, Yangon, Myanmar.
(1.) Halstead SB. Pathogenesis of dengue: challenges to molecular biology. Science 1988;239:476-81.
(2.) Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, et al. Dengue viremia viremia /vi·re·mia/ (vi-re´me-ah) the presence of viruses in the blood.
The presence of viruses in the bloodstream. titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis 2000; 181:2-9.
(3.) Ngo NT CX, Kneen R, Wills B, Nguyen VMN VMN Visiting Mobile Node
VMN Voicemail Notification
VMN Virtual Manufacturing Network (Production Management) , Nguyen TQ, Chu VT, et al. Acute management of dengue shock syndrome: a randomized ran·dom·ize
tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es
To make random in arrangement, especially in order to control the variables in an experiment. double-blind comparison of four intravenous fluid regimens in the first hour. Clin Infect Dis 2001;32:204-13.
(4.) Halstead SB, Nimmannitya S, Cohen cohen
(Hebrew: “priest”) Jewish priest descended from Zadok (a descendant of Aaron), priest at the First Temple of Jerusalem. The biblical priesthood was hereditary and male. SN. Observations related to pathogenesis of dengue hemorrhagic fever. IV. Relation of disease severity to antibody response and virus recovered. Yale J Biol Med 1970;42:311-28.
(5.) Halstead SB, Nimmannitya S, Yamarat C, Russell PK. Hemorrhagic fever in Thailand; recent knowledge regarding etiology. Japanese Journal of Medical Science and Biology 1967;20;96-103.
(6.) Rothman AL, Ennis FA. Immunopathogenesis of dengue hemorrhagic fever. Virology 1999;257:1-6.
(7.) Halstead SB. Immunological parameters of Togavirus disease syndromes. In: Schlesinger RW, editor. The Togaviruses, biology, structure, replication. New York: Academic Press; 1980. p. 107-73.
(8.) Kliks SC, Nimmannitya S, Nisalak A, Burke DS. Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg 1988;38:411-9.
(9.) Horzinek MC, Osterhaus AD. Feline infectious peritonitis: a coronavirus disease of cats. Small Anim Pract 1978;19:623-30.
(10.) Horzinek MC, Osterhaus AD. The virology and pathogenesis of feline infectious peritonitis: brief review. Arch Virol 1979;59:1-15.
(11.) Weiss RC, Scott FW. Feline infectious peritonitis. In: Kirk RW, editor. Current veterinary therapy. Philadelphia: W.B. Saunders; 1980. p. 1288-92.
(12.) Vaughn DW, Green S, Kalayanrooj S, Innis BL, Nimmannitya S, Suntayakorn S, et al. Dengue in the early febrile phase: viremia and antibody responses. J Infect Dis 1997;176:322-30.
(13.) Kuno G, Gomez I, Gubler DJ. An ELISA procedure for the diagnosis of dengue infections. J Virol Methods 1991;33:101-13.
(14.) Innis BL, Nisalak A, Nimmannitya S, Kusalerdchariya S, Chongswasdi V, Suntayakorn S, et al. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis cocirculate.
Am J Trop Med Hyg 1989;40:418-27.
(15.) Clarke DH, Casals J. Techniques for hemagglutination and hemagglutination inhibition with arthropod-borne viruses. Am J Trop Med Hyg 1958; 7:561-73.
(16.) World Health Organization. Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. 2nd edition. Geneva Geneva, canton and city, Switzerland
Geneva (jənē`və), Fr. Genève, canton (1990 pop. 373,019), 109 sq mi (282 sq km), SW Switzerland, surrounding the southwest tip of the Lake of Geneva. : The Organization; 1997.
(17.) Halstead SB, Scanlon J, Umpaivit P, Udomsakdi S. Dengue and chikungunya
(18.) Halstead SB. Observations related to pathogenesis of dengue hemorrhagic fever. VI. Hypotheses and discussion. Yale J Biol Med 1970;42:350-62.
(19.) Fischer DB, Halstead SB. Observations related to pathogenesis of dengue hemorrhagic fever. V. Examination of age-specific sequential infection rates using a mathematical model. Yale J Biol Med 1970;42:329-49.
(20.) Kliks SC, Nisalak A, Brandt WE, Wahl L, Burke DS. Antibody-dependent enhancement of dengue virus growth in human monocytes monocytes,
n.pl the largest of the white blood cells. They have one nucleus and a large amount of grayish-blue cytoplasm. Develop into macrophages and both consume foreign material and alert T cells to its presence. as a risk factor for dengue hemorrhagic fever. Am J Trop Med Hyg 1989;40:444-51.
(21.) Weiss RC, Scott FW. Pathogenesis of feline infectious peritonitis: nature and development of viremia. Am J Vet Res 1981;42:382-90.
(22.) Weiss RC, Scott FW. Antibody-mediated enhancement of disease in feline infectious peritonitis: comparisons with dengue hemorrhagic fever. Comp Immunol Microbiol Infect Dis 1981 ;4:175-88.
(23.) Pederson NC, Boyle JF. Immunologic phenomena in the effusive form of feline infectious peritonitis. Am J Vet Res 1980;41:868-76.
(24.) Siddell SG. The Coronaviridae. In: Siddell SG, editor. The Coronaviridae. New York: Plenum Press; 1995.
(25.) Lai MMC See MultiMediaCard and Microsoft Management Console. . Recombination in large RNA viruses: coronaviruses. Seminars in Virology 1996;7:381-8.
(26.) Herrewegh AA, Smeenk I, Horzinek MC, Rottier PJ, de Groot RJ. Feline coronavirus type II strains 79-1683 and 79-1146 originate from a double recombination between feline coronavirus type I and canine coronavirus. J Virol 1998;72:4508-14.
(27.) Hohdatsu T, Tatekawa T, Koyama H. Enhancement of feline infectious peritonitis virus type I infection in cell cultures using low-speed centrifugation. J Virol Methods 1995;51:357-62.
(28.) Olsen CW. A review of feline infectious peritonitis virus: molecular biology, immunopathogenesis, clinical aspects, and vaccination. Vet Microbiol 1993;36:1-37.
(29.) Hohdatsu T, Tokunaga J, Koyama H. The role of IgG subclass In programming, to add custom processing to an existing function or subroutine by hooking into the routine at a predefined point and adding additional lines of code.
subclass - derived class of mouse monoclonal antibodies in antibody-dependent enhancement of feline infectious peritonitis virus infection of feline macrophages. Arch Virol 1994;139:273-85.
(30.) Olsen CW, Corapi WV, Jacobson RH, Simkins RA, Saif L J, Scott FW. Identification of antigenic sites mediating antibody-dependent enhancement of feline-infectious peritonitis peritonitis (pĕr'ĭtənī`tĭs), acute or chronic inflammation of the peritoneum, the membrane that lines the abdominal cavity and surrounds the internal organs. virus infectivity. J Gen Virol 1993;74:745-9.
(31.) Gollins SW, Porterfield JS. Flavivirus infection enhancement in macrophages: an electron microscopic study of viral cellular entry. J Gen Virol 1985;66:1969-82.
(32.) Mady BJ, Erbe DV, Kurane I, Fanger MW, Ennis FA. Antibody-dependent enhancement of dengue virus infection mediated by bispecific antibodies against cell surface molecules other than Fc-gamma receptor. J Immunol 1991;147:3139-44.
(33.) Corapi WV, Olsen CW, Scott FW. Monoclonal antibody analysis of neutralization and antibody-dependent enhancement of feline infectious peritonitis virus. J Virol 1992;66:6695-705.
(34.) Olsen CW, Corapi WV, Ngichabe CK, Baines JD, Scott FW. Monoclonal antibodies to the spike protein of feline infectious peritonitis virus mediate antibody-dependent enhancement of infection of feline macrophages. J Virol 1992;66:956-65.
(35.) Pedersen NC. Animal virus infections that defy vaccination: equine infectious anemia equine infectious anemia
A viral disease in horses marked by progressive anemia, a staggering gait, and fever. , caprine cap·rine
pertaining to or emanating from goats.
caprine arthritis-encephalitis (CAE) arthritis-encephalitis, maedi-visna, and feline infectious peritonitis. Adv Vet Sci Comp Med 1989;33:413-28.
(36.) Pedersen NC, Black JW. Attempted immunization of cats against feline infectious peritonitis, using avirulent live virus or sublethal sublethal /sub·le·thal/ (-le´thal) insufficient to cause death.
Not sufficient to cause death. amounts of virulent virus. Am J Vet Res 1983;44:229-34.
(37.) Vennema H, DeGroot RJ, Harbour DA, Dalderup M, Gruffydd-Jones T, Horzinek MC, et al. Early death after feline infectious peritonitis challenge due to recombinant vaccinia virus immunization. J Virol 1990;64:1407-9.
(38.) Vennema H, DeGroot RJ, Harbour DA, Horzinek M, Spaan WJM WJM Western Journal of Medicine . Primary structure of the membrane and nucleocapsid protein genes of feline infectious peritonitis virus and immunogenicity immunogenicity /im·mu·no·ge·nic·i·ty/ (-je-nis´it-e) the property enabling a substance to provoke an immune response, or the degree to which a substance possesses this property. of recombinant vaccine viruses in kittens. Virology 1991; 181:327-35.
(39.) Chalmers WSK WSK Wiretap Secret Key
WSK Webb School of Knoxville (Knoxville, Tennessee)
WSK Webmaster Starter Kit
WSK Winsock Kernel , Horsburgh BC, Baxendale W, Brown TDK TDK Türk Dil Kurumu (Turkish Language Council)
TDK The Dark Knights (gaming clan)
TDK Tokyo Denkikagaku Kogyo KK (TDK Electronics Co. Ltd. . Enhancement of FIP FIP
feline infectious peritonitis. in cats immunize with vaccina virus recombinants expressing CCV CCV
canine coronavirus. and TGEV spike glycoproteins. In: Laude H, Vautherot JF, editors. Coronoviruses. New York: Plenum Press; 1994. p. 359-64.
(40.) Watts DM, Porter KR, Putvatana P, Vasquez B, Calampa C, Hayes CG, et al. Failure of secondary infection with American genotype dengue 2 to cause dengue haemorrhagic fever [see comments]. Lancet 1999;354:1431-4.
(41.) Kochel TJ, Watts DM, Halstead SB, Hayes CC4 Espinosa A, Felices V, et al. Neutralization of American genotype dengue 2 viral infection by dengue 1 antibodies may have prevented dengue hemorrhagic fever in Iquitos, Peru. Lancet 2002;360:310-2.
Scoff B. Halstead, * Nguyen Trong Lan, ([dagger]) Thein Thein Myint, ([double dagger]) Than Nu Shwe, ([double dagger]) Ananda Ananda
(flourished 6th century BC, India) First cousin and disciple of the Buddha. A monk who served as the Buddha's personal attendant, he became known as the “beloved disciple.” It was Ananda who persuaded the Buddha to allow women to become nuns. Nisalak, ([section]) Siripen Kalyanarooj ([paragraph]), Suchitra Nimmannitya, ([paragraph]) Soegeng Soegijanto, (#) David W. Vaughn, ([section]) and Timothy P. Endy ([section])
* Uniformed Services University of the Health Sciences The university currently has two mottos: "Learning to Care For Those In Harm's Way" and "Providing Good Medicine In Bad Places." USU School of Medicine
With an enrollment of approximately 167 students per class, USU School of Medicine is located in Bethesda, Maryland on the , Bethesda, Maryland, USA; ([dagger]) Children's Hospital No. 1, Ho Chi Minh City, Vietnam; ([double dagger]) Yangon Children's Hospital, Yangon, Myanmar; ([section]) Armed Forces Research Institute of the Medical Sciences, Bangkok, Thailand; ([paragraph]) Queen Sirikit National Institute of Child Health, Bangkok, Thailand; and (#) Dr. Soetomo Hospital, Airlangga University Medical School, Surabays, Indonesia
Dr. Halstead is adjunct professor in the Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland. His research interests include the epidemiology, pathogenesis, and immunology of flavivirus infections and vaccines for dengue fever dengue fever (dĕng`gē, –gā), acute infectious disease caused by four closely related viruses and transmitted by the bite of the Aedes mosquito; it is also known as breakbone fever and bone-crusher disease. and Japanese encephalitis.
Address for correspondence: Scott B. Halstead, 5824 Edson Lane, Rockville, MD 20852, USA; fax: 301-984-8042; e-mail: firstname.lastname@example.org