Graham R R, Juffrie M, Tan R, Hayes C G, Laksono I, Ma'roef C, Porter K R, Halstead S B
Naval Medical Research Unit No. 2 (NAMRU-2), Jakarta, Indonesia.
Am J Trop Med Hyg. 1999 Sep;61(3):412-9. doi: 10.4269/ajtmh.1999.61.412.
A prospective study on dengue (DEN) viruses was initiated in October 1995 in Gondokusuman kecamatan, Yogyakarta, Indonesia. This report presents data from the first year of the study. The studied cohort included all children 4-9 years of age living in the kecamatan. Blood samples for serology were collected from 1,837 children in October 1995 and again in October 1996. Blood samples for virus isolation and serology were collected from cohort children who were seen in municipal health clinics with febrile syndromes or admitted to hospitals with a provisional diagnosis of dengue hemorrhagic fever. Dengue serotype antibody prevalence and 1995-1996 infection rates were calculated using a single dilution (1:60) 70% plaque reduction endpoint neutralization test. Prevalence of dengue antibody at the beginning of the study was DEN 1 = 12%, DEN 2 = 16%, DEN 3 = 2%, DEN 4 = 4%, and two or more dengue infections = 22%. Total dengue antibody prevalence increased from 38% in 4-year-old children to 69% in 9-year-old children. During the observation period, primary dengue infection rates were DEN 1 = 4.8%, DEN 2 = 7.7%, DEN 3 = 4.2%, and DEN 4 = 3.4%, while two or more dengue infections occurred in 6.7% of the study population. The secondary dengue infection rate was 19.0%. From febrile cases, all four dengue viruses were isolated with DEN 3 predominating. Seven children were hospitalized, including one fatal case with a hospital diagnosis of dengue shock syndrome. Based upon presence of antibody in the initial cohort bleeding and the serologic response both weeks and several months following illness, all had secondary dengue infections. Neutralizing antibody patterns in the initial cohort bleeding and in late convalescent serum samples permitted recognition of dengue infection sequence in five patients: DEN 2-DEN 1 (3), DEN 2-DEN 4 (1), DEN 1-DEN 3 (1), and none in the sequence DEN 1-DEN 2. In the total cohort 6.5% of the observed secondary infections were of the sequence DEN 2-DEN 1, while 4.9% were DEN 1-DEN 2, a highly pathogenic sequence in previous studies. Reduced pathogenic expression of secondary DEN 2 with enhanced pathogenic expression of secondary DEN 1 infections was an unexpected finding. Further studies will be required to understand the respective contributions to pathogenicity of antibody from initial dengue infections versus the biological attributes of the second infecting dengue viruses.
1995年10月，在印度尼西亚日惹市贡多库苏曼区启动了一项关于登革热病毒的前瞻性研究。本报告呈现了该研究第一年的数据。研究队列包括居住在该地区所有4至9岁的儿童。1995年10月从1837名儿童中采集了血清学检测的血样，并于1996年10月再次采集。从出现发热症状的市立卫生诊所就诊的队列儿童或因疑似登革出血热入院的儿童中采集用于病毒分离和血清学检测的血样。使用单一稀释度（1:60）70%蚀斑减少终点中和试验计算登革热血清型抗体患病率和1995 - 1996年感染率。研究开始时登革热抗体患病率为：登革1型 = 12%，登革2型 = 16%，登革3型 = 2%，登革4型 = 4%，两种或更多种登革热感染 = 22%。登革热抗体总患病率从4岁儿童的38%上升至9岁儿童的69%。在观察期内，原发性登革热感染率为：登革1型 = 4.8%，登革2型 = 7.7%，登革3型 = 4.2%，登革4型 = 3.4%，而6.7%的研究人群发生了两种或更多种登革热感染。继发性登革热感染率为19.0%。从发热病例中分离出了所有四种登革热病毒，其中登革3型占主导。七名儿童住院治疗，包括一例医院诊断为登革休克综合征的死亡病例。根据初始队列出血时的抗体存在情况以及患病后数周和数月的血清学反应，所有患者均为继发性登革热感染。初始队列出血时和恢复期晚期血清样本中的中和抗体模式使我们能够识别五名患者的登革热感染序列：登革2型 - 登革1型（3例），登革2型 - 登革4型（1例），登革1型 - 登革3型（1例），登革1型 - 登革2型序列中无病例。在整个队列中，观察到的继发性感染中6.5%为登革2型 - 登革1型序列，而4.9%为登革1型 - 登革2型序列，这是先前研究中的高致病性序列。继发性登革2型致病性表达降低而继发性登革1型感染致病性表达增强是一个意外发现。需要进一步研究以了解初始登革热感染产生的抗体与第二种感染的登革热病毒的生物学特性对致病性的各自贡献。
