Correlation between complement component levels and disease severity in dengue patients in Indonesia.

Dengue hemorrhagic fever (DHF) is a severe form of dengue fever (DF). Recent in vitro studies indicate that complement reduces the infection-enhancing activity of dengue antibodies, suggesting its in vivo role in controlling viremia levels and disease severity. In this study, the complement hemolytic activity (CH50) and levels of complement components and related factors in dengue patients in Indonesia were assessed. Based on the number of days since fever onset, DF patients were compared with patients at the DHF pre-critical phase who showed deterioration within 2 days. The mean CH50 values and levels of C2, C4, and factors B and H in the DHF pre-critical phase group were significantly lower than those in the DF group. The mean CH50 values were significantly correlated with C4, factor B, or factor H levels, indicating their responsibility for reduced CH50 values. Furthermore, a significantly higher proportion of the DHF pre-critical phase group (78%) than the DF group (33%) was positive for the nonstructural protein 1 (NS1) antigen. These results suggested that antibody-dependent enhancement of infection occurs during a period of low complement activity, which is associated with NS1 levels during the acute phase in some patients, thereby leading to increased viremia levels and greater disease severity.

Dengue virus infection-enhancing and neutralizing antibody balance in children of the Philippines and Indonesia.

Dengue fever and dengue hemorrhagic fever are important diseases worldwide. Although antibody-dependent enhancement of infection has been proposed as a mechanism for increased disease severity, enhancing antibodies in endemic people have not been thoroughly investigated. Recently, we established a serological assay system to measure the balance of enhancing and neutralizing activities, which provides useful information for estimating in vivo antibody status. We measured the balance of these activities against four dengue virus (DENV) types in endemic populations, and analyzed the proportion of sera containing enhancing and neutralizing antibodies. Predominantly healthy Filipino children were used for analysis, although a population of Indonesian children was also investigated. In the Filipino population, the highest proportion of neutralizing activities was shown against DENV2, followed by DENV1. A greater proportion of sera exhibited enhancing rather than neutralizing antibodies against other virus types. Neutralizing activities were complement-dependent, while enhancing activities were complement-independent. The Indonesian population showed a similar dengue antibody status. Our results indicate that a relatively high proportion of endemic children possessed complement-independent enhancing antibodies against some DENV types.

Displacement of the predominant dengue virus from type 2 to type 1 with a subsequent genotype shift from IV to I in Surabaya, Indonesia 2008-2010.

Indonesia has annually experienced approximately 100,000 reported cases of dengue fever (DF) and dengue hemorrhagic fever (DHF) in recent years. However, epidemiological surveys of dengue viruses (DENVs) have been limited in this country. In Surabaya, the second largest city, a single report indicated that dengue virus type 2 (DENV2) was the predominant circulating virus in 2003-2005. We conducted three surveys in Surabaya during: (i) April 2007, (ii) June 2008 to April 2009, and (iii) September 2009 to December 2010. A total of 231 isolates were obtained from dengue patients and examined by PCR typing. We found that the predominant DENV shifted from type 2 to type 1 between October and November 2008. Another survey using wild-caught mosquitoes in April 2009 confirmed that dengue type 1 virus (DENV1) was the predominant type in Surabaya. Phylogenetic analyses of the nucleotide sequences of the complete envelope gene of DENV1 indicated that all 22 selected isolates in the second survey belonged to genotype IV and all 17 selected isolates in the third survey belonged to genotype I, indicating a genotype shift between April and September 2009. Furthermore, in December 2010, isolates were grouped into a new clade of DENV1 genotype I, suggesting clade shift between September and December 2010. According to statistics reported by the Surabaya Health Office, the proportion of DHF cases among the total number of dengue cases increased about three times after the type shift in 2008. In addition, the subsequent genotype shift in 2009 was associated with the increased number of total dengue cases. This indicates the need for continuous surveillance of circulating viruses to predict the risk of DHF and DF.