Accurate detection of Zika virus IgG using a novel immune complex binding ELISA.

OBJECTIVES: Accurate serological assays are urgently needed to support public health responses to Zika virus (ZIKV) infection with its potential to cause foetal damage during pregnancy. Current flavivirus serology for ZIKV infections lacks specificity due to cross-reacting antibodies from closely related other flaviviruses. In this study, we evaluated novel serological tests for accurate ZIKV IgG detection. METHODS: Our ELISAs are based on immune complex binding. The high specificity is achieved by the simultaneous incubation of labelled ZIKV antigen and unlabelled flavivirus homolog protein competitors. Two assays were validated with a panel of 406 human samples from PCR-confirmed ZIKV patients collected in Brazil (n = 154), healthy blood donors and other infections from Brazil, Europe, Canada and Colombia (n = 252). RESULTS: The highest specificity (100% [252/252, 95% confidence interval (CI) 98.5-100.0]) was shown by the ZIKV ED3 ICB ELISA using the ED3 antigen of the ZIKV envelope. A similar test using the NS1 antigen (ZIKV NS1 ICB ELISA) was slightly less specific (92.1% [232/252, 95% CI 88.0-95.1]). The commercial Euroimmun ZIKV ELISA had a specificity of only 82.1% (207/252, 95% CI 76.8-86.7). Sensitivity was high (93-100%) from day 12 after onset of symptoms in all three tests. Seroprevalence of ZIKV IgG was analysed in 87 samples from Laos (Asia) confirming that the ED3 ELISA showed specific reactions in other populations. CONCLUSIONS: The novel ED3 ICB ELISA will be useful for ZIKV-specific IgG detection for seroepidemiological studies and serological diagnosis for case management in travellers and in countries where other flavivirus infections are co-circulating.

Promoter haplotypes of the interleukin-10 gene influence proliferation of peripheral blood cells in response to helminth antigen.

Since interleukin (IL)-10 is a key mediator of immunosuppression, and immunosuppression is considered an important element of helminth infection, we studied variants of the putative IL-10 gene promoter in 337 individuals from 130 families heavily exposed to infection by the tissue nematode Onchocerca volvulus. As shown by transmission disequilibrium tests, variants of the IL-10 promoter at positions -1082(G/A), -819(C/T), and -592(C/A) in the haplotype of ATA were significantly associated with high peripheral blood cell (PBC) proliferative responses to O. volvulus antigen (OvAg). No associations were observed using phytohemagglutinin-induced PBC proliferation or with qualitative or quantitative phenotypes of onchocerciasis or onchocerciasis-related skin disease. The findings are compatible with the hypothesis that the ATA haplotype causes a decrease in IL-10 production by OvAg-reactive type-1 regulatory T-lymphocytes, thereby alleviating the suppression of other T cells. To our knowledge, this is the first time that an influence of IL-10 promoter variants is shown on the adaptive immune response.

Spleen size determined by ultrasound in patients with sickle cell trait, HbAC trait and glucose-6-phosphate-dehydrogenase deficiency in a malaria hyperendemic area (Ashanti Region, Ghana).

The occurrence of enlarged spleens and its age distribution has long been used as a crude measure to estimate malaria endemicity in cross-sectional surveys. Spleen size, however, is influenced by several variables that should be considered if they are observed in a population under study. We hypothesized that spleen indices are dependent on distinct red blood cell polymorphisms. Accordingly, we expected a lower prevalence of splenomegaly among patients with the sickle-cell trait (HbAS), HbAC trait and G6PD deficiency than in patients without red cell disorders, possibly due to the lower incidence of malaria attacks in these individuals. In our survey, however, spleen rates and sizes did not differ significantly between HbAA-, HbAS- and HbAC-positive individuals. Furthermore, enlargement of spleens was found at similar frequencies in persons with and without glucose-6-phosphate-dehydrogenase (G6PD)-deficiency (G6PD-A(-)).

Malariometric update for the rainforest and savanna of Ashanti region, Ghana.

The epidemiological features of human infection with Plasmodium were studied in a community-based survey of 35 villages in the Ashanti region of Ghana. The overall prevalences of malarial parasitaemia in subjects aged > or = 2 years were 50.72% in forest areas and 49.72% in savanna. Plasmodium falciparum was the predominant species everywhere, followed by P. malariae in the savanna and P. ovale in the forest. The highest prevalence of asexual parasitaemia (of any species) occurred in the youngest age-group (2-9 years). The geometric mean intensities of parasitaemia among the parasitaemic (i.e. the parasite density indices) were 557, 640 and 452 parasites/microliter for P. falciparum, P. ovale and P. malariae, respectively. For each Plasmodium species encountered, the mean intensity of parasitaemia decreased with age. Mixed infections were observed in 24% and 30% of the parasitaemic subjects from the forest and savanna, respectively. Those infected with P. falciparum were more likely to carry P. ovale (odds ratio = 2.02) or P. malariae (odds ratio = 2.63) than those who were not infected with P. falciparum. Mean intensities of the parasitaemias in mixed infections were substantially higher than the sums of those in the corresponding single infections. When comparing villages, parasite density indices were found to be correlated with the prevalences of parasitaemia (r = 0.56).