Letter to the editor: Specificity of Zika virus ELISA: interference with malaria

Abstract

We evaluated the specificity of this test on convalescent samples of 10 PCR-confirmed dengue patients (n = 3 DENV-1, n = 4 DENV-2, n = 2 DENV-3 and n = 1 DENV-4) with high IgM antibody ratios and a positive (n = 9) or negative (n = 1) result for IgG antibodies. We also tested the assay on 10 samples with high titres of neutralising antibodies against yellow fever virus and on five samples positive for rheumatoid factor. Except for one borderline result (ratio between 0.8 and 1.1) of ZIKV IgM in the convalescent sample from a patient infected with DENV-1 after a stay in Thailand, all results for ZIKV IgM and IgG were negative.However, when we tested samples from malaria patients with a current infection (thick smear and PCR-positive) with Plasmodium falciparum (n = 12), P. falciparum/P. ovale (n = 1), P. vivax (n = 3), P. ovale (n = 5) or P. malariae (n = 5), or a recently treated P. falciparum infection (microscopy-negative, PCR-positive) (n = 8), 14 of these 34 samples tested positive or borderline for ZIKV IgM, IgG or both. Positive or borderline results for both ZIKV IgM and IgG were registered in two of 13 samples from patients with a current infection with P. falciparum (including the patient with the mixed P. falciparum/P. ovale infection) and in one of eight samples from patients with a recently treated P. falciparum infection. Nine samples tested positive or borderline for ZIKV IgM only: four from patients with a current P. falciparum, two each from patients with a P. vivax and recently treated P. falciparum infection, and one from a patient with a P. malariae infection. Finally, one of 13 samples from patients with a current P. falciparum infection and one of five samples from patients with a P. ovale infection tested positive for ZIKV IgG only.Virus neutralisation tests could not demonstrate a ZIKV infection in 11 of the 14 samples with positive or borderline results. Notably, we confirmed a recent ZIKV infection in one patient with a recently treated P. falciparum infection who had travelled in several African countries in the first half of 2015 and most recently in Cameroon (ZIKV IgM and IgG ratios in the ELISA were 2.61 and 7.50 respectively). The results from two patients with P. ovale (ZikV IgG ratio: 1.84) and P. vivax (ZIKV IgM ratio: 0.87) infection were not conclusive. The samples from patients with a current or recently treated P. falciparum infection with false positive ZIKV ELISA results showed ratios between 1.10 and 6.93 for ZIKV IgM and between 0.92 and 7.02 for IgG. One sample from a patient with a P. vivax infection tested borderline for ZIKV IgM. The ELISA ratio for ZIKV IgM in the sample from the patient with a P. malariae infection was 1.10.False positive results were not correlated with parasite densities.Plasmodium is known for its ability to trigger polyclonal B-cell activation resulting in the production of antibodies that are not microorganism-specific [2], possibly leading to false positive results in serological assays. Samples from malaria patients should therefore be includ...

Dengue and Chikungunya among Febrile Outpatients in Kinshasa, Democratic Republic of Congo: a cross-sectional study

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No serological evidence for Zika virus infection and low specificity for anti-Zika virus ELISA in malaria positive individuals among pregnant women from Madagascar in 2010

“…falciparum infection as previously reported [17]. As ZIKV virus often occurs in malaria-endemic regions, this shortcoming of the ZIKV ELISA has to be taken into account.…”

“…However, recently, false positive results were described with serum samples from malaria patients [17]. …”

Zika Virus Strains Potentially Display Different Infectious Profiles in Human Neural Cells

“…However, Cape Verde has reported an outbreak and several cases were recently found in Guinea-Bissau (both due to ZIKV of the Asian lineage) in 2015–2016. Occasional studies or reports show that ZIKV AF strains are currently circulating and support the need to closely monitor ZIKV AF (Baraka and Kweka, 2016, Grard et al, 2014, Van Esbroeck et al, 2016). …”