Pregnant women co-infected with HIV and Zika: Outcomes and birth defects in infants according to maternal symptomatology.

BACKGROUND: Zika virus (ZIKV) was first isolated in Uganda in 1947. In Brazil, the first reported case of ZIKV infection was in May 2015. Additionally, dengue (DENV) is endemic and there has been a recent outbreak of chikungunya (CHIKV). Since the clinical manifestations of different arboviral infections (AI) can be similar, definitive diagnosis requires laboratory testing. OBJECTIVES: To determine the prevalence of ZIKV, DENV, and CHIKV infections in a Brazilian cohort of HIV-infected pregnant women, to assess clinical/immunological characteristics and pregnancy outcomes of women with evidence of recent AI. STUDY DESIGN: Laboratory diagnosis of ZIKV, DENV and CHIKV infections utilized serological assays, RT-PCR and PRNT. The tests were performed at the first visit, 34-36 weeks of gestation and at any time if a woman had symptoms suggestive of AI. Mann-Whitney tests were used for comparison of medians, Chi-square or Fisher's to compare proportions; p< 0.05 was considered statistically significant. Poisson regression was used to analyze risk factors for central nervous system (CNS) malformations in the infant according to maternal symptomatology. RESULTS: Of 219 HIV-infected pregnant women enrolled, 92% were DENV IgG+; 47(22%) had laboratory evidence of recent AI. Of these, 34 (72%) were ZIKV+, nine (19%) CHIKV+, and two (4%) DENV+. Symptoms consistent with AI were observed in 23 (10%) women, of whom 10 (43%) were ZIKV+, eight (35%) CHIKV+. No CNS abnormalities were observed among infants of DENV+ or CHIKV+ women; four infants with CNS abnormalities were born to ZIKV+ women (three symptomatic). Infants born to ZIKV+ women had a higher risk of CNS malformations if the mother was symptomatic (RR = 7.20), albeit not statistically significant (p = 0.066). CONCLUSIONS: Among HIV-infected pregnant women with laboratory evidence of a recent AI, 72% were ZIKV-infected. In this cohort, CNS malformations occurred among infants born to both symptomatic and asymptomatic pregnant women with Zika infection.

Balanced cytokine-producing pattern in mice immunized with an avirulent Trypanosoma cruzi.

We have previously demonstrated that inoculation of BALB/c mice with trypomastigotes of CL-14, an avirulent Trypanosoma cruzi clone, prevents the development of parasitemia and mortality after challenge with virulent CL strain. In this report, we investigated the cytokine and antibody profiles induced by inoculation with CL-14 clone. Groups of mice were inoculated with trypomastigotes of CL-14 clone and challenged with infective CL strain. Challenged CL-14-inoculated mice had lower levels of IFN-gamma and higher production of IgG1 antibodies as compared to CL strain-infected mice. Previous inoculation with CL-14 clone partially prevented the suppression of IL-2 production caused by CL strain infection. No significant differences were found regarding IL-4 production by splenocytes from CL-14-inoculated or control groups after challenge with CL-strain. Our results show that protection against acute T. cruzi infection induced by CL-14 inoculation correlates with a balanced T1/T2 cytokine production, a profile likely to be beneficial for the host.

Trypanosoma cruzi: requirements for induction and maintenance of protective immunity conferred by immunization.

Immunization with CL-14-trypomastigotes generates efficient humoral and cellular responses against infective challenge. Herein, we investigated the relevance of these mechanisms in vivo. Immunization with live CL-14-trypomastigotes protected only part of beta2m(-/-) mice but efficiently protected perforin-knockout mice. Fixed CL-14-trypomastigotes could successfully immunize BALB/c, though live trypomastigotes lowered the requirements for doses and time intervals. Post-immune depletion of CD4 or CD8 subsets did not affect protection conferred by immunization, but switched the production of anti-Trypanosoma cruzi antibodies to IgG2a. Sublethal irradiation partially broke the resistance of immune mice, leading to development of late parasitemia. Passive serum transfer from immune mice conferred protection to nai;ve mice. Our results indicate that presentation of cytosolic antigens by MHC class I molecules is involved in the generation of immunity and suggest that the humoral response contributes to a great extent to keep CL-14-immunized mice protected against infective challenge.

Balanced cytokine-producing pattern in mice immunized with an avirulent Trypanosoma cruzi

We have previously demonstrated that inoculation of BALB/c mice with trypomastigotes of CL-14, an avirulent Trypanosoma cruzi clone, prevents the development of parasitemia and mortality after challenge with virulent CL strain. In this report, we investigated the cytokine and antibody profiles induced by inoculation with CL-14 clone. Groups of mice were inoculated with trypomastigotes of CL-14 clone and challenged with infective CL strain. Challenged CL-14-inoculated mice had lower levels of IFN-g and higher production of IgG1 antibodies as compared to CL strain-infected mice. Previous inoculation with CL-14 clone partially prevented the suppression of IL-2 production caused by CL strain infection. No significant differences were found regarding IL-4 production by splenocytes from CL-14-inoculated or control groups after challenge with CL-strain. Our results show that protection against acute T. cruzi infection induced by CL-14 inoculation correlates with a balanced T1/T2 cytokine production, a profile likely to be beneficial for the host