Serial real-time RT-PCR and serology measurements substantially improve Zika and Dengue virus infection classification in a co-circulation area.

BACKGROUND: Real-time RT-PCR (Reverse Transcriptase Polymerase Chain Reaction) is considered the gold standard for Zika virus (ZIKV) infection diagnosis, despite its low sensitivity. Diagnosis using recommended serologic cutoffs in co-circulating Flaviviruses areas maybe inadequate due to in-vitro cross-reactivities of Flaviviruses-specific antibodies. We evaluated Zika diagnosis in symptomatic patients using serial RT-PCR and develop a classification model using serial Dengue virus (DENV) and ZIKV serologies. METHODS: A prospective longitudinal multicentric study in Southern Mexico (NCT02831699) enrolled symptomatic and non-symptomatic participants. In the classification model, true positives were symptomatic (using a modified World Health Organization/Pan American Health Organization definition) with RT-PCR positive for ZIKV or DENV. True negatives were non-symptomatic with negative RT-PCR. Serial serology measurements were used to predict disease status. RESULTS: Analyzing ZIKV and DENV RT-PCR at 3 timepoints between days 3 and 13 of symptom onset detected 25% more cases than a single RT-PCR analysis between day 0 and 6. When considering sensitivity and specificity together, the serial serology model predicted all categories of disease and negatives better than manufactures cutoffs. Their cutoffs optimized sensitivity or specificity but not both. CONCLUSIONS: We demonstrated the importance of serial RT-PCR and antibody measurements to diagnose arbovirus infection in symptomatic patients living in regions with co-circulating flaviviruses.

Randomized controlled trial of Hepatitis B virus vaccine in HIV-1-infected patients comparing two different doses.

BACKGROUND: Co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is not infrequent as both share same route of exposure. The risk of developing chronic hepatitis B virus is 6%, in general population but can reach 10-20% in HBV/HIV co-infected patients. When compared to general population, the response rate to HBV vaccine in HIV-infected patients is diminished, so previous studies have tried to improve this response using variety of schedules, doses and co-administration of immunomodulators. The purpose of this study was to evaluate two doses of recombinant HBV vaccine (10 or 40 microg), IM at 0, 1 and 6 months. Vaccination response was measured 30-50 days after last dose; titers of >9.9 IU/L were considered positive. RESULTS: Seventy-nine patients were included, 48 patients (60.7%) serconverted. Thirty-nine patients (49.3%) received 10 microg vaccine dose, 24 patients (61.5%) seroconverted. Forty patients (50.7%) received 40 microg vaccine dose, 24 (60%) seroconverted. There were no differences between two doses. A statistically significant higher seroconversion rate was found for patients with CD4 cell counts at vaccination > or = 200 cel/mm3 (33 of 38 patients, 86.8%), compared with those with CD4 < 200 cel/mm3 (15 of 41, 36.6%), [OR 11.44, 95% IC 3.67-35.59, p = 0.003], there were no differences between two vaccine doses. Using the logistic regression model, CD4 count <200 cel/mm3 were significantly associated with non serologic response (p = 0.003). None other variables such as gender, age, risk exposure for HIV, viral load, type or duration of HAART or AIDS-defining illness, were associated with seroconversion. CONCLUSION: In this study, an increase dose of HBV vaccine did not show to increase the rate of response in HIV infected subjects. The only significant findings associated to the response rate was that a CD4 count > or = 200 cel/mm3, we suggest this threshold at which HIV patients should be vaccinated.