Jorge Murillo

EFFECT OF PRIMING WITH CARRIER ON RESPONSE TO CONJUGATE VACCINE

To examine whether prior immunity against a carrier protein modulates the serological response to injected peptide haptens attached to the same carrier in man, baseline tetanus antitoxin levels in volunteers who received a malaria sporozoite peptide-tetanus toxoid conjugate vaccine were compared with post-vaccination IgM and IgG antibody titres against the sporozoite antigen. In tetanus-vaccinated North American recipients of low doses of conjugate vaccine there were significant dose-dependent negative correlations between these variables, which suggests that epitopic suppression may occur in man. In contrast, Venezuelans living in non-malarious areas and mostly naive to tetanus toxoid showed a notable IgM response to the sporozoite antigen. The findings indicate that epitopic suppression and immune enhancement occur in man, and that the specific immunological responses to conjugate peptide vaccines may be difficult to predict.

Effect of GSTM1-Polymorphism on Disease Progression and Oxidative Stress in HIV Infection: Modulation by HIV/HCV Co- Infection and Alcohol Consumption

Objective To examine the effects of GSTM1 null-allele polymorphism on oxidative stress and disease progression in HIV infected and HIV/hepatitis C (HCV) co-infected adults. Methods HIV-infected and HIV/HCV co-infected participants aged 40–60 years old with CD4 cell count >350 cells/ µl, were recruited. GSTM1 genotype was determined by quantitative PCR. Oxidative stress (mitochondrial 8-oxo-2’-deoxyguanosine [8-oxo-dG], malondialdehyde [MDA], oxidized glutathione and Complexes I and IV), apoptosis and HIV disease (CD4 count and viral load) markers were measured. Gene copies were not quantified, thus the Hardy-Weinberg formula was not applicable. Results Of the 129 HIV-infected participants, 58 were HIV/HCV co-infected. GSTM1 occurred in 66% (62/94) in those of African descent, and 33% (11/33) of the Caucasians. Those with GSTM1 coding for the functional antioxidant enzyme Glutathione S-transferase (GST), had higher CD4 cell count (β=3.48, p=0.034), lower HIV viral load (β=−0.536, p=0.018), and lower mitochondrial 8-oxo-dG (β=−0.28, p=0.03). ART reduced oxidative stress in the participants with the GSTM1 coding for the functional antioxidant enzyme. HIV/HCV co-infected participants with the GSTM1 coding for the functional antioxidant enzyme also had lower HIV viral load, lower 8-oxo-dG and lower rate of apoptosis, but also higher oxidized glutathione. Alcohol consumption was associated with lower HIV viral load but higher oxidized glutathione in those with the GSTM1 genotype coding for the functional antioxidant enzyme. Conclusion The GSTM1 genotype coding for the functional antioxidant enzyme is associated with lower HIV disease severity, and with lower oxidative stress, compared to GSTM1 null-allele polymorphism. HCV co-infection and alcohol use may be associated with increased oxidative stress even in the presence of the GSTM1 coding for the functional antioxidant enzyme. The null-gene, on the contrary, appears to have a detrimental effect on immune function, viral load control, and antioxidant status, suggesting a potential benefit from antioxidants in HIV infected patients with the defective gene.

The ever changing landscape of Zika virus infection. Learning on the fly

Zika virus (ZIKV) has gone a long way since its humble discovery in a Rhesus sentinel primate in the Zika Forest of Uganda in 1947, to become a potentially devastating international health threat nowadays. For more than half a century ZIKV virus seemed to pose little threat to human beings and for that reason, epidemiological, clinical and therapeutic advances for ZIKV infection have been slow, as a reflection of the relatively small amount of research carried out on the subject as compared with other mosquito-borne viral diseases. Historically restricted to Africa and Asia, outbreaks with variable impact of autochthonous Zika Fever (ZIKF) were reported in the Pacific region since 2007 and then, as predicted from the distribution of the vectors Aedes aegypti and Aedes albopictus, ZIKV began to infect patients in South America in 2014, and eventually spread to Central and North America. The first molecularly confirmed case of Zika virus infection in the Americas Region was reported from Brazil in March 2015. In contrast to the relatively slow spread of Ebola virus through West Africa, the ZIKF epidemics in the Pacific and Americas regions moved very rapidly. Indeed, based on the severity of the health threat associated with the continuing spread of ZIKV disease in Latin America and the Caribbean, on 1 February 2016, the World Health Organization declared Zika virus-associated clusters of microcephaly and related neurological disorders a ‘Public Health Emergency of International Concern’. The number of patients affected by ZIKF in the Western Hemisphere increased sharply. As of August 22, 2016 45 countries and Territories throughout the Americas have reported more than 577,000 locally-acquired cases, with estimates of several million real cases, over a period of about one year and a half. Mathematical models have estimated the basic reproduction number (R0), or number of cases one case generates on average over the course of its infectious period in an otherwise uninfected population, for ZIKV in the region from 1.4 to 6.6 as key measure of transmissibility in a number of settings. The underlying reasons for the observed global spread of ZIKV are not fully understood highlighting how little we still understand about the global spread of flaviviruses and other vector-borne diseases. Hypotheses currently under consideration include possibilities as diverse as adaptive evolution of ZIKV allowing for an enhanced infectivity to urban Aedes species vectors, or alternatively, adaptive evolution in the human host, leading to higher levels of viremia which would instead enhance both the transmission by the biting mosquitos and the risk of transplacental fetal transmission. Not least important appears to be the

Congenital Chagas’ disease transmission in the United States: Diagnosis in adulthood

Two brothers with congenitally-acquired Chagas’ disease (CD) diagnosed during adulthood are reported. The patients were born in the USA to a mother from Bolivia who on subsequent assessment was found to be serologically positive for Trypanosoma cruzi. Serologic screening of all pregnant women who migrated from countries with endemic CD is strongly recommended.