Observational study on immune response to yellow fever and measles vaccines in 9 to 15-month old children. Is it necessary to wait 4 weeks between two live attenuated vaccines?

BACKGROUND: The use of 2 live attenuated vaccines (LAV) is recommended to be simultaneous or after an interval of at least four weeks between injections. The primary objective of this study was to compare the humoral response to yellow fever (YF) and measles vaccines among children vaccinated against these two diseases, either simultaneously or separated by an interval of 7-28 days. SUBJECTS AND METHODS: A prospective, multicenter observational study was conducted among children aged 9-15 months. The primary endpoint was the occurrence of positive yellow fever antibodies after YF vaccine by estimating the titers of neutralizing antibodies from venous blood samples. Children vaccinated against YF 7-28 days after receiving the vaccine against measles (test group) were compared with children vaccinated the same day against these two diseases (referent group). RESULTS: Analysis was performed on 284 children. Of them, fifty-four belonged to the test group. Measles serology was positive in 91.7% of children. Neutralizing antibodies against YF were detected in 90.7% of the test group and 92.9 of the referent group (p=0.6). In addition, quantitative analysis of the immune response did not show a lower response to YF vaccination when it took place 1-28 days after measles vaccination. DISCUSSION: In 1965, Petralli showed a lower response to the smallpox vaccine when injected 4-20 days after measles vaccination. Since then, recommendations are to observe an interval of four weeks between LAV not injected on the same day. Other published studies failed to show a significant difference in the immune response to a LAV injected 1-28 days after another LAV. These results suggest that the usual recommendations for immunization with two LAV may not be correct. CONCLUSION: In low income countries, the current policy should be re-evaluated. This re-evaluation should also be applied to travelers to yellow fever endemic countries.

Climatic drivers of seasonal influenza epidemics in French Guiana, 2006-2010.

OBJECTIVES: Influenza seasonality remains poorly studied in Equatorial regions. Here we assessed the seasonal characteristics and environmental drivers of influenza epidemics in French Guiana, where influenza surveillance was established in 2006. METHODS: Sentinel GPs monitored weekly incidence of Influenza-like illnesses (ILI) from January 2006 through December 2010 and collected nasopharyngeal specimens from patients for virological confirmation. Times series analysis was used to investigate relationship between ILI and climatic parameters (rainfall and specific humidity). RESULTS: Based on 1533 viruses identified during the study period, we observed marked seasonality in the circulation of influenza virus in the pre-pandemic period, followed by year-round activity in the post-pandemic period, with a peak in the rainy season. ILI incidence showed seasonal autoregressive variation based on ARIMA analysis. Multivariate dynamic regression revealed that a 1 mm increase of rainfall resulted in an increase of 0.33% in ILI incidence one week later, adjusting for specific humidity (SH). Conversely, an increase of 1 g/kg of SH resulted in a decrease of 11% in ILI incidence 3 weeks later, adjusting for rainfall. CONCLUSIONS: Increased rainfall and low levels of specific humidity favour influenza transmission in French Guiana.

Resequencing microarray method for molecular diagnosis of human arboviral diseases.

BACKGROUND: Resequencing DNA microarray (RMA) technology uses probes designed to identify a panel of viral sequences. It can be used for detecting emerging viruses by revealing the nucleotide polymorphisms within the target of interest. OBJECTIVES/STUDY DESIGN: As a new tool for molecular diagnosis of arbovirus infection, high density PathogenID v2.0 RMA (PID2-RMA) was assessed for the detection and genetic analysis of dengue, West Nile, and Chikungunya viruses in spiked blood samples or sera from individuals infected with dengue virus. Viral RNAs extracted from biological samples were retrotranscribed into cDNA and amplified using the Phi 29 polymerase-based method. This amplified cDNA was used for hybridization on PID2-RMA. RESULTS: A good specificity of RMA-based detection was demonstrated using a panel of arboviruses including Dengue, West Nile and Chikungunya viruses. This technology was also efficient for the detection and genetic analysis of the different serotypes of dengue virus in sera of infected patients. Furthermore, the mixing of dengue, West Nile and Chikungunya prototype viruses within a single sample of human blood did not interfere with the sensitivity of PID2-RMA. CONCLUSIONS: Our data show that high density PID2-RMA was suitable for the identification of medically important arboviruses. It appears to be particularly adapted to the genetic analysis of dengue, West Nile, and Chikungunya viruses in urgent clinical situations where the rapid identification and characterization of the pathogen is essential.

[Singular, systemic, self-reactive IgG patterns related to age: relationship with cerebral malaria susceptibility in exposed subjects residing in an endemic area in Abidjan, Côte-d'Ivoire]. / Singularité des profils d'autoréactivité systémique en fonction de l'âge: relations avec la susceptibilité au neuropaludisme chez les sujets exposés en région endémique à Abidjan, Côte-d'Ivoire.

The impact of autoimmunity on malaria-infection evolution reported by various works has led us to compare reactive patterns of self-dependent systemic IgG from 54 patients aged less than 15 years old to those from 46 subjects older than 15 years. These subjects were divided into 34 Plasmodium falciparum asymptomatic carriers (ACs), 30 cases of uncomplicated malaria (UM), and 36 patients suffering from cerebral malaria (CM) living in the same endemic area. The reactivity of the plasma antibodies against human brain tissue extract was assessed by western blotting. Comparative analysis of reactive bands (linear discriminant analysis, LDA) revealed the existence of patterns that distinguish, among the more susceptible subjects aged less than 15 years old, the different clinical forms. In contrast, in less susceptible subjects aged more than 15 years old, the patterns are homogenous and do not allow the separation of these clinical forms. This self-reactive repertoire might be witnessed as an imprint of the clinical tolerance acquired during the years of living in endemic areas. The singularity of this profile under the age of 15 years might have a prognostic value.

[Dengue virus infection in neotropical forest mammals: incidental hosts or potential reservoirs?]. / Infection par le virus de la dengue de mammifères sauvages en région néotropicale: hôtes accidentels ou réservoirs potentiels?

The arboviral disease with the highest human incidence in South America is dengue fever. In French Guiana, where all four dengue serotypes, i.e., DENV-1, DENV-2, DENV-3 and DENV-4, are present, the disease is endemic with epidemic outbreaks. Though previous serological studies have suggested a sylvatic cycle, involvement of wild mammals in the dengue cycle in the neotropics has never been confirmed. The purpose of this study was to search for the presence of DENV in wild animals captured at two different sites between 2001 and 2007. About 10,000 trap/nights were performed leading to the capture of 464 non-flying mammals (rodents and marsupials). In addition, mistnests placed in the same zone yielded 152 bats. Reverse transcription-polymerase chain reaction amplification to detect infection by any of the four dengue serotypes demonstrated viral RNA in the livers and/or sera of 92 captured animals. Sequence analysis of amplification products revealed that the DENV-1, DENV-3 and DENV-4 serotypes were distinct from those circulating in humans at the same periods. Analysis for DENV-2 showed that some strains were divergent from concurrent human strains but that others were identical. The latter finding suggests that wild neotropical mammals living in periurban area can be infected by dengue virus strains circulating in humans. However, further investigation will be needed to determine if neotropical mammals are incidental hosts or potential reservoirs of dengue virus.

Wild terrestrial rainforest mammals as potential reservoirs for flaviviruses (yellow fever, dengue 2 and St Louis encephalitis viruses) in French Guiana.

A serological survey for yellow fever virus (YFV), dengue 2 virus (DENV-2), and St Louis encephalitis virus (SLEV) was undertaken using a seroneutralization technique in 27 wild forest mammal species (574 individuals) in French Guiana. Evidence of yellow fever infection was observed in 10 species, with high prevalence recorded in howler monkey (18%) and agouti (20%). Antibodies against DENV-2 and SLEV were found sporadically in various species. This potential host diversity and the range of potential vectors might explain the behaviour of the viruses in epidemic outbreaks and the emergence of periurban loci.

Expression of a human endogenous retrovirus, HERV-K, in the blood cells of leukemia patients.

Human endogenous retroviral sequences (HERVs) are believed to be possible pathogenic agents in carcinogenesis. HERV-K is the most biologically active form, since members of this family have intact open reading frames for the gag, pol or env genes. Antibody response against HERV-K peptides has been reported in leukemia patients, suggesting a possible overexpression of this sequence in leukemic cells. Using real-time quantitative RT-PCR (TaqMan), we found that in six of the eight leukemia samples we collected, transcriptional activity of HERV-K10-like gag gene was 5- to 10-fold higher than in normal peripheral blood mononuclear cells (PBMCs) or mononuclear cells from cord blood. The overexpression was marked enough to be detected by Northern blot. In addition, there was no significant variation of HERV-K expression in normal PBMCs after exposure to different factors (PHA, gamma irradiation, 5-azacytidine) that potentially modulate HERV expression. This suggests that HERV-K relative overexpression in leukemia samples might be specifically associated with tumor development. The origin of these transcriptional variations is therefore worth being investigated further.

Molecular analysis of endogenous retrovirus HRES-1: identification of frameshift mutations in region encoding putative 28-kDa autoantigen.

A possible involvement of HTLV-1-related endogenous sequence 1 (HRES-1) in autoimmune diseases has been recently reported. In primate cells, PCRs and RT-PCRs using specific primers reveal the presence and the transcription of gag-related sequences. However antisera generated against selected HRES-1 peptides failed to detect a 28-kDa protein deduced from the translated gag ORF and described previously. Such discordant results led us to perform DNA cloning and sequencing of LTR- and gag-related nucleotidic fragments. Repeated sequence analyses on distinct samples revealed frameshift mutations in the gag and LTR ORFs. Our sequence analyses detected a stop codon in the gag-related ORF, which is inconsistent with the expression of a 28-kDa protein. Instead of the two ORFs previously found, our gag-related region contained three ORFs. One of them demonstrated higher nucleotidic and peptidic homologies with the p19 gag of HTLV-I. However, the molecular analyses of our new sequence did not show evidence of potent translation capacities.

Surveillance of dengue fever in French Guiana by monitoring the results of negative malaria diagnoses.

Surveillance of dengue fever is mainly based on specific laboratory tests. However non-specific systems, such as clinical surveillance, are also required. In French Guiana, we have tested a non-specific laboratory surveillance system where different biological examinations performed for other reasons than the diagnosis of dengue fever were analysed as methods for dengue fever surveillance. The number of negative malaria diagnoses in Cayenne and Kourou was found to be the best indicator of dengue fever infections in these towns. This surveillance system appears to be very simple and reliable, and a test which could serve as an indicator that is likely to be found everywhere.