The Use of Simple Laboratory Parameters in the Differential Diagnosis of Acute-Phase Zika and Dengue Viruses.

BACKGROUND: Differential diagnosis between acute-phase Zika and dengue is challenging because of a similar clinical presentation and the lack of available molecular diagnosis tools in most of endemic areas. OBJECTIVES: Our study aimed to evaluate the use of simple laboratory parameters to differentiate these infections. METHODS: We retrospectively compared simple hematology and biochemistry values in 81 and 341 patients with confirmed Zika and dengue, respectively, collected from June 2013 to March 2014 during the French Polynesia outbreaks. RESULTS: Thrombocytopenia, neutropenia, leukopenia, lymphopenia, and elevated aspartate aminotransaminases were significantly more frequent in dengue than in Zika (p < 0.001). Platelets <100 × 109/L, neutrophils <0.5 × 109/L, lymphocytes <0.5 × 109/L, and aspartate aminotransaminases >100 IU/mL were found in dengue but not in Zika. The positive predictive value of the -association of leukocytes <4 × 109/L + lymphocytes <1 × 109/L + aspartate aminotransaminases >40 IU/mL for the diagnosis of dengue was 90%, with an accuracy of 82.4%. CONCLUSION: For the differential diagnosis between acute-phase Zika and dengue, there is no specific standard laboratory pattern. We identified cutoff values and a combination of laboratory parameters that are a strong argument against Zika and in favor of dengue.

Zika Virus Infection during Pregnancy and Effects on Early Childhood Development, French Polynesia, 2013-2016.

Congenital Zika virus syndrome consists of a large spectrum of neurologic abnormalities seen in infants infected with Zika virus in utero. However, little is known about the effects of Zika virus intrauterine infection on the neurocognitive development of children born without birth defects. Using a case-control study design, we investigated the temporal association of a cluster of congenital defects with Zika virus infection. In a nested study, we also assessed the early childhood development of children recruited in the initial study as controls who were born without known birth defects,. We found evidence for an association of congenital defects with both maternal Zika virus seropositivity (time of infection unknown) and symptomatic Zika virus infection during pregnancy. Although the early childhood development assessment found no excess burden of developmental delay associated with maternal Zika virus infection, larger, longer-term studies are needed.

Molecular detection of Zika virus in blood and RNA load determination during the French Polynesian outbreak.

Zika virus (ZIKV) viremia is reported as low and transient; however, these estimates rely on limited data. We report RNA loads in sera collected from symptomatic patients during the 2013-2014 French Polynesian ZIKV outbreak. We performed molecular detection of ZIKV RNA in sera from 747 patients presenting with suspected acute phase ZIKV infection. Among patients with confirmed infection, we analyzed the duration of viremia, assessed viral RNA loads and recorded the main clinical symptoms. A total of 210/747 (28.1%) sera tested positive using a ZIKV-specific RT-PCR. Viral RNA loads in symptomatic patients that ranged from 5 to 3.7 × 106 copies/mL (mean 9.9 × 104 copies/mL) were not related to a particular clinical presentation, and were significantly lower than those previously obtained from asymptomatic ZIKV infected blood donors. The rate of detection of ZIKV RNA in sera from suspected cases of acute phase ZIKV infection was low. ZIKV RNA loads were lower in symptomatic patients compared to asymptomatic blood donors and were lower than RNA loads usually reported in dengue infections. As there is no abrupt onset of symptoms in ZIKV infections, we suggest that infected patients sought for medical attention when viremia was already decreasing or had resolved.

Detection of chikungunya virus in saliva and urine.

BACKGROUND: Saliva and urine have been used for arthropod-borne viruses molecular detection but not yet for chikungunya virus (CHIKV). We investigated the use of saliva and urine for molecular detection of CHIKV during the French Polynesian outbreak. METHODS: During the French Polynesian chikungunya outbreak (2014-2015), we collected the same day blood and saliva samples from 60 patients with probable chikungunya (47 during the 1st week post symptoms onset and 13 after), urine was available for 39 of them. All samples were tested using a CHIKV reverse-transcription PCR. RESULTS: Forty eight patients had confirmed chikungunya. For confirmed chikungunya presenting during the 1st week post symptoms onset, CHIKV RNA was detected from 86.1 % (31/36) of blood, 58.3 % (21/36) of saliva and 8.3 % (2/24) of urine. Detection rate of CHIKV RNA was significantly higher in blood compared to saliva. For confirmed chikungunya presenting after the 1st week post symptoms onset, CHIKV RNA was detected from 8.3 % (1/12) of blood, 8.3 % (1/12) of saliva and 0 % (0/8) of urine. CONCLUSIONS: In contrast to Zika virus (ZIKV), saliva did not increased the detection rate of CHIKV RNA during the 1st week post symptoms onset. In contrast to ZIKV, dengue virus and West Nile virus, urine did not enlarged the window of detection of CHIKV RNA after the 1st week post symptoms onset. Saliva can be used for molecular detection of CHIKV during the 1st week post symptoms onset only if blood is impossible to collect but with a lower sensitivity compared to blood.

Potential sexual transmission of Zika virus.

In December 2013, during a Zika virus (ZIKV) outbreak in French Polynesia, a patient in Tahiti sought treatment for hematospermia, and ZIKV was isolated from his semen. ZIKV transmission by sexual intercourse has been previously suspected. This observation supports the possibility that ZIKV could be transmitted sexually.

Emergence of Zika virus.

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) of the family Flaviviridae, genus Flavivirus, transmitted by the bite of infected mosquitoes. ZIKV was first isolated from a non-human primate in 1947, ZIKV infections in humans were sporadic during 60 years before emerging in the Pacific in 2007 and 2013 and in Brazil in 2015. Due to a non-specific clinical presentation, Zika fever can be misdiagnosed with other arboviruses such as dengue and chikungunya. ZIKV infections were associated with mild illness before the large French Polynesia outbreak in 2013-2014 in which severe neurological complications were reported. Routine laboratory diagnosis of Zika fever relies on the detection of specific ZIKV RNA by PCR. Serological diagnosis is complicated due to cross reactivity with other flaviviruses. ZIKV adapted to an urban cycle involving humans and domestic mosquito vectors that are widely distributed, such as Aedes aegypti and Ae. albopictus. This adaptation highlights the potential for ZIKV to emerge in tropical, intertropical and also temperate areas.

Leptospira diversity in animals and humans in Tahiti, French Polynesia.

BACKGROUND: Leptospirosis is a highly endemic bacterial zoonosis in French Polynesia (FP). Nevertheless, data on the epidemiology of leptospirosis in FP are scarce. We conducted molecular studies on Leptospira isolated from humans and the potential main animal reservoirs in order to identify the most likely sources for human infection. METHODOLOGY/PRINCIPAL FINDINGS: Wild rats (n = 113), farm pigs (n = 181) and domestic dogs (n = 4) were screened for Leptospira infection in Tahiti, the most populated island in FP. Positive samples were genotyped and compared to Leptospira isolated from human cases throughout FP (n = 51), using secY, 16S and LipL32 sequencing, and MLST analysis. Leptospira DNA was detected in 20.4% of rats and 26.5% of pigs. We identified two Leptospira species and three sequence types (STs) in animals and humans: Leptospira interrogans ST140 in pigs only and L. interrogans ST17 and Leptospira borgpetersenii ST149 in humans and rats. Overall, L. interrogans was the dominant species and grouped into four clades: one clade including a human case only, two clades including human cases and dogs, and one clade including human cases and rats. All except one pig sample showed a unique L. interrogans (secY) genotype distinct from those isolated from humans, rats and dogs. Moreover, LipL32 sequencing allowed the detection of an additional Leptospira genotype in pigs, clearly distinct from the previous ones. CONCLUSIONS/SIGNIFICANCE: Our data confirm rats as a major potential source for human leptospirosis in FP. By contrast to what was expected, farm pigs did not seem to be a major reservoir for the Leptospira genotypes identified in human patients. Thus, further investigations will be required to determine their significance in leptospirosis transmission in FP.

Fatal leptospirosis and chikungunya co-infection: Do not forget leptospirosis during chikungunya outbreaks.

In endemic areas, leptospirosis can be missed by erroneous clinical or laboratory diagnosis of arboviroses or co-infections with arboviruses and an increase in mortality due to leptospirosis has already been reported during arboviruses outbreaks. During the French Polynesian chikungunya virus outbreak in 2014-2015, two leptospirosis and chikungunya co-infections were reported, one of which was fatal. Diagnosis of leptospiroses was delayed in the context of chikungunya outbreak. In the context of arbovirus outbreak, the risk of misdiagnosis of leptospirosis is maximum and clinicians should initiate early antibiotic therapy if leptospirosis is suspected. A delayed diagnosis of leptospirosis can be responsible for fatal outcome. Leptospirosis should be considered even if dengue or chikungunya virus infections are confirmed by reference molecular testing.

Detection of Zika virus in saliva.

BACKGROUND: During the largest Zika virus (ZIKV) outbreak ever reported that occurred from October 2013 to March 2014 in French Polynesia, we observed that several patients presenting the symptoms of acute phase Zika fever were tested negative in blood by ZIKV real-time PCR (RT-PCR). OBJECTIVES: As we have previously detected ZIKV RNA in the saliva of a young child, we investigated the use of saliva as an alternative sample for routine ZIKV RNA detection. STUDY DESIGN: Over a 6 month period, 1,067 samples collected from 855 patients presenting symptoms of Zika fever (saliva only, blood only or both samples) were tested using a specific ZIKV RT-PCR. A medical questionnaire was available for most of the patients. RESULTS: ZIKV was more frequently detected in saliva compared to blood. For the 182 patients with both samples collected, tests were positive for 35 (19.2%) in saliva while negative in blood and tests were positive for 16 (8.8%) in blood while negative in saliva; the difference in mean days after symptoms onset and the percentage of the main symptoms of Zika fever for patients only positive in saliva or in blood was not significant. CONCLUSION: The use of saliva sample increased the rate of molecular detection of ZIKV at the acute phase of the disease but did not enlarge the window of detection of ZIKV RNA. Saliva was of particular interest when blood was difficult to collect (children and neonates especially).

Microbiological investigation and clinical significance of Corynebacterium spp. in respiratory specimens.

The purpose of this retrospective study was to evaluate the pathogenic role of Corynebacterium species in lower respiratory tract infections as well as their routine laboratory investigation. From April 2007 to August 2009, 27 clinical isolates were significantly recovered from respiratory specimens of 27 different patients clinically suspected of having lower respiratory tract infections. The average age of patients was 65 years, while 22 (81%) patients presented at least 1 predisposing condition. Of the 27 patients, 15 (56%) were classified as infected according to Centers for Disease Control and Prevention/National Healthcare Safety Network criteria, with 93% of infections being hospital acquired. All isolates were accurately identified to the species level using molecular methods (i.e., 17 Corynebacterium pseudodiphtheriticum, 7 Corynebacterium striatum, and 3 Corynebacterium accolens), whereas phenotypic methods remained frequently unreliable for identifying C. striatum and C. accolens strains. All tested isolates were susceptible to amoxicillin, imipenem, vancomycin, linezolid, and tigecycline, whereas most of them were resistant to erythromycin.