Case Report: Diagnosis and Assessment of Cure Approaches for Acute Schistosomiasis in Pre-School Children.

Acute schistosomiasis (AS) manifests with a broad spectrum of clinical features in pediatric populations. Diagnosis may be difficult in the absence of detectable numbers of eggs. As a result, new approaches may be required to achieve an accurate diagnosis. Optimal praziquantel (PZQ) treatment regimen for young children is debatable. Also, the post-treatment response is still poorly evaluated due to the lack of reliable markers. A group of 6 children (a toddler and 5 pre-school children) and one pre-adolescent were investigated for AS clinical manifestations and followed-up for two years after treatment. Ova detection was performed by Kato-Katz (KK) and presence of Schistosoma mansoni DNA was assessed by real-time PCR (rt-PCR) in stool samples. IgG and IgE anti-Schistosoma levels and urinary antigen were detected by ELISA and point-of-care circulating cathodic antigen (POC-CCA) testing in serum and urine, respectively. AS clinical symptoms were present in 5/7 (71.4%) of the infected children, and hypereosinophilia was detected in all of them. Ova detection and serology were positive in only 3/7 (44.9%) and 4/7 (57.1%), respectively. However, real-time PCR (rt-PCR) showed the presence of Schistosoma DNA in 6/7 (85.7%) of the cases, and urinary antigen was detected in all infected children. The long-term follow-up after treatment with three doses of PZQ (80mg/kg/dose), showed high cure rates (CR) as demonstrated by the DNA-based assay as well as reduced levels of side effects. CR based on urinary antigen detection ranged from 28.6 to 100%, being the highest CR due to double testing the 2-year post-treatment samples. The results suggest that high dose and repeated treatment with PZQ might be effective for AS in young children. Also, new laboratory markers should be considered to diagnosis and monitor the drug response.

2-D Shear Wave Elastography for the Evaluation of Liver Fibrosis in Hepatosplenic Schistosomiasis: Reliability of a Single Measurement and Inter-Hepatic Lobe Variability.

Data on liver and spleen stiffness by 2-D shear wave elastography (2-D SWE) in hepatosplenic schistosomiasis (HES) remain scarce. We aimed to assess the correlation between single to multiple measurements of liver and spleen stiffness and to evaluate inter-hepatic lobe variability of liver stiffness measurement (LSM) using 2-D SWE in HES patients. Liver and spleen elastography were performed in HES patients in this cross-sectional study. A total of four stiffness measurements were performed in the right lobe (RL), left lobe (LL), and spleen. The correlation between the first measurement and the median of four measurements was assessed. Liver stiffness measurement of both hepatic lobes was compared. Twenty-six HES patients were included. Liver stiffness measurement was higher in the left than in the right hepatic lobe (17.9 kPa [11.3-92.0] versus 14.9 kPa [5.6-44.4]; P = 0.019). The first measurement was similar to the median of the four measurements for the RL (14.6 [5.6-60.8] versus 14.9 kPa [5.6-44.4]; P = 0.87), LL (17.4 [8.0-128.1] versus 17.9 kPa [11.3-92.0]; P = 0.54), and spleen (50.5 [10.0-157.0] versus 55.7 kPa [19.1-119.4]; P = 0.48). An excellent correlation between the first measurement and the median of four measurements for the RL (r = 0.93; P < 0.001), LL (r = 0.88; P < 0.001), and spleen (r = 0.89; P < 0.001) was observed. In HES, LSM of the LL seems to be higher than that of the right hepatic lobe. Considering the excellent correlation between the first measurement and the median of four measurements in both hepatic lobes and spleen, a single measurement would be sufficient to evaluate liver and splenic stiffness in patients with HES.

The Advances in Molecular and New Point-of-Care (POC) Diagnosis of Schistosomiasis Pre- and Post-praziquantel Use: In the Pursuit of More Reliable Approaches for Low Endemic and Non-endemic Areas.

Like soil-transmitted helminth infections, schistosomiasis is an important neglected tropical disease (NTD) related to poverty with a major impact on public health in developing countries. Diagnosis of active infection is crucial for surveillance of controlled or post-elimination schistosomiasis areas. In addition, the use of conventional diagnostic tools in non-exposed populations (such as travelers) results in misdiagnoses in the prepatent period of infection. Also, the accuracy of standard tests applied in low-endemicity areas (LEAs) decreases after several rounds of treatment. We aimed to determine whether it would be necessary to replace schistosomiasis conventional diagnostic tests such as parasitological methods in LEAs. Also, we evaluate the use of new tools in non-endemic areas. Reliable, cheap and easy-to-use diagnostic tools are needed to respond to the demands of a new era of elimination and eradication of schistosomiasis. To this end, molecular diagnosis-including nucleic acid-based assays (loop-mediated isothermal amplification, polymerase chain reaction) and circulating cathodic and anodic antigen detection tests have become promising strategies. In this review, we attempt to address the use of alternative diagnostic tests for active infection detection and drug-monitoring after specific schistosomiasis treatment.

Fatal Human Case of Zika and Chikungunya Virus Co-Infection with Prolonged Viremia and Viruria.

Zika virus (ZIKV) infection usually presents as a mild and self-limited illness, but it may be associated with severe outcomes. We describe a case of a 30-year-old man with systemic erythematous lupus and common variable immunodeficiency who became infected with both Zika (ZIKV) and Chikungunya (CHIKV) virus during the 2016 outbreak in Rio de Janeiro, Brazil. The patient presented with intense wrist and right ankle arthritis, and ZIKV RNA and virus particles were detected in synovial tissue, blood and urine, and CHIKV RNA in serum sample, at the time of the diagnosis. During the follow up, ZIKV RNA persisted for 275 days post symptoms onset. The patient evolved with severe arthralgia/arthritis and progressive deterioration of renal function. Fatal outcome occurred after 310 days post ZIKV and CHIKV co-infection onset. The results show the development of severe disease and fatal outcome of ZIKV infection in an immunosuppressed adult. The data suggests a correlation between immunodeficiency and prolonged ZIKV RNA shedding in both blood and urine with progressive disease. The results also indicate a possible role for arbovirus co-infections as risk factors for severe and fatal outcomes from ZIKV infection.

Zika virus shedding in human milk during lactation: an unlikely source of infection?

Zika virus (ZIKV) transmission through non-mosquito-dependent routes has become increasingly important since reports of sexual transmission. Breastfeeding is a potential means of ZIKV transmission, but data on this remain limited. The cases of four mothers with laboratory-proven infections are reported. No disease evolved in three of the breastfed babies despite detectable maternal viremia and viruria, the presence of viral RNA shedding, and the isolation of infective particles in one milk sample. Fever and rash in one infant of a ZIKV-infected mother proved to be related to chikungunya virus infection. The results suggest that the presence of infective particles in breast milk may not be sufficient for the efficient perinatal transmission of ZIKV.

Transient elastography evaluation of hepatic and spleen stiffness in patients with hepatosplenic schistosomiasis.

BACKGROUND: Hepatosplenic schistosomiasis (HES) has not been evaluated by transient elastography so far and its correlation with ultrasound variables remains to be defined. AIMS: The aim of this study was to describe the parameters of liver and spleen stiffness in HES assessed by transient elastography in comparison with cirrhotics and controls evaluating its correlation with ultrasonographic data. PATIENTS AND METHODS: HES, hepatitis C virus-cirrhotic, and control patients were included in this sectional study. Liver and spleen stiffness were compared among the three groups. The ultrasonographic parameters were compared with transient elastography in HES patients. RESULTS: Thirty HES, 30 hepatitis C virus-cirrhotic patients, and 17 controls were included. Those with HES presented liver stiffness that was significantly higher than the controls and lower than the cirrhotics: 9.7 (3.6-75.0) versus 3.7 (2.8-5.4) versus 27.0 (14.7-61.5) kPa (P<0.001). Spleen stiffness values were comparable between hepatosplenic and cirrhotics: 66.4 (25.7-75.0) versus 69.1 (18.0-75.0) kPa (P=0.78) and were significantly higher than the controls 16.5 kPa (6.3-34.3) (P<0.001). In patients with HES, high spleen stiffness was associated with right liver lobe diameter (P=0.015), splenic artery resistance index (P=0.002), portal vein diameter (P=0.021), portal vein area (P=0.008), portal vein congestion index (P=0.035), splenic vein diameter (P=0.013), and spleen diameter (P=0.021). CONCLUSION: Liver stiffness may be a useful tool to differentiate portal hypertension related to cirrhosis from that of HES. High spleen stiffness is a potential surrogate marker of portal hypertension in this population.

Schistosomiasis in areas of low endemicity: a new era in diagnosis.

Parasitological detection of Schistosoma is the cornerstone of schistosomiasis diagnosis in areas of transmission worldwide. However, a steep decrease of sensitivity in low-endemicity areas (LEAs) compromises estimation of schistosomiasis. Despite the restricted utilization of molecular and immunodiagnostic techniques, recent improvements and advances have been contributing to change this scenario, especially in LEAs. Nonetheless, the main issue in a new era of diagnosis overcomes technical advances per se and relates to the loss of 'gold standards' in schistosomiasis diagnosis in LEAs. Here, we review and discuss the current role of molecular and immunodiagnostic methods in schistosomiasis management.

MIF participates in Toxoplasma gondii-induced pathology following oral infection.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is essential for controlling parasite burden and survival in a model of systemic Toxoplasma gondii infection. Peroral T. gondii infection induces small intestine necrosis and death in susceptible hosts, and in many aspects resembles inflammatory bowel disease (IBD). Considering the critical role of MIF in the pathogenesis of IBD, we hypothesized that MIF participates in the inflammatory response induced by oral infection with T. gondii. METHODOLOGY/PRINCIPAL FINDINGS: Mif deficient (Mif(-/-)) and wild-type mice in the C57Bl/6 background were orally infected with T. gondii strain ME49. Mif(-/-) mice had reduced lethality, ileal inflammation and tissue damage despite of an increased intestinal parasite load compared to wt mice. Lack of MIF caused a reduction of TNF-α, IL-12, IFN-γ and IL-23 and an increased expression of IL-22 in ileal mucosa. Moreover, suppressed pro-inflammatory responses at the ileal mucosa observed in Mif(-/-) mice was not due to upregulation of IL-4, IL-10 or TGF-ß. MIF also affected the expression of matrix metalloproteinase-9 (MMP-9) but not MMP-2 in the intestine of infected mice. Signs of systemic inflammation including the increased concentrations of inflammatory cytokines in the plasma and liver damage were less pronounced in Mif(-/-) mice compared to wild-type mice. CONCLUSION/SIGNIFICANCE: In conclusion, our data suggested that in susceptible hosts MIF controls T. gondii infection with the cost of increasing local and systemic inflammation, tissue damage and death.

Genital schistosomiasis mansoni concomitant to genital tumor in areas of low endemicity: challenging diagnosis.

Genital infection by Schistosoma mansoni is usually misdiagnosed in individuals who reside in, or travel to endemic areas. We describe two cases of genital tumor associated with S. mansoni infection manifested by methrorragy. Surgical specimens revealed leiomyomas in both cases associated with S. mansoni. In one of them, granulomas were found in the ovary and in the other they were found in the uterine tube. Although none presented intestinal/hepatic disease, fecal egg excretion was detected in one. Both had elevated pretreatment antibody reactivity to S. mansoni antigen, but follow-up showed different outcomes. Schistosomiasis should be considered as a diagnosis in individuals with methrorragy residing in or having traveled to endemic areas. Since diagnosis follows genital amputation, and cure control is troublesome, improvement of diagnostic tools and follow-up markers are important priorities to decrease schistosomiasis morbidity.

Genital schistosomiasis mansoni concomitant to genital tumor in areas of low endemicity: challenging diagnosis

Genital infection by Schistosoma mansoni is usually misdiagnosed in individuals who reside in, or travel to endemic areas. We describe two cases of genital tumor associated with S. mansoni infection manifested by methrorragy. Surgical specimens revealed leiomyomas in both cases associated with S. mansoni. In one of them, granulomas were found in the ovary and in the other they were found in the uterine tube. Although none presented intestinal/hepatic disease, fecal egg excretion was detected in one. Both had elevated pretreatment antibody reactivity to S. mansoni antigen, but follow-up showed different outcomes. Schistosomiasis should be considered as a diagnosis in individuals with methrorragy residing in or having traveled to endemic areas. Since diagnosis follows genital amputation, and cure control is troublesome, improvement of diagnostic tools and follow-up markers are important priorities to decrease schistosomiasis morbidity.