RESUMO
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.
Assuntos
Anti-Helmínticos/uso terapêutico , Parasitologia , Praziquantel/uso terapêutico , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/tratamento farmacológico , Adolescente , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/urina , Biomarcadores/sangue , Biomarcadores/urina , Pré-Escolar , DNA de Helmintos/genética , Ensaio de Imunoadsorção Enzimática , Fezes/parasitologia , Feminino , Glicoproteínas/urina , Proteínas de Helminto/urina , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Lactente , Masculino , Contagem de Ovos de Parasitas , Testes Imediatos , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Schistosoma mansoni/genética , Schistosoma mansoni/imunologia , Esquistossomose mansoni/parasitologia , Testes Sorológicos , Resultado do TratamentoRESUMO
BACKGROUND: Accurate diagnostic techniques for schistosomiasis are essential for prevalence determination and identification of positive patients. A point-of-care test for detecting schistosome circulating cathodic antigen (POC-CCA) has been evaluated for its accuracy in different endemic regions. This reagent strip/dipstick based assay has showed high sensitivity for individuals with high or moderate worm burden, but the interpretation of light infections is less clear, especially for trace readings. METHODOLOGY/PRINCIPAL FINDINGS: We introduced a urine lyophilization step to the POC-CCA assay to improve its sensitivity and clarify the interpretation of traces. We evaluated POC-CCA sensitivity and specificity within individuals with low parasite burdens in a Brazilian endemic area where a high number of traces were detected. Patients that were positive for other helminths were also evaluated for cross reactions. In all cases, a combined parasitological diagnosis using Kato-Katz (24 slides) and Saline Gradient (1 g of feces) were used as reference. At baseline, diagnosis by POC-CCA (1-2 cassettes) showed 6% sensitivity, inaccurately predicting a low prevalence of Schistosoma mansoni infections (2 POC-CCA positives/32 egg positives). After urine lyophilization, the sensitivity was increased significantly (p < 0.05). Prevalence rates changed from 2% to 32% (27 POC-CCA positives/32 egg positives), equivalent to parasitological techniques. Most of the trace readings changed to positive after lyophilization while some negatives turned into traces. Cross reaction analysis confirmed the specificity of POC-CCA. CONCLUSIONS/SIGNIFICANCE: Trace readings cannot be primarily defined as positive or negative cases. It is critical to verify case-by-case by concentrating urine 10 fold by lyophilization for the diagnosis. Following lyophilization, persistent trace readings should be read as negatives. No trained technician is needed and cost is restricted to the cost of a lyophilizer and the electricity to run it.
Assuntos
Antígenos de Helmintos/urina , Liofilização/métodos , Glicoproteínas/urina , Proteínas de Helminto/urina , Testes Imediatos , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/urina , Albendazol/administração & dosagem , Albendazol/uso terapêutico , Animais , Anti-Helmínticos , Fezes/parasitologia , Humanos , Contagem de Ovos de Parasitas , Parasitologia/métodos , Praziquantel/administração & dosagem , Praziquantel/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Sensibilidade e EspecificidadeRESUMO
We evaluated the applicability of circulating antigen detection in serum and urine for the diagnosis of Schistosoma infections in a low endemic area. In total 389 individuals from Saramacca (Surinam) participated in the survey. Stool samples were examined using the Kato method, while circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) were determined by highly specific monoclonal antibody-based ELISA's. Also schistosome specific IgM antibodies were measured by the indirect immunofluorescence assay, but the diagnostic performance of this test was found to be poor in this population. S. mansoni eggs were found in 29% of the examined cases, while CAA and CCA could be demonstrated in 23% and 17% of the serum samples and in 3% and 28% of the urine samples, respectively. Forty three percent of the study population was positive in at least one of these diagnostic assays, indicating that each individual test misses a substantial part of the subjects with an active infection. In most positive cases, intensities of infection were very low. As 204 individuals participated in all screening assays, diagnostic performance of each test was evaluated in this sub-population. The highest sensitivities were achieved with the urine-CCA assay and the parasitological examination, detecting 59 and 58 out of the 107 cases with an active infection, respectively. The serum-CAA assay detected 47 positive cases. Our results demonstrate that determination of circulating antigens, especially CCA in urine and CAA in serum, provides information additional to the parasitological examination, for the assessment of prevalence and intensity of Schistosoma infection in low endemic areas.