Microfilaruria of Dirofilaria immitis in a dog from Italy.

Dirofilaria immitis is a mosquito-borne nematode-causing canine heartworm disease, with adult worms localized in the pulmonary arteries and right heart. In rare cases, ectopic migration might occur, and adults and blood circulating microfilariae can be found in unusual organs or fluids (e.g., eyes, abdominal cavity, bone marrow, and urine). A 17-year-old mixed-breed female dog was presented in a private veterinary clinic in Italy for hematuria and dysuria. Physical examination showed cardiac mitral murmur with marked respiratory distress and cyanotic mucous membranes after handling. Abdominal ultrasounds revealed a non-specific chronic cystopathy, while the echocardiography showed enlargement of the right heart associated with tricuspid insufficiency and mitral regurgitation, with the presence of an adult filariae in the right ventricular chamber. Circulating microfilariae were observed in the blood smear and molecularly identified as D. immitis. Unusual microfilaruria was detected in the urine sediment. Data presented raise awareness about the occurrence of microfilariae in unusual locations, such as the bladder, suggesting the need of a thorough clinical and laboratory assessment where D. immitis is endemic.

Investigation of Intestinal and Blood Parasites in People Returning to Turkey with a History of Traveling Abroad During the Pandemic

Objective: To investigate intestinal and blood parasites in people who have a history of traveling abroad during the Coronavirus disease-2019 pandemic and returning to Turkey. Methods: In this study, 104 patients with gastrointestinal system and/or fever complaints who had traveled abroad during the pandemic period and returned to Turkey were included. Parasitic agents were investigated by taking blood and stool samples from the patients. Additionally, urine samples were obtained from patients with hematuria or dysuria with the suspicion of schistosomiasis. A direct microscopic examination, the Crypto-Giardia immunochromatographic test, and ELISA methods were used in the examination of the stool samples. In order to detect Plasmodium species, blood samples were examined by preparing both the rapid diagnostic test and thick drop and thin smear preparations. Results: One or more parasite species were detected in 38 (38.5%) of 104 patients included in the study. While intestinal parasites were detected in 16 (32%) of 50 patients who traveled to Iran and 16 (33.3%) of 48 patients who traveled to Northern Iraq, blood parasites were not found. Schistosoma mansoni was detected in all 5 of the patients with a history of traveling to Sudan. Plasmodium falciparum was detected in 1 patient who traveled to the African continent. Conclusion: It is vital to take precautions to prevent parasitic diseases, such as malaria and schistosomiasis, during travels to African countries. During travels to neighboring countries of Turkey, such as Northern Iraq and Iran, hygiene should be paid attention to, so as to prevent contracting intestinal parasitic diseases. In addition, it was concluded that people who plan to travel abroad should have information about the endemic parasitic diseases of the country that they are going to.

Characterisation of tetraspanins from Schistosoma haematobium and evaluation of their potential as novel diagnostic markers.

Schistosoma haematobium is the leading cause of urogenital schistosomiasis and it is recognised as a class 1 carcinogen due to the robust association of infection with bladder cancer. In schistosomes, tetraspanins (TSPs) are abundantly present in different parasite proteomes and could be potential diagnostic candidates due to their accessibility to the host immune system. The large extracellular loops of six TSPs from the secretome (including the soluble excretory/secretory products, tegument and extracellular vesicles) of S. haematobium (Sh-TSP-2, Sh-TSP-4, Sh-TSP-5, Sh-TSP-6, Sh-TSP-18 and Sh-TSP-23) were expressed in a bacterial expression system and polyclonal antibodies were raised to the recombinant proteins to confirm the anatomical sites of expression within the parasite. Sh-TSP-2, and Sh-TSP-18 were identified on the tegument, whereas Sh-TSP-4, Sh-TSP-5, Sh-TSP-6 and Sh-TSP-23 were identified both on the tegument and internal tissues of adult parasites. The mRNAs encoding these TSPs were differentially expressed throughout all schistosome developmental stages tested. The potential diagnostic value of three of these Sh-TSPs was assessed using the urine of individuals (stratified by infection intensity) from an endemic area of Zimbabwe. The three Sh-TSPs were the targets of urine IgG responses in all cohorts, including individuals with very low levels of infection (those positive for circulating anodic antigen but negative for eggs by microscopy). This study provides new antigen candidates to immunologically diagnose S. haematobium infection, and the work presented here provides compelling evidence for the use of a biomarker signature to enhance the diagnostic capability of these tetraspanins.

Unprotected water sources and low latrine coverage are contributing factors to persistent hotspots for schistosomiasis in western Kenya.

BACKGROUND: Evidence indicates that whereas repeated rounds of mass drug administration (MDA) programs have reduced schistosomiasis prevalence to appreciable levels in some communities referred to here as responding villages (R). However, prevalence has remained high or less than anticipated in other areas referred to here as persistent hotspot villages (PHS). Using a cross-sectional quantitative approach, this study investigated the factors associated with sustained high Schistosoma mansoni prevalence in some villages despite repeated high annual treatment coverage in western Kenya. METHOD: Water contact sites selected based on observation of points where people consistently go to collect water, wash clothes, bathe, swim or play (young children), wash cars and harvest sand were mapped using hand-held smart phones on the Commcare platform. Quantitative cross-sectional surveys on behavioral characteristics were conducted using interviewer-based semi-structured questionnaires administered to assess water usage/contact patterns and open defecation. Questionnaires were administered to 15 households per village, 50 pupils per school and 1 head teacher per school. One stool and urine sample was collected from 50 school children aged 9-12 year old and 50 adults from both responding (R) and persistent hotspot (PHS) villages. Stool was analyzed by the Kato-Katz method for eggs of S. mansoni and soil-transmitted helminths. Urine samples were tested using the point-of-care circulating cathodic antigen (POC-CCA) test for detection of S. mansoni antigen. RESULTS: There was higher latrine coverage in R (n = 6) relative to PHS villages (n = 6) with only 33% of schools in the PHS villages meeting the WHO threshold for boy: latrine coverage ratio versus 83.3% in R, while no villages met the girl: latrine ratio requirement. A higher proportion of individuals accessed unprotected water sources for both bathing and drinking (68.5% for children and 89% for adults) in PHS relative to R villages. In addition, frequency of accessing water sources was higher in PHS villages, with swimming being the most frequent activity. As expected based upon selection criteria, both prevalence and intensity of S. mansoni were higher in the PHS relative to R villages (prevalence: 43.7% vs 20.2%; P < 0.001; intensity: 73.8 ± 200.6 vs 22.2 ± 96.0, P < 0.0001), respectively. CONCLUSION: Unprotected water sources and low latrine coverage are contributing factors to PHS for schistosomiasis in western Kenya. Efforts to increase provision of potable water and improvement in latrine infrastructure is recommended to augment control efforts in the PHS areas.

Molecular approach to the epidemiology of urinary schistosomiasis in France.

BACKGROUND: The diagnosis of urogenital schistosomiasis is based on the complementarity of serological technique and microscopic examination (ME). Between 2015 and 2019, the number of urinary schistosomiasis tests received in our laboratory increased sharply from 300 to 900 per year. Therefore, we wanted to evaluate the reliability of urine microscopic examination (ME, reference and routine technique) from urine sample by comparing it to other techniques (antigenic technique and PCR). To this end, we optimized two real-time PCRs targeting respectively Schistosoma haematobium (Sh) and Schistosoma mansoni (Sm). METHODOLOGY/PRINCIPAL FINDINGS: 914 urine samples from 846 patients suspected of urogenital schistosomiasis were prescribed and analyzed by PCR and also by antigenic technique for the first 143 samples. The antigenic technique evaluated was Schisto POC-CCA, Rapid Medical Diagnostics. These results (antigenic technique and PCR) were compared to ME which was performed from all urines. The percentage of 14% (128/914) positive cases with the PCR technique and the percentage of 6.0% (54/914) positive cases with ME is significantly different (Chi 2 test, p<0.001). These 128 positive PCRs correspond to 120 different patients, 88.3% (106/120) of them were young migrants and 11.7% (14/120) were French patients returning from travel. Among these migrants, more than 75% (80/106) came from French-speaking West Africa. In addition, the Schisto POC-CCA showed a specificity of 39% (46/117), too poor to be used as a screening tool in low or non-endemic areas. CONCLUSION/SIGNIFICANCE: Targeted Sh and Sm PCRs in urine are reliable techniques compared to ME (reference technique). In view of our results, we decided to screen urinary schistosomiasis by direct ME always coupled by the PCR technique, which has shown better reliability criteria.

Accuracy of Two Circulating Antigen Tests for the Diagnosis and Surveillance of Schistosoma mansoni Infection in Low-Endemicity Settings of Côte d'Ivoire.

In low-endemicity settings, current tools for the diagnosis and surveillance of schistosomiasis are often inaccurate in detecting true infection. We assessed the accuracy of an up-converting phosphor lateral flow circulating anodic antigen (UCP-LF CAA) test and a point-of-care circulating cathodic antigen (POC-CCA) urine cassette test for the diagnosis of Schistosoma mansoni. Our study was conducted in eight schools of western Côte d'Ivoire. Fifty children, aged 9-12 years, were enrolled per school. From each child, a single urine specimen and two stool specimens were collected over consecutive days for diagnostic work-up. Urine samples were subjected to UCP-LF CAA and POC-CCA tests. From each stool sample, triplicate Kato-Katz thick smears were examined. Overall, 378 children had complete data records. The prevalence of S. mansoni, as assessed by six Kato-Katz thick smears, was 4.0%. The UCP-LF CAA and POC-CCA tests revealed S. mansoni prevalence of 25.4% and 30.7%, respectively, when considering trace results as positive, and prevalence of 23.3% and 10.9% when considering trace results as negative. In the latter case, based on a composite "gold" standard, the sensitivity of UCP-LF CAA (80.7%) was considerably higher than that of POC-CCA (37.6%) and six Kato-Katz thick smears (13.8%). The negative predictive value of UCP-LF CAA, POC-CCA, and six Kato-Katz thick smears was 92.8%, 79.8%, and 74.1%, respectively. Our results confirm that UCP-LF CAA is more accurate than Kato-Katz and POC-CCA for the diagnosis of S. mansoni in low-endemicity settings.

Comparison of conventional and non-invasive diagnostic tools for detecting Plasmodium falciparum infection in southwestern Cameroon: a cross-sectional study.

BACKGROUND: Malaria remains a significant health challenge in sub-Saharan Africa, with early diagnosis critical to reducing its morbidity and mortality. Despite the increasing Plasmodium spp. diagnostic capabilities, access to testing is limited in some cases by the almost absolute requirement for blood from potentially infected subjects as the only sample source for all conventional methods. A rapid test on non-invasive specimen with comparable performance to microscopy for the screening or diagnosis of all participants is invaluable. This study sought to compare conventional and non-invasive diagnostic tools for detecting Plasmodium falciparum. METHODS: This was a cross-sectional study, carried out between March and August 2019 to evaluate and compare the diagnostic performance of a PfHRP2/pLDH-based malaria rapid diagnostic test (mRDT) on patients' blood, saliva and urine relative to conventional light microscopy and nested PCR at outpatient clinics in the Buea and Tiko health districts of Southwestern Cameroon. The significance of differences in proportions was explored using the Pearson's χ2 test whereas differences in group means were assessed using analyses of variance. RESULTS: A total of 359 individuals of both sexes, aged 1-92 years, were enrolled into the study. Of the 301 individuals tested by light microscopy and mRDTs on blood, saliva and urine, 84 (27.9%), 81 (26.9%), 87 (28.9%) and 107 (35.5%) respectively were positive. However, only 34.3%, 90.5%, 91.4%, 83.9% and 65.4% febrile, light microscopy and mRDT positives on blood, saliva and urine respectively had P. falciparum infection as confirmed by PCR. The sensitivity and specificity of presumptive diagnosis, light microscopy and mRDT on blood, saliva and urine were 86.9% and 19.7%, 77.8% and 96.1%, 75.8% and 96.6%, 74.5% and 93.1%, and 70.7% and 81.8%, respectively. The agreement between mRDT on saliva (k = 0.696) and microscopy (k = 0.766) compared to PCR was good. CONCLUSION: The study highlighted the low performance of presumptive diagnosis, reinforcing the need for parasitological tests prior to antimalarial therapy. The higher PfHRP2/pLDH mRDT parasite detection rates and sensitivity in saliva compared to urine suggests that the former is a practical adjunct to or alternative worth optimising for the routine diagnosis of malaria. Flow chart for diagnosis of P. falciparum infection by light microscopy, rapid diagnostic tests and nested PCR.

Giant Red Kidney Worm (Dioctophyma renale) Screening and Treatment Protocol and Aberrant Worm Migration In Dogs From Ontario and Manitoba, Canada.

The life cycle of Dioctophyma renale involves an intermediate host (oligochaete), a paratenic hosts (fish and frogs), and a definitive host (mustelids and canids). Dogs are at risk of infection with D. renale when they consume paratenic hosts infected with the larval form of D. renale. Water containing the oligochaete intermediate host cannot be disregarded as another source of infection. Infections occur mainly in the right kidney, but worms have also been found in the abdominal cavity as well as other organs. Most dogs appear asymptomatic and infections are usually noted as incidental findings on necropsy. Recently, the Ontario Society for the Prevention of Cruelty to Animals (SPCA) and Humane Society conducted transports of dogs located in northern remote communities. In 2016, some female dogs were found to be infected with D. renale upon ovariohysterectomy. In response to this discovery, we developed a screening protocol to screen for D. renale infections. In 2018, a total of 130 intact dogs were transferred from 2 northern communities in the provinces of Ontario and Manitoba. A prevalence of 7.94% (95% confidence interval 3.87-14.11%) was found from dogs from the northern communities. The screening protocol we developed provides a method of screening for dogs that are transported from communities that could be at risk of infection with D. renale.

Analysis of Daily Variation for 3 and for 30 Days of Parasite-Specific IgG in Urine for Diagnosis of Strongyloidiasis by Enzyme-Linked Immunosorbent Assay.

Recent work has found urine analysis to be as sensitive as serology for diagnosis of strongyloidiasis. Here, we examined the daily variation of Strongyloides-specific IgG in urine by qualitative and quantitative ELISA and its effects on diagnostic accuracy and reliability. In the first part of the study, matched urine and fecal samples were collected from project participants in northeast Thailand for three consecutive days. Urine samples were analyzed for Strongyloides-specific IgG by ELISA using Strongyloides ratti as the antigen source. Performance of urine ELISA was compared with parasitological diagnosis by agar plate culture technique (APCT) and formalin-ethyl acetate concentration technique (FECT). In the second part of the study, urine IgG levels were compared daily for thirty consecutive days. The prevalence of Strongyloides infection, as measured by urine ELISA for three consecutive days, was significantly higher than that found using parasitological methods (63.1% vs. 22%). There was slight daily variation in prevalence estimates according to urine ELISA while there were significant variations according to parasitological examination methods over three consecutive days. For the 3-day experiment, urine ELISA had 83-86% diagnostic sensitivity when compared with the fecal examination method or with a composite standard (combined results from fecal examination methods (APCT or FECT) and/or urine ELISA). The levels of parasite-specific IgG in urine were stable throughout both the 3-day and the 30-day studies. In conclusion, diagnosis of strongyloidiasis by urine ELISA is more sensitive than by fecal methods, with minimal daily variation for qualitative and quantitative diagnosis. Urine ELISA has potential for clinical diagnosis and population screening of strongyloidiasis.

Polyparasitism with Schistosoma haematobium, Plasmodium and soil-transmitted helminths in school-aged children in Muyuka-Cameroon following implementation of control measures: a cross sectional study.

BACKGROUND: Despite the ubiquity of polyparasitism, its health impacts have been inadequately studied. The aim of this study was to determine the prevalence and determinants of polyparasitism with Schistosoma haematobium, Plasmodium and soil-transmitted helminths (STH) following sustained control measures, as well as evaluate the outcomes and clinical correlates of infection in school-aged children (SAC) living in the schistosomiasis endemic focus of Muyuka-Cameroon. METHODS: In a cross-sectional study, urine, blood and stool samples were each collected from SAC (4-14 years) selected at random between March and June 2015. Microhaematuria in urine was detected using reagent strip and S. haematobium ova by filtration/microscopy methods. Plasmodium was detected using Giemsa-stained blood films and complete blood count was obtained using an auto-haematology analyser. STH in stool was detected by the Kato-Katz method. Categorical and continuous variables were compared as required, Kappa value estimated and the adjusted odds ratio (aOR) in the multivariate analysis was used to evaluate association of the risk factors with infection. RESULTS: Out of the 638 SAC examined, single infection was prevalent in 33.4% while polyparasitism was 19.9%. Prevalence of S. haematobium + Plasmodium was 7.8%; S. haematobium + STH was 0.8%; Plasmodium + STH was 0.8%; while S. haematobium + Plasmodium + STH was 0.9%. Higher preponderance of S. haematobium + Plasmodium infection occurred in females, those from Likoko, did not use potable water, practiced bathing in stream and carried out open defecation than their equivalents. However, being female (aOR = 2.38, P = 0.009) was the only significant risk factor identified. Anaemia was a common morbidity (74.3%) with a slight agreement with microscopy in predicting S. haematobium and Plasmodium infections. The sensitivity and specificity of haematuria (13.0%) in predicting S. haematobium infection was 46.5% and 100% with a moderate agreement with microscopy. Co-infection with S. haematobium and malaria parasite was significantly associated with threefold odds of history of fever in the last three days. CONCLUSIONS: Polyparasitism is a public health problem in Muyuka with females most at risk. Anaemia prevalence is exacerbated in co- and triple-infections and together with a history of fever are of value in predicting polyparasitism.

Diagnostic comparison of stool exam and point-of-care circulating cathodic antigen (POC-CCA) test for schistosomiasis mansoni diagnosis in a high endemicity area in northeastern Brazil.

This study aimed to evaluate the performance of the point-of-care circulating cathodic antigen (POC-CCA) test in a highly endemic area in Brazil, comparing it to the Kato-Katz (KK) technique for sensitivity, specificity and the intensity of the reaction of the test in relation to the parasitic load. The community in Sergipe, Brazil, participated in the study, providing three stool samples, one of urine (POC-CCA) and fingers tick blood sample was tested by enzyme-linked immunosorbent assay (ELISA). Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, kappa coefficient and Spearman's correlation were calculated for the POC-CCA test using the KK as the reference. The prevalence of schistosomiasis by KK testing was 48.82%; POC-CCA (t+) 66.14%; POC-CCA (t-) 45.24%. ELISA results showed 100% agreement in individuals with high and moderate eggs per gram (EPG). POC-CCA presented good diagnostic performance in individuals with medium and high EPG, but there were a high number of false negatives in individuals with low intensity infections. As observed, POC-CCA-filter test improves accuracy and sensitivity compared to a conventional test.

Medical treatment for an isolated renal multilocular hydatid cyst in an elderly: a case report.

BACKGROUND: Almost all cases of renal hydatid cysts need surgical intervention for treatment. We report a case of isolated renal hydatid cyst treated successfully only with medical therapy. CASE PRESENTATION: This case is a 79-year-old veterinarian presented with right flank pain, hydatiduria and positive echinococcus granulosus serology. A 70*50 mm cyst with daughter cysts in mid-portion of right kidney on presentation was changed into a 60*40 mm cyst without daughter cysts at last follow-up. Due to patient's refusal of surgery, our patient received medical treatment including praziquantel and albendazole. After completion of first round of treatment, recurrence occurred and the same treatment was repeated. At last, the cyst became inactive and calcified with negative serology and no clinical symptoms under medical treatment. CONCLUSION: The treatment of choice in renal hydatid cyst is surgery; although there are some reports about the efficacy of medical treatments for hydatid cysts but lower rates of recurrence and higher efficacy put surgery in a superior position compared to medical approaches. Our case showed relative success of medical treatment, despite the presence of a large multilocular renal involvement. Thus, medical therapy without surgery can be considered in very particular cases with isolated renal hydatid cysts.

Analytical and Clinical Assessment of a Portable, Isothermal Recombinase Polymerase Amplification (RPA) Assay for the Molecular Diagnosis of Urogenital Schistosomiasis.

Accurate diagnosis of urogenital schistosomiasis is crucial for disease surveillance and control. Routine diagnostic methods, however, lack sensitivity when assessing patients with low levels of infection still able to maintain pathogen transmission. Therefore, there is a need for highly sensitive diagnostic tools that can be used at the point-of-care in endemic areas. Recombinase polymerase amplification (RPA) is a rapid and sensitive diagnostic tool that has been used to diagnose several pathogens at the point-of-care. Here, the analytical performance of a previously developed RPA assay (RT-ShDra1-RPA) targeting the Schistosoma haematobium Dra1 genomic region was assessed using commercially synthesised S. haematobium Dra1 copies and laboratory-prepared samples spiked with S. haematobium eggs. Clinical performance was also assessed by comparing diagnostic outcomes with that of a reference diagnostic standard, urine-egg microscopy. The RT-ShDra1-RPA was able to detect 1 × 101 copies of commercially synthesised Dra1 DNA as well as one S. haematobium egg within laboratory-spiked ddH2O samples. When compared with urine-egg microscopy, the overall sensitivity and specificity of the RT-ShDra1-RPA assay was 93.7% (±88.7-96.9) and 100% (±69.1-100), respectively. Positive and negative predictive values were 100% (±97.5-100) and 50% (±27.2-72.8), respectively. The RT-ShDra1-RPA therefore shows promise as a rapid and highly sensitive diagnostic tool able to diagnose urogenital schistosomiasis at the point-of-care.

Evaluating the potential of using urine and saliva specimens for malaria diagnosis in suspected patients in Ghana.

BACKGROUND: This study aimed at detecting PfHRP2 and pLDH malaria antigens in urine and salivary specimens of suspected malaria patients using RDT kits, and identifying factors influencing the detection of these antigens. METHODS: Malaria rapid test kit (SD Bioline RDT kit) was used to detect malaria antigens, PfHRP2 and pLDH, in blood, urine and saliva samples received from patients suspected of malaria. Subsequently, malaria parasitaemia was determined. From the same patients, body temperature readings and haemoglobin concentrations were recorded. Also, micro-haematuria and saliva occult blood were determined. Relative to blood, the sensitivities and the performance of urine and saliva as alternative samples were evaluated. RESULTS: A total of 706 suspected malaria patients provided all three specimens. Prevalence of malaria by microscopy and RDT was 44.2% and 53.9%, respectively. Compared to blood, the sensitivities of urine and saliva were 35.2% and 57.0% respectively. Haemoglobin concentration < 9.9 g/dL, body temperature > 38.7 °C and occult blood influenced the detection of malaria antigens in both urine and saliva. Furthermore, the antigens were not detected in urine and saliva when parasitaemia was < 60,000 parasites/µL and < 40,000 parasites/µL, respectively. CONCLUSION: Saliva, with or without blood contamination, was found to be more efficient that urine samples. Therefore these non-blood specimens have the potential to be used as non-invasive samples for malaria diagnosis. However, this approach is useful in severe to moderate anaemia, hyperthermia, parasitaemia > 60,000 parasites/µL and samples contaminated with blood.

Accuracy of real-time polymerase chain reaction to detect Schistosoma mansoni - infected individuals from an endemic area with low parasite loads.

Due to the efforts to control schistosomiasis transmission in tropical countries, a large proportion of individuals from endemic areas present low parasite loads, which hinders diagnosis of intestinal schistosomiasis by the Kato-Katz (KK) method. Therefore, the development of more sensitive diagnostic methods is essential for efficient control measures. The aim was to evaluate the accuracy of a real-time polymerase chain reaction (RT-PCR) to detect Schistosoma mansoni DNA in fecal samples of individuals with low parasite loads. A cross-sectional population-based study was conducted in a rural community (n = 257) in Brazil. POC-CCA® was performed in urine and feces were used for RT-PCR. In addition, fecal exams were completed by 18 KK slides, saline gradient and Helmintex techniques. The combined results of the three parasitological tests detected schistosome eggs in 118 participants (45.9%) and composed the consolidated reference standard (CRS). By RT-PCR, 117 out of 215 tested samples were positive, showing 91.4% sensitivity, 80.2% specificity and good concordance with the CRS (kappa = 0.71). RT-PCR identified 86.9% of the individuals eliminating less than 12 eggs/g of feces, demonstrating much better performance than POC-CCA® (50.8%). Our results showed that RT-PCR is a valuable alternative for the diagnosis of intestinal schistosomiasis in individuals with very low parasite loads.

Circulating Anodic Antigen (CAA): A Highly Sensitive Diagnostic Biomarker to Detect Active Schistosoma Infections-Improvement and Use during SCORE.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was funded in 2008 to conduct research that would support country schistosomiasis control programs. As schistosomiasis prevalence decreases in many places and elimination is increasingly within reach, a sensitive and specific test to detect infection with Schistosoma mansoni and Schistosoma haematobium has become a pressing need. After obtaining broad input, SCORE supported Leiden University Medical Center (LUMC) to modify the serum-based antigen assay for use with urine, simplify the assay, and improve its sensitivity. The urine assay eventually contributed to several of the larger SCORE studies. For example, in Zanzibar, we demonstrated that urine filtration, the standard parasite egg detection diagnostic test for S. haematobium, greatly underestimated prevalence in low-prevalence settings. In Burundi and Rwanda, the circulating anodic antigen (CAA) assay provided critical information about the limitations of the stool-based Kato-Katz parasite egg-detection assay for S. mansoni in low-prevalence settings. Other SCORE-supported CAA work demonstrated that frozen, banked urine specimens yielded similar results to fresh ones; pooling of specimens may be a useful, cost-effective approach for surveillance in some settings; and the assay can be performed in local laboratories equipped with adequate centrifuge capacity. These improvements in the assay continue to be of use to researchers around the world. However, additional work will be needed if widespread dissemination of the CAA assay is to occur, for example, by building capacity in places besides LUMC and commercialization of the assay. Here, we review the evolution of the CAA assay format during the SCORE period with emphasis on urine-based applications.

Evaluation, Validation, and Recognition of the Point-of-Care Circulating Cathodic Antigen, Urine-Based Assay for Mapping Schistosoma mansoni Infections.

Efforts to control Schistosoma mansoni infection depend on the ability of programs to effectively detect and quantify infection levels and adjust programmatic approaches based on these levels and program goals. One of the three major objectives of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) has been to develop and/or evaluate tools that would assist Neglected Tropical Disease program managers in accomplishing this fundamental task. The advent of a widely available point-of-care (POC) assay to detect schistosome circulating cathodic antigen (CCA) in urine with a rapid diagnostic test (the POC-CCA) in 2008 led SCORE and others to conduct multiple evaluations of this assay, comparing it with the Kato-Katz (KK) stool microscopy assay-the standard used for more than 45 years. This article describes multiple SCORE-funded studies comparing the POC-CCA and KK assays, the pros and cons of these assays, the use of the POC-CCA assay for mapping of S. mansoni infections in areas across the spectrum of prevalence levels, and the validation and recognition that the POC-CCA, although not infallible, is a highly useful tool to detect low-intensity infections in low-to-moderate prevalence areas. Such an assay is critical, as control programs succeed in driving down prevalence and intensity and seek to either maintain control or move to elimination of transmission of S. mansoni.

Membranoproliferative Glomerulonephritis and Mixed Cryoglobulinemia as a Form of Presentation of Visceral Leishmaniasis.

BACKGROUND Visceral leishmaniasis (VL) is an endemic systemic disease in the Mediterranean countries, including Spain. This vector-borne infection can present with several clinical presentations, from asymptomatic to severe forms. Renal impairment is frequently described in VL but is usually mild and related to interstitial nephritis, being that glomerular involvement is rarely found. CASE REPORT We describe a case of a 69-year-old Spanish male presenting with subacute renal failure due to membranoproliferative glomerulonephritis and mixed cryoglobulinemia accompanied by other autoimmune features (hypocomplementemia, antinuclear and antiDNA antibodies). No hepatosplenomegaly was found with abdominal ultrasound. Hepatotropic viruses and human immunodeficiency virus serological markers were negatives. We initially suspect the presence of an autoimmune disease and the patient was treated with steroids without improvement. After an extensive study including renal and bone marrow biopsy, a correct diagnosis of visceral leishmaniasis was made, and treatment with liposomal amphotericin B was initiated, achieving renal function recovery and normalization of immunological manifestations. CONCLUSIONS Renal involvement can be an important feature of VL and it might be associated with increased morbidity and mortality. The association between mixed cryoglobulinemia and renal involvement in VL have rarely been described. VL is frequently associated with diverse autoimmune manifestations and it can be initially misdiagnosed, which could lead to fatal consequences. The role of the immune system in the formation of cryoglobulins are discussed. In our case, an autoimmune disease was initially suspected, and starting treatment with steroids pulses was initiated. However, the presence of mixed cryoglobulinemia in this patient who was hepatitis C serological marker negative and who had poor renal function recovery after immunosuppressive treatment made us suspect other pathologies. The presence of cryoglobulinemia with renal disease in endemic areas of Leishmania should make us exclude this infection before starting immunosuppressive treatment.

Assessing expanded community wide treatment for schistosomiasis: Baseline infection status and self-reported risk factors in three communities from the Greater Accra region, Ghana.

BACKGROUND: This paper reports on the baseline prevalence and associated risk factor findings of a pilot, longitudinal study exploring community-wide treatment of schistosomiasis and soil-transmitted helminthiasis, using albendazole plus praziquantel in the Greater Accra region of Ghana. METHOD: From three communities, at least, 658 individuals were enrolled into the study via random household selection. Prevalence and intensity of schistosomiasis and STH infection were determined from stool and urine samples with a questionnaire being administered in order to explore other morbidities and risk factors. Factor analysis of household demographic variables was undertaken to generate a socioeconomic score; this was then further categorised into tertiles. Proportional-odds cumulative logit generalised estimating equation (GEE) models were used to investigate categorical ordinal intensity of infection associations with morbidity. Separately, logistic GEE models were used to investigate risk factor associations with infection prevalence. RESULTS: Both Schistosoma haematobium and S. mansoni were prevalent in the three communities, with the prevalence of S. haematobium ranging from 3.3% (24/679; 95% CI = 1.9-4.7) to 19% (114/632; 95% CI = 15.8-22.2) and S. mansoni ranging from 30% (202/679; 95% CI = 26.5-33.5) to 78.3% (409/536; 95% CI = 74.7-81.9). The total prevalence of STH across all three sites was negligible at 1.3% (24/1847; 95% CI = 0.8-1.9) comprising mainly hookworm (10/1847). Multivariable statistical models indicated males to be 2.3 (95% CI = 1.7-3.3) times more likely to have a high intensity S. mansoni infection and 1.5 (95% CI = 1.1-2) times more likely to have a high intensity of S. haematobium infection compared to females. There was no significant difference in the likelihood of infection with S. mansoni between adults and school age children (SAC), however S. haematobium infections were found to be 2.5 (95% CI = 1.8-3.5) times more likely to occur in school age children than in adults. Multivariable statistical models (adjusted for age and sex) indicated an association between schistosomiasis and a number of self-reported morbidity indicators (notably diarrhoea and blood in stool and urine). Low socio-economic status was also associated with SCH infection (OR: 2; 95% CI = 1.3-3.2). CONCLUSION: The communities targeted by this study showed a range of Schistosoma prevalence's of infection, from hypo-endemic through to meso-endemic and hyper-endemic. The prevalence of SCH across the different age groups in the study locations highlights the large number of individuals currently being left out of the standard morbidity control method of annual treatment of the SAC.

Efficacy of single versus four repeated doses of praziquantel against Schistosoma mansoni infection in school-aged children from Côte d'Ivoire based on Kato-Katz and POC-CCA: An open-label, randomised controlled trial (RePST).

BACKGROUND: Preventive chemotherapy with praziquantel (PZQ) is the cornerstone of schistosomiasis control. However, a single dose of PZQ (40 mg/kg) does not cure all infections. Repeated doses of PZQ at short intervals might increase efficacy in terms of cure rate (CR) and intensity reduction rate (IRR). Here, we determined the efficacy of a single versus four repeated treatments with PZQ on Schistosoma mansoni infection in school-aged children from Côte d'Ivoire, using two different diagnostic tests. METHODS: An open-label, randomized controlled trial was conducted from October 2018 to January 2019. School-aged children with a confirmed S. mansoni infection based on Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) urine cassette test were randomly assigned to receive either a single or four repeated doses of PZQ, administered at two-week intervals. The primary outcome was the difference in CR between the two treatment arms, measured by triplicate KK thick smears 10 weeks after the first treatment. Secondary outcomes included CR estimated by POC-CCA, IRR by KK and POC-CCA, and safety of repeated PZQ administration. PRINCIPAL FINDINGS: During baseline screening, 1,022 children were assessed for eligibility of whom 153 (15%) had a detectable S. mansoni infection, and hence, were randomized to the standard treatment group (N = 70) and the intense treatment group (N = 83). Based on KK, the CR was 42% (95% confidence interval (CI) 31-52%) in the standard treatment group and 86% (95% CI 75-92%) in the intense treatment group. Observed IRR was 72% (95% CI 55-83%) in the standard treatment group and 95% (95% CI 85-98%) in the intense treatment group. The CR estimated by POC-CCA was 18% (95% CI 11-27%) and 36% (95% CI 26-46%) in the standard and intense treatment group, respectively. Repeated PZQ treatment did not result in a higher number of adverse events. CONCLUSION/SIGNIFICANCE: The observed CR using KK was significantly higher after four repeated treatments compared to a single treatment, without an increase in adverse events. Using POC-CCA, the observed CR was significantly lower than measured by KK, indicating that PZQ may be considerably less efficacious as concluded by KK. Our findings highlight the need for reliable and more accurate diagnostic tools, which are essential for monitoring treatment efficacy, identifying changes in transmission, and accurately quantifying the intensity of infection in distinct populations. In addition, the higher CR in the intense treatment group suggests that more focused and intense PZQ treatment can help to advance schistosomiasis control. TRIAL REGISTRATION: www.clinicaltrials.gov NCT02868385.