Liver morbidity due to Schistosoma mekongi in Cambodia after seven rounds of mass drug administration

Severe liver disease due to Schistosoma mekongi was frequent in northern Cambodia. Between 1995 and 2002, seven rounds of mass chemotherapy (praziquantel) reduced infection from 50% to below 3%. In 2002, we assessed hepatosplenic morbidity by historical, clinical and ultrasonographic investigations in adults (older than 14 years) from endemic (n = 342) and non-endemic (n = 103) areas (Kratie province). Clinical hepatomegaly (25 vs. 0%), splenomegaly (55 vs. 0%), reported blood in stool (41 vs. 20%) and abdominal pain (78 vs. 57%) were significantly higher in the endemic area. In this area, significantly more subjects reported a family history of death due to schistosomiasis (12 vs. 0%); 63% (vs. 0%) reported having at least three treatments of praziquantel in previous years; and only 11% (vs. 99%) had normal liver ultrasonographic examination. Periportal fibrosis with portal hypertension was diagnosed in 46% (vs. 0%) of people in this area; 18% (vs. 0%) and 5% (vs. 0%) of portal hypertension was classified as moderate and severe, respectively. People aged between 24 and 35 years were mostly affected. There was no gender difference. The pathology in the endemic district is most probably residual morbidity of S. mekongi infections. Contributions of co-infections (hepatitis) cannot be excluded. Careful monitoring of the affected communities is require

Diversity II water quality parameters from ENVISAT (2002–2012): a new global information source for lakes

The use of ground sampled water quality information for global studies is limited due to practical and financial constraints. Remote sensing is a valuable means to overcome such limitations and to provide synoptic views of ambient water quality at appropriate spatio-temporal scales. In past years several large data processing efforts were initiated to provide corresponding data sources. The Diversity II water quality dataset consists of several monthly, yearly and 9-year averaged water quality parameters for 340 lakes worldwide and is based on data from the full ENVISAT MERIS operation period (2002–2012). Existing retrieval methods and datasets were selected after an extensive algorithm intercomparison exercise. Chlorophyll-a, total suspended matter, turbidity, coloured dissolved organic matter, lake surface water temperature, cyanobacteria and floating vegetation maps, as well as several auxiliary data layers, provide a generically specified database that can be used for assessing a variety of locally relevant ecosystem properties and environmental problems. For validation and accuracy assessment, we provide matchup comparisons for 24 lakes and a group of reservoirs representing a wide range of bio-optical conditions. Matchup comparisons for chlorophyll-a concentrations indicate mean absolute errors and bias in the order of median concentrations for individual lakes, while total suspended matter and turbidity retrieval achieve significantly better performance metrics across several lake-specific datasets. We demonstrate the use of the products by illustrating and discussing remotely sensed evidence of lake-specific processes and prominent regime shifts documented in the literature. The Diversity II data are available from https://doi.pangaea.de/10.1594/PANGAEA.871462, and Python scripts for their analysis and visualization are provided at https://github.com/odermatt/diversity/.</p

Exploiting Fluorescent Reporter Molecules for Process Analytical Technology (PAT): FH – HES

Process Analytical Technology (PAT) launched by the U.S. Food and Drug Administration (FDA) aims to ensure the quality of pharmaceutical products. One important tool to obtain a deeper process understanding is the use of modern real-time process sensors and analyzers. In this context an industrially accepted optical probe for turbidity measurement (Aquasant probe) has been adapted for on-line and real-time fluorescence measurement in (bio-)reactors. By tagging product proteins with fluorescent reporter molecules (e.g. GFP) it was possible to quantify product concentrations during a fermentation process with the new probe. The on-line obtained signal showed a high correlation to the off-line signal. This new method has remarkable advantages compared to classical off-line product lab analyses and can serve as a platform-independent quantification method of products to be used in either up- or downstream processing

Foci of Schistosomiasis mekongi, Northern Cambodia: II. Distribution of infection and morbidity.

In the province of Kracheh, in Northern Cambodia, a baseline epidemiological survey on Schistosoma mekongi was conducted along the Mekong River between December 1994 and April 1995. The results of household surveys of highly affected villages of the East and the West bank of the river and of school surveys in 20 primary schools are presented. In household surveys 1396 people were examined. An overall prevalence of infection of 49.3% was detected by a single stool examination with the Kato-Katz technique. The overall intensity of infection was 118.2 eggs per gram of stool (epg). There was no difference between the population of the east and west shore of the Mekong for prevalence (P = 0.3) or intensity (P = 0.9) of infection. Severe morbidity was very frequent. Hepatomegaly of the left lobe was detected in 48.7% of the population. Splenomegaly was seen in 26.8% of the study participants. Visible diverted circulation was found in 7.2% of the population, and ascites in 0.1%. Significantly more hepatomegaly (P = 0.001), splenomegaly (P = 0. 001) and patients with diverted circulation (P = 0.001) were present on the west bank of the Mekong. The age group of 10-14 years was most affected. The prevalence of infection in this group was 71.8% and 71.9% in the population of the West and East of the Mekong, respectively. The intensity of infection was 172.4 and 194.2 epg on the West and the East bank, respectively. In the peak age group hepatomegaly reached a prevalence of 88.1% on the west and 82.8% on the east bank. In the 20 schools 2391 children aged 6-16 years were examined. The overall prevalence of infection was 40.0%, ranging from 7.7% to 72.9% per school. The overalls mean intensity of infection was 110.1 epg (range by school: 26.7-187.5 epg). Both prevalence (P = 0.001) and intensity of infection (P = 0.001) were significantly higher in schools on the east side of the Mekong. Hepatomegaly (55.2%), splenomegaly (23.6%), diverted circulation (4. 1%), ascites (0.5%), reported blood (26.7%) and mucus (24.3%) were very frequent. Hepatomegaly (P = 0.001), splenomegaly (P = 0.001), diverted circulation (P = 0.001) and blood in stool (P = 0.001) were significantly more frequent in schools of the east side of the Mekong. Boys suffered more frequently from splenomegaly (P = 0.05), ascites (P = 0.05) and bloody stools (P = 0.004) than girls. No difference in sex was found for the prevalence and intensity of infection and prevalence of hepatomegaly. On the school level prevalence and intensity of infection were highly associated (r = 0. 93, P = 0.0001). The intensity of infection was significantly associated only with the prevalence of hepatomegaly (r = 0.44, P = 0. 05) and blood in stool (r = 0.40, P = 0.02). This comprehensive epidemiological study documents for the first time the public health importance of schistosomiasis mekongi in the Province of Kracheh, Northern Cambodia and points at key epidemiological features of this schistosome species, in particular the high level of morbidity associated with infection

Activity of tribendimidine and praziquantel combination therapy against the liver fluke Opisthorchis viverrini in vitro and in vivo

Opisthorchiasis, caused by the liver fluke Opisthorchis viverrini, a food-borne trematode, is an important public health problem; however, only a single drug, praziquantel is available. We investigated tribendimidine-praziquantel combinations against O. viverrini in vitro and in vivo. The IC50 values of 0.16μg/ml and 0.05μg/ml were determined for praziquantel and tribendimidine, respectively, against adult O. viverrini in vitro. When O. viverrini was exposed to both drugs simultaneously (using a drug ratio based on the IC50 (1:3.2)) a synergistic effect was calculated (combination index (CI) at the IC50=0.7). A similar result was observed when drug addition in vitro was spaced by the respective half-lives of the drugs (a CI of 0.78 at the IC50 for tribendimidine followed by praziquantel and a CI of 0.47 at the IC50 for praziquantel followed by tribendimidine). In vivo median-effect dose (ED50) values of 191mg/kg and 147mg/kg were calculated for praziquantel and tribendimidine, respectively. Low to moderate worm burden reductions (38-62%) were observed in O. viverrini infected hamsters when both drugs were administered simultaneously or on subsequent days, pointing to antagonistic effects in vivo. Further studies are necessary to understand the striking differences between the in vitro and in vivo observations using combinations of praziquantel and tribendimidine on O. viverrin

The use of morbidity questionnaires to identify communities with high prevalences of schistosome or geohelminth infections in Tanzania

Parasitic infections were investigated in Morogoro Rural District, Tanzania, between October 1992 and June 1993. A total of 4589 schoolchildren (aged 7-17 years) from 30 primary schools was screened for infection with Ascaris lumbricoides, Trichuris trichiura, hookworms (3456 children only), Schistosoma mansoni and S. haematobium. The children were also asked about their recent experiences of the following: diarrhoea, abdominal pain, blood in stool, perception of suffering from schistosomiasis, and worm infection and examined for spleen and liver enlargement. Among schools, there were correlations between the prevalence of S. mansoni infection and bloody stools, spleen enlargement and liver enlargement, and between S. haematobium infection and the presence of blood in urine. To exclude ecological explanations for the correlations, logistic regression was used to estimate the adjusted odds ratio (OR) for each infection and each sign or symptom. No sign or symptom was significantly associated with any geohelminth infection. Reported blood in stool was significantly associated with S. mansoni infection (OR = 1·62, P = 0·045). Reported blood in urine was significantly associated with S. haematobium infection (OR = 7·71, P < 0·001), as was reported blood in stool (OR = 11·52, P < 0·001), indicating that presence of blood in either form of excreta was related to the local term for schistosomiasis. These results support the possibility of using reported blood in stool as a means of rapid assessment for identifying communities with a high prevalence of S. mansoni infectio

Epidemiology of Schistosoma mansoni infection in Ituri Province, north-eastern Democratic Republic of the Congo

BACKGROUND: Schistosomiasis, caused by Schistosoma mansoni, is of great significance to public health in sub-Saharan Africa. In the Democratic Republic of Congo (DRC), information on the burden of S. mansoni infection is scarce, which hinders the implementation of adequate control measures. We assessed the geographical distribution of S. mansoni infection across Ituri province in north-eastern DRC and determined the prevailing risk factors. METHODS/PRINCIPAL FINDINGS: Two province-wide, community-based studies were conducted. In 2016, a geographical distribution study was carried out in 46 randomly selected villages across Ituri. In 2017, an in-depth study was conducted in 12 purposively-selected villages, across the province. Households were randomly selected, and members were enrolled. In 2016, one stool sample was collected per participant, while in 2017, several samples were collected per participant. S. mansoni eggs were detected using the Kato-Katz technique. In 2017, a point-of-care circulating cathodic S. mansoni antigen (POC-CCA) urine test was the second used diagnostic approach. Household and individual questionnaires were used to collect data on demographic, socioeconomic, environmental, behavioural and knowledge risk factors. Of the 2,131 participants in 2016, 40.0% were positive of S. mansoni infection. Infection prevalence in the villages ranged from 0 to 90.2%. Of the 707 participants in 2017, 73.1% were tested positive for S. mansoni. Prevalence ranged from 52.8 to 95.0% across the health districts visited. Infection prevalence increased from north to south and from west to east. Exposure to the waters of Lake Albert and the villages' altitude above sea level were associated with the distribution. Infection prevalence and intensity peaked in the age groups between 10 and 29 years. Preschool children were highly infected (62.3%). Key risk factors were poor housing structure (odds ratio [OR] 2.1, 95% 95% confidence interval [CI] 1.02-4.35), close proximity to water bodies (OR 1.72, 95% CI 1.1-2.49), long-term residence in a community (OR 1.41, 95% CI 1.11-1.79), lack of latrine in the household (OR 2.00, 95% CI 1.11-3.60), and swimming (OR 2.53, 95% CI 1.20-5.32) and washing (OR 1.75, 95% CI 1.10-2.78) in local water bodies. CONCLUSIONS/SIGNIFICANCE: Our results show that S. mansoni is highly endemic and a major health concern in Ituri province, DRC. Infection prevalence and intensity, and the prevailing socioeconomic, environmental, and behavioural risk factors in Ituri reflect intense exposure and alarming transmission rates. A robust plan of action is urgently needed in the province

Morbidity associated with Schistosoma mansoni infection in north-eastern Democratic Republic of the Congo

BACKGROUND: Reducing morbidity is the main target of schistosomiasis control efforts, yet only rarely do control programmes assess morbidity linked to Schistosoma sp. infection. In the Democratic Republic of Congo (DRC), and particularly in north-eastern Ituri Province, little is known about morbidity associated with Schistosoma mansoni infection. For this reason, we aimed to assess intestinal and hepatosplenic morbidity associated with S. mansoni infection in Ituri Province. METHODS/PRINCIPAL FINDINGS: In 2017, we conducted a cross-sectional study in 13 villages in Ituri Province, DRC. S. mansoni infection was assessed with a Kato-Katz stool test (2 smears) and a point-of-care circulating cathodic antigen (POC-CCA) urine test. A questionnaire was used to obtain demographic data and information about experienced intestinal morbidity. Each participant underwent an abdominal ultrasonography examination to diagnose hepatosplenic morbidity. Of the 586 study participants, 76.6% tested positive for S. mansoni. Intestinal morbidity reported in the two preceding weeks was very frequent, and included abdominal pain (52.7%), diarrhoea (23.4%) and blood in the stool (21.5%). Hepatosplenic morbidity consisted of abnormal liver parenchyma patterns (42.8%), hepatomegaly (26.5%) and splenomegaly (25.3%). Liver pathology (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.06-1.37, p = 0.005) was positively and significantly associated with S. mansoni infection. Hepatomegaly (aOR 1.52, 95% CI 0.99-2.32, p = 0.053) and splenomegaly (aOR 1.12, 95% CI 0.73-1.72, p = 0.619) were positively but not significantly associated with S. mansoni infection at the individual level. At the village level, S. mansoni prevalence was positively associated with the prevalence of hepatomegaly and splenomegaly. High-intensity S. mansoni infections were associated with diarrhoea, blood in the stool, hepatomegaly, splenomegaly, and liver parenchyma (C, D, E and F pathology patterns). Four study participants were diagnosed with ascites and five reported hematemesis. CONCLUSIONS/SIGNIFICANCE: Our study documents a high burden of intestinal and hepatosplenic morbidity associated with S. mansoni infection status in Ituri Province. The findings call for targeted interventions to address both S. mansoni infection and related morbidity

Patients with severe schistosomiasis mansoni in Ituri Province, Democratic Republic of the Congo

BACKGROUND: Severe hepatosplenic complications arise in patients with chronic Schistosoma mansoni infection after heavy exposure to disease agents in endemic areas. These complications are rarely reported and, hence, underestimated. CASE PRESENTATION: We report on eight patients with severe morbidity associated with S. mansoni infection in Ituri Province, northeastern Democratic Republic of Congo (DRC). The patients were identified during a community-based survey in 2017; one patient was seen at the district hospital. After taking the patients' history, a clinical examination and an abdominal ultrasonographical examination were performed. S. mansoni infection was diagnosed in fecal (Kato-Katz technique) and urine (point-of-case circulating cathodic antigen test) samples. These eight patients with severe intestinal and hepatosplenic complications were identified from four villages with high S. mansoni infection prevalence and related morbidity. The patients' ages ranged from 19 to 57 years; four patients were women. Three patients reported hematemesis. Two patients were severely anemic. All patients reported non-specific abdominal symptoms, such as diarrhea (six patients), abdominal pain (seven patients), and blood in the stool (five patients), as well as weight loss (two patients). Abdominal ultrasonography revealed ascites in four patients. All patients had portal hypertension with hepatomegaly (seven patients) or splenomegaly (five patients). Of the six patients with a discernable liver parenchyma pattern, five displayed pattern F and three patient displayed pattern E. Liver parenchyma was not visible for two patients with severe ascites. An S. mansoni infection was confirmed in six patients, with infection intensity ranging from light to heavy. All S. mansoni positive patients were treated with praziquantel (40 mg/kg body weight) and referred to the district hospital for follow-up. One patient with severe ascites died two weeks after we saw her. Due to security and accessibility reasons, the villages could not be visited again and the patients were lost to follow-up. CONCLUSIONS: Our observations of patients with severe schistosomiasis document the severe degree of endemicity of S. mansoni in the province and suggest an urgent need for adequate schistosomiasis control measures that target vulnerable population groups and address severe complications