Schistosomiasis at the crossroad to elimination: review of eclipsed research with emphasis on the post-transmission agenda

While chronic schistosomiasis is pathologically well defined, the acute form of the disease is less well understood. It is generally agreed that early lesions, such as lung nodules and bladder polyps, are reversible, which impedes identification of the time elapsed since exposure. The intermediate stage between the acute and the chronic forms of schistosomiasis requires further investigation, as does the clinical stage due to lesions remaining after treatment. With current schistosomiasis control efforts gradually progressing to elimination, there is a need to focus on post-transmission schistosomiasis, which not only refers to remaining lesions from previous infections, but also accounts for the potential presence of surviving worms after treatment. This issue is particularly salient for migrants from endemic to non-endemic countries and should be kept in mind for returning expatriates from schistosomiasis-endemic countries. Negative stool examination or urine filtration are generally taken as indicative of cure since rectoscopy for Schistosoma mansoni infection, or cystoscopy for S. haematobium infection, are rarely performed. However, pathology of affected organs may persist indefinitely, while potentially remaining live worms could produce additional pathology. Hence, post-transmission schistosomiasis can prevail for years after elimination of the disease, and thus, warrant further attention

Elimination of Schistosomiasis Transmission in Zanzibar: Baseline Findings before the Onset of a Randomized Intervention Trial.

Gaining and sustaining control of schistosomiasis and, whenever feasible, achieving local elimination are the year 2020 targets set by the World Health Organization. In Zanzibar, various institutions and stakeholders have joined forces to eliminate urogenital schistosomiasis within 5 years. We report baseline findings before the onset of a randomized intervention trial designed to assess the differential impact of community-based praziquantel administration, snail control, and behavior change interventions. In early 2012, a baseline parasitological survey was conducted in ∼20,000 people from 90 communities in Unguja and Pemba. Risk factors for schistosomiasis were assessed by administering a questionnaire to adults. In selected communities, local knowledge about schistosomiasis transmission and prevention was determined in focus group discussions and in-depths interviews. Intermediate host snails were collected and examined for shedding of cercariae. The baseline Schistosoma haematobium prevalence in school children and adults was 4.3% (range: 0-19.7%) and 2.7% (range: 0-26.5%) in Unguja, and 8.9% (range: 0-31.8%) and 5.5% (range: 0-23.4%) in Pemba, respectively. Heavy infections were detected in 15.1% and 35.6% of the positive school children in Unguja and Pemba, respectively. Males were at higher risk than females (odds ratio (OR): 1.45; 95% confidence interval (CI): 1.03-2.03). Decreasing adult age (OR: 1.04; CI: 1.02-1.06), being born in Pemba (OR: 1.48; CI: 1.02-2.13) or Tanzania (OR: 2.36; CI: 1.16-4.78), and use of freshwater (OR: 2.15; CI: 1.53-3.03) showed higher odds of infection. Community knowledge about schistosomiasis was low. Only few infected Bulinus snails were found. The relatively low S. haematobium prevalence in Zanzibar is a promising starting point for elimination. However, there is a need to improve community knowledge about disease transmission and prevention. Control measures tailored to the local context, placing particular attention to hot-spot areas, high-risk groups, and individuals, will be necessary if elimination is to be achieved

Confocal Laser Scanning Microscopy, a New In Vivo Diagnostic Tool for Schistosomiasis

BACKGROUND: The gold standard for the diagnosis of schistosomiasis is the detection of the parasite's characteristic eggs in urine, stool, or rectal and bladder biopsy specimens. Direct detection of eggs is difficult and not always possible in patients with low egg-shedding rates. Confocal laser scanning microscopy (CLSM) permits non-invasive cell imaging in vivo and is an established way of obtaining high-resolution images and 3-dimensional reconstructions. Recently, CLSM was shown to be a suitable method to visualize Schistosoma mansoni eggs within the mucosa of dissected mouse gut. In this case, we evaluated the suitability of CLSM to detect eggs of Schistosoma haematobium in a patient with urinary schistosomiasis and low egg-shedding rates. METHODOLOGY/PRINCIPAL FINDINGS: The confocal laser scanning microscope used in this study was based on a scanning laser system for imaging the retina of a living eye, the Heidelberg Retina Tomograph II, in combination with a lens system (image modality). Standard light cystoscopy was performed using a rigid cystoscope under general anaesthesia. The CLSM endoscope was then passed through the working channel of the rigid cystoscope. The mucosal tissue of the bladder was scanned using CLSM. Schistoma haematobium eggs appeared as bright structures, with the characteristic egg shape and typical terminal spine. CONCLUSION/SIGNIFICANCE: We were able to detect schistosomal eggs in the urothelium of a patient with urinary schistosomiasis. Thus, CLSM may be a suitable tool for the diagnosis of schistosomiasis in humans, especially in cases where standard diagnostic tools are not suitable

Confocal Laser Scanning Microscopy for Detection of Schistosoma mansoni Eggs in the Gut of Mice

Background: The gold standard for diagnosing Schistosoma mansoni infections is the detection of eggs from stool or biopsy specimens. The viability of collected eggs can be tested by the miracidium hatching procedure. Direct detection methods are often limited in patients with light or early infections, whereas serological tests and PCR methods fail to differentiate between an inactive and persistent infection and between schistosomal species. Recently, confocal laser scanning microscopy (CLSM) has been introduced as a diagnostic tool in several fields of medicine. In this study we evaluated CLSM for the detection of viable eggs of S. mansoni directly within the gut of infected mice. Methodology/Principal Findings: The confocal laser scanning microscope used in this study is based on the Heidelberg Retina Tomograph II scanning laser system in combination with the Rostock Cornea Module (image modality 1) or a rigid endoscope (image modality 2). Colon sections of five infected mice were examined with image modalities 1 and 2 for schistosomal eggs. Afterwards a biopsy specimen was taken from each colon section and examined by bright-field microscopy. Visualised eggs were counted and classified in terms of viability status. Conclusions/Significance: We were able to show that CLSM visualises eggs directly within the gut and permits discrimination of schistosomal species and determination of egg viability. Thus, CLSM may be a suitable non-invasive too

Quinine Treatment Selects the pfnhe-1 ms4760-1 Polymorphism in Malian Patients with Falciparum Malaria

Background. The mechanism of Plasmodium falciparum resistance to quinine is not known. In vitro quantitative trait loci mapping suggests involvement of a predicted P. falciparum sodium-hydrogen exchanger (pfnhe-1) on chromosome 13. Methods. We conducted prospective quinine efficacy studies in 2 villages, Kolle and Faladie, Mali. Cases of clinical malaria requiring intravenous therapy were treated with standard doses of quinine and followed for 28 days. Treatment outcomes were classified using modified World Health Organization protocols. Molecular markers of parasite polymorphisms were used to distinguish recrudescent parasites from new infections. The prevalence of pfnhe-1 ms4760-1 among parasites before versus after quinine treatment was determined by direct sequencing. Results. Overall, 163 patients were enrolled and successfully followed. Without molecular correction, the mean adequate clinical and parasitological response (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account for new infections, the corrected ACPR was 100%. The prevalence of ms4760-1 increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3% (n = 54) after therapy (P = .01). In a control sulfadoxine-pyrimethamine study, the prevalence of ms4760-1 was similar before and after treatment. Conclusions. This study supports a role for pfnhe-1 in decreased susceptibility of P. falciparum to quinine in the field.Howard Hughes Medical Institute [55005502]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; European and Developing Countries Clinical Trials Partnership [EDCTP IP_07_31060_002]info:eu-repo/semantics/publishedVersio

Towards the Establishment of a Porcine Model to Study Human Amebiasis

BACKGROUND: Entamoeba histolytica is an important parasite of the human intestine. Its life cycle is monoxenous with two stages: (i) the trophozoite, growing in the intestine and (ii) the cyst corresponding to the dissemination stage. The trophozoite in the intestine can live as a commensal leading to asymptomatic infection or as a tissue invasive form producing mucosal ulcers and liver abscesses. There is no animal model mimicking the whole disease cycle. Most of the biological information on E. histolytica has been obtained from trophozoite adapted to axenic culture. The reproduction of intestinal amebiasis in an animal model is difficult while for liver amebiasis there are well-described rodent models. During this study, we worked on the assessment of pigs as a new potential model to study amebiasis. METHODOLOGY/PRINCIPAL FINDINGS: We first co-cultured trophozoites of E. histolytica with porcine colonic fragments and observed a disruption of the mucosal architecture. Then, we showed that outbred pigs can be used to reproduce some lesions associated with human amebiasis. A detailed analysis was performed using a washed closed-jejunal loops model. In loops inoculated with virulent amebas a severe acute ulcerative jejunitis was observed with large hemorrhagic lesions 14 days post-inoculation associated with the presence of the trophozoites in the depth of the mucosa in two out four animals. Furthermore, typical large sized hepatic abscesses were observed in the liver of one animal 7 days post-injection in the portal vein and the liver parenchyma. CONCLUSIONS: The pig model could help with simultaneously studying intestinal and extraintestinal lesion development

Helminth and Intestinal Protozoa Infections, Multiparasitism and Risk Factors in Champasack Province, Lao People's Democratic Republic

Multiparsitism is a general public health concern in tropical countries, and is of particular importance in the Mekong River basin of Southeast Asia. Here, we report results obtained from an in-depth study of hepato-biliary and intestinal multiparasitism and associated risk factors in three settings of the most southern province of Lao People's Democratic Republic. Multiple species intestinal parasite infections were very common: more than 80% of the study participants harbored at least two and up to seven different intestinal parasites concurrently. Of particular concerns are the high prevalence of the liver fluke Opisthorchis viverrini (64.1%) and the moderate prevalence of the blood fluke Schistosoma mekongi (24.2%), as these fluke infections are responsible for severe hepato-biliary morbidity, including the bile duct cancer cholangiocarcinoma. Hookworm was the most common nematode infection (76.8%). We conclude that given the very high prevalence rates of parasite infections and the extent of multiparasitism, regular deworming is warranted and that this intervention should be coupled with health education and improved assess to clean water and adequate sanitation to consolidate morbidity control and ensure long-term sustainability

Change of isoenzyme pattern during long-term polyxenic cultivation of

Isoenzymes of phosphoglucomutase and hexokinase were repeatedly evaluated using starch gel electrophoresis in polyxenic cultures of Entamoeba histolytica. In two out of 18 strains spontaneous changes of isoenzyme patterns were recorded. While originally they were categorized into virulent group of zymodemes, following isoenzyme analysis classified them as non-virulent. The relation between virulence and isoenzyme pattern is questionable

Larval stages of medically important flukes (Trematoda) from Vientiane province, Laos.

Metacercariae of five small flukes transmitted to humans, Opistorchis viverrini (family Opisthorchiidae), Centrocestus formosanus, Haplorchis pumilio, H. taichui and Stellantchasmus falcatus (family Heterophyidae), were found in fish from Laos. All metacercariae, recorded from Laos for the first time, are described in detail and figured with special attention to the armature of ventrogenital complex of heterophyid larvae. Fish Hampala macrolepitoda and Cyclo-cheilichthys repasson represent new second intermediate hosts for O. viverrini; Esomus longimana for C. formosanus; H. macrolepidota and E. longimana for H. pumilio, H. macrolepidota, H. dispar and Mystacoleucus marginatus for H. taichui, and Xenentodon concila for S. falcatus