Spillover, hybridization, and persistence in schistosome transmission dynamics at the human-animal interface.

Zoonotic spillover and hybridization of parasites are major emerging public and veterinary health concerns at the interface of infectious disease biology, evolution, and control. Schistosomiasis is a neglected tropical disease of global importance caused by parasites of the Schistosoma genus, and the Schistosoma spp. system within Africa represents a key example of a system where spillover of animal parasites into human populations has enabled formation of hybrids. Combining model-based approaches and analyses of parasitological, molecular, and epidemiological data from northern Senegal, a region with a high prevalence of schistosome hybrids, we aimed to unravel the transmission dynamics of this complex multihost, multiparasite system. Using Bayesian methods and by estimating the basic reproduction number (R0 ), we evaluate the frequency of zoonotic spillover of Schistosoma bovis from livestock and the potential for onward transmission of hybrid S. bovis × S. haematobium offspring within human populations. We estimate R0 of hybrid schistosomes to be greater than the critical threshold of one (1.76; 95% CI 1.59 to 1.99), demonstrating the potential for hybridization to facilitate spread and establishment of schistosomiasis beyond its original geographical boundaries. We estimate R0 for S. bovis to be greater than one in cattle (1.43; 95% CI 1.24 to 1.85) but not in other ruminants, confirming cattle as the primary zoonotic reservoir. Through longitudinal simulations, we also show that where S. bovis and S. haematobium are coendemic (in livestock and humans respectively), the relative importance of zoonotic transmission is predicted to increase as the disease in humans nears elimination.

Hybridized Zoonotic Schistosoma Infections Result in Hybridized Morbidity Profiles: A Clinical Morbidity Study amongst Co-Infected Human Populations of Senegal.

Hybridization of infectious agents is a major emerging public and veterinary health concern at the interface of evolution, epidemiology, and control. Whilst evidence of the extent of hybridization amongst parasites is increasing, their impact on morbidity remains largely unknown. This may be predicted to be particularly pertinent where parasites of animals with contrasting pathogenicity viably hybridize with human parasites. Recent research has revealed that viable zoonotic hybrids between human urogenital Schistosoma haematobium with intestinal Schistosoma species of livestock, notably Schistosoma bovis, can be highly prevalent across Africa and beyond. Examining human populations in Senegal, we found increased hepatic but decreased urogenital morbidity, and reduced improvement following treatment with praziquantel, in those infected with zoonotic hybrids compared to non-hybrids. Our results have implications for effective monitoring and evaluation of control programmes, and demonstrate for the first time the potential impact of parasite hybridizations on host morbidity.

Prevalence and distribution of schistosomiasis in human, livestock, and snail populations in northern Senegal: a One Health epidemiological study of a multi-host system.

BACKGROUND: Schistosomiasis is a neglected tropical disease of global medical and veterinary importance. As efforts to eliminate schistosomiasis as a public health problem and interrupt transmission gather momentum, the potential zoonotic risk posed by livestock Schistosoma species via viable hybridisation in sub-Saharan Africa have been largely overlooked. We aimed to investigate the prevalence, distribution, and multi-host, multiparasite transmission cycle of Haematobium group schistosomiasis in Senegal, West Africa. METHODS: In this epidemiological study, we carried out systematic surveys in definitive hosts (humans, cattle, sheep, and goats) and snail intermediate hosts, in 2016-18, in two areas of Northern Senegal: Richard Toll and Lac de Guiers, where transmission is perennial; and Barkedji and Linguère, where transmission is seasonal. The occurrence and distribution of Schistosoma species and hybrids were assessed by molecular analyses of parasitological specimens obtained from the different hosts. Children in the study villages aged 5-17 years and enrolled in school were selected from school registers. Adults (aged 18-78 years) were self-selecting volunteers. Livestock from the study villages in both areas were also randomly sampled, as were post-mortem samples from local abattoirs. Additionally, five malacological surveys of snail intermediate hosts were carried out at each site in open water sources used by the communities and their animals. FINDINGS: In May to August, 2016, we surveyed 375 children and 20 adults from Richard Toll and Lac de Guiers, and 201 children and 107 adults from Barkedji and Linguère; in October, 2017, to January, 2018, we surveyed 386 children and 88 adults from Richard Toll and Lac de Guiers, and 323 children and 85 adults from Barkedji and Linguère. In Richard Toll and Lac de Guiers the prevalence of urogenital schistosomiasis in children was estimated to be 87% (95% CI 80-95) in 2016 and 88% (82-95) in 2017-18. An estimated 63% (in 2016) and 72% (in 2017-18) of infected children were shedding Schistosoma haematobium-Schistosoma bovis hybrids. In adults in Richard Toll and Lac de Guiers, the prevalence of urogenital schistosomiasis was estimated to be 79% (52-97) in 2016 and 41% (30-54) in 2017-18, with 88% of infected samples containing S haematobium-S bovis hybrids. In Barkedji and Linguère the prevalence of urogenital schistosomiasis in children was estimated to be 30% (23-38) in 2016 and 42% (35-49) in 2017-18, with the proportion of infected children found to be shedding S haematobium-S bovis hybrid miracidia much lower than in Richard Toll and Lac de Guiers (11% in 2016 and 9% in 2017-18). In adults in Barkedji and Linguère, the prevalence of urogenital schistosomiasis was estimated to be 26% (17-36) in 2016 and 47% (34-60) in 2017-18, with 10% of infected samples containing S haematobium-S bovis hybrids. The prevalence of S bovis in the sympatric cattle population of Richard Toll and the Lac de Guiers was 92% (80-99), with S bovis also found in sheep (estimated prevalence 14% [5-31]) and goats (15% [5-33]). In Barkedji and Linguère the main schistosome species in livestock was Schistosoma curassoni, with an estimated prevalence of 73% (48-93) in sheep, 84% (61-98) in goats and 8% (2-24) in cattle. S haematobium-S bovis hybrids were not found in livestock. In Richard Toll and Lac de Guiers 35% of infected Bulinus spp snail intermediate hosts were found to be shedding S haematobium-S bovis hybrids (68% shedding S haematobium; 17% shedding S bovis); however, no snails were found to be shedding S haematobium hybrids in Barkedji and Linguère (29% shedding S haematobium; 71% shedding S curassoni). INTERPRETATION: Our findings suggest that hybrids originate in humans via zoonotic spillover from livestock populations, where schistosomiasis is co-endemic. Introgressive hybridisation, evolving host ranges, and wider ecosystem contexts could affect the transmission dynamics of schistosomiasis and other pathogens, demonstrating the need to consider control measures within a One Health framework. FUNDING: Zoonoses and Emerging Livestock Systems programme (UK Biotechnology and Biological Sciences Research Council, UK Department for International Development, UK Economic and Social Research Council, UK Medical Research Council, UK Natural Environment Research Council, and UK Defence Science and Technology Laboratory).

Multihost Transmission of Schistosoma mansoni in Senegal, 2015-2018.

In West Africa, Schistosoma spp. are capable of infecting multiple definitive hosts, a lifecycle feature that may complicate schistosomiasis control. We characterized the evolutionary relationships among multiple Schistosoma mansoni isolates collected from snails (intermediate hosts), humans (definitive hosts), and rodents (definitive hosts) in Senegal. On a local scale, diagnosis of S. mansoni infection ranged 3.8%-44.8% in school-aged children, 1.7%-52.6% in Mastomys huberti mice, and 1.8%-7.1% in Biomphalaria pfeifferi snails. Our phylogenetic framework confirmed the presence of multiple S. mansoni lineages that could infect both humans and rodents; divergence times of these lineages varied (0.13-0.02 million years ago). We propose that extensive movement of persons across West Africa might have contributed to the establishment of these various multihost S. mansoni clades. High S. mansoni prevalence in rodents at transmission sites frequented by humans further highlights the implications that alternative hosts could have on future public health interventions.

Delayed diagnosis of vascular injuries during lumbar discectomy.

We report an accidental perforation of the left iliac artery and vein during lumbar discectomy in the kneeling position. During the surgical procedure, a brief and transient hypotension occurred, although the surgeon did not observe any abnormal bleeding in the operating field. In the recovery room, arterial blood pressure decreased, and tachycardia, pallor, and abdominal pain occurred. Retroperitoneal bleeding was suspected. Immediate fluid resuscitation was initiated, anesthesia was continued, and red blood cells were ordered. The use of medical antishock trousers enabled temporization until vascular surgeons were ready. An emergent laparotomy was performed to repair vascular injuries. The delayed symptoms, use of medical antishock trousers, and implications for anesthetists are discussed.

Bile and blood ratios of cyclosporin and its metabolites in patients on continuous infusion during the first three weeks after liver transplantation.

Ten patients with orthotopic liver transplants were investigated during routine therapeutic monitoring to study the relationship between the concentrations of cyclosporin and its metabolites in blood, bile and urine, and whether this information can provide early signs of severe hepatic disorders post-transplantation. Cyclosporin (Sandimmun®) was administered by continuous infusion at a constant rate of 5 mg/kg/day, modified to keep the blood cyclosporin concentration within the target range (400 to 500 µg/L). The concentrations of cyclosporin and combined cyclosporin-metabolites in blood, bile and urine were assayed daily during the 3 post-transplantation weeks that the patients spent in intensive care.All patients developed cholestatis and cytolysis during the first week. The severity of these liver transplant disorders increased in 5 patients and decreased in the other 5 in the second week. The pharmacokinetics of cyclosporin differed in the 2 groups: in patients without severe hepatic disorders, the blood metabolites/cyclosporin ratio (M/C) stabilised at 1.2 ± 0.4 in week 2 and at 0.8 ± 0.2 in week 3, bile cyclosporin/blood cyclosporin (bile C/blood C) fluctuated around 13.5 (13.5 ± 9.5 in week 2 and 13.5 ± 9.0 in week 3) and the bile metabolite/blood metabolite (bile M/blood M) ratio was very high and variable (131 ± 86 in week 2 and 159 ± 116 in week 3). Metabolites significantly accumulated in the blood of patients with severe hepatic disorders (M/C = 2.8 ± 0.6 in week 2 and 3.5 ± 1.0 in week 3); bile C/blood C (2.6 ± 2.1 in week 2 and 3.4 ± 1.1 in week 3) and bile M/blood M (11.9 ± 7.8 in week 2 and 12.5 ± 7.9 in week 3) significantly decreased and showed less interindividual variability.Blood cyclosporin is usually monitored to help optimise the dosage. However, if this was extended to include the monitoring of metabolites in the blood, and cyclosporin and metabolites in the bile, it could provide an early indication of severe hepatic disorders in patients with transplanted livers.

Intrapleural bupivacaine analgesia after thoraco-abdominal incision for oesophagectomy.

Intrapleural bupivacaine administration is said to produce good analgesia for the pain induced by a subcostal incision. However, reports of its efficacy after thoracotomy are conflicting. The goal of this study was to compare the analgesia produced by intrapleural administration of bupivacaine after oesophagectomy using a thoraco-abdominal incision with that obtained from intrapleural saline. After informed consent and institutional approval were obtained, 20 patients were randomly assigned to two groups of 10 patients each. Subjects received intrapleurally 10 ml of either 0.25% bupivacaine with 1:200,000 adrenaline or normal saline, every 8 h, beginning on the first post-operative day and lasting for 4 days. Pain was evaluated using a visual-analogue scale 2 h after the first daily treatment at rest and during physiotherapy. Pain scores were significantly lower in the bupivacaine group than in the saline group. Additionally, PaO2 was significantly higher in the bupivacaine group than in the saline group on Day 1 (P less than 0.05). The plasma bupivacaine concentration never reached the level of toxicity. Plasma bupivacaine concentrations on Day 1 after the first intrapleural bupivacaine injection were less than 350 ng ml-1; on Day 4 after the last injection they were less than 1300 ng ml-1. In conclusion, intrapleural administration of bupivacaine produces effective analgesia after oesophagectomy performed with a thoracoabdominal incision. The technique is easy to perform and is safe.

[Multiple-organ procurement for transplantation]. / Les prélèvements multiples d'organes en vue de transplantation.

In the last few years, the tremendous growth of clinical transplantations has greatly increased the need for grafts. Combined heart, liver and kidney harvesting in a same donor could provide an answer. The results are presented of multiple organ retrieval (MOR) carried out in an University hospital located in an area with 1,350,000 inhabitants. In addition to the usual problems of donor maintenance and legal aspects, it was necessary to carry out a specific work-up for each organ to be harvested. The job of the local coordinator was extremely important in the search for potential recipients and the organization of the procedure (time-table, air transport) in order to give optimal conditions. The priority given to retrieving the heart and in situ cooling of the liver and kidneys guaranteed the good quality of the harvested organs. Over a period of three years, 28 MOR have been carried out. Of the 94 organs harvested, 88 were transplanted in France or another European country (49 kidneys, 23 hearts, 16 livers); 75 are still functioning (47 kidneys, 19 hearts, 9 livers). As a result of this experience, and taking into account the need for organs, all brain dead patients should be considered as potential multiple organ donors, and not just as kidney donors. The intervention of several teams, often quite distant from the site of retrieval, requires careful planning. The surgical procedure, even when performed by a trained team, is often complex, perfect synchronization of the surgical steps of the operation being the most important point.(ABSTRACT TRUNCATED AT 250 WORDS)