Demand for Taenia solium Cysticercosis Vaccine: Lessons and Insights From the Pig Production and Trading Nodes of the Uganda Pig Value Chain.

Taenia solium cysticercosis disease remains a key challenge to the pig sector in low- and middle-income countries in sub-Saharan Africa, Latin America and South East Asia, resulting in both economic losses and public health impacts. The World Health Organization has ranked it first on the global scale of foodborne parasites. A One Health approach has been recommended for reduction of infection pressure and eradication in the longer term. A new vaccine TSOL18 (Cysvax™), applied in combination with oxfendazole (Paranthic 10%™), a dewormer drug has been developed and field tested for the control of T. solium cysticercosis, with high potential to break the disease cycle. It is however unclear whether the products can be marketed through a market driven approach, and if smallholder pig farmers would be willing to take up and pay for the vaccine-oxfendazole combination. A choice experiment methodology was used to assess the potential demand and willingness to pay for the vaccine-oxfendazole combination by Ugandan smallholder pig farmers, and demand for vaccinated pigs by pig traders. The results showed that farmers highly valued quality assurance attributes and were not keen on the vaccine if there were no associated returns in the form of premium price for vaccinated pigs during sales. They were willing to pay US$ 2.31 for the vaccine if it resulted in a premium price for vaccinated pigs. Furthermore, they preferred an accompanying vaccine viability detector as part of its quality assurance. The pig traders on the other hand preferred high carcass weight of pigs, potentially achieved by using oxfendazole. The results show that unless the pig market systems pay a premium price for vaccinated pigs, and quality assurance systems guarantee quality vaccine, uptake of the TSOL18 vaccine and oxfendazole by farmers through market mechanisms may be unsuccessful. The current pig marketing system does not reward food safety, the focus is mainly on carcass weight. Alternative delivery mechanisms for the vaccine through a mix of private-public investments needs to be explored, as the benefits of vaccinated pigs are societal and include reduction and elimination of neurocysticercosis in the long run.

Coexistence of Antiphospholipid Syndrome and Heparin-Induced Thrombocytopenia in a Patient with Recurrent Venous Thromboembolism.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction in which heparin forms complexes with platelet factor 4 forming neoantigens that are recognized by autoantibodies. Antiphospholipid syndrome (APS) is similar to HIT in that it is mediated by autoantibodies that are also prothrombotic. We present a case of rare coexistence of antiphospholipid antibody syndrome and heparin-induced thrombocytopenia.

An extremely indolent T-cell leukemia: an 18-year follow-up.

T-cell prolymphocytic leukemia (T-PLL) is a rare malignancy that comprises about 2% of all mature lymphoid neoplasms. Patients usually present with prominent peripheral blood lymphocytosis, splenomegaly, hepatomegaly, lymphadenopathy, B symptoms, and occasionally with skin lesions.¹ The disease follows an aggressive clinical course with rapid progression and typically has a median survival of less than 1 year. In some cases, the disease is indolent for a period of time before becoming aggressive.² In 2002, 7 years after initial diagnosis in 1995, the case discussed herein was reported as a rare, indolent form of T-PLL.³ We now present 11 additional years of follow-up of this case, during which time the patient remained asymptomatic with respect to his lymphoid neoplasm.

Reflex anuria: a rare cause of acute kidney injury.

BACKGROUND: Acute Kidney Injury results from pre renal, post renal or intrinsic renal causes. Reflex anuria is a very rare cause of renal impairment which happens due to irritation or trauma to one kidney or ureter, or severely painful stimuli to other nearby organs. CASE PRESENTATION: Here we present a case of acute kidney injury secondary to reflex anuria in a patient who underwent extensive gynecological surgery along with ureteral manipulation which recovered spontaneously. CONCLUSION: Reflex Anuria is a rare and often not considered as cause of acute kidney injury. This case illustrates that this should be kept as a differential in potential cause of acute kidney injury in patient undergoing urogenital or gynecological surgeries.

Early infection during burn-induced inflammatory response results in increased mortality and p38-mediated neutrophil dysfunction.

Following burn injury, the host is susceptible to bacterial infections normally cleared by healthy patients. We hypothesized that during the systemic immune response that follows scald injury, the host's altered immune status increases infection susceptibility. Using a murine model of scald injury under inhaled anesthesia followed by intraperitoneal infection, we observed increased neutrophil numbers and function at postburn day (PBD) 1 compared with sham-burned and PBD4 mice. Further, increased mortality, bacteremia, and serum IL-6 were observed in PBD1 mice after Pseudomonas aeruginosa (PA) infection compared with sham-burned and PBD4 mice infected with PA. To examine these disparate responses, we investigated neutrophils isolated at 5 and 24 h following PA infection from PBD1 and sham-burned mice. Five hours after infection, there was no significant difference in number of recruited neutrophils; however, neutrophils from injured mice had decreased activation, active-p38, and oxidative burst compared with sham-burned mice. In direct contrast, 24 h after infection, we observed increased numbers, active-p38, and oxidative burst of neutrophils from PBD1 mice. Finally, we demonstrated that in neutrophils isolated from PBD1 mice, the observed increase in oxidative burst was p38 dependent. Altogether, neutrophil activation and function from thermally injured mice are initially delayed and later exacerbated by a p38-dependent mechanism. This mechanism is likely key to the observed increase in bacterial load and mortality of PBD1 mice infected with PA.

T cells are potent early mediators of the host response to sepsis.

The complex immune response associated with sepsis results in a high rate of morbidity and mortality, despite substantial basic science and clinical advances. Most of the research has centered on the innate immune response, in contrast to the adaptive immune system. This is likely caused by the perceived time frame during which these two responses are understood to mediate their effects. Interestingly, a large degree of lymphocyte apoptosis occurs within the first 24 h of septic insult, suggesting an earlier role for the adaptive response. As we outline, recent studies have shown that reducing T-cell apoptosis dramatically improves survival and bacterial clearance, likely through at least two mechanisms. First, the prevention of lymphocyte apoptosis can limit macrophage phagocytosis of dead T cells and the subsequent production of interleukin 10 and transforming growth factor-ß. Second, T lymphocytes can generate interferon-γ and interleukin 17 within the first 24 h that can enhance the early innate immune function sufficient to blunt bacterial infection. However, these and other potent cytokines may have divergent effects that depend upon the severity of sepsis. In more severe sepsis models, activated T cells can increase sepsis morbidity and tissue injury. Conversely, in less severe models, functional T cells decrease mortality and bacterial load. Altogether, the mechanisms underlying protective versus pathological T-cell responses in sepsis remain to be elucidated. As the complex interplay between T cells and innate immune cells is elucidated, novel treatment and therapeutic strategies may be designed that allow for better outcomes in the management of sepsis.

Divergent adaptive and innate immunological responses are observed in humans following blunt trauma.

BACKGROUND: The immune response to trauma has traditionally been modeled to consist of the systemic inflammatory response syndrome (SIRS) followed by the compensatory anti-inflammatory response syndrome (CARS). We investigated these responses in a homogenous cohort of male, severe blunt trauma patients admitted to a University Hospital surgical intensive care unit (SICU). After obtaining consent, peripheral blood was drawn up to 96 hours following injury. The enumeration and functionality of both myeloid and lymphocyte cell populations were determined. RESULTS: Neutrophil numbers were observed to be elevated in trauma patients as compared to healthy controls. Further, neutrophils isolated from trauma patients had increased raft formation and phospho-Akt. Consistent with this, the neutrophils had increased oxidative burst compared to healthy controls. In direct contrast, blood from trauma patients contained decreased naïve T cell numbers. Upon activation with a T cell specific mitogen, trauma patient T cells produced less IFN-gamma as compared to those from healthy controls. Consistent with these results, upon activation, trauma patient T cells were observed to have decreased T cell receptor mediated signaling. CONCLUSIONS: These results suggest that following trauma, there are concurrent and divergent immunological responses. These consist of a hyper-inflammatory response by the innate arm of the immune system concurrent with a hypo-inflammatory response by the adaptive arm.

Differential immunological phenotypes are exhibited after scald and flame burns.

A dysfunctional immune system is known to be part of the pathophysiology after burn trauma. However, reports that support this have used a variety of methods, with numerous variables, to induce thermal injury. We hypothesized that, all other parameters being equal, an injury infliction by a scald would yield different immunological responses than one inflicted by a flame. Here, we demonstrated that both burn methods produced a full-thickness burn, yet there was more of an increase in subdermal temperature, hematocrit, mortality, and serum IL-6 concentrations associated with the scald burn. On postinjury day 1, the scald-burned mice showed diminished lymphocyte numbers, interferon gamma production, and lymphocyte T-bet expression as compared with sham- and flame-burned mice. On postburn day 8, spleens from both sets of thermally injured animals showed an increase in proinflammatory myeloid cells as compared with sham-burned mice. Furthermore, the T-cell numbers, T-bet expression, and phenotype were changed such that interferon gamma production was higher in scald-burned mice than in sham- and flame-burned mice. Altogether, the data show that differential immunological phenotypes were observed depending on the thermal injury method used.