Animal models of neglected parasitic diseases: In vivo multimodal imaging of experimental trypanosomatid infections.

African trypanosomiases and leishmaniases are significant neglected tropical diseases (NTDs) that affect millions globally, with severe health and socio-economic consequences, especially in endemic regions. Understanding the pathogenesis and dissemination of Trypanosoma brucei and Leishmania spp. parasites within their hosts is pivotal for the development of effective interventions. Whole-body bioluminescence and fluorescence imaging systems (BLI and FLI, respectively), are powerful tools to visualize and quantify the progression and distribution of these parasites in real-time within live animal models. By combining this technology with the engineering of stable T. brucei and Leishmania spp. strains expressing luciferase and/or fluorescent proteins, crucial aspects of the infection process including the parasites' homing, the infection dynamics, the tissue tropism, or the efficacy of experimental treatments and vaccines can be deeply investigated. This methodology allows for enhanced sensitivity and resolution, elucidating previously unrecognized infection niches and dynamics. Importantly, whole-body in vivo imaging is non-invasive, enabling for longitudinal studies during the course of an infection in the same animal, thereby aligning with the "3Rs" principle of animal research. Here, we detail a protocol for the generation of dual-reporter T. brucei and L. major, and their use to infect mice and follow the spatiotemporal dynamics of infection by in vivo imaging systems. Additionally, 3D micro-computed tomography (µCT) coupled to BLI in T. brucei-infected animals is applied to gain insights into the anatomical parasite distribution. This Chapter underscores the potential of these bioimaging modalities as indispensable tools in parasitology, paving the way for novel therapeutic strategies and deeper insights into host-parasite interactions.

Hippocampal Atrophy/Sclerosis Is Associated with Old, Calcified Parenchymal Brain Neurocysticercosis, But Not with More Recent, Viable Infections.

Magnetic resonance images from 197 patients with calcified neurocysticercosis (NCC), 38 with viable NCC and 197 NCC-free healthy rural villagers were evaluated to compare the frequency of hippocampal atrophy/sclerosis (HAS) across these populations. Scheltens' medial temporal atrophy scale was used for hippocampal rating. The median age of the 432 study participants was 46 years (interquartile range, 29-62 years), and 58% were women. Hippocampal atrophy/sclerosis was disclosed in 26.9% patients with calcified NCC, compared with 7.9% in patients with viable NCC and 8.1% in healthy rural villagers. After adjusting for age, gender, and history of epilepsy, hippocampal atrophy/sclerosis was more frequent in patients with calcified NCC than in those with viable cysts (RR, 3.60; 95% CI, 1.18- 0.99; P = 0.025) and healthy rural villagers (RR, 3.43; 95% CI, 1.94-6.06; P < 0.001), suggesting that hippocampal damage develops late in the course of this parasitic disease.

Cerebral Coenurosis of a Long-Tailed Goral, Naemorhedus caudatus, in Korea.

We intended to describe a case of cerebral coenurosis in a long-tailed goral, Naemorhedus caudatus, from Hwacheon-gun, Gangwon-do (Province), in the Korea. The goral, a 10-year-old male, was suffering from neurological symptoms, such as turning the circle to one side without lifting the head straight, and died at 30 days after admission to the wildlife medical rescue center in Chuncheon-si, Gangwon-do. A fluid-filled cyst was detected in the left cerebral hemisphere by computed tomography and magnetic resonance imaging. The cyst removed from the deceased goral was transparent, about 3×3 cm in size, contained a clear fluid and approximately 320 protoscolices invaginating from the internal germinal layer. The protoscolex had 4 suckers and a rostellum with 28 hooklets arranged in 2 rows. By the present study, a case of cerebral coenurosis was first confirmed in a long-tailed goral, N. caudatus, from Gangwon-do, in Korea. The residents frequently exposed in the sylvatic environment should be careful the accidental infections of zoonotic metacestode of Taenia multiceps, Coenurus cerebralis, in Korea.

Focal spleen lesions in visceral leishmaniasis, a neglected manifestation of a neglected disease: report of three cases and systematic review of literature.

BACKGROUND: The Mediterranean area is endemic for the zoonotic form of visceral leishmaniasis (VL) caused by Leishmania infantum, a species which has been recently associated with unexpected epidemiological and clinical features. METHOD: We report the result of a systematic review of the literature on VL unusually presenting with spleen focal lesions, including three previously unpublished cases. RESULTS: A total of 28 cases of VL with multiple spleen focal lesions were retrieved. Twenty-six (93%) were acquired in the Mediterranean area, where L. infantum is endemic. Thirteen cases were diagnosed in children, and the remaining 15 cases in middle-aged adults, of whom 9 were immunosuppressed. Four patients (14%) underwent diagnostic splenectomy, while the diagnosis was confirmed by less invasive techniques in the remaining patients. The most common radiological patterns were: multiple subcentimetric or centimetric spleen lesions (size ≤ 1 cm in 14 of 19 cases, 74%), hypoechoic at ultrasonography (25 of 26 cases, 99%) and hypodense at CT scan (9 of 10 cases, 90%). PET-CT (available for four patients) showed an intense FDG spleen uptake. MRI and contrast-enhanced ultrasonography, available for two and one cases each, showed complex patterns. CONCLUSIONS: VL must be added to the list of possible differential diagnosis of spleen focal lesions and health care provider awareness about this condition will avoid unnecessary invasive diagnostic procedures.

Temporomandibular joint MR images: Incidental head and neck findings and pathologies.

OBJECTIVE: To report the number and frequency of incidental findings (IFs) detected during magnetic resonance (MR) imaging screening of the temporomandibular joint (TMJ) and to define related diseases. METHODS: Bilateral TMJ MR images in the sagittal and coronal sections, from 518 patients with TMJ symptoms were evaluated retrospectively. Patients who were diagnosed with IFs were sent for consultation and clarification of the findings. Patient age, gender, IFs, locations, and diseases were classified and noted.  Results: Seventy-eight (15%) patients were diagnosed with 117 IFs. Of them, 43 were diagnosed with a single IF, and 35 were diagnosed with more than one IF. The most frequent locations were paranasal sinuses and mastoid air cells. The most frequent diseases were inflammatory and cystic lesions.  Discussion: While examining TMJ MR images, it is important to check for evidence of IFs or pathologies that may have mimicked signs and symptoms of TMJ disorders.

Could SUVmax be an auxiliary parameter in the clinical management of pulmonary hydatid disease?

OBJECTIVE: The aim of this study was to investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (FDG-PET/CT) in the diagnosis and treatment of pulmonary hydatid disease and also compare the morphological characteristics of the lesions with SUVmax values and identify complicated disease. METHODS: Thirty-six patients with a diagnosis of pulmonary hydatid disease who underwent 18F-FDG PET/CT imaging were included in this retrospective study. The size of the lesions, morphological characteristics, accompanying parenchymal and pleural findings, SUVmax and HUmean values and FDG uptake in mediastinal lymph nodes were noted. The relationship between morphologic properties, SUVmax of the lesions and lymphatic FDG uptake was analysed. RESULTS: A total of 99 lesions of 36 patients were classified as solid (7.1%), cystic (53.5%), semisolid (20.2%) and cavitary (19.2%). Thirty-two of the lesions were encapsulated, 38 of the lesions had border irregularity. Accompanying consolidation was present in 10 cases, bronchial obstruction in 9, pleural thickening in 28 and effusion in 3. There was positive correlation between lesions HUmean and SUVmax values (r = 0.285). SUVmax values were significantly higher in lesions with irregular borders, solid or semisolid type and presence of consolidation, bronchial obstruction and pleural thickening. Also more lymphatic FDG uptake was detected in this group. CONCLUSION: Higher SUVmax values may be a useful parameter in the diagnosis of complicated pulmonary hydatid disease. FDG-PET may provide guidance for determining the priority of lesion for surgery in cases with multiple lesions and may be helpful to evaluate the response to medical treatment.

Rare case of neglected large sacral Chordoma in a young female treated by wide En bloc resection and Sacrectomy.

BACKGROUND: Sacral chordoma is a locally aggressive malignant tumour originating from ectopic notochordal cells. The natural history of sacral chordoma is a slow growing tumour arising at the midline of the lower sacrum that can invade the sacrum and progressively increase in size expanding cranially and anteriorly. Metastasis is very rare even when the tumour is large. Sacral chordoma affects males more than females and is more commonly found in middle age and elderly patients. CASE PRESENTATION: A 25 years old female had neglected an extremely large midline sacral mass for 2 years. On presentation to hospital, she had been bed bound for the past 2 years. The sacral mass was so large that it prevented her from lying down supine and sitting on the wheelchair comfortably. Clinical examination showed a 40 cm × 30 cm × 20 cm hard mass over the sacrum that involved both buttocks and the gluteal fold. Neurological exam of bilateral lower limb was normal. Computed Tomography Scan of the Pelvis showed a large destructive sacrococcygeal mass measuring 43 cm × 38 cm × 27 cm with extension into the presacral space resulting in anterior displacement of the rectum, urinary bladder and uterus; and posterior extension into the dorsal soft tissue with involvement of the gluteus, piriformis, and left erector spinae muscles. Biopsy taken confirmed Chordoma. This patient was managed by a multidisciplinary team in an Oncology referral centre. The patient had undergone Wide En Bloc Resection and Sacrectomy, a complex surgery that was associated with complications namely bleeding, surgical site infection and neurogenic bowel and bladder. Six months post operatively the patient was able to lie supine and sit on wheelchair comfortably. She required extensive rehabilitation to help her ambulate in future. CONCLUSION: This is a rare case of neglected sacral chordoma in a young female treated with Wide En Bloc Resection and Sacrectomy associated with complications of this complex surgery. Nevertheless, surgery is still worthwhile to improve the quality of life and to prevent complications secondary to prolonged immobilization. A multidisciplinary approach is ideal and team members need to be prepared to address the complications once they arise.

Repeated Percutaneous Treatment of Massive Hepatic Cystic Echinococcosis in a Child.

Because of mostly asymptomatic cyst growth and often-neglected nonspecific low-grade symptoms, many cases of cystic echinococcosis (CE) caused by Echinococcus granulosus in the pediatric population are diagnosed at school age, in an advanced and even complicated stage. In 2003, after 5 months of intermittent dull upper-right abdominal pain and nausea, a 13-year-old boy was diagnosed with massive liver CE, with ∼20 round-shaped double-walled medium-sized infective cysts, which permeated the whole liver. Because of their wide distribution across the liver tissue and the risky superficial position of some cysts, liver transplantation emerged as the optimal therapeutic option. Despite being described as only an exceptionally used method for CE, we subjected our patient on 4 occasions to a radiofrequency energy thermoablation (RFT) procedure similar to the one used for malignant neoplasms. In total, 9 superficially situated cysts were initially treated with RFT by using a 14-gauge outer needle and a temperature of 70°C for 8 minutes per cyst, and the remaining cysts were treated with the puncture-aspiration-instillation-reaspiration procedure, along with albendazole (15 mg/kg per day) therapy, for a period of 20 months. After 2 years of follow-up, 4 residual small-sized semisolidified cysts were seen in the liver, and the patient showed no signs of relapse. Although not routinely used, RFT, along with puncture-aspiration-instillation-reaspiration and prolonged albendazole therapy, has shown good tolerability and long-term efficacy in the treatment of multiple infective CE, which could suggest the usefulness of the RFT method beyond salvage situations in pediatric patients.

Primary Spinal Intramedullary Neurocysticercosis: A Report of 3 Cases.

We describe a series of 3 cases of the rare intramedullary form of primary spinal neurocysticercosis. The cases were seen in varied age groups and showed different profiles at presentation. All the cases were thoroughly evaluated clinically and radiologically. Serologic tests were not conducted. In all cases, magnetic resonance imaging showed a large intramedullary lesion in the thoracic spinal cord consisting of a cystic lesion with a well-defined intramural nodule. One case was managed with steroids and cysticidal therapy, a second case was managed with steroids and surgery (2 emergency procedures), while the third case was managed without any medical or surgical intervention, as the patient was unwilling for either. All cases showed good neurologic recovery. In the second case where surgery was done, histologic examination of the resected specimen demonstrated the cysticercal parasite surrounded by mixed inflammatory infiltrate. As there were no intracranial lesions in all 3 cases, the final diagnosis was primary isolated intramedullary neurocysticercosis. Primary isolated intramedullary-neurocysticercosis remains a rare condition afflicting the spinal cord. It forms a small subset of cysticercal infestation of the neuraxis. Such evidence is rare, and only anecdotal reports are available. Our case series captures the wide spectrum of presentations, as well as the management options, and highlights the varied ways in which these cases were managed.

Lessons from a 15-year-old boy with advanced schistosomiasis japonica in China: a case report.

Schistosomiasis is a chronic, parasitic disease caused by flukes (trematodes) of the genus Schistosoma, which presents the most important global burden of the 17 neglected tropical diseases listed by the World Health Organization. China has made great achievements in schistosomiasis control, and now China is planning to move forward, to eliminate schistosomiasis within 2020, but the fact cannot be denied that the possibility of schistosome infection is still there in some endemic due to its zoonotic nature as well as wide distribution of its intermediate hosts (snails). Thus, how to interrupt the transmission in areas with distribution of schistosomes and intermediate snails becomes a very serious challenge that China is facing. In this paper, it is reported an advanced schistosomiasis japonica case of a 15-year-old boy which is extremely rare in the current schistosomiasis control in China. Thus, it is supposed to strengthen health education of school children and to train professional physicians of local hospitals.

Medical Imaging of Neglected Tropical Diseases of the Americas.

Neglected tropical diseases are a group of protozoan, parasitic, bacterial, and viral diseases endemic in 149 countries causing substantial illness globally. Extreme poverty and warm tropical climates are the 2 most potent forces promoting the spread of neglected tropical diseases. These forces are prevalent in Central and South America, as well as the U.S. Gulf Coast. Advanced cases often require specialized medical imaging for diagnosis, disease staging, and follow-up. This article offers a review of epidemiology, pathophysiology, clinical manifestations, diagnosis (with special attention to medical imaging), and treatment of neglected tropical diseases specific to the Americas.

Use of Ultrasound in the Diagnosis and Treatment of Tropical Diseases in Uganda.

This manuscript will present a review of the use of ultrasound to diagnose and treat tropical diseases seen most commonly in Uganda.

Ilizarov techniques with limited adjunctive surgical procedures for the treatment of preadolescent recurrent or neglected clubfeet.

When choosing the Ilizarov technique for the treatment of recurrent or neglected clubfeet deformity, there was a consensus on the treatment of 3-8-year-old children by the soft-tissue distraction 'bloodless method' either alone or with an adjunctive-limited soft tissue release; whereas, in older children, adjunctive osteotomies were required. Major foot osteotomies such as V, U, Y, or supramalleolar types were established for patients after puberty when the foot bones become fully ossified. So, children falling in the age group between 8 and 13 years (preadolescents) represents a transitional growing stage that has its identity that makes carrying out major foot osteotomies unsuitable. Twenty-five feet in 21 patients with a mean age at the time of operation of 10.9 years (range, 9-13 years) with recurrent or neglected clubfeet deformity who presented to the orthopedic department at Alexandria (Egypt) between February 2004 and December 2008 were treated with the Ilizarov technique combined with adjunctive limited bony and/or soft-tissue procedures as will be discussed. After a mean follow-up period of 3.6 years (range, 2-7 years), 21 children showed good results, four children showed fair results, and no poor results were recorded. No major complications were reported. The Ilizarov technique with limited bony and/or soft-tissue procedures can be considered as a suitable, convenient, efficient, and successful salvage procedure for preadolescent recurrent or neglected clubfeet.

The taylor spatial frame™ for correction of neglected fracture dislocation of the ankle.

Treatment of neglected fracture dislocations of the ankle poses a surgical challenge. Extensive open reduction can frequently be contraindicated because of local skin conditions and contractures. The Taylor Spatial Frame™ (TSF) has been used to reduce and maintain reduction of complex fractures. Its use in fracture dislocation of the ankle joint has not been described. We describe a case where a TSF was used to reduce and treat a 6-week-old fracture dislocation of the ankle. The TSF is a versatile device, which has a role in the management of both acute and neglected fractures.

Neglected femoral neck fractures in adults.

PURPOSE: To assess treatment outcomes in adults with neglected femoral neck fractures, and propose a treatment protocol based on bone quality measured by the Singh index. METHODS: 16 men and 6 women aged 18 to 48 (mean, 33) years presented with neglected (>3 weeks old) femoral neck fractures. Those with good bone quality (Singh index, >3) underwent closed reduction and valgus osteotomy and fixation with 120º double angle blade plates (group 1, n=8), whereas those with poor bone quality (Singh index, >3) and/or communition of the posterior femoral neck underwent fibular grafting and internal fixation with one or two 7-mm cannulated cancellous screws (group 2, n=14). Functional outcome was assessed at the 6-month follow-up, according to modified Askin and Bryan criteria. RESULTS: The mean delay in surgery was 12 (range, 4-21) weeks. Patients were followed up for a mean of 19 (range, 12-24) months. The mean time to union was 20 (range, 12-52) weeks. The mean time to full weight bearing was 18 (range, 12-40) weeks. All patients achieved bone union except one in group 1 who had non-union and breakage of the blade plate at week 20 and underwent total hip arthroplasty. Other complications included slippage of fibular graft (n=1), delayed union (n=1), avascular necrosis of the femoral head (n=2), limb length discrepancy (n=3), and superficial infection (n=1). Functional outcome was excellent in 2 patients, good in 17, and poor in 3. CONCLUSION: Valgus osteotomy and double angle blade plate fixation, and fibular grafting and cancellous screw fixation appeared to be appropriate treatments for neglected femoral neck fractures in adults.