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GE Portuguese Journal of... Jun 2024
PubMed: 38757063
DOI: 10.1159/000534801 -
The Lancet. Global Health Jul 2024Nodding syndrome is a poorly understood neurological disorder that predominantly occurs in Africa. We hypothesised that nodding syndrome is a neuroinflammatory disorder,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Nodding syndrome is a poorly understood neurological disorder that predominantly occurs in Africa. We hypothesised that nodding syndrome is a neuroinflammatory disorder, induced by antibodies to Onchocerca volvulus or its Wolbachia symbiont, cross-reacting with host neuronal proteins (HNPs), and that doxycycline can be used as treatment.
METHODS
In this randomised, double-blind, placebo-controlled, phase 2 trial, we recruited participants from districts affected by nodding syndrome in northern Uganda. We included children and adolescents aged 8-18 years with nodding syndrome, as defined by WHO consensus criteria. Participants were randomly assigned (1:1) to receive either 100 mg doxycycline daily or placebo for 6 weeks via a computer-generated schedule stratified by skin microscopy results, and all parties were masked to group assignment. Diagnoses of O volvulus and antibodies to HNPs were made using luciferase immunoprecipitation system assays and immunohistochemistry. The primary outcome was change in the proportion with antibodies to HNPs, assessed at 24 months. All participants were included in safety analyses, and surviving participants (those with samples at 24 months) were included in primary analyses. Secondary outcomes were: change in concentrations of antibodies to HNPs at 24 months compared with baseline; proportion of participants testing positive for antibodies to O volvulus-specific proteins and concentrations of Ov16 or OVOC3261 antibodies at 24 months compared with baseline; change in seizure burden, proportion achieving seizure freedom, and the proportions with interictal epileptiform discharges on the diagnostic EEG; overall quality of life; disease severity at 24 months; and incidence of all-cause adverse events, serious adverse events, and seizure-related mortality by 24 months. This trial is registered with ClinicalTrials.gov, NCT02850913.
FINDINGS
Between Sept 1, 2016, and Aug 31, 2018, 329 children and adolescents were screened, of whom 240 were included in the study. 140 (58%) participants were boys and 100 (42%) were girls. 120 (50%) participants were allocated to receive doxycycline and 120 (50%) to receive placebo. At recruitment, the median duration of symptoms was 9 years (IQR 6-10); 232 (97%) participants had O volvulus-specific antibodies and 157 (65%) had autoantibodies to HNPs. The most common plasma autoantibodies were to human protein deglycase DJ-1 (85 [35%] participants) and leiomodin-1 (77 [32%] participants) and, in cerebrospinal fluid (CSF), to human DJ-1 (27 [11%] participants) and leiomodin-1 (14 [6%] participants). On immunohistochemistry, 46 (19%) participants had CSF autoantibodies to HNPs, including leiomodin-1 (26 [11%]), γ-aminobutyric acid B receptors (two [<1%]), CASPR2 (one [<1%]), or unknown targets (28 [12%]). At 24 months, 161 (72%) of 225 participants had antibodies to HNPs compared with 157 (65%) of 240 at baseline. 6 weeks of doxycycline did not affect the concentration of autoantibodies to HNPs, seizure control, disease severity, or quality of life at the 24-month follow-up but substantially decreased Ov16 antibody concentrations; the median plasma signal-to-noise Ov16 ratio was 16·4 (95% CI 6·4-38·4), compared with 27·9 (8·2-65·8; p=0·033) for placebo. 14 (6%) participants died and, other than one traffic death, all deaths were seizure-related. Acute seizure-related hospitalisations (rate ratio [RR] 0·43 [95% CI 0·20-0·94], p=0·028) and deaths (RR 0·46 [0·24-0·89], p=0·028) were significantly lower in the doxycycline group. At 24 months, 96 (84%) of 114 participants who received doxycycline tested positive for antibodies to Ov16, compared with 97 (87%) of 111 on placebo (p=0·50), and 74 (65%) participants on doxycycline tested positive for antibodies to OVOC3261, compared with 57 (51%) on placebo (p=0·039). Doxycycline was safe; there was no difference in the incidence of grade 3-5 adverse events across the two groups.
INTERPRETATION
Nodding syndrome is strongly associated with O volvulus and the pathogenesis is probably mediated through an O volvulus induced autoantibody response to multiple proteins. Although it did not reverse disease symptoms, doxycycline or another prophylactic antibiotic could be considered as adjunct therapy to antiseizure medication, as it might reduce fatal complications from acute seizures and status epilepticus induced by febrile infections.
FUNDING
Medical Research Council (UK).
TRANSLATION
For the Luo translation of the abstract see Supplementary Materials section.
Topics: Humans; Child; Adolescent; Female; Male; Doxycycline; Nodding Syndrome; Double-Blind Method; Uganda; Treatment Outcome; Anti-Bacterial Agents; Onchocerca volvulus
PubMed: 38754459
DOI: 10.1016/S2214-109X(24)00102-5 -
Cureus Apr 2024We are reporting a case of gastric volvulus in a 52-year-old man in the setting of a paraesophageal hernia initially identified on computerized tomography (CT). CT of...
We are reporting a case of gastric volvulus in a 52-year-old man in the setting of a paraesophageal hernia initially identified on computerized tomography (CT). CT of the abdomen showed a large paraesophageal hernia with intra-thoracic herniation of the distal stomach and gastroduodenal junction, resulting in mesenteroaxial rotation consistent with acute gastric volvulus. Esophagogastroduodenoscopy (EGD) confirmed the presence of the gastric volvulus, which was initially temporized with endoscopic detorsion. He subsequently had nasogastric tube placement and ultimately underwent a laparoscopic gastropexy. He recovered uneventfully with plans for Roux-en-Y gastric bypass surgery.
PubMed: 38741858
DOI: 10.7759/cureus.58198 -
Parasites & Vectors May 2024The main vectors of onchocerciasis in Africa are Simulium damnosum sensu lato, which transmit the causative agent Onchocerca volvulus. The force of transmission is...
BACKGROUND
The main vectors of onchocerciasis in Africa are Simulium damnosum sensu lato, which transmit the causative agent Onchocerca volvulus. The force of transmission is driven by the vector density, hence influencing the disease prevalence and intensity. Onchocerciasis is currently targeted for elimination using mass drug administration (MDA) of ivermectin, a potent microfilaricide. MDA in Cameroon began in 1987 in the Vina Valley, an endemic cross-border area with Chad, known for high vector densities and precontrol endemicity. Evaluations in 2008-2010 in this area showed ongoing transmission, while border areas in Chad were close to interrupting transmission. This study aimed to evaluate transmission in this area after several rounds of MDA since the last evaluation surveys.
METHODS
Black flies were collected by human landing catches at seven border sites in Cameroon, twice a week, from August 2021 to March 2022. A fraction of the flies was dissected for parity assessment and identification of Onchocerca larval stages. The transmission indices were estimated. Black fly larvae were also collected from the breeding sites at the fly catching sites and identified to species level by cytotaxonomy.
RESULTS
A total of 14,303 female flies were collected, and 6918 were dissected. Of these, 4421 (64.0%) were parous. The total biting rates were high, reaching up to 16,407 bites/person/study period, and transmission potential (third-stage larvae (L3) from head/all L3) were 367/702, 146/506, 51/55, 20/32, 0/3, 0/0, and 0/0 infective larvae/person, respectively, for Mbere-Tchad, Babidan, Hajam/V5, Gor, Djeing, Touboro, and Koinderi. Infectivity rates (L3 from head) were 16.00, 12.75, 5.15, and 4.07 infective females (L3H)/1000 parous flies for Haijam, Mbere-Tchad, Babidan, and Gor, respectively. These values exceed the World Health Organization (WHO) thresholds of ≤ 20 annual transmission potential (ATP) or < 1 infective female/1000 parous females. The major vectors identified were Simulium damnosum sensu stricto, S. squamosum, and for the first time in the area, S. yahense.
CONCLUSIONS
More than 20 years of MDA has not eliminated onchocerciasis in the study area; hence, this area is a potential source of reintroduction of onchocerciasis in Chad and would require alternative treatment strategies. Many factors such as MDA efficiency, effectiveness of ivermectin, and cytospecies composition may be contributing to transmission persistence.
Topics: Onchocerciasis; Animals; Cameroon; Ivermectin; Simuliidae; Humans; Onchocerca volvulus; Insect Vectors; Female; Mass Drug Administration; Chad; Larva; Filaricides; Male
PubMed: 38741212
DOI: 10.1186/s13071-024-06284-8 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... May 2024Magnet ingestion in children can lead to serious complications, both acutely and chronically. This case report discusses the treatment approach for a case involving... (Review)
Review
Magnet ingestion in children can lead to serious complications, both acutely and chronically. This case report discusses the treatment approach for a case involving multiple magnet ingestions, which resulted in a jejuno-colonic fistula, segmental intestinal volvulus, hepa-tosteatosis, and renal calculus detected at a late stage. Additionally, we conducted a literature review to explore the characteristics of intestinal fistulas caused by magnet ingestion. A six-year-old girl was admitted to the Pediatric Gastroenterology Department pre-senting with intermittent abdominal pain, vomiting, and diarrhea persisting for two years. Initial differential diagnoses included celiac disease, cystic fibrosis, inflammatory bowel disease, and tuberculosis, yet the etiology remained elusive. The Pediatric Surgery team was consulted after a jejuno-colonic fistula was suspected based on magnetic resonance imaging findings. The physical examination revealed no signs of acute abdomen but showed mild abdominal distension. Subsequent upper gastrointestinal series and contrast enema graphy confirmed a jejuno-colonic fistula and segmental volvulus. The family later reported that the child had swallowed a magnet two years prior, and medical follow-up had stopped after the spontaneous expulsion of the magnets within one to two weeks. Surgical intervention was necessary to correct the volvulus and repair the large jejuno-colonic fistula. To identify relevant studies, we conducted a detailed literature search on magnet ingestion and gastrointestinal fistulas according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We identified 44 articles encompassing 55 cases where symptoms did not manifest in the acute phase and acute abdomen was not observed. In 29 cases, the time of magnet ingestion was unknown. Among the 26 cases with a known ingestion time, the average duration until fistula detection was 22.8 days (range: 1-90 days). Fistula repairs were performed via laparotomy in 47 cases.
Topics: Humans; Female; Intestinal Fistula; Child; Foreign Bodies; Magnets; Malabsorption Syndromes; Jejunal Diseases; Intestinal Volvulus; Colonic Diseases
PubMed: 38738679
DOI: 10.14744/tjtes.2024.50845 -
Cureus Apr 2024Abdominal volvulus represents a critical condition characterized by the abnormal twisting of the GI tract, potentially leading to obstruction and vascular compromise.... (Review)
Review
Abdominal volvulus represents a critical condition characterized by the abnormal twisting of the GI tract, potentially leading to obstruction and vascular compromise. Prompt recognition and appropriate management are essential to prevent complications and improve patient outcomes. This comprehensive review examines the anatomy, pathophysiology, clinical presentation, and diagnostic evaluation of, and management strategies for abdominal volvulus. Non-operative techniques, including detorsion and decompression, as well as surgical interventions, such as laparoscopic and open approaches, are discussed. Additionally, the importance of multidisciplinary collaboration and postoperative care is emphasized. Despite significant advancements, unresolved issues remain, necessitating further research to refine diagnostic and therapeutic approaches. Future directions, including exploring emerging technologies, offer promise for enhancing the management of this challenging condition. Overall, this review provides clinicians with valuable insights into the optimal management of abdominal volvulus, aiming to improve patient outcomes and enhance clinical practice.
PubMed: 38738029
DOI: 10.7759/cureus.57978 -
Clinical Case Reports May 2024Transverse colonic volvulus (TCV) is a serious condition with a mortality rate of up to 33%. It is very rare, especially in children. Despite its rarity, surgeons should...
Transverse colonic volvulus (TCV) is a serious condition with a mortality rate of up to 33%. It is very rare, especially in children. Despite its rarity, surgeons should have a high index of suspicion and include it in the list of differential diagnoses, especially in patients with developmental delays and associated uncommon syndromes. Resection and anastomosis, whether as a one-stage or two-stage procedure, proved to be the best treatment options for children. Since prompt identification and management are vital, this paper presents useful information on the presentation, treatment, and outcome of this case report.
PubMed: 38736570
DOI: 10.1002/ccr3.8828 -
PLoS Neglected Tropical Diseases May 2024
Topics: Onchocerca volvulus; Humans; Animals; Onchocerciasis; Nodding Syndrome; Epilepsy
PubMed: 38722927
DOI: 10.1371/journal.pntd.0012076 -
Journal of Surgical Case Reports May 2024Meckel's diverticula are one of the most common gastrointestinal anomalies, yet mesodiverticular bands are rare. The treatment of these bands commonly requires surgery....
Meckel's diverticula are one of the most common gastrointestinal anomalies, yet mesodiverticular bands are rare. The treatment of these bands commonly requires surgery. A healthy patient in his 20s presented to the emergency department with a 1 day history of acute onset abdominal pain. Computed tomography imaging was consistent with volvulus of the large intestine. In the operating room, the patient was noted to have a band between the ileal mesentery and tip of a Meckel's diverticulum, consistent with a mesodivertiular band, through which cecum had volvulized. The patient underwent resection. The patient recovered without major complications. Mesodiverticular bands are rare, but may present as hemoperitoneum, small bowel obstruction, or volvulus. Pre-operative diagnosis of a mesodiverticular band is often difficult and they are most commonly diagnosed intraoperatively. Treatment should include surgery and may include simple lysis of the band, bowel resection, or more extensive resection if other pathology is present.
PubMed: 38721257
DOI: 10.1093/jscr/rjae296 -
Cureus Apr 2024Gastric volvulus (GV) is a rare condition characterized by the rotation of all or part of the stomach around its transversal or longitudinal axis. We report the case of...
Gastric volvulus (GV) is a rare condition characterized by the rotation of all or part of the stomach around its transversal or longitudinal axis. We report the case of a 76-year-old woman with the acute form of GV, likely exacerbated by hiatal hernia and age-related ligamentous relaxation, evolving for a week before her admission. She underwent a midline laparotomy with fundoplication at 270° and anterior gastropexy. GV poses life-threatening risks in its acute presentation. Surgical management entails restoring the hemodynamic stability, surgical detorsion of the volvulus, and addressing the etiology (hiatal hernia).
PubMed: 38707140
DOI: 10.7759/cureus.57591