Antibody-Secreting Cell Responses after Vibrio cholerae O1 Infection and Oral Cholera Vaccination in Adults in Bangladesh

Infection with Vibrio cholerae and oral cholera vaccines (OCVs) induce transient circulating plasmablast responses that peak within approximately 7 days after infection or vaccination. We previously demonstrated that plasmablast responses strongly correlate with subsequent levels of V. cholerae-specific duodenal antibodies up to 6 months after V. cholerae infection. Hence, plasmablast responses provide an early window into the immunologic memory at the mucosal surface. In this study, we characterized plasmablast responses following V. cholerae infection using a flow cytometrically defined population and compared V. cholerae-specific responses in adult patients with V. cholerae O1 infection and vaccinees who received the OCV Dukoral (Crucell Vaccines Canada). Among flow cytometrically sorted populations of gut-homing plasmablasts, almost 50% of the cells recognized either cholera toxin B subunit (CtxB) or V. cholerae O1 lipopolysaccharide (LPS). Using a traditional enzyme-linked immunosorbent spot assay (ELISPOT), we found that infection with V. cholerae O1 and OCVs induce similar responses to the protein antigen CtxB, but responses to LPS were diminished after OCV compared to those after natural V. cholerae infection. A second dose of OCV on day 14 failed to boost circulating V. cholerae-specific plasmablast responses in Bangladeshi adults. Our results differ from those in studies from areas where cholera is not endemic, in which a second vaccination on day 14 significantly boosts plasmablast responses. Given these results, it is likely that the optimal boosting strategies for OCVs differ significantly between areas where V. cholerae infection is endemic and those where it is not.     

Diffuse alveolar hemorrhage and pulmonary capillaritis due to propylthiouracil

Propylthiouracil (PTU) has recently been observed to be associated with antineutrophil cytoplasmic antibody (ANCA)-positive small vessel vasculitis, resulting in crescentic glomerulonephritis and, infrequently, diffuse alveolar hemorrhage (DAH). We describe a case of a 23-year-old pregnant woman who developed a perinuclear ANCA and antimyeloperoxidase-positive small vessel vasculitis manifesting as DAH and crescentic glomerulonephritis after she began taking PTU. An open lung biopsy was consistent with pulmonary capillaritis. She responded to corticosteroid therapy and discontinuation of PTU. DAH can be caused by pulmonary capillaritis, bland hemorrhage, or diffuse alveolar damage. To our knowledge, this represents the first documentation of an underlying pulmonary capillaritis in a case of PTU-induced DAH.     

Laparoscopic Transplantation Following Transvaginal Insertion of the Kidney: Description of Technique and Outcome

Laparoscopic kidney transplantation (LKT) is well accepted modality of treatment for ESRD patients at our center. Usually, the kidney is inserted through small Pfannenstiel incision. With the permission of the Internal Review Board, we carried out LKT in eight female recipients following insertion of the kidney through the vagina. The kidney was procured by the retroperitoneoscopic approach. Antibiotic prophylaxis was given. All cases were carried out successfully with immediate graft function and 100% graft and patient survival at 1 year of follow‐up. Estimated glomerular filtration rate at 1 month and 1 year was similar to eight randomly selected female recipients who underwent open kidney transplantation (OKT). No analgesia was required in seven out of eight patients after the 3rd postoperative day. In summary, vaginal insertion of kidney and LKT is safe and feasible in a selected group of patients. It is associated with better analgesia and has similar allograft function as compare to OKT.     

A 4-year study of the epidemiology of Vibrio cholerae in four rural areas of Bangladesh

How Vibrio cholerae spreads around the world and what determines its seasonal peaks in endemic areas are not known. These features of cholera have been hypothesized to be primarily the result of environmental factors associated with aquatic habitats that can now be identified. Since 1997, fortnightly surveillance in 4 widely separated geographic locations in Bangladesh has been performed to identify patients with cholera and to collect environmental data. A total of 5670 patients (53% <5 years of age) have been studied; 14.3% had cholera (10.4% due to V. cholerae O1 El Tor, 3.8% due to O139). Both serogroups were found in all locations; outbreaks were seasonal and often occurred simultaneously. Water-use patterns showed that bathing and washing clothes in tube-well water was significantly protective in two of the sites. These data will be correlated with environmental factors, to develop a model for prediction of cholera outbreaks.     

Mechanisms and significance of eryptosis, the suicidal death of erythrocytes

Eryptosis, the suicidal death of erythrocytes, is characterized by erythrocyte shrinkage, blebbing, and phospholipid scrambling of the cell membrane. Eryptosis is triggered by increased cytosolic Ca(2+) activity, which may result from Ca(2+) entry through PGE(2)-activated Ca(2+)-permeable cation channels. The Ca(2+) sensitivity of the scrambling machinery is enhanced by ceramide, which is formed by an acid sphingomyelinase, an enzyme stimulated by platelet-activating factor. Eryptosis is enhanced in a variety of clinical conditions such as sickle-cell anemia, β-thalassemia, glucose-6-phosphate dehydrogenase deficiency, hereditary spherocytosis, paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome, phosphate depletion, iron deficiency, sepsis, hemolytic uremic syndrome, renal insufficiency, diabetes, malaria, mycoplasma infection, and Wilson's disease. Eryptosis is enhanced in mouse models of sickle cell anemia and thalassemia, as well as in mice lacking functional annexin 7, cGMP-dependent protein kinase type I, AMP-activated protein kinase, Janus kinase 3, anion exchanger 1, adenomatous polyposis coli, or Klotho. Eryptosis is triggered by osmotic shock, oxidative stress, energy depletion, hyperthermia, and a myriad of small molecules. Eryptosis is inhibited by a variety of substances including nitric oxide and catecholamines. Erythropoietin counteracts eryptosis in part by inhibiting the Ca(2+)-permeable cation channels. Excessive erythropoietin concentrations lead, however, to formation of erythrocytes, which are particularly sensitive to eryptotic stimuli. Accelerated eryptosis may be compensated by enhanced erythropoiesis, which is apparent from reticulocytosis. If the compensation is not sufficient, clinically relevant anemia develops. Beyond that, adhesion of eryptotic erythrocytes to the vascular wall may lead to impairment of microcirculation.     

Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

Current oral cholera vaccines induce lower levels of protective efficacy and shorter durations of protection in young children than in adults. Immunity against cholera is serogroup specific, and immune responses to Vibrio cholerae lipopolysaccharide (LPS), the antigen that mediates serogroup-specific responses, are associated with protection against disease. Despite this, responses against V. cholerae O-specific polysaccharide (OSP), a key component of the LPS responsible for specificity, have not been characterized in children. Here, we report a comparison of polysaccharide antibody responses in children from a region in Bangladesh where cholera is endemic, including infants (6 to 23 months, n = 15), young children (24 to 59 months, n = 14), and older children (5 to 15 years, n = 23) who received two doses of a killed oral cholera vaccine 14 days apart. We found that infants and young children receiving the vaccine did not mount an IgG, IgA, or IgM antibody response to V. cholerae OSP or LPS, whereas older children showed significant responses. In comparison to the vaccinees, young children with wild-type V. cholerae O1 Ogawa infection did mount significant antibody responses against OSP and LPS. We also demonstrated that OSP responses correlated with age in vaccinees, but not in cholera patients, reflecting the ability of even young children with wild-type cholera to develop OSP responses. These differences might contribute to the lower efficacy of protection rendered by vaccination than by wild-type disease in young children and suggest that efforts to improve lipopolysaccharide-specific responses might be critical for achieving optimal cholera vaccine efficacy in this younger age group.     

Antibody Avidity in Humoral Immune Responses in Bangladeshi Children and Adults following Administration of an Oral Killed Cholera Vaccine

Antibody avidity for antigens following disease or vaccination increases with affinity maturation and somatic hypermutation. In this study, we followed children and adults in Bangladesh for 1 year following oral cholera vaccination and measured the avidity of antibodies to the T cell-dependent antigen cholera toxin B subunit (CTB) and the T cell-independent antigen lipopolysaccharide (LPS) in comparison with responses in other immunological measurements. Children produced CTB-specific IgG and IgA antibodies of high avidity following vaccination, which persisted for several months; the magnitudes of responses were comparable to those seen in adult vaccinees. The avidity of LPS-specific IgG and IgA antibodies in vaccinees increased significantly shortly after the second dose of vaccine but waned rapidly to baseline levels thereafter. CTB-specific memory B cells were present for only a short time following vaccination, and we did not find significant memory B cell responses to LPS in any age group. For older children, there was a significant correlation between CTB-specific memory T cell responses after the second dose of vaccine and CTB-specific IgG antibody avidity indices over the subsequent year. These findings suggest that vaccination induces a longer-lasting increase in the avidity of antibodies to a T cell-dependent antigen than is measured by a memory B cell response to that antigen and that early memory T cell responses correlate well with the subsequent development of higher-avidity antibodies.     

What's your diagnosis?: Skin lesions in a young female with Behcet's disease

A young female with known Behcet's disease presented with skin lesions over lower limbs. The lesions were biopsied and found to be pyoderma gangrenosum. The lesions responded to oral steroids for 6 weeks.     

Long-term outcomes following single-bundle transtibial arthroscopic posterior cruciate ligament reconstruction

Purpose

Posterior cruciate ligament (PCL) injury has a reported incidence of 3–20 %. PCL reconstruction is aimed at reducing onset of premature articular degeneration and improving function. Numerous operative techniques have been described with varying degrees of result consistency.

Methods

We evaluated 15 patients treated for isolated primary posterior cruciate ligament injury with a mean follow-up of 4.1 years (range one to nine). Post-reconstruction clinical assessment included the Lysholm and Tegner knee scoring scale, international knee documentation committee (IKDC) ligament evaluation, and KT2000 arthrometer assessment.

Results

On the Lysholm knee score 11 patients (73 %) had excellent results, three patients (20 %) had good results and one patient (7 %) had a poor result. On the Tegner activity score the majority of patients scored 7–8 with a return to high level sports. At the final follow-up, the post-reconstruction IKDC score was normal or nearly normal (A and B) in 14 (93 %) patients, and abnormal (C) in one (7 %) patient. According to KT-2000 arthrometer measurements at final follow-up review, 11 patients (73 %) were rated as normal (A, 0–2 mm), and four patients (27 %) as nearly normal (B, 3–5 mm). These results were independent of age, mechanism of injury, time elapsed to surgical reconstruction, and length of follow-up.

Conclusions

Despite being a technically demanding procedure, the outcomes reported in this study show that single bundle transtibial arthroscopic PCL repair using four strands hamstring autograft provides satisfactory and consistent functional outcomes.