Urban lymphatic filariasis in the city of Tanga,Tanzania, after seven rounds of mass drug administration

Urban lymphatic filariasis (LF) has been listed among the challenges to the ongoing global efforts to eliminate LF. This is partly because the control strategies developed for rural areas – where most LF occurs – do not easily comply with human organization and behaviour in urban areas, and partly because the urban vectors thrive and proliferate in poorly planned urban settlements. This study investigated LF infection, disease and transmission in the medium-sized city of Tanga (approx. 300,000 inhabitants), Tanzania, after seven rounds of mass drug administration (MDA). Three representative sites with varying distance from the city centre were selected for the study. Pupils from one public primary school at each site were screened for circulating filarial antigens (CFA; marker of adult worm infection) and antibodies to Bm14 (marker of exposure to transmission). Community members were examined for CFA, microfilariae and chronic manifestations. Questionnaires were administered to pupils and heads of community households, and vector surveys were carried out in selected households. Although there was evidence of considerable reduction in infection and transmission, there was still LF in the city, with mf and CFA prevalences well above the cut-off levels for stopping MDA. In this respect, the LF situation resembled that seen in nearby rural areas outside the city. The study emphasizes the importance of motivating the urban individuals to engage and comply with the full range of LF intervention measures (MDAs, use of mosquito proofing measures including bed nets, environmental sanitation to prevent vector breeding) in order to reach successful LF control in the city. The high LF disease burden noted, despite the reduction in infection and transmission, moreover emphasizes the importance of allocating resources for morbidity management, to ensure true elimination of LF as a public health problem.     

Consequences of hydrocele and the benefits of hydrocelectomy: a qualitative study in lymphatic filariasis endemic communities on the coast of Ghana

A study using focus group discussions and in-depth interviews was conducted to determine the consequences of hydrocele and the benefits of hydrocelectomy on physical activity and social life in three lymphatic filariasis endemic villages where males had recently been offered surgical operations to repair their hydroceles. Respondents were of the view that hydrocele, especially large ones, severely reduced the patients’ work capacity and impaired sexual function, and that overall it had a considerable negative effect on the quality of living for the patients, their families and the community. The main reasons for refusing hydrocelectomy in the past were the high cost of surgery, and to some extent fear of death, impotence and/or sterility that might result from the operation. The recently offered hydrocele operations, which included 40 males, were financially supported and preceded by appropriate counselling, and from the patients’ point of view were highly successful. Patients spent between 4 and 12 days in the hospital and there were no post-operative complications. Patients observed that, between 3 and 6 months after surgery, there were remarkable improvements in their work capacity and sexual function, and restoration of self-esteem, thus enabling them to participate more actively in community activities. The need for hydrocelectomy to be incorporated as an important morbidity control measure in lymphatic filariasis control programmes is discussed.     

Renal disease in lymphatic filariasis: evidence for tubular and glomerular disorders at various stages of the infection

Brugia malayi-infected patients, endemic normals with high levels of specific antibodies and European controls were investigated for kidney disorders by noninvasive techniques. Groups of patients with filarial infections included asymptomatic, microfilaraemic cases (group 1), patients with filarial fever (group 2) and with obstructive filariasis (group 3). Several patients underwent a treatment course with diethylcarbamazine (DEC) when blood and urine samples were collected. Urine samples were investigated for proteinuria and analysed by SDS-PAGE to discriminate between proteinurias caused by tubular and glomerular disorders. In addition, urine levels of α-1 microglobulin, of the brush border antigen gp400 and of N-acetyl-β-glucosaminidase (NAG) activity were determined as indicators of tubular disorders, the albumin content of the urines served as indicator of glomerular alterations. IgG rheuma factors were also determined in the serum as possible reasons for glomerulonephritis. Neither in the endemic normals nor in the European controls there was evidence for kidney disorders. Infected patients had significantly increased proteinuria compared to controls. There were no significant differences between the 3 groups of infected persons, although the mean protein levels were highest in cases with chronic disease and lowest in asymptomatic patients. Quantitative urine analyses and results of accompanying tests suggest predominantly tubular but generally relatively weak disorders in asymptomatic infections; abundant involvement of the kidney which involves both compartments of the organ in the course of filarial fever; and partly severe and probably chronically progredient kidney alterations, which predominantly affect the glomerula in symptomatic cases. IgG rheuma factors do not seem to play a role in filarial infection associated renal disease. DEC-treatment indeed did not significantly alter degree and chatacter of the proteinuria, but relatively high albumin levels in the urine of treated persons yet suggest increased glomerular disorders in these cases. In conclusion, renal disease appears to be a common event in Brugia filariasis; involving both the tubular and glomerular compartment of the organ its pathogenesis is obviously complex and not only immune complex-mediated.     

Need for a differential criteria to stop mass drug administration,based on an epidemiological perspective of lymphatic filariasis in Thiruvananthapuram,Kerala, India

ObjectiveTo determine the prevalence of any of the clinical manifestations of lymphatic filariasis, parasitological and entomological indices in Thiruvananthapuram district, Kerala, India, prior to launching mass drug administration (MDA) in the district in 2005.MethodsA cross sectional survey was conducted in 7 endemic wards of the district, in a sample of 2 472 individuals above the age of one year. The study consisted of data collection using questionnaire, night blood smear examination and mosquito collection followed by identification and dissection.ResultsThe prevalence of any of the clinical manifestations of filariasis in this endemic area was 3% (73/2 472) (95% CI between 2.3% to 3.7%). The microfilaria rate was found to be 0.38%. Culex quinquefasciatus formed the predominant mosquito species. The vector infection rate was 1.4% and infectivity rate was 0.47%. Half of the population had satisfactory knowledge regarding the disease. In almost an equal number, the knowledge was poor and only about 10% had good knowledge. Most of the people had not heard about the MDA program.ConclusionsThe prevalence of filariasis even in an area considered to be endemic in Kerala, was low. Microfilaraemia was much lower than the clinical manifestations. However, the potential risk of transmission of disease continues. For such areas which had a pre-MDA mf rate less than 1%, there needs to be more stringent criteria for evaluating the effectiveness of the programme, doing transmission assessment surveys and stopping MDA.     

Regulation of the immune response in lymphatic filariasis: perspectives on acute and chronic infection with Wuchereria bancrofti in South India

Delineating the immune responses in lymphatic filariasis has been complicated not only by the rapidly expanding knowledge of new immunological mediators and effortors, but also by new methodologies (in particular, circulating filarial antigen detection) for defining and categorizing filarial-infected individuals. By using assays for circulating antigen in the sera collected as part of the many immunological studies performed on individuals in a Wuchereria bancrofti-endemic region of South India, we have attempted to explore the influence of patency on the antigen-driven proliferative and cytokine responses seen in peripheral blood mononuclear cells of individuals with varying clinical manifestations of lymphatic filarial infection. Moreover, we have provided perspectives on the differences between acute and chronic infection with W. bancrofti and suggested mechanisms that may underly the modulation of the immune response as patency occurs.     

Predictors of solid extra-hepatic non-skin cancer in liver transplant recipients and analysis of survival: A long-term follow-up study

Introduction and objectivesDe novo malignancies represent an important cause of death for liver transplant recipients. Our aim was to analyze predictors of extra-hepatic non-skin cancer (ESNSC) and the impact of ESNSC on the long-term outcome.PatientsWe examined data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics with a retrospective observational cohort study. Cox Regression was performed to identify predictors of ESNSC. A 1:2 cohort sub-study was developed to analyze the impact of ESNSC on 10-year survival.ResultsWe analyzed data from 367 subjects (median follow-up: 15 years). Patients with ESNSC (n = 47) more often developed post-LT diabetes mellitus (DM) (57.4% versus 35,9%, p = 0.004). At multivariate analysis, post-LT DM independently predicted ESNSC (HR 1.929, CI 1.029-3.616, p = 0.040). Recipients with ESNSC showed a lower 10-year survival than matched controls (46,8% versus 68,1%, p = 0.023).ConclusionsPost-LT DM seems to be a relevant risk factor for post-LT ESNSC. ESNSC could have a noteworthy impact on the long-term survival of LT recipients.     

Low short-term and long-term cardiovascular and all-cause mortality in absence of coronary artery calcium: A 22-year follow-up observational study from large cohort

ObjectivesWe sought to evaluate the gender-specific predictive value of coronary artery calcium (CAC) score on all-cause mortality and cardiovascular disease (CVD) mortality in individuals with and without diabetes mellitus (DM).BackgroundCAC score is a robust predictor of CVD and all-cause mortality during long-term follow-up in large cohorts in adults with DM. However, less is known about its sex-specific impact on all-cause mortality in DM.MethodsWe evaluated 25,563 asymptomatic participants with no known history of coronary artery disease (CAD) who underwent clinically indicated CAC. 1999 (7.8%) individuals had diabetes. CAC was characterized as an Agatston score of 0, 1–99, 100–300, and ?300. We evaluated the association between CAC and all-cause mortality and CVD mortality.ResultsOverall, 1345 individuals died (5.3%) from all causes during a mean follow-up of 14.7 ± 3.8 years. CAC score was 0 in 57.5% females and 34.4% of males without DM, while 36.6% females and 20.3% males with DM had CAC-0. The frequency of CAC ? 300 was 18% and 36% in females and males with DM, respectively. CAC score of zero was associated with low all-cause mortality event rate in females and males with diabetes (1.7 and 2.5 events per 1000 person-years, respectively). Cardiovascular mortality per 1000 person years was ?1 in females and males with CAC score of 0 irrespective of their diabetes. Adjusted multivariable analysis, compared to CAC-0, HR for all-cause mortality associated with CAC 1–99, 100–299 and ?300 were 1.74(95% CI 0.65, 4.63, P-0.20), 5.54(95% CI 2.16, 14.22, P ? 0.001) and 5.75(95% CI 2.30, 14.37, P ? 0.001) in females with DM respectively; in males with DM HR associated with CAC 1–99, 100–299 and ?300 were 1.87(95% CI 0.95, 3.66, P-0.06), 2.15(95% CI 1.05, 4.38, P-0.035) and 2.60(95% CI 1.34, 5.0, P-0.004), respectively.ConclusionPresence of subclinical atherosclerosis varies among individuals with DM. The absence of CAC was associated with very low cardiovascular as well as all-cause mortality events in all subgroups during long term follow-up.     

A 5-year follow-up study on the incidence of retinopathy in type 1 diabetes mellitus in relation to medical risk indicators

Objectives . The aim of the present study was to describe the 5-year incidence of retinopathy in type 1 diabetes mellitus and to characterize risk indicators for the development and progression of retinopathy. Design . A cross-sectional study of type 1 diabetic patients taken care of at a medical department. Setting . All type 1 diabetic patients attending the Department of Internal Medicine, University Hospital, Lund, during a 2-year period were offered ophthalmological examination. Subjects . A total of 396 out of 461 (85.9%) initially examined type 1 diabetic patients formed the basis for this 5-year follow-up study. Main outcome measures . The degree of retinopathy was based on fundus photography or biomicroscopy. Degree of metabolic control was assessed by HbA_1c levels, signs of nephropathy by albumin creatinine clearance ratio and urinary albumin levels. Blood pressure was measured in the supine position. Duration of diabetes, age, and insulin dosage were registered. Results . The incidence of retinopathy was 47.2%, and progression from background to severe retinopathy occurred in 41%. Risk indicators for the development of retinopathy were duration of diabetes (P < 0.001), degree of metabolic control (P < 0.001), insulin dosage (P < 0.05) and signs of nephropathy based on measurements of albumin creatinine clearance ratio (P < 0.01) and urinary albumin concentration (P < 0.05). Two risk indicators could be identified for progression of retinopathy, i.e. the degree of metabolic control (P < 0.01) and diastolic blood pressure (P < 0.05). Conclusions . The results suggest that apart from poor metabolic control, development of retinopathy in type 1 diabetes is associated with long diabetes duration and clinical signs of diabetic nephropathy. Progression of retinopathy is associated with poor metabolic control and elevated diastolic blood pressure levels.     

Acute pancreatitis in Chile: A multicenter study on epidemiology,etiology and clinical outcome. Retrospective analysis of clinical files

BackgroundEpidemiology of acute pancreatitis (AP) is variable in different geographical regions.ObjectivesTo compare etiology and severity of AP to published data from South America and the rest of world, study impact of demographical factors and treatment on its outcome in Chilean hospitals.MethodsMulticenter observational study. Data of consecutive patients with AP were collected at the moment of discharge from 11 centers and retrospectively analyzed.ResultsData of 962 patients were included in the analysis, 447 men and 515 women. Mean age was 48,2 years. Biliary etiology was significantly more frequent in women (70%) than in men (52%). Conversely, alcohol was responsible for about 17% of AP in men but exceptional in women. Mild AP was seen in 73.4%, moderately severe in 14.1% and severe in 13%. The overall mortality was 2.5% (24 of 962): 0.3%, 3.1% and 15.1% in mild, moderately severe and severe cases, respectively. No difference was found in the mortality and severity of biliary versus alcoholic AP, while hypertriglyceridemia induced AP was more severe, without increased mortality. Severity and mortality increased with age. ERCP was performed in 16% of biliary pancreatitis. Adherence to main guidelines was heterogeneous: more than half of mild AP patients were admitted to critical care units and antibiotics were used in about 25% them.ConclusionThis is the first multicenter study in Chile on AP. When compared to literature, we found similar severity distribution and an acceptably low mortality. Biliary etiology was dominant, but alcohol was also important in men.     

Efficacy of low dose long-term interferon monotherapy in aged patients with chronic hepatitis C genotype 1 and its relation to alpha-fetoprotein: A pilot study

Aim: The objective of this study was to examine the efficacy and safety of low dose long-term interferon (IFN) therapy in aged patients with chronic hepatitis C genotype 1. Methods: The IFN therapy was performed in Shin-Kokura Hospital on 44 patients aged 60 or older with chronic hepatitis C. All patients had high viral loads of genotype 1. Three million units of natural IFN-alpha was administered intramuscularly or intrasubcutaneously, three times a week for three years. A control group of 44 subjects not treated with IFN, matched for age, gender and hepatic histology, was formed. Results: Two of the 44 patients showed a sustained virological response. Alanine aminotransferase was below the upper limit of normal in 59% (23/39) of the patients and alpha-fetoprotein was less than 40 ng/mL in 97% (38/39) on the completion of treatment. Sustained biochemical response was observed in 53% (19/36) of the patients. In the liver cirrhosis group, serum albumin values and platelet counts increased in 38% (6/16) and 33% (6/18) of patients, respectively. Hepatocellular carcinoma (HCC) appeared in three patients by 13 months after the start of treatment, but no cases were reported thereafter. The cumulative non-carcinogenesis rate of HCC in the liver cirrhosis group was significantly higher in the IFN treatment group compared to the control group (log-rank test, P = 0.046). Conclusion: Low dose long-term interferon monotherapy to prevent carcinogenesis of HCC was considered useful in aged patients for whom peg-interferon and ribavirin combination therapy is difficult.     

Long-term clinical course of extra-oesophageal manifestations in patients with gastro-oesophageal reflux disease: A prospective follow-up analysis based on the ProGERD study

BACKGROUND: Gastro-oesophageal reflux disease can be associated with extra-oesophageal reflux disease such as chronic cough or laryngeal symptoms. The aim of this study was to analyse the clinical course of extra-oesophageal reflux disease in a large population with gastro-oesophageal reflux disease and extra-oesophageal reflux disease under routine clinical care. METHODS: ProGERD is a prospective multicentre cohort study of 6215 outpatients with gastro-oesophageal reflux disease. At baseline all patients underwent endoscopies and were interviewed for extra-oesophageal reflux disease. Initial standardised treatment was esomeprazole for up to 8 weeks. After 2 years of follow-up, reflux symptoms and the prevalence of extra-oesophageal reflux disease were assessed. A multivariate analysis was performed with resolved versus persistent symptoms for chronic cough and laryngeal symptoms as dependent predictors. Independent variables were gender, age, body mass index (BMI), alcohol consumption, cigarette smoking, gastro-oesophageal reflux disease classification, history of gastro-oesophageal reflux disease in the family, duration of gastro-oesophageal reflux disease and proton pump inhibitors medication. RESULTS: Four thousand four hundred and four patients (71%) were available for analysis at 2 years, including 570 and 454 patients who had chronic cough and laryngeal disorders at baseline, respectively. In 63% and 74% of the patients, chronic cough and laryngeal disorders had resolved. Patients with persistent respiratory symptoms in year 2 had significantly more reflux symptoms. Further clinically relevant associations were smoking and non-steroidal anti-inflammatory drugs use. According to the multivariate analysis, classification of gastro-oesophageal reflux disease, proton pump inhibitors medication or duration of gastro-oesophageal reflux disease were not associated with the resolution of cough or laryngeal symptoms. CONCLUSION: In most patients with gastro-oesophageal reflux disease and extra-oesophageal reflux disease, respiratory symptoms resolve during long-term routine care. A high reflux symptom load was associated with the persistence of respiratory disorders.     

Application of the platelet count/spleen diameter ratio to rule out the presence of oesophageal varices in patients with cirrhosis: A validation study based on follow-up

BACKGROUND: Screening for oesophageal varices represents an important part of the diagnostic work-up of cirrhotic patients. We have previously shown that the platelet count/spleen diameter ratio is a parameter that can rule out the presence of oesophageal varices safely and in a cost-effective fashion. AIM: To evaluate the prognostic and diagnostic accuracy of the platelet count/spleen diameter ratio for ruling out the presence of oesophageal varices in the follow-up of a cohort of cirrhotic patients without oesophageal varices at inclusion. METHODS: After initial endoscopy, the 106 cirrhotic patients without oesophageal varices who participated in our previous study were followed-up with annual or biannual surveillance endoscopy. Patients were censored at the time of diagnosis of oesophageal varices or at their last visit, and at that time platelet count and spleen diameter were recorded. Sixty-eight patients made up the study cohort after excluding patients who were lost to follow-up or died before undergoing control endoscopy. RESULTS: During the follow-up, 27 patients (40%) developed oesophageal varices. Patients with higher baseline platelet count/spleen diameter ratios (p<0.0001) as well as a ratio above 909 were less likely to develop oesophageal varices (p<0.0005). At follow-up, a platelet count/spleen diameter ratio < or = 909 had 100% negative predictive value and 84% efficiency in identifying the presence of oesophageal varices. CONCLUSIONS: The use of the platelet count/spleen diameter ratio proved to be an effective means for ruling out the presence of oesophageal varices even in the longitudinal follow-up of patients.