Assessments of the transmission of Onchocerca volvulus by Simulium sanctipauli in the Upper Denkyira District, Ghana, and the intermittent disappearance of the vector.

Following studies on the transmission of Onchocerca volvulus (Leuckart) by Simulium sanctipauli Vajime & Dunbar (Diptera, Simuliidae) in Upper Denkyira District in Ghana in 2001 and 2002 (Kutin et al., Med Vet Ent 18:167-173, 2004), further assessments were carried out in 2006 and 2013/2014 to determine whether transmission parameters had changed since community-directed ivermectin treatment (CDTI) began in 1999. There were no marked changes of the transmission intensities in 2006. Only slight, but non-significant, reductions were observed in infection rates of parous flies with larval stages (L1-L3) of O. volvulus from 44.1 % (of 1672 parous flies) in 2001/2002 to 42.1 % (506) in 2006 and from 6.5 to 5.9 % of flies carrying infective larvae in their heads. This suggested that there was an ongoing transmission in the area and the parasite reservoir in the human population was still high. Unexpectedly, further assessments conducted in October 2013 and March and October 2014 revealed that the vector S. sanctipauli had apparently disappeared and transmission had ceased, probably as a result of intensified gold mining activities along the rivers Ofin and Pra. The water of both rivers was extremely turbid, heavily loaded with suspended solids, probably preventing the development of blackfly larvae. Some breeding and biting of Simulium yahense Vajime & Dunbar was observed in a small tributary of the Pra, the Okumayemfuo, which is not affected by gold mining. However, the infection rate of flies was low, only 3.7 % of 163 parous flies were infected with first stage (L1) larvae of O. volvulus.

Pharmacokinetics of rifampin and clarithromycin in patients treated for Mycobacterium ulcerans infection.

In a randomized controlled trial in Ghana, treatment of Mycobacterium ulcerans infection with streptomycin (SM)-rifampin (RIF) for 8 weeks was compared with treatment with SM-RIF for 4 weeks followed by treatment with RIF-clarithromycin (CLA) for 4 weeks. The extent of the interaction of RIF and CLA combined on the pharmacokinetics of the two compounds is unknown in this population and was therefore studied in a subset of patients. Patients received CLA at a dose of 7.5 mg/kg of body weight once daily, rounded to the nearest 125 mg. RIF was administered at a dose of 10 mg/kg, rounded to the nearest 150 mg. SM was given at a dose of 15 mg/kg once daily as an intramuscular injection. Plasma samples were drawn at steady state and analyzed by liquid chromatography-tandem mass spectroscopy. Pharmacokinetic parameters were calculated with the MW/Pharm (version 3.60) program. Comedication with CLA resulted in a 60% statistically nonsignificant increase in the area under the plasma concentration-time curve (AUC) for RIF of 25.8 mg x h/liter (interquartile ratio [IQR], 21.7 to 31.5 mg x h/liter), whereas the AUC of RIF was 15.2 mg x h/liter (IQR, 15.0 to 17.5 mg x h/liter) in patients comedicated with SM (P = 0.09). The median AUCs of CLA and 14-hydroxyclarithromycin (14OH-CLA) were 2.9 mg x h/liter (IQR, 1.5 to 3.8 mg x h/liter) and 8.0 mg x h/liter (IQR, 6.7 to 8.6 mg x h/liter), respectively. The median concentration of CLA was above the MIC of M. ulcerans, but that of 14OH-CLA was not. In further clinical studies, a dose of CLA of 7.5 mg/kg twice daily should be used (or with an extended-release formulation, 15 mg/kg should be used) to ensure higher levels of exposure to CLA and an increase in the time above the MIC compared to those achieved with the currently used dose of 7.5 mg/kg once daily.

Excision of pre-ulcerative forms of Buruli ulcer disease: a curative treatment?

BACKGROUND: Previous investigations have revealed that Mycobacterium ulcerans is extensively distributed spatially throughout ulcerative lesions, including in the margins of excised tissue. In contrast, bacilli in pre-ulcerative lesions are assumed to be concentrated in the center of the lesion. In order to assess the extent to which the surgical excision of pre-ulcerative lesions is capable of removing all infected tissue, we subjected the excision margins of pre-ulcerative lesions to laboratory analysis. PATIENTS AND METHODS: Eleven patients with laboratory-confirmed pre-ulcerative lesions were included in the study. The diameter of the lesion and excised tissue and the "surgical distance" between the border of the lesion and excision margin were measured. The entire excision margin was cut into segments and subjected to IS2404 PCR. RESULTS: The results from the PCR analysis on the samples of excision margins were highly significantly associated with the surgical distance (p < 0.001). The margin samples of nodules were significantly more often PCR positive than the plaques (p = 0.025). The size of the lesion and the size of the excised tissue did not significantly influence the PCR results. Statistically, a surgical distance of more than 9 mm was found to reduce the risk of remaining infected tissue to less than 10%, that of 13 mm to reduce the risk to less than 5%, and that of 25 mm to reduce the risk to nearly 0%. CONCLUSION: The results of this study show that in preulcerative Buruli ulcer disease, bacilli may extend beyond the actual size of the lesion and that there is a strong correlation between the presence of M. ulcerans in the margin samples and the surgical distance. Excision with a surgical distance of 25 mm avoided the risk of remaining mycobacteria in this study. However, no recurrences occurred in the patients with M. ulcerans-positive excision margins. The need of postoperative antimycobacterial treatment in these patients remains to be determined.

A stepwise approach to the laboratory diagnosis of Buruli ulcer disease.

OBJECTIVE: In view of technical and financial limitations in areas of endemicity, the current practice and recommendations for the laboratory diagnosis of Buruli ulcer disease (BUD) may have to be reconsidered. We reviewed diagnostic results in order to explore options for a modified, more practicable, cost-effective and timely approach to the laboratory diagnosis of BUD. METHODS: Diagnostic specimens from 161 clinically diagnosed BUD patients from four different treatment centres in Ghana were subjected to laboratory analysis. The positivity rates of the laboratory assays were compared. RESULTS: The number of laboratory-confirmed clinically diagnosed BUD cases with one positive confirmative test was 20% higher than that with two positive confirmative tests. The specificity of microscopy (MIC) and PCR was 96.6% and 100%, respectively. Subsequent analysis of specimens from surgically excised pre-ulcerative tissue-by-tissue MIC and tissue PCR rendered 65% laboratory-confirmed BUD cases. Subsequent analysis of diagnostic swabs from ulcerative lesions by swab smear MIC and swab PCR rendered 70% of laboratory-confirmed BUD cases. CONCLUSIONS: The specificity of the diagnostic tests used in this study suggests that one positive diagnostic test may be considered sufficient for the laboratory confirmation of BUD. Subsequent application of different diagnostic tests rendered a laboratory confirmation of 65% pre-ulcerative and of 70% ulcerative lesions. Implementation of a stepwise, subsequent analysis of diagnostic specimens will result in considerable cost saving compared with simultaneous testing of specimens by several diagnostic assays.

External quality assurance for the laboratory diagnosis of Buruli ulcer disease in Ghana.

OBJECTIVE: To assure the quality of the laboratory diagnosis of Buruli ulcer disease; microscopy and PCR were subjected to external quality assurance (EQA). METHODS: Slides were read by test laboratory staff, followed by blinded re-reading by the controller. Parallel testing of PCR specimens was carried out at the local and external reference laboratory. Slides and PCR specimens with discordant results were subjected to a second reading/testing by the controller to determine the final result. For training purposes, slides and PCR specimens with discrepant results were subsequently re-read/re-tested under supervision at the test laboratory. RESULTS: Microscopy. First reading: concordance rate 82.9%, discordance rate 17.1%, percentage false negatives 27.1% (sensitivity 72.9%), percentage false positives 10.1% (specificity 89.9%). Second reading: concordance rate 97.9%, discordance rate 2.1%, percentage false negatives 4.2% (sensitivity 95.8%), percentage false positives 0.6% (specificity 99.4%). PCR. First testing: concordance rate 87.9%, discordance rate 12.1%, percentage false negatives 8.2% (sensitivity 91.8%), percentage false positives 19.1% (specificity 80.9%). Second testing: concordance rate 96.2%, discordance rate 3.8%, percentage false negatives 4.7% (sensitivity 95.3%), percentage false-positives 2.1% (specificity 97.9%). CONCLUSIONS: EQA identified deficiencies in the laboratory performance. Corrective action consisted in on-site training and reduced the number of false-negative and false-positive microscopy and PCR results.

The objective assessment of international collaboration between pathology laboratories.

Collaboration between clinical laboratories in different countries is widespread but rarely subject to critical analysis. We developed a management tool for assessing the quality of an international pathology laboratory collaboration. Key areas of activity were identified and relevant performance indicators were established. There was no evidence of improved staff morale arising from the project but research, education, equipment, protocols and ethics activities all had demonstrable outputs. Identification of suboptimal performance in areas of the project allowed effective improvement planning. International collaboration may consume significant resources. Objective assessment should be used to measure performance and to enhance quality.

Post-surgical assessment of excised tissue from patients with Buruli ulcer disease: progression of infection in macroscopically healthy tissue.

OBJECTIVE: The current standard of treatment of Buruli ulcer disease (BUD) is surgical excision of lesions. Excision size is determined macroscopically assuming the complete removal of all infected tissue. However, dissemination of infection beyond the excision margins into apparently healthy tissue, possibly associated with recurrences, cannot be excluded in this way. To assess the central to peripheral progression of Mycobacterium ulcerans infection and the mycobacterial infiltration of excision margins, excised tissue was examined for signs of infection. METHODS: 20 BUD lesions were excised in general anaesthesia including all necrotic and subcutaneous adipose tissue down to the fascia and at an average of 40 mm into the macroscopically unaffected tissue beyond the border of the lesion. Tissue samples were subjected to PCR and histopathology. RESULTS: Although the bacillary load decreased from central to peripheral, M. ulcerans infection was detected throughout all examined tissue specimens including the peripheral segments as well as excision margins of all patients. During the post-operative hospitalization period (averaging 2 months) no local recurrences were observed. CONCLUSION: Available data suggest a correlation of surgical techniques with local recurrences. The results of this study indicate the unnoticed early progression of mycobacterial infection into macroscopically healthy tissue. Thus, the removal of all infected tissue cannot always be verified visually by the surgeon. Provided that long-term follow up of patients with positive excision margins will establish the clinical relevance of these findings, on-site laboratory assessment of excised tissue in combination with follow up may contribute to reduce recurrence rates.

Dry-reagent-based PCR as a novel tool for laboratory confirmation of clinically diagnosed Mycobacterium ulcerans-associated disease in areas in the tropics where M. ulcerans is endemic.

After tuberculosis and leprosy, Buruli ulcer (BU), caused by Mycobacterium ulcerans, is the third most common mycobacterial disease in immunocompetent humans. The disease occurs in tropical countries, with foci in West Africa, Central Africa, and the western Pacific. BU is defined as an infectious disease involving the skin and the subcutaneous adipose tissue characterized by a painless nodule, papule, plaque, or edema, evolving into a painless ulcer with undermined edges and often leading to invalidating sequelae. Due to the fundamental lack of understanding of modes of transmission, disease control in endemic countries is limited to early case detection through improved active surveillance and surgical treatment. The laboratory confirmation of BU is complicated by the absence of a diagnostic "gold standard." Therefore, misclassification and delayed diagnosis of BU may occur frequently, causing a considerable socioeconomic impact in terms of treatment costs due to prolonged hospitalization. In order to respond to the urgent need to develop reliable tools for early case detection and to overcome technical difficulties accompanying the implementation of diagnostic PCR procedures in tropical countries, a dry-reagent-based PCR formulation for the detection of M. ulcerans in diagnostic specimens has been developed at the Bernhard Nocht Institute for Tropical Medicine. Following technical and clinical validation, the assay has been successfully installed and field tested at the Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi, Ghana. Preliminary results show an excellent diagnostic sensitivity of >95%.

The species Mycobacterium africanum in the light of new molecular markers.

The findings of recent studies addressing the molecular characteristics of Mycobacterium tuberculosis complex isolates have initiated a discussion on the classification of M. africanum, especially of those isolates originating from East Africa (cluster F, subtype II) and displaying phenotypic and biochemical characteristics more similar to those of M. tuberculosis. To further address this question, we analyzed a representative collection of 63 M. tuberculosis complex strains comprising 30 M. africanum subtype I strains, 20 M. africanum subtype II strains, 10 randomly chosen M. tuberculosis isolates, and type strains of M. tuberculosis, M. bovis, and M. africanum for the following biochemical and molecular characteristics: single-nucleotide polymorphisms (SNPs) in gyrB and narGHJI and the presence or absence of RD1, RD9, and RD12. For all molecular markers analyzed, subtype II strains were identical to the M. tuberculosis strains tested. In contrast, the subtype I strains as well as the M. africanum type strain showed unique combinations of SNPs in gyrB and genomic deletions (the absence of RD9 and the presence of RD12), which proves their independence from M. tuberculosis and M. bovis. Accordingly, all subtype I strains displayed main biochemical characteristics included in the original species description of M. africanum. We conclude that the isolates from West Africa were proved to be M. africanum with respect to the phenotypic and genetic markers analyzed, while the isolates from East Africa must be regarded as phenotypic variants of M. tuberculosis (genotype Uganda). We propose the addition of the molecular characteristics defined here to the species description of M. africanum, which will allow clearer species differentiation in the future.

Pilot randomized double-blind trial of treatment of Mycobacterium ulcerans disease (Buruli ulcer) with topical nitrogen oxides.

Mycobacterium ulcerans disease (Buruli ulcer) is a serious ulcerating skin disease which is common in many tropical countries. Standard treatment, by extensive excision and skin grafting, is not available in rural communities where the disease is common. We evaluated the efficacy and safety of treatment with topical nitrogen oxides. Thirty-seven patients with a clinical diagnosis of Buruli ulcer caused by M. ulcerans disease were randomly assigned to one of two groups. In one group, two creams containing sodium nitrite (6%, wt/wt) or citric acid monohydrate (9%, wt/wt) were applied daily for 6 weeks, while the other group received a placebo. In the second 6 weeks, both groups received the nitrogen oxide-generating combination of creams. Treatment was continued for another 4 weeks for patients whose ulcers were not healed after 12 weeks. The ulcer surface area was monitored by weekly tracings made by assessors blinded to the treatment. In the first 6 weeks, patients on sodium nitrite and citric acid monohydrate (group I, active treatment) showed a rapid decrease in ulcer size from 28.6 +/- 5.6 cm2 (mean +/- standard error) to 12.6 +/- 3.2 cm2, a decrease significantly greater than that in group II (from 15.3 +/- 3.1 to 11.7 +/- 3.7 cm2; P = 0.03). Five ulcers in the placebo group enlarged during this period, compared with one in the active group. In the second 6 weeks (both groups on active treatment), the rates of healing were similar for the two groups and there was a significant reduction in ulcer size in group II (previously on placebo) compared to the first 6 weeks. Yellow pigmentation of the skin, which disappeared 3 days after treatment was stopped, was the only side effect to date. We conclude that creams releasing nitrogen oxides increase the healing rate of ulcers caused by M. ulcerans infection with minimal adverse events. This is the first controlled trial of any form of therapy which demonstrates efficacy in treating this disease.

An outreach education and treatment project in Ghana for the early stage of Mycobacterium ulcerans disease.

Mycobacterium ulcerans disease starts as a painless, subcutaneous nodule, excision of which prevents the development of large Buruli ulcers. An outreach programme was set up in Ghana to promote nodule recognition and excision. The programme was cost-effective and shifted the pattern of disease presentation. This could from a model for other countries.

The efficacy of antifibrinolytics in the reduction of blood loss during complex adult reconstructive spine surgery.

STUDY DESIGN: Controlled study to assess the efficacy of aprotinin and Amicar in reducing blood loss during complex spinal fusions. OBJECTIVES: To compare blood loss and the clotting profile with a thromboelastogram in patients with spinal deformities undergoing sequential anterior and posterior spinal fusions treated intraoperatively with either aprotinin or Amicar. SUMMARY OF BACKGROUND DATA: Spinal fusion for correction of adult spinal deformities is associated with large blood losses despite the implementation of multiple factors to reduce this blood loss. The antifibrinolytics aprotinin and Amicar have both been shown to reduce blood loss in other surgical procedures with the potential for large blood loss. Hence, we compared their efficacy for reducing blood loss in complex spinal fusions. METHODS: Sixty patients for elective sequential anteroposterior thoracolumbosacral fusions were randomly assigned to three groups: control, aprotinin, and Amicar. Patients were assessed for blood loss, transfusion requirements, postoperative complications, and coagulation profile using a thromboelastogram. RESULTS: The study demonstrated a significant reduction in total blood loss (aprotinin 3628 mL, Amicar 4056 mL, control 5181 mL) and transfusion requirements using the half-dose aprotinin regimen compared with Amicar or control. Aprotinin also preserved the thromboelastogram mean clot formation time, clot strength, and clotting index compared with Amicar or control. CONCLUSIONS: For complex spinal operations with large blood losses, the half-dose aprotinin regimen will reduce blood loss and the need for blood components and may have a role in reducing postoperative lung injury.

Depletion of wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment.

Ivermectin is the drug used for mass chemotherapy of onchocerciasis within the WHO African Programme for Onchocerciasis Control. This approach aims to eliminate the disease as a public health problem but using one dose per year may not completely interrupt transmission since it does not suppress microfilaridermia thoroughly enough. Here we show that additional treatment with doxycycline, previously shown to sterilise adult female worms for a few months by depletion of symbiotic wolbachia endobacteria, significantly enhances ivermectin-induced suppression of microfilaridermia, rendering anti-wolbachia treatment a promising basis for blocking transmission by a drug-based approach.

Clinical value of routine preoperative magnetic resonance imaging in adolescent idiopathic scoliosis. A prospective study of three hundred and twenty-seven patients.

BACKGROUND: The prevalence of intraspinal pathology associated with scoliosis has been reported to be as high as 26% in some series, and, on the basis of this finding, preoperative magnetic resonance imaging is used in the screening of patients with adolescent idiopathic scoliosis. However, this practice continues to be highly controversial. In order to better resolve this issue, we performed what we believe to be the largest prospective study to evaluate the need for preoperative magnetic resonance imaging in patients with adolescent idiopathic scoliosis requiring arthrodesis of the spine. METHODS: A total of 327 consecutive patients with adolescent idiopathic scoliosis were evaluated between December 1991 and March 1999. All patients in the study presented with an adolescent idiopathic scoliosis curve pattern and had a complete physical and neurologic examination. Magnetic resonance imaging of the brain and the spinal cord were performed as part of their preoperative work-up. RESULTS: Seven patients had an abnormality noted on magnetic resonance imaging. These abnormalities included a spinal cord syrinx in two patients (0.6%) and an Arnold-Chiari type-I malformation in four (1.2%). One patient had an abnormal fatty infiltration of the tenth thoracic vertebral body. No patient required neurosurgical intervention or additional work-up. All patients who underwent spinal arthrodesis with segmental instrumentation tolerated the surgery without any immediate or delayed neurologic sequelae. CONCLUSIONS: The fact that magnetic resonance imaging did not detect any important pathology in the large number of patients in this study strongly suggests that magnetic resonance imaging is not indicated prior to arthrodesis of the spine in patients with an adolescent idiopathic scoliosis curve pattern and a normal physical and neurologic examination.

Surgical treatment of adolescent idiopathic scoliosis: a comparative study of two segmental instrumentation systems.

This study compares two different surgical techniques and instrumentation types in the treatment of adolescent idiopathic scoliosis. The charts and radiographs of 116 patients with adolescent idiopathic scoliosis treated by posterior spine fusion with Isola or Cotrel-Dubousset instrumentation were reviewed. Patients were separated into two equivalent groups matched for age, sex, curve type, and curve magnitude. All patients had a minimum of 2 years follow-up. The instrumentation in group 1 consisted of hooks, wires, and pedicle screws. That used in group 2 was limited to hooks and rods. The Mann-Whitney, Wilcoxin, and the paired Student t tests for matched pairs were used for statistical analysis. Patients in group 1 had increased curve correction (66% vs. 52%), apical vertebral translation (63% vs. 30%), and correction of the end vertebral tilt angle (11 degrees vs. 3 degrees) (p < 0.001). The percentage of coronal curve correction in curves larger than 65 degrees also was greater in group 1 (59% vs. 40%). Physiologic sagittal alignment was obtained in 80% of the patients in group 1 and 25% in group 2. No major complication or pseudoarthrosis occurred in either group. This study supports improved correction of curve magnitude, apical translation, and end vertebral tilt angle with the use of multiple anchor types compared with the correction achieved with standard hook-and-rod constructs.

Multiple vertebral osteotomies in the treatment of rigid adult spine deformities.

STUDY DESIGN: Retrospective review of the clinical and radiographic results in adult revision spine deformity surgery using the techniques of osteotomies to effect spine balance and curve correction. OBJECTIVES: To assess the efficacy of multiple vertebral osteotomies in correction of rigid spine deformities in adult patients undergoing revision surgery. METHOD: The records and radiographs of 27 adult patients with idiopathic scoliosis who underwent revision surgery requiring anterior release (discectomy and/or osteotomy) and posterior osteotomy to correct rigid spinal deformities were retrospectively reviewed. RESULTS: All 27 patients were available for follow-up evaluation. Fifteen patients had anterior discectomies followed by posterior osteotomies, whereas 12 had anterior and posterior osteotomies in staged or sequential (same day) fashion. Diagnosis was idiopathic scoliosis for the index operation. At revision, the primary deformity was flatback deformity in 10 patients and pseudarthrosis with progressive deformity in 17 patients. Eleven patients had predominant sagittal decompensation, 11 patients had multiplanar decompensation, and five patients were balanced. The average number of osteotomies performed anteriorly was 4.3 levels (range, 1-8) and the average number of osteotomies posteriorly was 4.6 levels (range, 1-10). There were a total of nine complications in eight patients including three pseudarthroses (11%), five hardware failures (19%), and one transient neurologic deficit (4%). There were no deep wound infections, deep vein thromboses, pulmonary emboli, or deaths. The average scoliosis correction was 40% (range, 5-81%), whereas the average sagittal balance was corrected 6.5 cm (range, -5-29.5 cm), on average, and coronal balance was corrected 2.5 cm (range, 1-6 cm), on average. CONCLUSION: This study demonstrates multiple vertebral osteotomies (anterior and/or posterior) in the management of rigid adult spine deformities and deformity correction with an acceptable complication rate. Use of vertebral osteotomies for patients undergoing revision spine surgery is a safe and reasonable approach to obtain an arthrodesis.

Medical complications in scoliosis surgery.

Several medical complications can occur after scoliosis surgery in children and adolescents. They include the syndrome of inappropriate antidiuretic hormone; pancreatitis; cholelithiasis; superior mesenteric artery syndrome; ileus; pnemothorax; hemothorax; chylothorax; and fat embolism. This review focuses on the pathophysiology, diagnosis, and treatment of the various conditions that occur after correction of spinal deformity. Attention is given to recent literature specifically related to scoliosis surgery. Surgical complications like urinary tract infection, wound infection, and hardware failure will not be addressed.

Evidence of lung injury during reconstructive surgery for adult spinal deformities with pulmonary artery pressure monitoring.

STUDY DESIGN: Observational analyses of 55 adult patients who underwent elective sequential anterior-posterior thoracolumbosacral surgical corrections for spinal deformities were used to evaluate the efficacy of pulmonary artery catheter monitoring. OBJECTIVE: To demonstrate that during complex reconstructive surgery for spinal deformities, pulmonary artery catheter monitoring identifies a subset of patients with pulmonary injury and is essential in their management. SUMMARY OF BACKGROUND DATA: Patients who undergo sequential anterior-posterior thoracolumbosacral surgical corrections for spinal deformities experience significant perioperative morbidity. Although the value of pulmonary artery catheter monitoring is controversial, its use in these procedures may help identify potential physiologic complications and improve surgical outcome. METHODS: All patients were monitored with a pulmonary artery catheter during surgery until at least postoperative day 1. Outcome measurements included blood loss, vertebral levels fused, operative time, postoperative respiratory complications, and days in intensive care. RESULTS: Eight (8/55; 14.5%) patients according to pulmonary artery catheter monitoring demonstrated elevated pulmonary vascular resistance and noncardiac pulmonary edema. These patients had longer operative procedures with greater blood loss and had more postoperative respiratory complications. They were treated appropriately in intensive care and discharged without further complications. CONCLUSION: Pulmonary artery catheter monitoring of patients who undergo complex spinal fusion facilitates the identification of patients with pulmonary injury and is essential in the management of these patients in the postoperative period. It may, also, be a marker for embolic injury to the lung.

The incidence of protrusio acetabuli in Marfan's syndrome and its relationship to bone mineral density.

Twenty-one patients with Marfan's syndrome participated in a study to assess the incidence of and radiographic measurements significant for protrusio acetabuli. Our data show that the incidence of protrusio acetabuli in Marfan's syndrome is 31%. The most sensitive radiographic parameter to determine protrusio acetabuli is crossing of the acetabular line by the iliopectineal line. The presence of protrusio in Marfan's syndrome was not related to the bone mineral content of the hip and pelvis. Protrusio acetabuli in Marfan syndrome's also did not correlate with clinical symptoms. Based on our results, the presence of protrusio acetabuli alone is not an indication for early surgical intervention.

Endosymbiotic bacteria in worms as targets for a novel chemotherapy in filariasis.

Endosymbiotic bacteria living in plasmodia or worm parasites are required for the homoeostasis of their host and should be excellent targets for chemotherapy of certain parasitic diseases. We show that targeting of Wolbachia spp bacteria in Onchocerca volvulus filariae by doxycycline leads to sterility of adult worms to an extent not seen with drugs used against onchocerciasis, a leading cause of blindness in African countries.