Annual mass treatment with albendazole might eliminate human oesophagostomiasis from the endemic focus in northern Ghana.

As a follow-up to the study by Ziem et al., in this issue, efforts to control human oesophagostomiasis and hookworm infections in northern Ghana were pursued, and the results evaluated in collaboration with the Lymphatic Filariasis Elimination Programme. This phase of evaluation of the impact of mass treatment was no longer limited to a small-scale research setting: it was done both in the context of an operationally viable national control programme and as a continuation of the Oesophagostomum Intervention Research Project (OIRP). The methods of evaluation included classical stool examination with Kato thick smears, stool culture and ultrasound examination of the colon wall. The results showed that yearly population-based albendazole-ivermectin treatment in 11 villages scattered over north-eastern Ghana, with a treatment coverage of 70-75%, resulted in a reduction of Oesophagostomum prevalence from about 20% pre-intervention to less than 1% after 2 years of mass treatment. Simultaneously, hookworm prevalence went down from 70% to approximately 15%. The data, however, cannot be readily compared with those of Ziem et al. because of the relatively crude diagnostic (single stool cultures) screening system that had to be used for the evaluation of the large-scale control programme. In the research area of the OIRP, interruption of mass treatment resulted in a rising hookworm prevalence. The Oesophagostomum prevalence, on the other hand, continued to go down. Transmission of human oesophagostomiasis appears interruptible and small numbers of persistent cases of Oesophagostomum infection were shown insufficient to serve as a nucleus of renewed spread of the infection. The data suggest that both the infection with and the pathology due to human oesophagostomiasis can be eliminated and that elimination is likely to be achieved through operationally feasible albendazole-ivermectin treatment as used by the Global Alliance for the Elimination of Lymphatic Filariasis.

Mass treatment with albendazole reduces the prevalence and severity of Oesophagostomum-induced nodular pathology in northern Ghana.

Previous surveys conducted in northern Ghana where Oesophagostomum bifurcum is endemic showed that O. bifurcum-induced nodular pathology could be detected in up to 50% of the inhabitants. The impact of albendazole-based mass treatment to control both infection and morbidity is assessed and compared with the situation in a control area where no mass treatment has taken place. A significant reduction in the prevalence of infection based on stool cultures was achieved following two rounds of mass treatment in one year: from 52.6% (361/686) pre treatment to 5.2% (22/421) 1 year later (chi(1)(2)=210.1; P<0.001). At the same time, the morbidity marker of ultrasound-detectable nodules declined from 38.2% to 6.2% (chi(1)(2)=138.1; P<0.001). There was a shift from multinodular pathology, often seen in heavy infections, to uninodular lesions. In the control villages where no treatment took place, O. bifurcum infection increased from 17.8% (43/242) to 32.2% (39/121) (chi(1)(2)=9.6; P<0.001). Nodular pathology decreased slightly from 21.5% to 19.0%, but a higher proportion of these subjects developed multinodular pathology compared with baseline (chi(1)(2)=5.5; P=0.019). It is concluded that repeated albendazole treatment significantly reduces O. bifurcum-induced morbidity.

Oesophagostomum bifurcum-induced nodular pathology in a highly endemic area of Northern Ghana.

Human infection with Oesophagostomum bifurcum is rare globally, but focally endemic and common in Ghana and Togo. Two clinical presentations are identified: uni-nodular disease, which may be recognized as a 'Dapaong Tumour', and multi-nodular disease. Here, we describe the prevalence of O. bifurcum infection and the association with nodular pathology in northern Ghana. The study was performed in October 2002. Out of a well-defined population of approximately 18000, 928 subjects of all ages were randomly selected for parasitological and ultrasound examination. In stool cultures, 44% had detectable third-stage O. bifurcum larvae present. Females were more often infected than males (P<0.05). In 34% of the samples, nodules were detected along the colon wall, with the ascending and the transverse colon being the most affected regions. Significant correlations existed between the intensity of infection and the presence of nodules, both at the village and the individual level (P<0.001 for both). Patients with multi-nodular pathology had significantly higher larval counts than patients with uni-nodular pathology. The present data suggest that nodular pathology, and probably the severity of the disease, are directly related to intensity of the infection.

Intraobserver and interobserver variation of ultrasound diagnosis of Oesophagostomum bifurcum colon lesions.

Infection by the nematode Oesophagostomum bifurcum is focally distributed in Africa and causes a syndrome of abdominal pain, obstruction, or abdominal mass because of its predilection for invasion of colonic mucosa. To determine the reliability of ultrasound for the detection of colon pathology induced by this parasite, three studies to assess the intraobserver and interobserver variation of the technique were performed. In an area of northern Ghana endemic for O. bifurcum, 181 people from a low-prevalence village and 62 people from a high-prevalence village were examined twice by the same observer, and 111 people were independently examined by two observers in a moderately endemic village. The kappa statistics for the prevalence observations in the three studies were 0.82, 0.87, and 0.81, respectively, and kappa values for the intensity observations were 0.66, 0.63, and 0.71, respectively. The upper 95% confidence intervals of the average absolute difference in nodule size measurements in Study 1 and Study 3 were 3.6 and 4.5 mm, respectively. Therefore, ultrasound is useful in the diagnosis and management of O. bifurcum colon infection.

Ultrasonographic detection and assessment of preclinical oesophagostomum bifurcum-induced colonic pathology.

In northern Ghana and Togo, Oesophagostomum bifurcum infects an estimated 250,000 people, as determined by cultures of stool samples. The juvenile stages of the helminth develop within colonic wall nodules, causing Dapaong tumor or multinodular disease, at the rate of 1 case per week at Nalerigu Hospital in Ghana. Our aim was to discover whether suspected colonic-wall pathology is ultrasonographically visible in asymptomatic individuals living in the area where O. bifurcum is endemic. A total of 464 persons from 3 villages, ranging from highly infected to noninfected, were examined with ultrasonography. Anechogenic colonic lesions with posterior wall enhancement were observed in 71 (54.2%) of 131 and 57 (24.5%) of 233 persons from the villages of endemicity, and no lesions were seen in persons from the village outside the area of endemicity. We describe the lesions noted in this study as nodules caused by O. bifurcum, on the basis of their association at a population level with prevalence of larvae in stools, their expected ultrasonographic appearance and distribution (on the basis of our surgical experience with oesophagostomiasis), and the lack of a convincing differential diagnosis.

Evidence for a long-term effect of a single dose of praziquantel on Schistosoma mansoni-induced hepatosplenic lesions in northern Uganda.

Treatment with praziquantel reduces the prevalence and intensity of Schistosoma mansoni infection. However, reversibility of periportal fibrosis of the liver, which potentially leads to fatal complications, is not unequivocally substantiated. In the Nile District of Uganda, 460 patients were parasitologically (Kato-Katz method) and ultrasonographically examined during October 1991, October 1992, and May 1994. Treatment with praziquantel at a dosage of 40 mg per kilogram of body weight was given in October 1991 and October 1992 to 460 individuals (group A). Another 192 patients were seen during the baseline study in October 1991 and missed the follow-up in October 1992 but took part in the second follow-up in May 1994. Thus, they received praziquantel only once in October 1991 (group B) and had an interval of 2.7 years until the next investigation in May 1994. Periportal thickening (PT) of the liver was assessed by ultrasound at each time point. Praziquantel therapy reduced the prevalence of S. mansoni in group A from 84% in 1991 to 31% in 1992 and 30% in 1994. The respective intensities of infection (geometric means of egg output) were 81 eggs per gram (epg) of stool in 1991, 31 epg in 1992, and 30 epg in 1994. Periportal thickening was found in 46% of patients in 1991, 32% of patients in 1992, and 35% of patients in 1994. Reversibility of PT was influenced by age (markedly lower reversibility in individuals older than 30 years) and sex (women and girls responded less favorably than did men and boys). Surprisingly, no significant difference was detected between group A and group B with respect to reversibility of PT The outcome between the 2 groups did not differ significantly. This may indicate that a single dose of praziquantel (as given to group B) may have a longer lasting effect than previously thought, that is, more than 2.5 years.

Schistosoma mansoni-related morbidity on Ukerewe Island, Tanzania: clinical, ultrasonographical and biochemical parameters.

One thousand six hundred and ninety-five inhabitants of 3 rural villages on Ukerewe Island, Lake Victoria, Tanzania, were examined by clinical, parasitological, ultrasonographic and--in part--serological means to evaluate Schistosoma (S.) mansoni-related morbidity on a community level. Villagers frequently complained of typical colitis symptoms (abdominal pain 80.1%, bloody stools 43.1%, diarrhoea 35.1%); haematemesis, on the other hand, was rare (and reports doubtful in most cases). 16.9% of the population had been given praziquantel previously. Overall S. mansoni prevalence was 86.3%, with a median egg output of 176 eggs per gram (e.p.g.) and maximum output of 17,984 e.p.g. Children and adolescents were infected more severely than adults, men more severely than women. Pretreated individuals excreted significantly fewer ova (median 124 vs 192e.p.g., P < 0.001). Hepatomegaly (determined by ultrasonography) was present in 35%, splenomegaly in 80%. Organomegaly was significantly related to egg output. Pretreated persons had lower rates of splenomegaly and left lobe hepatomegaly. Low-degree periportal fibrosis was common, while severe grades of fibrosis (MANAGIL score II and III) were present in about 6%. About 10% had other abnormalities on liver sonography (irregular parenchymal texture and/or shape); these person passed significantly more S. mansoni ova than others. Clear sonographic signs of portal hypertension were seen in 2.1%. Serum procollagen-IV-peptide and gamma-glutamyl-transferase levels were increased in persons with severe periportal fibrosis, irregular liver texture of portofugal collateral vessels. Thus, S. mansoni infection in the western part of Ukerewe Island is frequent and often severe, leading to a high prevalence of gastrointestinal symptoms. Hepatosplenic involvement does occur, although symptomatic cases of portal hypertension were not identified beyond doubt. The overall level of schistosomal morbidity is thus considered intermediate. Serum procollagen-IV-peptide may be a promising marker of schistosomal liver disease. Our data suggest that S. mansoni infection may also be related to diffuse liver parenchyma alterations in this area.

Serum erythropoietin levels in patients with sepsis and septic shock.

The role of the immune system in the control of the production of erythropoietin is still poorly understood. Herein, the levels of circulating immunoreactive erythropoietin, tumour necrosis factor alpha, interleukin-1 beta and interleukin-6 were determined in 10 septic patients for up to 4 d following the admission to an internal intensive care unit. The data show that the production of erythropoietin was not suppressed despite an increase in the levels of proinflammatory cytokines. Circulating erythropoietin and interleukin-6 greatly increased in the 6 nonsurviving patients. The pattern of the serum erythropoietin level in the nonsurvivors resembled that of acute phase proteins and was independent of the blood haemoglobin concentration. Similar to interleukin 6, abnormally high serum erythropoietin levels appear to be a negative prognostic indicator in patients suffering from septic shock.

Amanita phalloides intoxications in a family of russian immigrants. Case reports and review of the literature with a focus on orthotopic liver transplantation.

Alpha-amanitin, the main toxin of the death cap fungus (Amanita phalloides) is one of the most dangerous natural poison. This toxin damages eukaryotic cells by inhibiting their transcription. Lesions are seen in cells with rapid protein synthesis, particular in liver and renal cells, even at low toxin concentrations. Without adequate intensive therapy, the outcome of alpha-amanitin poisoning is very poor. This article reports various courses of amanitin intoxication in a family. In 3/4 patients, severe hepatic failure developed as assessed by a decrease of all coagulation factors, mainly Quick's test and factor V (< 10%-15%). Despite vigorous replacement of coagulation factors, in 1 of the patients orthotopic liver transplantation had to be performed on day 4, whereas in all other patients liver function improved spontaneously. All patients survived their intoxication. Both the pharmacological basis and clinical manifestations of Amanita intoxication are discussed. On this basis a treatment scheme is presented which the authors believe may be useful to clinicians.

[Pregnancy, labor and postpartum development after kidney transplantation and triple therapy with cyclosporin A--follow-up in relation to literature review]. / Schwangerschaft, Entbindung und postpartale Entwicklung nach Nierentransplantation und Triple-Therapie mit Cyclosporin A--Eine Verlaufsbeschreibung im Spiegel der Literatur.

This report pertains to a 26-year old primigravida three years after kidney transplantation and still on immunotherapy. Her pregnancy progressed without severe complications until the 33rd week of gestation. Then a sudden and rapidly worsening pre-eclampsia led to admission and delivery. The postoperative period was complicated by an episode of severe septic shock. Reported is a review of the literature. Problems following pregnancy after kidney transplantation and triple therapy including Cyclosporin A are pointed out.

Comparative study on the antihypertensive efficacy of torasemide and indapamide in patients with essential hypertension.

In a double-blind randomized multicenter study the antihypertensive efficacy of 2.5 mg torasemide (1- isopropyl-3-([4-(3-methyl-phenylamino)pyridine]-3-sulfony)urea) and 2.5 mg indapamide was compared in patients with essential hypertension, known as responders to diuretic therapy. After a wash-out period of 4 weeks patients with a sitting diastolic blood pressure of 100-115 mmHg were included in the 12-weeks active treatment period. After 4 weeks of treatment with a once daily 2.5 mg dose of each drug, doses could once be doubled if blood-pressure decrease was considered to be insufficient. 66 patients qualified for the statistical evaluation, 32 in the torasemide group and 34 in the indapamide group. In these patients both drugs caused a similar fall in blood pressure leading to a normalization of blood pressure in most of the patients. Serum parameters remained within normal limits. Only serum potassium was significantly lower with 2.5 mg indapamide compared to 2.5 mg torasemide at the end of the study. No side effects were reported for both drugs. As the lowest effective dose of a diuretic should be used for the treatment of hypertensive patients, 2.5 mg torasemide, which is below the threshold dose for significantly enhanced diuresis, seems to be the recommended dose for antihypertensive treatment.

[MR tomography following kidney transplantation]. / MR-Tomographie nach Nierentransplantation.

The results obtained by MR tomography in 30 patients after renal grafting are compared with the clinical and histological data in respect of corticomedullary contrast (CMC). In 22 patients with regular functioning of the transplant the CMC was normal at 19.4%. Eight MR examinations yielded a clearly reduced CMC below 14%. In 7 of these 8 patients it was possible to prove histologically the existence of an acute tubular necrosis or of a transplant rejection. Noninvasive MR tomography yielded an early indication for treating the acute renal transplant rejection without being able to differentiate between such a rejection and acute renal failure.

Defective N-oxidation of sparteine in man: a new pharmacogenetic defect.

Sparteine, an antiarrhythmic and oxytocic drug, is metabolised by N1-oxidation. The sparteine-N1-oxide rearranges with loss of water to 2- and 5-dehydrosparteine. 18 (i.e., 5%) out of 360 subjects were unable to metabolise the drug. These persons, who were designated as nonmetabolisers, excreted almost 100% of the administered dose in urine as unchanged drug. The defective metabolism of sparteine was found to have a genetic basis. Sparteine-N1-oxidation appears to be determined by two allelic genes at a single locus where nonmetabolisers are homozygous for an autosomal recessive gene.

Influence of the defective metabolism of sparteine on its pharmacokinetics.

Sparteine is metabolized by N1-oxidation, which in some subjects is defective. The defect has a pronounced effect on the kinetics of the drug. In nonmetabolisers elimination of sparteine proceeds entirely via renal excretion by a capacity-limited process, 99,9% of the dose being excreted as unchanged drug. In metabolisers the drug is mainly eliminated by metabolic degradation. Pronounced differences in beta-phase half-life and total plasma clearance were observed between metabolisers (156 min; 535 ml . min-1) and nonmetabolisers (409 min; 180 ml . min-1).