Outbreak of zoonotic cutaneous leishmaniasis with local dissemination in Balkh, Afghanistan.

OBJECTIVES: In Afghanistan zoonotic cutaneous leishmaniasis (CL) due to Leishmania major has been less widely reported than anthroponotic CL due to L. tropica. However, an outbreak of zoonotic CL occurred amongst a group of British soldiers at a military camp near Mazar-e-Sharif in the Balkh province of northern Afghanistan in 2004. METHODS: A study was performed to assess the epidemiology, clinical features, parasitology results, treatment outcomes and environmental health measures associated with this incident. RESULTS: Twenty (17%) of 120 soldiers developed CL due to L. major and the risk of infection increased with the proximity of their accommodation to an area of recently cleared scrub, where many wild rodents were observed. Most cases had features of local dissemination, including secondary lesions from the pseudo-Koebner phenomenon, sporotrichoid lymphatic spread, lymphadenopathy and satellite papules or milia formation around healing lesions. Several cases responded poorly to fluconazole and low dose (10 mg/kg) sodium stibogluconate, which were considered suitable treatments at the time. Environmental health measures at the military camp were found to be deficient. CONCLUSIONS: Zoonotic CL due to L. major is a significant threat for foreign troops based in Balkh, Afghanistan and may present with unusually severe clinical features and be resistant to previously recommended treatments.

Helminth infections in British troops following an operation in Sierra Leone.

One hundred and fifty-three British soldiers and 86 Royal Air Force (RAF) personnel were deployed on a hostage rescue operation in Sierra Leone. For 3 days they were exposed to various infection risks and 6 weeks later some of the soldiers presented with gastrointestinal complaints. Both groups were screened with structured questionnaires, blood investigations and (where indicated) faecal microscopy and charcoal culture for helminths. Definite and probable cases of helminth infection were treated with albendazole and all soldiers were screened again after 3 months. Among the soldiers investigated, 73/145 (50%) reported gastrointestinal symptoms and 70/139 (50%) had eosinophilia. Among these, 17/66 (26%) had hookworm infection, 6/66 (9%) had Strongyloides stercoralis infection and 1/66 (2%) had Giardia lamblia infection. Eosinophilia was most strongly associated with entering the enemy camp and being in the platoon that attacked the area around the camp latrines. Among RAF personnel, who were not involved in activities on the ground, 3/86 (3%) had borderline eosinophilia. Treatment of 105/153 (69%) soldiers with albendazole was well tolerated and, on follow-up screening 3 months later, 23/124 soldiers (19%) had gastrointestinal symptoms and 18/121 (15%) had eosinophilia. Faecal investigations and schistosomiasis serology tests were all negative at this stage.

Birth outcomes following prenatal exposure to fluoxetine.

BACKGROUND: Although pregnancy has frequently been described as a time of emotional well-being, some women experience significant antenatal depression that may require treatment with antidepressants. The purpose of this investigation was to examine the relative effects of early and late trimester exposure to fluoxetine and perinatal outcome. METHODS: Obstetric and neonatal records were reviewed for 64 mother-infant pairs where there was documented use of fluoxetine at some point during pregnancy. Differences in several measures of obstetrical outcome and neonatal well-being were examined in early trimester- and late trimester-exposed infants. RESULTS: No differences in birth weight and acute neonatal outcome were evident across the two groups, though there was a higher frequency of special care nursery admissions for infants with exposure to fluoxetine late in pregnancy. Special care nursery admissions could not be attributed to any specific factor. CONCLUSIONS: Given the growing numbers of women who are treated with antidepressants, including fluoxetine, during pregnancy, and the strong association between depression during pregnancy and risk for postpartum depression, patients may be best advised to continue treatment with antidepressants through labor and delivery versus making any change in intensity of treatment during the acute peripartum period.

Calcium, magnesium, and phosphorus metabolism in dogs given intravenous triacetin.

Previous studies suggested that acetate in parenteral solutions may adversely affect mineral metabolism by causing sequestration of inorganic phosphate and calcium in the liver. In this study, triacetin, a short-chain triglyceride of acetate and a potential parenteral nutrient, was infused for 3 h at an isocaloric rate in mongrel dogs (n = 6) to test its effects on serum phosphorus, calcium, and magnesium metabolism. There was no change in serum P or Ca. The serum Mg concentration decreased from 0.7 +/- 0.03 to 0.57 +/- 0.03 mmol/L (p less than 0.001) by 90 min and remained at this level for the remainder of the study. The triacetin infusion did not influence fractional urinary Mg excretion; thus, the decrease in serum Mg was likely because of an increase in cellular transport of this cation. A short-chain triglyceride administered to dogs at a rate approximating resting energy expenditure has no demonstrable adverse effects on mineral metabolism.

Effect of parenteral administration of short-chain triglycerides on leucine metabolism.

The present studies investigated the effects of intravenous administration of the short-chain triglyceride triacetin on leucine metabolism in dogs. Animals received infusions of triacetin at 1.0 x estimated resting energy expenditure (REE), hyperenergetic triacetin at 1.5 x REE, glycerol, or saline during infusion of [1-14C]leucine. During both triacetin infusions, plasma alpha-ketoisocaproate concentrations increased (P < 0.05). During triacetin infusion at 1.5 REE, the plasma leucine concentration decreased (P < 0.05) and leucine rate of appearance decreased by approximately 19% (P < 0.05); this was significantly greater than the changes that occurred during triacetin at 1.0 x REE and glycerol (P < 0.05). There was no difference in leucine oxidation between the dogs given triacetin at 1.0 x REE and control groups, whereas leucine oxidation decreased by 53% during triacetin infusion at 1.5 x REE (P < 0.05). Nonoxidative leucine disappearance, an indicator of protein synthesis, did not change in any of the studies. These results indicate that triacetin has effects on leucine metabolism similar to those previously reported with long-chain triglyceride emulsions. Because of its water solubility, lack of toxicity, and favorable effects on protein metabolism, further studies are warranted regarding the use of triacetin as a parenteral nutrient.

Parenteral nutrition with short- and long-chain triglycerides: triacetin reduces atrophy of small and large bowel mucosa and improves protein metabolism in burned rats.

The effect of total parenteral nutrition with combinations of long-chain triglycerides (LCTs) and triacetin, the water-soluble triglyceride of acetate, on structural components of the gastrointestinal tract and protein metabolism was assessed in burned (30% body surface area) rats. Rats received isovolemic, isocaloric, and isonitrogenous diets that delivered 672 kJ.kg-1.d-1 (160 kcal.kg-1.d-1), 9.6 g amino acids.kg-1.d-1, and 30% nonprotein calories as 90% triacetin/10% LCTs, 50% triacetin/50% LCTs, or 100% LCTs for 7 d. Daily and cumulative nitrogen balances and whole-body leucine kinetics and fractional protein synthetic rates in rectus muscle and liver were determined on the last day of nutrition. DNA, protein, and total weight were determined in mucosal scrapings from segments of jejunum and colon. Plasma acetate concentrations were substantially higher in both triacetin groups. Parenteral nutrition with 50% triacetin and 50% LCTs promoted a positive nitrogen balance similar to that of 100% LCTs, increased protein in rectus muscle and liver, smaller and more numerous mucosal cells in jejunum and colon, and increased colonic mucosal weight compared with the other groups. Triacetin did not appreciably affect whole-body and tissue leucine kinetics. The equicaloric provision of triacetin and LCTs improved protein utilization and structural components of the small and large bowel and reduced the development of intestinal mucosal atrophy associated with conventional parenteral nutrition in burn injury.

Fatty acid composition of adipose tissue in aged rats: effects of dietary restriction and exercise.

Little is known about the long-term effects of diet restriction, exercise, and aging on the fatty acid composition of adipose tissue. To investigate these effects, male Wistar rats were placed in one of four experimental groups: 1) ad libitum fed, nonexercised; 2) ad libitum fed, exercised; 3) diet restriction, nonexercised; and 4) diet restriction, exercised. Exercise consisted of swimming on alternate days, and diet-restricted animals were fed every other day. Animals were assigned to one of the four treatment groups at weaning, and the fatty acid composition in the epididymal, perirenal, and inguinal fat depots were determined every 4 months from 12 to 28 months of age. All animals were fed the same diet so the relative percentage of fatty acids in the diet did not contribute to the changes observed in adipose tissue fatty acid composition. Regardless of treatment groups and fat depot, the concentration of saturated fatty acids in adipose tissue tended to decrease as body weight increased. Saturated fatty acid composition was greater in the diet-restricted than the ad libitum-fed groups. The saturated fatty acid concentration was different between the three fat depots (perirenal 27.8%, inguinal 24.7%, and epididymal 21.6%; P < 0.001). The linoleic acid content did not change with age in the epididymal or perirenal fat depot; however, the change was significant for the inguinal fat depot. Following a large decrease in inguinal linoleic concentration through 20 months, linoleic acid concentration increased in all treatments between 20 and 28 months. The results indicate that diet restriction, exercise, and aging have significant effects on adipose tissue fatty acid composition and these effects are different depending on the anatomical location of the adipose tissue depot.

Effects of intravenous methyl palmoxirate on the turnover and oxidation of fatty acids in conscious dogs.

Methyl palmoxirate (MP) is a member of a class of hypoglycemic agents that inhibit fatty acid oxidation in vitro. The studies presented here were undertaken to determine the effects of intravenous (IV) MP on tracer-determined rates of fatty acid oxidation and systemic adipose tissue lipolysis in dogs. MP (40 mg/kg) was administered IV to five mongrel dogs using a primed continuous infusion of [1-14C]palmitate to determine palmitate kinetics. Palmitate concentration and rate of appearance decreased rapidly (from 155 +/- 25 to 47 +/- 6 mumol/L and 2.9 +/- 0.5 to 0.9 +/- 0.2 mumol.kg-1.min-1, respectively, at 15 minutes, both P less than .05). Palmitate oxidation also decreased, from 1.5 +/- 0.4 to 0.3 +/- 0.1 mumol.kg-1.min-1, P less than .05. Oxidative clearance decreased by approximately 50% 90 minutes after MP administration (P less than .05). Fractional oxidation of palmitate also decreased by approximately 40% (P less than .05). Plasma insulin increased from 45 +/- 6 to 240 +/- 93 pmol/L at 15 minutes (P less than .05). Plasma glucose decreased over the course of study by approximately 20% (P less than .05). In summary, MP has a specific inhibitory effect on plasma free fatty acid (FFA) oxidation in dogs, confirming previous in vitro observations in an in vivo model. In addition, it has a potent antilipolytic effect when administered IV, an effect likely mediated by stimulation of insulin secretion. The observation that systemic FFA oxidation was only partially suppressed at this relatively high dose of MP is consistent with previous studies suggesting that MP may exert its major effect in the liver, and may be less potent in extrahepatic tissues.

Metabolism of ketone bodies by skeletal muscle in starvation and uncontrolled diabetes.

Previous studies have suggested that skeletal muscle may be responsible for as much as 25% of ketone body (KB) production in poorly controlled diabetes. In the present studies, acetoacetate (AcAc) and beta-hydroxybutyrate production was quantitated in the canine hindlimb from surgically placed arterial and venous catheters in conscious insulin-withdrawn diabetic (n = 5) and 4-day fasted (n = 7) dogs. A two-pool modeling technique, using simultaneous infusions of 13C acetoacetate and 14C beta-hydroxybutyrate (beta OHB) was employed to quantitate total body and hindlimb KB kinetics. Total KB production was 9.4 and 39.3 mumol.kg-1.min-1 in the fasted and diabetic animals, respectively. Hindlimb KB production was negligible in both groups. The two-pool model estimates of hindlimb KB utilization were similar to the values obtained by an arterial-venous difference calculation. In conclusion, the hindlimb does not contribute to de novo synthesis of KBs in either fasted or diabetic dogs. Since species differences in KB metabolism occur, it is possible that muscle may be a site for KB production in humans.

Chronic Strongyloides stercoralis infection in former British Far East prisoners of war.

BACKGROUND: Chronic infections with the nematode worm Strongyloides stercoralis can occur in former WWII Far East prisoners of war (FEPOWs). The condition may be asymptomatic, but frequently causes a characteristic urticarial 'larva currens' rash. Under conditions of immunosuppression (particularly systemic corticosteroid treatment) potentially fatal dissemination of larvae ('hyperinfection') may occur. AIM: To review our total experience of strongyloidiasis in former FEPOWs, and investigate its prevalence, characteristics and risk factors. DESIGN: Retrospective case series. METHODS: We reviewed 2072 records of all FEPOWs seen at the Liverpool School of Tropical Medicine, 1968-2002. Cases with strongyloidiasis were compared with non-infected controls. RESULTS: There were 248 (12%) with strongyloidiasis. Diagnostic features included larva currens rash (70%), eosinophilia (66%), positive faecal culture (30%), positive faecal microscopy (26%), and positive serology (64%). Mean (+/-SD) age of cases was 65 +/- 7 years, and as expected, their blood eosinophil counts were significantly higher than controls (775 vs. 238 x 10(6)/l, p < 0.001). Captivity on the Thai-Burma Railway (vs. elsewhere) was significantly associated with strongyloidiasis (78% cases vs. 40% controls, OR 4.19, CI 2.70-6.81, p < 0.001). In terms of prevalence, strongyloidiasis occurred in 166/1032 men imprisoned on the Burma Railway (16.1%). Malaria (88% vs. 69%, p < 0.001) and tropical ulcer (53% vs. 42%, p < 0.02) were more common amongst cases than controls, probably because these diseases were very common on the Burma Railway. DISCUSSION: S. stercoralis infection is common amongst ex-FEPOWs, particularly those from the Thai-Burma Railway project. It is usually characterized by a 'larva currens' rash and marked eosinophilia. The condition is eminently treatable, and continued diagnostic surveillance is needed, if cases of potentially fatal hyperinfection are to be avoided.

A comparison of parasitological methods for the diagnosis of gambian trypanosomiasis in an area of low endemicity in Côte d'Ivoire.

The card agglutination test for trypanosomiasis (CATT) was used to examine 8974 inhabitants in 14 village areas south-west of Daloa, Côte d'Ivoire; 114 (1.3%) were CATTT or +/-, and were further examined by one or more of 6 methods for the direct detection of trypanosomes: lymphatic gland puncture, stained thick blood film (TBF), haematocrit centrifugation technique (HCT), mini-anion exchange column (MAEC), quantitative buffy coat method (QBC), and kit for in vitro isolation of trypanosomes (KIVI). Trypanosomes were seen by at least one method in 16 (14.0%) of the CATT+ group. Blood from 356 of the 8860 CATT- group was inoculated into KIVI; trypanosomes grew from the blood of 1 person. Eleven of the 17 patients with detectable trypanosomes were screened by all 6 methods: 6 were HCT+; 7 were gland+; 10 were MAEC+; 10 were KIVI+; 11 were both TBF+ and QBC+. One CATT+ patient was KIVI+ but otherwise negative, although TBF was not done. The overall prevalence of trypanosomes was 0.2% rising to 0.8% in one village area. The results support previous evidence that a reappraisal of procedures is required in the customary system of surveillance for gambian sleeping sickness.

Isolation of Trypanosoma brucei gambiense from northern Uganda: evaluation of the kit for in vitro isolation (KIVI) in an epidemic focus.

867 individuals from 3 sites near the town of Adjumani in the East Moyo region of north-west Uganda were investigated clinically and serologically for evidence of current trypanosome infections. Blood samples were taken from 94 persons with a positive card agglutination test for trypanosomiasis (CATT) and clinical suspects and inoculated into the kit for in vitro isolation of Trypanosoma brucei gambiense (KIVI). Amongst this group, 30 parasitaemic individuals were identified by microhaematocrit centrifugation and the quantitative buffy coat technique (QBC). Only 80% of these isolates, and one isolate from an aparasitaemic individual, grew in culture. The success or failure of cultures from parasitaemic patients was unrelated to the size of the trypanosome inoculum. The implications of these results and possible reasons for the failure of KIVI are discussed.

A British Second World War veteran with disseminated strongyloidiasis.

A case is described of a 78-year-old British veteran of the Second World War (1939-45) who was stationed in Southeast Asia and who developed a recurrent pneumonia with blood eosinophilia. He was treated with steroids, and eventually died with a severe Pseudomonas pneumonia. Just prior to death, larvae of Strongyloides stercoralis were identified in his sputum, and a specific serum ELISA test was later positive. At autopsy no other organs were involved, but bronchoalveolar carcinoma was found. Longstanding (57 years) chronic strongyloidiasis in a veteran who served in Southeast Asia but who was not a prisoner of war is very unusual. The pattern of dissemination was also not that of a true hyperinfection syndrome, and the case demonstrates the continued need for diagnostic vigilance amongst former soldiers who were based in the Far East.

Immunodiagnosis of Strongyloides stercoralis infection: a method for increasing the specificity of the indirect ELISA.

Indirect enzyme-linked immunosorbent assay (ELISA) allows sensitive detection of serum immunoglobulin (Ig) G against a soluble extract of Strongyloides stercoralis infective larvae. In this study, 40/40 (100%) human strongyloidiasis sera had high levels of anti-S. stercoralis IgG, but 30/40 (75%) filariasis sera, and 12/40 (30%) necatoriasis sera also had higher levels than control sera from UK residents. In attempts to increase the assay specificity by absorption of cross-reactive IgG, the effectiveness of pre-incubation of sera with extracts of different parasitic nematodes was investigated. One hour of incubation with 20 micrograms/ml aqueous extract of Onchocerca gutturosa absorbed cross-reactive IgG in most filariasis and necatoriasis sera, reducing the proportion with IgG levels above the positivity threshold by more than one-half. Preliminary results suggest that absorption with extracts of other filarial nematodes is equally effective, and that some of the cross-reactive IgG is directed against phosphorylcholine. Cross-reactive IgG in most necatoriasis sera was effectively absorbed with 20 micrograms/ml extract of Necator americanus. Cross-reactive IgG was not effectively absorbed with an extract of Ascaris lumbricoides. Absorption of cross-reactive IgG is an effective means of increasing the specificity of the indirect ELISA, for use in the immunodiagnosis and immuno-epidemiology of S. stercoralis infection.

Humoral responses in human strongyloidiasis: correlations with infection chronicity.

Strongyloides stercoralis L3-specific antibody isotype responses amongst individuals with known long-standing (28-46 years) infection were compared with those of 'young' (6-29 years of age) and 'old' (30-80 years of age) infected individuals from an endemic Jamaican population. Characterization of age-dependent isotype patterns in the endemic community showed that immunoglobulin (Ig) G1 responses were significantly inversely correlated with age. Additionally, a trend towards lower IgE levels in the older age group was observed. Comparison with responses amongst known chronically infected individuals showed that IgG1 and IgE levels were similar to those of the 'old' endemic group, but were significantly lower than those of the 'young' group. In contrast, IgA levels were similar in both endemic groups, but were elevated in chronically infected individuals. IgG4 levels were similar in all groups studied. These findings suggest that age correlates with infection chronicity in communities endemic for S. stercoralis, and that individuals acquire infection early in their lives and remain infected into adulthood. Early and sustained upregulation of IgG4 may facilitate the establishment of infection and, in combination with developing IgE hyporesponsiveness, may promote chronic asymptomatic strongyloidiasis. Conversely, upregulated IgA may be involved in controlling chronic infection levels which are reflected in reduced IgG1 production.

Triacetin: a potential parenteral nutrient.

UNLABELLED: Triacetin, the water-soluble triglyceride of acetate, was infused in mongrel dogs at isocaloric (N = 6) or hypercaloric (approximately 1.5 REE, N = 7) rates in mongrel dogs for 3 hr. Ketone body and glucose production rates were quantified with [13C2] acetoacetate and [3H]glucose, respectively. Four additional animals were infused with glycerol to serve as controls for the hypercaloric triacetin infusion. Energy expenditure was determined in the isocaloric experiments. RESULTS: no evidence of acute toxicity was observed during triacetin infusion at either rate. Plasma acetate concentrations increased from basal levels to approximately 1 and approximately 13 mmol/liter in the isocaloric and hypercaloric experiments, respectively. Plasma lactate and pyruvate concentrations decreased dramatically after 30 min of both isocaloric and hypercaloric triacetin infusions. Glucose production rates did not increase in either group, but glucose clearance decreased significantly in both groups (p less than 0.05) over the last hour of triacetin infusion. Plasma ketone body concentrations increased from 1.4 to 3.5 and 1.8 to 13.5 mumol/kg.min, respectively, during isocaloric and hypercaloric triacetin infusion. Resting energy expenditure increased from 3.0 +/- 0.3 to 4.0 +/- 0.5 kcal/kg.hr during isocaloric triacetin infusion (p less than 0.05). These studies indicate that triacetin can be administered to dogs at high rates without overt toxicity. The decrease in glucose clearance may represent competition between carbohydrate (glucose) and lipid (acetate). Triacetin infusion resulted in significant increases in ketone body production and concentration. These preliminary data indicate that triacetin may have a future role as a parenteral nutrient, and that further studies of its use are warranted.

Effects of the short-chain triglyceride triacetin on intestinal mucosa and metabolic substrates in rats.

Diets containing either triacetin (the water-soluble triglyceride of acetate) or long-chain triglycerides (LCTs) were fed to rats to determine the effects on intestinal mucosa cells and plasma substrates. Male Sprague-Dawley rats were fed one of three diets, a control diet containing 5% of energy as LCTs or one of two experimental diets that contained 30% of energy as lipid. The lipid component of the two experimental diets was either 100% LCTs or 95% triacetin/5% LCTs. Plasma lactate, glucose, and total ketone body concentrations were not significantly different among dietary treatment groups. Compared with animals fed LCTs and control diet, plasma pyruvate and free fatty acid concentrations were decreased in animals fed triacetin. In contrast, plasma triglyceride concentrations were elevated in animals fed triacetin compared with other groups. Intestinal biochemical measures included total DNA, RNA, protein, and the protein:DNA ratio. Histologic indices measured were villus height in the jejunum and crypt depth in the colon. No significant difference in mucosal protein concentration was observed in the jejunum and colon. Jejunal RNA was significantly decreased in animals fed triacetin compared with other diets. Triacetin feeding significantly increased the DNA content in the jejunum and colon (thereby lowering the protein:DNA ratio), indicating smaller, more numerous cells. Jejunal villus height and colonic crypt depth were not significantly different among dietary treatment groups. Provision of a balanced diet containing 28.5% of the total calories as triacetin had no adverse effects on metabolic substrates and resulted in smaller and more numerous mucosal cells in the jejunum and colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence that dietary arachidonic acid increases circulating triglycerides.

Male Syrian hamsters and male CD-1 mice were fed diets supplemented with ethyl esters of oleic, linoleic, arachidonic, and eicosapentaenoic acids (1.1-5%, w/w) for 3-4 wk. Plasma and serum triglycerides were significantly higher in the arachidonic acid-supplemented animals compared to those in the other supplementation groups. Changes in serum insulin and glucose levels did not appear to be related to the changes in circulating triglycerides observed in the arachidonic acid-supplemented group. These data indicate that dietary arachidonic acid elevates circulating triglyceride levels compared to other unsaturated fatty acids in hamsters and mice by unknown mechanisms.

Anemia and intestinal parasitic infections in primary school students in Aracaju, Sergipe, Brazil.

Anemia is estimated to affect half the school-age children and adolescents in developing countries. The main causes are parasitic infections, malaria, and low iron intake. This study aimed to describe the prevalence of anemia, parasitic infections, and nutritional status of children attending public primary schools in Aracaju, Northeast Brazil. Of 360 students, 26.7% were anemic, and prevalence was higher in children under 8 and over 15 years of age. Overall prevalence of intestinal parasites was 42%, with Ascaris lumbricoides (28.7%), Trichuris trichiura (15.6%), and hookworm (1. 7%) most frequently found. There was an association between parasitic infections and poor sanitary conditions, but there was no association between anemia and presence of intestinal parasites. Height-for-age Z scores were lower than the NCHS standard, and prevalence of stunting was 5.4%. Although intestinal parasites were not associated with anemia, children with parasites had lower nutritional indices (weight- and height-for-age Z scores) than those without parasites.

The quantitative buffy coat for the diagnosis of trypanosomes.

The use of quantitative buffy coat (QBC) tubes developed for malaria diagnosis is described in the diagnosis of African trypanosomiasis. One hundred and thirty-four patients with Trypanosoma gambiense were examined using QBC plus either haematocrit (HCT) or mini anion exchange centrifugation (MAEC) or both. QBC was the only method that detected all 134 patients. QBC proved to be the most sensitive diagnostic test for the detection of trypanosomes in blood. It is simple to use, gives fast results and would be a useful test at the district hospital level.