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.

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.

Relapse of depression during pregnancy following antidepressant discontinuation: a preliminary prospective study.

OBJECTIVE: Pregnancy has frequently been referred to as a time of emotional well-being for patients. However, systematic data about the risk for relapse of depression during pregnancy are sparse. METHOD: We completed a longitudinal cohort study of thirty-two (N = 32) women with histories of depression who were euthymic at conception and who either discontinued or attempted to discontinue antidepressant therapy proximate to conception. Subjects were prospectively followed across pregnancy once per trimester using structured clinical interviews. Rates of relapse and time to relapse were examined. Factors distinguishing the population with respect to risk for relapse including demographic characteristics and illness history were also examined. RESULTS: Seventy-five percent (N = 24) of patients relapsed during pregnancy. The majority of relapses (79%, N = 19) occurred in the first trimester, and relapse was more prevalent in women with histories of more chronic depression. CONCLUSIONS: Pregnancy is not "protective" with respect to risk for relapse of depression. Careful treatment planning is necessary for those women on antidepressants who plan to conceive or who become pregnant.

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.

The stool examination reports amoeba cysts: should you treat in the face of over diagnosis and lack of specificity of light microscopy?

Amoebiasis is a common clinical diagnosis in tropical settings and clinicians continue to treat asymptomatic carriers diagnosed by light microscopy. A minority of carriers, however, are infected with Entamoeba histolytica and the remaining with the non-pathogenic Entamoeba dispar. We compared the diagnostic results of 298 asymptomatic residents of Aracaju, Brazil, obtained by different diagnostic methods, and ascertained their clinical symptoms, to highlight the implications for practitioners. Fifty-eight (19.4%) specimens were amoebae positive by microscopy. Of these, 38 (13%) were E. histolytica/E. dispar enzyme-linked immunosorbent assay (ELISA) positive and 4 (1%) E. histolytica ELISA positive. The frequent use of anti-amoebic treatment on the basis of non-specific symptoms and the findings of light microscopy tests is not justified. Methods for the specific diagnosis of E. histolytica infection for developing countries are urgently needed.

Zoonotic species of Cryptosporidium are as prevalent as the anthroponotic in HIV-infected patients in Thailand.

The epidemiology of chronic diarrhoea in adults with late-stage HIV infection was investigated in a prospective study in Bangkok, Thailand. During this investigation, 34 Cryptosporidium isolates were obtained from the faeces of 36 patients, with mean CD4(+) counts of only 14 x 10(6) CD4(+) cells/litre (range = 2 x 10(6) - 53 x 10(6)/litre), who had symptomatic cryptosporidiosis. Genotyping of these isolates, by RFLP analysis and DNA sequencing of the hypervariable region of the 18S rRNA gene, indicated that only 17 (50%) were of the C. parvum human genotype. The rest were of C. meleagridis (seven), the C. parvum 'bovine' genotype (five), C. felis (three) and C. canis (two). Extensive genotypic heterogeneity was observed among the C. parvum isolates, and two other isolates, one of C. meleagridis and the other of C. felis, produced atypical restriction patterns and were only identified by sequencing. This appears to represent the first report of C. canis and the 'bovine' genotype of C. parvum in HIV-infected Thai patients.

Obstetrical and neonatal outcome following clonazepam use during pregnancy: a case series.

BACKGROUND: Given the high prevalence of panic disorder in women, treatment decisions are frequently made regarding the use of anti-panic medications during the childbearing years and during pregnancy. The objective of this case series was to evaluate obstetric and neonatal outcome associated with treatment with clonazepam during pregnancy. METHODS: Subjects were 38 women with histories of panic disorder who used clonazepam during pregnancy. Information regarding the amount and duration of clonazepam use during pregnancy was obtained. Obstetrical records describing pregnancy, labor and delivery and infant Apgar scores were obtained for all subjects. Neonatal nursery records were obtained for 27 subjects. RESULTS: Maternal outcome assessed by obstetrical records and acute neonatal outcome assessed by Apgar scores were positive. Based on neonatal records, there were no cases of orofacial anomalies, neonatal apnea, benzodiazepine withdrawal syndromes, or temperature or other autonomic dysregulation. In 2 infants born to the same mother, use of clonazepam and imipramine at the time of delivery was associated with transient neonatal distress. CONCLUSION: Clonazepam use during pregnancy did not appear to be directly related to any obstetric complications during pregnancy, labor, or delivery. There was no evidence of neonatal toxicity or withdrawal syndromes in babies born to mothers who took clonazepam during pregnancy. Absence of serious maternal or neonatal compromise following clonazepam use during pregnancy in these mothers and infants is somewhat reassuring. One case of hypotonia and 1 case of respiratory distress in babies who were exposed to clonazepam in combination with imipramine at the time of delivery may suggest that coadministration of benzodiazepines with other psychotropic medications may require close neonatal observation.

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.

Prevalence of mood and anxiety disorders in women who seek treatment for premenstrual syndrome.

Many women experience symptoms of premenstrual irritability, reactivity of mood, anxiety, and change in appetite and sleep. Whereas some women experience these symptoms exclusively during the premenstrual phase of the menstrual cycle, others may have premenstrual complaints but actually suffer from mood and anxiety symptoms across the entire menstrual cycle. We sought to determine the extent to which women who seek treatment for premenstrual syndrome (PMS) actually suffer from symptoms of sufficient severity and duration to meet formal criteria for mood or anxiety disorders. Two hundred six women who responded to advertisements for a treatment study of premenstrual dysphoric disorder (PMDD) and who were screened by telephone for study eligibility were included in the current investigation. A telephone questionnaire keyed to the Structured Clinical Interview for Diagnosis (SCID-I/P) was used to screen for the presence of current mood and anxiety disorders. Approximately 39% (n = 80) of respondents met criteria for mood or anxiety disorders or both. Mood disorders were noted almost twice as commonly as anxiety disorders. The high prevalence of mood disorders in the sample underscores the need for clinicians to be aware of the overlap between reported PMS symptoms and underlying depressive disorder. Given that early identification and treatment of mood disorder can increase the likelihood of recovery and lower risk for recurrent illness, clinicians should have a low threshold for ruling out mood and anxiety disorders in women with complaints of premenstrual symptoms.

L3 antigen-specific antibody isotype responses in human strongyloidiasis: correlations with larval output.

Autoinfective strongyloidiasis is potentially fatal, yet the majority of infected individuals harbour asymptomatic and chronic infections. The role of humoral responses in modulating autoinfection was assessed by examining antibody isotype responses to filariform larval antigens amongst chronically infected ex-Far East Prisoners of War (exFEPOWs) with longstanding (> 30 years) infection. Serum immunoglobulin (Ig)G1, IgG4, IgE and IgA responses to whole Strongyloides stercoralis L3 extracts and their constituent antigenic components were characterized by ELISA and quantitative immunoblotting. Comparison of two groups of S. stercoralis infected exFEPOWs with and without detectable larvae in stool demonstrated novel trends. Significantly enhanced recognition of six immunodominant antigenic components by IgA was associated with undetectable larval output, as was enhanced IgE recognition of several components. Additionally, IgE and IgG4 exhibited parallel antigen recognition patterns. These findings are consistent with roles for IgA in modulating larval output, for IgE in regulating autoinfection, and for IgG4 in blocking IgE-mediated responses in human strongyloidiasis.

Serum concentrations of antidepressants and benzodiazepines in nursing infants: A case series.

OBJECTIVE: The relative risk of psychotropic medication use in women with puerperal psychiatric illness who are breastfeeding has yet to be quantified adequately. Although the emotional and medical benefits of breastfeeding and adverse effects of maternal depression on infant development are well described, how these absolute benefits weigh against the potential effects of psychotropic drug use during lactation to ultimately guide clinical decisions is still unclear. The objective of this report was to evaluate the extent that psychotropic medications were present in the serum of infants breastfed by mothers treated with antidepressants and benzodiazepines. DESIGN: Serum samples were obtained from 35 nursing infants whose mothers were treated with psychotropic medications while breastfeeding. When a detectable concentration of medication was reported, information regarding infant behavior was obtained by maternal report. SETTING: The Perinatal and Reproductive Psychiatry Program at Massachusetts General Hospital serves as a regional consultation center for the treatment of psychiatric disorders during pregnancy and the postpartum period. PATIENTS: Subjects were mothers referred to the Perinatal Psychiatry Program for consultation regarding the relative safety of psychotropic medication use while breastfeeding. PRIMARY OUTCOME MEASURES: Presence of detectable levels of medication in infants whose mothers breastfed while taking psychotropic medications during pregnancy and/or during the puerperium and the well-being (based on maternal report) of infants who had detectable serum concentrations of medication. RESULTS: Seventy-four percent (n = 26) of infants had serum medication concentrations below the laboratory limit of detection (assay sensitivity 5-50 ng/mL). In the remaining 26% of the sample (n = 9), serum concentrations of psychotropic medications and/or active metabolites were detected. In each of these cases, infants had been exposed to the medication during pregnancy. Medications were not detected in infant serum when mothers had taken these agents solely during the postpartum period. No readily apparent difficulties with the infants were reported by mothers. CONCLUSIONS: These data support the low incidence of infant toxicity and adverse effects associated with antidepressant and benzodiazepine use during breastfeeding. These data also suggest that infant serum monitoring is helpful in the assessment of medication exposure in children of mothers who breastfeed while using psychotropic medications. Given the limited accumulated data regarding serum concentrations of psychotropic medications in breastfeeding infants, no single agent seems to be safer than another. Therefore, choice of pharmacologic treatment should be guided by the likelihood that it will result in restoration of maternal psychiatric well-being.

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.

A nested-PCR-based schizodeme method for identifying Leishmania kinetoplast minicircle classes directly from clinical samples and its application to the study of the epidemiology of Leishmania tropica in Pakistan.

A nested PCR was developed to amplify the variable region of the kinetoplast minicircles of all Leishmania species which infect mammals. Each Leishmania parasite contains approximately 10,000 kinetoplast DNA minicircles, which are unequally distributed among approximately 10 minicircle classes. The PCR primers were designed to bind within the 120-bp conserved region which is common to all minicircle classes; the remaining approximately 600 bp of each minicircle is highly conserved within each minicircle class but highly divergent between classes. The nested PCR generated a strong signal from a minimum of 0.1 fg of Leishmania DNA. Restriction digests of the amplicons from the highest dilutions suggested that minicircles from only a limited number of minicircle classes had acted as template in the reaction. One PCR product was directly sequenced and found to be derived from only one minicircle class. Since the primers amplify all minicircle classes, this indicated that as little as 1/10 of one Leishmania parasite was present in the PCR template. This demonstrated that the nested PCR achieved very nearly the maximum theoretically possible sensitivity and is therefore a potentially useful method for diagnosis. The nested PCR was tested for sensitivity on 20 samples from patients from the Timargara refugee camp, Pakistan. Samples were collected by scraping out a small amount of tissue with a scalpel from an incision at the edge of the lesion; the tissue was smeared on one microscope slide and placed in a tube of 4 M guanidine thiocyanate, in which the sample was stable for at least 1 month. DNA for PCR was prepared by being bound to silica in the presence of 6 M guanidine thiocyanate; washed in guanidine thiocyanate, ethanol, and acetone; and eluted with 10 mM Tris-HCl. PCR products of the size expected for Leishmania tropica were obtained from 15 of the 20 samples in at least one of three replicate reactions. The negative samples were from lesions that had been treated with glucantime or were over 6 months old, in which parasites are frequently scanty. This test is now in routine use for the detection and identification of Leishmania parasites in our clinical laboratory. Fingerprints produced by restriction digests of the PCR products were defined as complex or simple. There were no reproducible differences between the complex restriction patterns of the kinetoplast DNA of any of the parasites from Timargara camp with HaeIII and HpaII. The simple fingerprints were very variable and were interpreted as being the product of PCR on a limited subset of minicircle classes, and consequently, it was thought that the variation was determined by the particular minicircle classes that had been represented in the template. The homogeneity of the complex fingerprints suggests that the present epidemic of cutaneous leishmaniasis in Timargara camp may be due to the spread of a single clone of L. tropica.

Human African trypanosomiasis in south-eastern Uganda: clinical diversity and isoenzyme profiles.

The spectrum of clinical manifestations of trypanosomiasis in south-eastern Uganda is extremely wide. Isoenzyme characterization of trypanosome strains isolated in this area during recent epidemics of sleeping sickness has shown that particular clinical features of the disease can be related to the zymodeme of the causative parasite. For example, B17, part of the 'busoga' group of isolates and a zymodeme identified from central areas of Busoga during outbreaks of sleeping sickness, is associated with severe early features and a high frequency of presentation with a chancre. Isolates belonging to the 'zambezi' group, most of which came from areas close to the lake shores or close to the River Nile, were more heterogenous and were associated with significantly different clinical features: a more chronic, prolonged illness; more frequent presentation with meningo-encephalitis, and less frequent chancres. The clinical spectrum of infection associated with the parasites currently in circulation indicates that the previous endemicity and the early epidemics could be explained on the basis of existing zymodemes.

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.

Acquisition and expression of humoral reactivity to antigens of infective stages of filarial larvae.

Measurement of anti-larval responses in filaria-exposed populations may shed light on the natural history of exposure to Wuchereria bancrofti. Using serum samples obtained by a cross-sectional survey of 172 individuals from two neighbourhoods in Leogane, Haiti, antibody responses directed against infective stage filarial larvae (L3) were assayed by enzyme-linked immunosorbent assay (ELISA), immunofluorescence (IFA), and immunoblot for the presence of anti-larval antibodies. ELISA results indicated that virtually all members of both neighbourhoods mounted an anti-larval antibody response within the first five years of life, suggesting that exposure to infection is universal. In a multiple linear regression analysis that modelled antibody levels as a function of age, gender, microfilaria status, and neighbourhood (as a proxy for transmission intensity), isotype-specific antibody levels were found to be significantly influenced by both age and neighbourhood. Antibodies directed against the surface of L3 also were age-dependent; the prevalence of IgG antibodies detected by IFA was significantly higher in children than in adults. The prevalence of antibody recognition of 16.7 and 72.3 kDa L3 antigens on immunoblots was significantly greater for serum samples from microfilaraemic than amicrofilaraemic persons. These results suggest that antibody responses to larval antigens are influenced to varying degrees by age, transmission intensity, and microfilaraemia status.

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.