Efficacy and safety of adjunctive treatment with perampanel in epilepsy patients.

INTRODUCTION: Epilepsy is a neurological disease with high global prevalence. Almost one-third of epilepsy patients continue having seizures despite adequate treatment. Perampanel has been widely used in the Western countries as an adjunctive therapy for both generalized and focal seizures. Owing to its high cost, the use of perampanel is limited in our country. MATERIALS AND METHODS: We conducted a descriptive, retrospective study among epilepsy patients treated with perampanel. We aimed to assess the efficacy and safety of perampanel as an adjunctive in our hospital. RESULTS AND CONCLUSIONS: From our cohort of 25 patients, most of the patients were either on one or three anti-seizure medications (ASMs) prior to initiation of perampanel. Perampanel was added in 88% of them due to persistent seizures. Twenty-two (88%) patients experienced reduction in seizure frequency. 12% experienced mild side effects, which were leg cramps, hyponatremia and drowsiness. Only 1 patient stopped perampanel due to its side effects. CONCLUSION: Perampanel is a well-tolerated ASM that should be widely used as an adjunctive. More studies with regards to its efficacy and safety involving more centres are encouraged in Malaysia.

Health-related quality of life of Malaysian patients with chronic non-malignant pain and its associated factors: a cross-sectional study.

BACKGROUND: Chronic pain has a major impact on a patient's quality of life, affecting physical and psychological functioning. It has debilitating consequences on social and economic aspects too. This study aimed to explore the status of health-related quality of life (HRQoL) of Malaysian patients suffering from chronic non-malignant pain. METHODS: Four hospitals offering pain clinic services were involved in this multicentre cross-sectional study conducted between June and September 2020. Adult patients who had been diagnosed with non-malignant chronic pain lasting for at least three months and able to communicate in English or Malay language were recruited in this study. Participants were informed about the study and were made aware that their participation was entirely voluntary. A battery of questionnaires consists of the EuroQol-5 dimensions-5 levels questionnaire (EQ-5D-5L) and the EuroQol visual analogue scale (EQ VAS), the Pain Self-Efficacy questionnaire (PSEQ) and the Pain Catastrophizing Scale (PCS) were self-administered by the patients. Besides, a structured questionnaire was used to collect their socio-demographic information, pain condition, sleep quality and working status. Participants' usage of pain medications was quantified using the Quantitative Analgesic Questionnaire (QAQ). RESULTS: A total of 255 patients participated in this study. A median EQ-5D index value of 0.669 (IQR: 0.475, 0.799) and a median EQ VAS score of 60.0 (IQR: 50.0, 80.0) were recorded. Malay ethnicity (Adj. B: 0.77; 95% CI: 0.029, 0.126; p = 0.002) and a higher level of self-efficacy (Adj. B: 0.008; 95% CI: 0.006, 0.011; p < 0.001) were predictors of a better HRQoL, while suffering from pain in the back and lower limb region (Adj. B: -0.089; 95% CI: - 0.142, - 0.036; p = 0.001), the use of a larger amount of pain medications (Adj. B: -0.013; 95% CI: - 0.019, - 0.006; p < 0.001), and a higher degree of pain magnification (Adj. B: -0.015; 95% CI: - 0.023, - 0.008; p < 0.001) were associated with a poorer HRQoL. CONCLUSIONS: These findings suggested that Malay ethnicity and a higher level of self-efficacy were predictors of a better HRQoL in patients with chronic pain, whereas pain-related factors such as higher usage of medication, specific pain site and pain magnification style were predictors of poorer HRQoL.

High intensity non-invasive positive pressure ventilation for refractory decompensated acute hypercapnic respiratory failure in advanced chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a debilitating progressive lung disease characterised by irreversible airflow obstruction. In addition to an increase in morbidity and mortality, exacerbation also results in frequent hospital visits, which place a burden on healthcare systems. Non-invasive positive pressure ventilation (NPPV) with conventional inspiratory pressures is the standard ventilatory support for patients in exacerbation. At present, the use of higher inspiratory pressures through high intensity noninvasive positive pressure ventilation (Hi-NPPV) during an exacerbation remains unknown. We describe a novel application of Hi-NPPV in a patient with acute exacerbation who was refractory to conventional NPPV.

A systematic review of the prevalence of limited health literacy in Southeast Asian countries.

OBJECTIVES: Health literacy is increasingly recognized as a public health concern. Most of the literature on health literacy concentrate in the Western countries. Therefore, this study aimed to systematically review and examine the available studies on health literacy in Southeast Asian countries and estimate its prevalence in this region. STUDY DESIGN: Systematic review. METHODS: A search for relevant articles was carried out using Cumulative Index to Nursing and Allied Health Literature (CINAHL) and MEDLINE (via EBSCOhost), Scopus, Science Direct, PubMed and Google Scholar with multiple search terms. Inclusion criteria comprised articles published in English language and assessing general health literacy. Risk of bias reduced with the involvement of two independent reviewers in the screening of the literature and the quality assessment process. RESULTS: A total of 11 studies were included, which only consist of studies from five countries out of 11 making up the Southeast Asian region. The overall prevalence of limited health literacy varied considerably, 1.6%-99.5% with a mean of 55.3% (95% confidence interval [CI]: 35.1%-75.6%). A much higher prevalence was noted in studies conducted in healthcare settings, 67.5% (95% CI: 48.6%-86.3%). The most common factors associated with limited health literacy were education attainment, age, income and socio-economic background. Other factors identified were gender and health behaviours. CONCLUSIONS: In summary, despite the little evidence available and existences of high heterogeneity among studies, limited health literacy is still prevalent in Southeast Asian countries. Urgent strategies to improve and promote health literacy in the region are highly warranted. Besides, more studies on health literacy with better quality on the methodology aspect are needed.

IGFBP-3 mediates TGF-beta1-induced cell growth in human airway smooth muscle cells.

Both insulin-like growth factor binding protein-3 (IGFBP-3) and transforming growth factor-beta (TGF-beta) have been separately shown to have cell-specific growth-inhibiting or growth-potentiating effects. TGF-beta stimulates IGFBP-3 mRNA and peptide expression in several cell types, and TGF-beta-induced growth inhibition and apoptosis have been shown to be mediated through the induction of IGFBP-3. However, a link between the growth stimulatory effects of TGF-beta and IGFBP-3-induction has not been shown. In this study, we investigated the role of IGFBP-3 in mediating TGF-beta1-induced cell growth using human airway smooth muscle (ASM) cells as our model. TGF-beta1 (1 ng/ml) treatment induced a 10- to 20-fold increase in the levels of expression of IGFBP-3 mRNA and protein. Addition of either IGFBP-3 or TGF-beta1 to the growth medium resulted in an approximately twofold increase in cell proliferation. Coincubation of ASM cells with IGFBP-3 antisense (but not sense) oligomers as well as with an IGFBP-3 neutralizing antibody (but not with control IgG) blocked the growth induced by TGF-beta1 (P < 0.001). Several IGFBP-3-associated proteins were observed in ASM cell lysates, which may have a role in the cellular responses to IGFBP-3. These findings demonstrate that IGFBP-3 is capable of mediating the growth stimulatory effect of TGF-beta in ASM cells.

Insulin-like growth factor-binding protein-3 is partially responsible for high-serum-induced apoptosis in PC-3 prostate cancer cells.

Cells are known to undergo apoptosis when cultured in high serum concentrations. However, the serum factors responsible for this induction of apoptosis have not been identified. The IGF-binding protein-3 (IGFBP-3), a negative growth regulator, is found at concentrations of 5 microgram/ml in serum. We have recently demonstrated that IGFBP-3 induces apoptosis in PC-3 cells, a prostate cancer cell line, at a concentration of 500 ng/ml. In this communication, we demonstrate the role of IGFBP-3 as one of the apoptosis-inducing agents in high serum concentrations. Treatment of PC-3 cells with increasing concentrations (40% to 90%) of intact human serum (HS) resulted in a dose-dependent decrease in cell growth. Valinomycin, an ionophore, was used as a positive control to measure the induction of apoptosis by serum treatment in PC-3 cells. Treatment with 90% serum showed significant suppression of growth (P<0.001) compared with the effect of 10% serum. Treatment with increasing concentrations of HS (40% to 90%) resulted in a dose-dependent increase in apoptosis. Treatment with 90% HS showed a 10-fold increase in apoptotic index compared with cells treated with 10% HS. Treatment of PC-3 cells with IGFs and IGFBP-3-depleted 90% human sera (depleted serum=DS) demonstrated significantly lower levels of apoptosis (50% reduction in the effect of 90% HS) suggesting a role of IGFBP-3 in inducing apoptosis in high serum concentration. Furthermore, treatment with DS supplemented with recombinant IGFBP-3 (500 ng/ml) brought the apoptotic index down close to the level of apoptosis induced by 90% intact serum treatment (P<0.001). However, DS supplemented with physiological concentrations of IGFs (500 ng/ml) showed only partial recovery of cell survival demonstrated by 90% DS. This data indicates that IGFBP-3 is one of the factors in serum that is responsible for high-serum-induced apoptosis.

Persistent high risk of diarrhea among foreigners in Nepal during the first 2 years of residence.

Although numerous studies have shown that diarrhea is the most common illness occurring during the first few weeks of travel, systematic studies of the incidence of diarrhea during long-term residence in developing countries have not been performed. We conducted a cohort study of the incidence and etiology of diarrhea among 77 expatriate adults who had lived in Nepal for <2 years. Persons were followed prospectively for up to 1 year (mean, 9 months). The incidence of diarrhea during the surveillance period was 3.3 episodes of diarrhea per person per year, or 0.27 episodes per person per month. The annual attack rate of specific pathogens was 42% for enterotoxigenic Escherichia coli, 32% for Cyclospora species, 16% for Giardia lamblia, 16% for Shigella species, 10% for Campylobacter species, > or =10% for rotavirus, and 6% for Entamoeba histolytica. This study suggests that adult persons from developed countries who move to developing countries such as Nepal remain at high risk for diarrhea during their first 2 years of residence.

Elevated levels of the IGF-binding protein protease MMP-1 in asthmatic airway smooth muscle.

We have previously demonstrated that the asthma-associated proinflammatory eicosanoid leukotriene D4 (LTD4) is co-mitogenic with insulin-like growth factors (IGFs) in airway smooth-muscle (ASM) cells in vitro. This synergistic effect of LTD4 and IGF on ASM cell growth involves proteolysis of ASM-produced IGF binding proteins (IGFBPs), which are cell growth-inhibitory proteins. We also identified this IGFBP protease to be the matrix metalloproteinase-1 (MMP-1), and showed that this enzyme had a significant role in modulating IGF action in ASM cells. In the present study, we tested the hypothesis that ASM hyperplasia in vivo involves induction of MMP-1 leading to IGFBP proteolysis. We detected the presence of MMP-1 and measured its levels in human airway tissue sections prepared from nonasthmatic and asthmatic subjects. Six nonasthmatic and six asthmatic airway tissue samples were analyzed for immunoreactive MMP-1 through an immunohistochemical detection method. Both the bronchial and tracheal smooth-muscle cells from different regions of the same sample were examined and documented. The immunostaining for MMP-1 was significantly elevated in both the bronchial and tracheal smooth-muscle cells of the airway sections from asthmatic samples relative to that of the nonasthmatic samples. The differences in levels of MMP-1, IGFBP-2, IGFBP-3, and IGFBP proteolytic activity were quantified using densitometric analyses of the ASM tissue extracts that were separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The MMP-1 levels in the asthmatic airway tissue extracts were 12-fold higher than those found in control samples. In addition, IGFBP-2 and IGFBP-3, which we have previously demonstrated to be proteolytic substrates of MMP-1, were found to be cleaved in asthmatic airway tissue extracts. Furthermore, the asthmatic airway extracts contained IGFBP proteolytic activity that was shown by immunodepletion studies to be due to MMP-1. These observations demonstrate that MMP-1 may play a significant role in inducing ASM hyperplasia and airway obstruction in asthma by modulating the IGF axis.

Decreased expression of Wilms' tumor gene WT-1 and elevated expression of insulin growth factor-II (IGF-II) and type 1 IGF receptor genes in prostatic stromal cells from patients with benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common proliferative disorder of unknown etiology. We have previously documented that the insulin-like growth factor (IGF) axis is critical for prostate cell growth and is abnormal in BPH. The type 1 IGF receptor (IGF-1R) is constitutively expressed by most body tissues and plays a significant role in regulating cell proliferation, consistent with the role of its ligands (IGF-I and IGF-II) as important mitogenic factors. The Wilms' tumor gene product (WT-1) is a tumor suppressor that has been shown to be altered in rare kidney tumors and is known to regulate IGF-II and IGF-1R. We investigated the possibility that the expression of prostatic WT-1, IGF-1R, and IGF-II genes is altered in patients with BPH. We utilized primary cultures of prostatic stromal cells grown from normal (n = 9) and hyperplastic (n = 9) surgical specimens and analyzed WT-1, IGF-1R, and IGF-II messenger RNA levels. In all of the BPH cell strains, WT-1 expression (measured by RT-PCR and RNase protection assays) was strikingly lower than that found in normal strains (0-20% of normal, mean 14% of normal, P < 0.01). The expression of both the IGF-1R (300% of normal, P < 0.05) and IGF-II (1000% of normal, P < 0.01) messenger RNAs was higher in BPH strains as compared with normal strains. No changes were seen in stromal cell strains derived from prostatic adenocarcinoma. Thus, in cultured human prostatic stromal cell strains from patients with BPH, decreased WT-1 gene expression is associated with increases in the expression of the IGF-1R and IGF-II genes that are known transcriptional targets of WT-1. These findings indicate that reduced expression of the WT-1 tumor suppressor gene and elevated IGF-1R and IGF-II gene expression may be involved in the pathophysiology of prostatic hyperplasia, implying a new role for the Wilms' tumor gene in nonmalignant states.

Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta1 on programmed cell death through a p53- and IGF-independent mechanism.

Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) is known to block IGF action and inhibit cell growth. IGFBP-3 is thought to act by sequestering free IGFs or, possibly, act via a novel IGF-independent mechanism. Supporting its role as a primary growth inhibitor, IGFBP-3 production has been shown to be increased by cell growth-inhibitory agents, such as transforming growth factor-beta (TGF-beta), and the tumor suppressor gene p53. In this paper, we demonstrate, for the first time, a novel function of IGFBP-3 as an apoptosis-inducing agent and show that this action is mediated through an IGF.IGF receptor-independent pathway. In the p53 negative prostate cancer cell line, PC-3, the addition of recombinant IGFBP-3 resulted in a dose-dependent induction of apoptosis. 125I-IGFBP-3 bound with high affinity to specific proteins in PC-3 cell lysates and plasma membrane preparations. These membrane-associated molecules may serve as receptors that mediate the direct effect of IGFBP-3 on apoptosis. In addition, in an IGF receptor-negative mouse fibroblast cell line, treatment with recombinant IGFBP-3 as well as transfection of the IGFBP-3 gene induced apoptosis, suggesting that neither IGFs nor IGF receptors are required for this action. Furthermore, treatment with TGF-beta1, a known apoptosis-inducing agent, resulted in the induction of IGFBP-3 expression 6-12 h before the onset of apoptosis. This effect of TGF-beta1 was prevented by co-treatment with IGFBP-3-neutralizing antibodies or IGFBP-3-specific antisense thiolated oligonucleotides. These findings suggest that IGFBP-3 induces apoptosis through a novel pathway independent of either p53 or the IGF.IGF receptor-mediated cell survival pathway and that IGFBP-3 mediates TGF-beta1 induced apoptosis in PC-3 cells.

All-trans-retinoic acid increases transforming growth factor-beta2 and insulin-like growth factor binding protein-3 expression through a retinoic acid receptor-alpha-dependent signaling pathway.

Retinoids, including retinol and retinoic acid derivatives, maintain the normal growth and differentiation of human bronchial epithelial cells. The signaling pathways through which retinoids mediate these effects have not been defined. Insulin-like growth factor binding protein-3 (IGFBP-3) and the transforming growth factor-beta (TGF-beta) gene family (beta1-3) were examined as potential components of the retinoid signaling pathway in normal human bronchial epithelial cells. All-trans-retinoic acid (t-RA) increased the levels of TGF-beta2 and IGFBP-3 mRNA and of secreted TGF-beta and IGFBP-3 proteins. An antagonist of retinoic acid receptor-alpha, LG100629, abrogated the increase in TGF-beta2 and IGFBP-3 mRNA levels induced by t-RA. t-RA increased IGFBP-3 mRNA levels transiently from 1 to 6 h, and subsequently a sustained increase began at 72 h, which coincided with the appearance of active TGF-beta in the media. Treatment with TGF-beta2 increased IGFBP-3 mRNA levels, but treatment with latency-associated peptide, which inactivates secreted TGF-beta, did not abrogate the effect of t-RA on IGFBP-3 expression. These findings provide evidence that t-RA increased TGF-beta2 and IGFBP-3 expression through an retinoic acid receptor-alpha-dependent pathway, and the increase in IGFBP-3 expression by t-RA did not require activation of the TGF-beta pathway by autocrine or paracrine mechanisms.

An Open Trial of Trimethoprim Alone against Cyclospora Infections.

Cyclospora is a coccidian parasite that infects the upper intestine and causes a prolonged illness consisting of fatigue, anorexia, and diarrhea. Untreated infections can last for several weeks.1 Trimethoprim-sulfamethoxazole (co-trimoxazole) was found to be an effective treatment for Cyclospora infections in a 1994 study performed in Nepal.2 However, people with known allergies to sulfa drugs cannot take co-trimoxazole. A number of antibiotics have been tried against Cyclospora infections without success, including norfloxacin, tinidazole, diloxanide furoate, and quinacrine hydrochloride. Azithromycin was not successful in a small open trial in 1993.3 Trimethoprim is not chemically related to sulfa, and allergy to co-trimoxazole is usually attributed to the sulfamethoxazole component. In order to find a treatment for people infected with Cyclospora who are allergic to sulfa drugs, we undertook an open trial of trimethoprim alone, in a dose of 200 mg twice a day for 7 days.

Leukotriene D4 induces MMP-1, which functions as an IGFBP protease in human airway smooth muscle cells.

We have previously demonstrated that the asthma-associated proinflammatory eicosanoid leukotriene D4 (LTD4) is comitogenic with insulin-like growth factors (IGF) in airway smooth muscle (ASM) cells. This synergistic effect of LTD4 and IGF on ASM cell growth involves proteolysis of ASM-produced inhibitory IGF-binding proteins (IGFBP). In this report, we analyzed the conditioned media (CM) from LTD4-treated human ASM cells (ASM-LTD4-CM) by Western ligand blotting and demonstrated a marked LTD4-induced reduction in the levels of the intact IGFBP (predominantly IGFBP-2) secreted by these cells. The IGFBP-2 in the ASM-LTD4-CM was identified as lower-molecular-weight fragments by Western immunoblotting. Incubation with 125I-labeled IGFBP demonstrated that an IGFBP protease was induced in the ASM cells in response to LTD4 treatment. Immunodepletion of ASM-LTD4-CM with anti-matrix metalloproteinase (MMP)-1 antibodies demonstrated a dose-dependent reduction of IGFBP proteolysis. Tissue inhibitor of MMP-1 and Batimastat (synthetic) inhibited proteolysis of IGFBP. Immunoblotting the ASM-LTD4-CM with anti-MMP-1 demonstrated a dose-dependent increase in MMP-1 protein. Similar results were also obtained by immunocytochemistry. Collectively, these observations demonstrate that MMP-1 is an IGFBP protease induced by leukotrienes that plays a significant role in modulating IGF action in ASM cells. A similar mechanism may be applicable in vivo in the airways of patients with asthma.

7S nerve growth factor is an insulin-like growth factor-binding protein protease.

Insulin-like growth factor (IGF)-binding protein (IGFBP) proteases modulate IGF action by cleaving IGFBPs into fragments with lower affinity to IGFs, thereby increasing the levels of free IGFs. We have previously documented that prostate-specific antigen (PSA), a serine protease of the kallikrein family, is an IGFBP-3 protease. In this study, we characterized the potential IGFBP proteolytic activity of nerve growth factor (NGF gamma-subunit), which shares high sequence homology with PSA. [125I]IGFBP-3 was cleaved by NGF (but not other kallikreins) at a 3-fold lower concentration than that of PSA, thus proving NGF to be a more potent IGFBP protease than PSA. NGF-generated, lower mol wt IGFBP-3 fragments, detected by immunoblotting and cross-linking to IGFs, had a lower affinity to IGFs than intact IGFBP-3. Unlike PSA, which cleaves primarily IGFBP-3 and -5, NGF also displayed potent proteolytic activity against IGFBP-4 and -6. These data suggest that NGF may be involved in the growth of cells by more than one mechanism. In addition to binding to its receptors, NGF is capable of cleaving IGFBPs and, thus, enhancing IGF action. This synergistic action between NGF and IGF may have important implications on cell growth, development, and repair in the brain and other tissues.

Epidemiology of diarrhea among expatriate residents living in a highly endemic environment.

OBJECTIVE: To determine the etiology of diarrhea among expatriate residents living in a developing country and identify risk factors for travelers' diarrhea that are difficult to evaluate in tourist populations. DESIGN: Clinic based case-control study. SETTING: Primary care travel medicine clinic in Kathmandu, Nepal. PARTICIPANTS: A total of 69 expatriate residents with diarrhea, compared with 120 tourists with diarrhea, and 112 asymptomatic resident and tourist controls, selected systematically during a 1-year period. MAIN OUTCOME MEASURES: Risk factors for diarrhea assessed by questionnaire and pathogen prevalence assessed by microbiologic analysis of stool specimens. RESULTS: The dominant risk factors for diarrhea among expatriate residents included younger age (P = .003), shorter duration of stay in Nepal (P < .001), and eating out in restaurants (P = .01). Eating raw vegetables, salads, fresh fruit, or ice served in restaurants was not significantly associated with diarrhea. Longer duration of residence was linearly correlated with protection. Enteric pathogens were identified in 44 (64%) of 69 residents with diarrhea compared with 100 (83%) of 120 tourists with diarrhea, with enterotoxigenic Escherichia coli, Campylobacter, and Shigella predominant for both groups. Pathogens were also found in stools from 32 (37%) of 87 asymptomatic resident controls and 13 (52%) of 25 tourist controls. The attack rate of diarrhea among expatriates was estimated to be 49% (95% confidence interval, 37% to 61%) per month during the first 2 years of residence. The highest-risk months were April through July. CONCLUSIONS: Diarrhea among expatriates in a highly endemic environment is a persistent risk. The extremely high prevalence of enteric pathogens among asymptomatic persons reflects widespread exposure. The most important risk factors for travellers' diarrhea are difficult to modify, including younger age, duration of stay, eating in restaurants, and seasonality. Preventive dietary recommendations may not be fully protective, suggesting that pretravel advice should emphasize empiric treatment in addition to strategies to avoid exposure.

Prevalence of Cyclospora species and other enteric pathogens among children less than 5 years of age in Nepal.

Stools from 124 Nepalese children aged 6 to 60 months with diarrhea were examined for organisms of the coccidian genus Cyclospora and for other enteric pathogens. Enterotoxigenic Escherichia coli, Giardia Lamblia, Campylobacter species, Cyclospora species, and Cryptosporidium species were the most common pathogens identified. Cyclospora species were detected in none of 74 children < 18 months of age compared with 6 (12%) of 50 children > or = 18 months of age (P = 0.004).

Is Blastocystis hominis a cause of diarrhea in travelers? A prospective controlled study in Nepal.

Although the pathogenicity of Blastocystis hominis has been extensively debated in the medical literature, controlled studies of the association between B. hominis and diarrhea are lacking. We conducted a case-control study among expatriates and tourists in Kathmandu, Nepal, in which we compared the prevalence of the organism among patients with diarrhea to that among a control group without diarrhea. B. hominis was detected in 56 (30%) of 189 patients with diarrhea, compared with 40 (36%) of 112 asymptomatic controls. Patients with diarrhea were significantly more likely to have > or = 10 B. hominis organisms per high-power (400x) field than were controls. However, among the 25 patients with this concentration of organisms, other enteric pathogens were detected in 17 (68%). Only 8 (4%) of 189 patients with diarrhea had > or = 10 B. hominis organisms per high-power field detected in the absence of other pathogens, compared with 5 (5%) of 112 asymptomatic controls. Thus, B. hominis in higher concentrations was not associated with diarrhea. There were no specific symptoms associated with B. hominis infection, and the presence of higher concentrations of the organism in stool was not associated with more-severe symptoms. Despite the high prevalence of the organism among travelers and expatriates in Nepal, the results of this study suggest that B. hominis does not cause diarrhea in this population.

Placebo-controlled trial of co-trimoxazole for Cyclospora infections among travellers and foreign residents in Nepal.

Cyclospora is a coccidian (previously referred to as cyanobacterium-like bodies) that has been implicated in cases of prolonged diarrhoea. The average duration of symptoms is more than three weeks, and no specific treatment has been shown to shorten the illness. A case report suggested that co-trimoxazole may be effective. Expatriate persons with gastrointestinal complaints and cyclospora detected on examination of faeces were recruited from two clinics in Kathmandu, Nepal, between May and August, 1994. Participants were assigned in a randomised, double-blinded manner to receive either cotrimoxazole (160 mg trimethoprim, 800 mg sulphamethoxazole) or placebo tablets twice daily for 7 days. Of 40 patients included in the study, 21 received cotrimoxazole and 19 placebo. There were no significant differences between these two groups in age, sex, time in Nepal, duration or severity of illness, or presence of other enteric pathogens. After 3 days, 71% of patients receiving co-trimoxazole still had cyclospora detected, compared with 100% of patients receiving placebo (p = 0.016). After 7 days, cyclospora was detected in 1 (6%) of 16 patients treated with co-trimoxazole who submitted stool specimens compared with 15 (88%) of 17 patients receiving placebo (p < 0.0001). Eradication of the organism was correlated with clinical improvement. There was no evidence of relapse of infection among treated patients followed for an additional 7 days. Treatment with co-trimoxazole for 7 days was effective in curing cyclospora infection among an expatriate population in Nepal.