187,052 research outputs found
Prevalence and risk factors of Strongyloides stercoralis in Takeo Province, Cambodia
No full textThe threadworm Strongyloides stercoralis, the most neglected helminth, affects an estimated 30-100 million people worldwide. Information on S. stercoralis infection is scarce in tropical and sub-tropical resource poor countries, including Cambodia. We determined S. stercoralis infection prevalence and risk factors for infection in the general population in Southern Cambodia.; A cross-sectional study was carried out between January and April 2011 among 2,861 participants living in 60 villages of Takeo province, using Koga-agar plate culture, the Baermann technique and the Kato-Katz technique on a single stool sample.; Eight intestinal helminth species were diagnosed. Hookworm (31.4%) and S. stercoralis (21.0%) occurred most frequently. Prevalence of S. stercoralis infection increased with age. In all age groups a higher prevalence was found among males than among females (OR: 1.7; 95% CI: 1.4 - 2.0; P > 0.001). Participants who had a latrine at home were significantly less frequently infected with S. stercoralis than those who did not (OR: 0.7; 95% CI: 0.4 - 0.8; P = 0.003). Muscle pain (OR: 1.3; 95% CI: 1.0 - 1.6; P = 0.028) and urticaria (OR: 1.4; 95% CI: 1.1 - 1.8; P = 0.001) were significantly associated with S. stercoralis infection.; S. stercoralis is highly prevalent among the general Cambodian population and should no longer be neglected. Access to adequate diagnosis and treatment is urgently needed
Helminth infection in southern Laos: high prevalence and low awareness
No full textBACKGROUND: Helminthiasis is a public health concern in Lao People’s Democratic Republic (Lao PDR, Laos). This study aimed to understand helminth infection and associated risk factors in relation to existing local knowledge, attitudes and practices regarding worm infections in endemic communities. METHODS: A cross-sectional survey was conducted in 10 randomly selected villages in Saravane district, Southern Laos. Two stool samples obtained from 574 members (aged ≥2 years) of selected households were examined using the Kato Katz method. Household heads (n = 130) were interviewed. Eight focus group discussions (FGDs) and direct observations were performed. Uni- and multivariate logistic regression analyses were conducted to predict infection. Content analysis was conducted for qualitative data. RESULTS: The prevalence of Opisthorchis viverrini, hookworm, Trichuris trichiura, Ascaris lumbricoides and Taenia sp. was 88.7%, 86.6%, 32.9%, 9.8% and 11.5%, respectively. Most individuals were co-infected with O. viverrini and hookworm. More men had multiple helminth infections than did women. Only one-third of household heads had heard about liver fluke before, of which 59.2% associated it with eating raw fish dish. Among the soil-transmitted helminths, roundworm was the most well known (70.8%) but was attributed to raw food consumption (91.3%). Eating raw fish was a common practice (75.4%); few households possessed a latrine (16.1%); less than half of the study participants mentioned health benefits from latrine use and personal hygiene. Focus group discussion participants had a low level of awareness of worm infections; more men liked eating raw fish than did women; some disliked using latrines because they were not used to it and because of their bad smell. Poor personal and village hygiene practices were observed. CONCLUSIONS: This study highlights a high helminth infection rate and poor community awareness of worm and associated risk factors. Only a sound awareness of worm infection and the underlying risk factors may prevent infection and re-infection after treatment
Low risk for transmission of zoonotic Giardia duodenalis from dogs to humans in rural Cambodia
No full textA number of epidemiological studies have demonstrated Giardia as prevalent in both humans and dogs worldwide and have postulated the occurrence of anthroponotic, zoonotic and animal-specific cycles of transmission, which may be geographically and regionally unique in its epidemiology. The aim of this study was to utilise molecular tools to determine the prevalence and compare genotypes of Giardia duodenalis infecting humans and dogs living in a previously identified Giardia-endemic village in rural Cambodia in order to ascertain zoonotic transmission risk.; The prevalence of G. duodenalis in humans and dogs was 18.3% (40/218) and 10.6% (10/94) by PCR, respectively. Molecular characterisation of the small subunit of ribosomal RNA (SSU rRNA) gene, triose phosphate isomerase (TPI) gene and sub-assemblage characterisation of the glutamate dehydrogenase (gdh) gene placed 27.5% (11/40) of Giardia positive humans into assemblage AII and 72.5% (29/40) into assemblage BIII of G. duodenalis. In dogs, 20.0% (2/10) of Giardia-positive samples were characterised as G. duodenalis assemblage BIII, 40.0% (4/10) as assemblage C and 40.0% (4/10) as mix infection between assemblage C and D.; Overall, just over 2% of dogs harboured potentially zoonotic assemblages of G. duodenalis in the studied communities and hence pose a minimal zoonotic risk for the transmission of Giardia to humans
The role of the endoplasmic reticulum in the metabolism of "xenobiotica"
No full textShort-chain dehydrogenase/reductase (SDR) enzymes play a key role in the metabolism of steroids, fatty acids, prostaglandins and xenobiotic chemicals. This thesis investigated the role of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the metabolism of xenobiotics. It further addressed species-specific differences of the inhibition of 11β-HSD1 and some related microsomal SDRs by xenobiotics. 11β-HSD1 catalyzes the conversion of the inactive glucocorticoids cortisone and 11-dehydrocorticosterone to the active cortisol and corticosterone, respectively. Recently, studies using microsomes and the unspecific inhibitor glycyrrhetinic acid (GA) suggested that 11β-HSD1 metabolizes the antidepressant drug bupropion to erythrohydrobupropion (EHB) and threohydrobupropion (THB), and the fungicide triadimefon to triadimenol. In the present work, the role of human 11β-HSD1 in the reduction of triadimefon and bupropion was studied in vitro using the recombinant 11β-HSD1 enzyme, a selective 11β-HSD1 inhibitor and microsomes from liver-specific 11β-HSD1 knock-out mice. Activities were determined using microsomes from human, rat and mouse liver to assess species-specific differences. The results suggest that 11β-HSD1 is the major enzyme responsible for triadimenol formation. Surprisingly, 11β-HSD1 exclusively formed THB but not EHB from bupropion. Due to lower activities of rat and mouse 11β-HSD1 towards these xenobiotics, they are models of limited value to study 11β-HSD1-dependent metabolism of bupropion and triadimefon. A comparison of IC50 values suggests that exposure to these compounds is unlikely to impair the 11β-HSD1-dependent activation of glucocorticoids. In contrast, elevated glucocorticoids during stress or upon pharmacological administration are likely to inhibit 11β-HSD1-dependent metabolism of these xenobiotics.
11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) catalyzes the conversion of the active glucocorticoid cortisol to the inactive cortisone. It has been reported that some organotins and dithiocarbamates are potent inhibitors of human 11β-HSD2. We found that the zebrafish enzyme is not inhibited by these organotins. Furthermore, the dithiocarbamate thiram showed a reduced inhibitory effect on zebrafish 11β-HSD2 compared with the human enzyme. Sequence comparison revealed the presence of an alanine at position 253 on zebrafish 11β-HSD2, corresponding to cysteine-264 in the substrate binding pocket of the human enzyme. Substitution of alanine-253 by cysteine resulted in a more than 10-fold increased sensitivity of zebrafish 11β-HSD2 to thiram. These findings are important, as the zebrafish is a widely used model in ecotoxicology, and 11β-HSD2 is catalyzing the conversion of 11β-hydroxytestosterone to 11-ketotestosterone, the main androgen in fish.
The gene encoding 11β-HSD1 in zebrafish is absent. Therefore, the mechanism how the ratio between active and inactive glucocorticoids is controlled in fish is unclear. It was suggested by a phylogenetic analysis that one of the two ancestors of 11β-HSD1 might reduce cortisone to cortisol. These ancestors are 11β-HSD3a and 11β-HSD3b. We cloned both zebrafish cDNAs and tested them for 11-oxosteroid reductase activity. Furthermore, we examined the metabolism of cortisone in zebrafish microsomes. Our results indicate that the 11-oxosteroid reductase activity is completely absent in zebrafish.
17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) catalyzes the conversion of Δ4-androstenedione to testosterone. We reported earlier that some UV filters inhibit the human enzyme. We tested whether these UV filters also inhibit the zebrafish enzyme. We found interesting species-specific differences of the inhibitory potential of UV filters on human and zebrafish 17β-HSD3. Furthermore, we were able to show additive inhibitory effects of UV filter mixtures and bioaccumulation of UV filters in vitro.
In conclusion, the results presented in this thesis significantly extend the knowledge of the role of 11β-HSD1 in the metabolism of xenobiotics. The thesis further emphasizes the importance of considering species-specific differences when trying to extrapolate effects of xenobiotics observed in animal models to humans
Epidemiology and morbidity of food-borne trematodiasis in Lao People's Democratic Republic with particular consideration to opisthorchiasis
No full textFood-borne trematodes, parasitizing the liver, lung and intestinal tract of
humans, are an emerging public health problem in countries of tropical regions. Today,
an estimated 40 million people are infected worldwide. More than half of those occur
in Asia, particularly in Southeast Asian countries. Infection with food-borne trematode
is associated with divers and severe morbidity, i.e. a long-lasting infection with
Opisthorchis viverrini gives rise to liver fibrosis, cholecystitis and cholangitis and may
induce a malignant cholangiocarcinoma (CCA).
In Lao People’s Democratic Republic (Lao PDR), particularly in the rural
settings the habit of consumption of undercooked or insufficiently cooked food is
frequent and deeply culturally rooted. In addition access to clean water is low and
adequate sanitary facilities are virtually absent, which reflects a socio-economically
disadvantaged situation. These areas are at high risk for the transmission of food-borne
trematodiasis (FBT) and intestinal helminhiasis. The prevalence of these parasites has
an extensive geographical overlap; thus leading in a single person to an infection with
several different species of parasites. The concurrent infection of multiple species, in
turn, might aggravate the morbidity of the host. Five specific objectives were pursued in this Ph.D. thesis: (i) to investigate
the epidemiology of O. viverrini and assess the extent of co-infection with other intestinal
parasites in a highly endemic setting, (ii) to describe the diversity of FBT with intestinal
and hepato-biliar tropism in different eco-epidemiological settings and assess their
contribution to the overall morbidity, (iii) to assess the relationship between socioeconomic
status and food-borne trematode infection, in particular O. viverrini in the
distinct eco-epidemiological settings, and (iv) to assess the concomitant infections of
intestinal parasites in the distinct eco-epidemiological settings and their inter-linking to
the environmental, socio-economic and behavioural risk factors. The data presented in this Ph.D. thesis was obtained from a
series of epidemiological studies. The data pertaining to the epidemiology of O. viverrini
and other intestinal parasites were first obtained from a cross-sectional study carried out
in February and March 2004 in the Saravane district, province of Saravane. Eligible
persons were randomly selected from the district in two steps, i.e. study villages and
households, based on the village register and household register available at the district
health office (DHO) and at village. Two questionnaires were administrated to collect the
data at the individual level (demographic, behavioural and personal hygienic data) and at
the household level (food preparing method with fish, characteristics of household head).
One single stool sample was obtained from each study participant and analysed by using
Kato-Katz technique (KK-technique). Fish species from different local rivers were
collected and examined for the infection with metacercariae. A second cross-sectional study was carried out in March and May 2006 in three
distinct eco-epidemiological settings in Champasack province, i.e. islands in Mekong
River (Khong district), plain area bordering Mekong River (Mounlapamok district) and
highlands (Paksong district). A pre-tested individual questionnaire was used. All enrolled
household members were interviewed for demographic data (e.g. age, sex, educational
attainment and professional activity) and behavioural risks (e.g. food consumption habits
and personal hygiene), whereas a household questionnaire was administered to the heads
of household to collect the socio-economic characteristics (e.g. building type and water
supply), asset ownership (e.g. farm engine and bicycle) and ownership of animals (e.g.
buffalo cow and pig). From each participant three stool samples were collected on
consecutive days. Stool analysis was performed with KK-technique on each sample and
supplemented with formalin-ethyl-acetate concentration technique (FECT) on one of the
samples. The geographical coordinates of each household were registered, using a handheld
global positioning system receiver (Garmin Ltd., Olathe, USA).
The data on morbidity induced by O. viverrini infection and multiparasitism,
especially morbidity related to a single infection with O. viverrini versus species and
double infection with O. viverrini and S. mekongi were obtained from an in-depth
hospital- and community-based study carried out in the year of 2005 and 2006 in the two
referral hospitals (Mahosot and Savannakhet provincial hospital) and communities of three provinces in central and southern Lao PDR (Savannakhet, Saravane and
Champasack). A purgative was added after praziquantel treatment (single oral dose: 40
mg/kg). All diarrhoeal stools produced were collected and repeatedly washed until the
supernatant became clear. The sediment was examined for the presence of adult worms as
follows. First, adult Taenia spp., Echinostoma spp., and O. viverrini worms were visually
searched. Second, the remaining sediment was examined with a stereo-microscope for the
presence of minute intestinal flukes (MIF). The number of each species of parasites was
recorded. Species identification was confirmed under light microscope after specimens
were colored. The detailed clinical data (physical examination, ultrasound examination,
liver function test and whole blood count) were obtained and were additionally associated
to the infection status. Our first study on the epidemiology of O. viverrini infection carried out in
Saravane province showed a high O. viverrini prevalence rate of 58.5% among 814 study
participants. Infection occurred in all age-groups including pre-school children of less
than 6 years (20.0%). The highest prevalence (> 80.0%) and infection intensity (mean
200 epg) was observed among the adult people aged between 45 and 55 years, indicating
an accumulation of this food-borne trematode infection over time. Soil-transmitted
helminths were found at lower rates, e.g. hookworm at 46.1%, A. lumbricoides at 15.7%,
and T. trichiura at 11.1%. Almost two-third of study participants harboured with two or
more parasite species. Examination of cyprinoid fish species in the local rivers showed
the high rates of infection with metacercariae. From 98 fish samples out of 23 cyprinoid
species, almost two-third; the metacercariae were found.
Our investigation in Champasack province revealed an overall prevalence of
O. viverrini infection of 64.3%. There were remarkable differences found between the
settings. High prevalence rates were observed in the low-lands of the Mekong plain (e.g.
Khong district 92.0% and Mounlapamok district 90.9%). In Paksong district the
prevalence was only 5.7%. The occurrence of soil-transmitted helminth infections was
distinctly different. All three major soil-transmitted helminths were higher in the
mountainous Paksong district compared to the settings in the plain (e.g. hookworm
94.8%, A. lumbricoides 85.9% and T. trichiura 55.7%). S. mekongi was highly prevalent
in Kong district (68.0%: 153/225), while only 3.9% (9/232) was observed among study participants living in Mounlapamok. There was no S. mekongi infection in Paksong
district. Regarding multiparasitism, 4 out of 5 study participants harboured two or more
parasite species. Habit of raw food consumption, unavailability of sanitary facilities and
socio-economic disadvantages were identified as being the key underlying risk factors for
O. viverrini infection and multiparasitism.
The results from our in-depth study on morbidity showed that 83% of the
examined person harboured at least 2 parasite species. Six different species of small
intestinal trematodes and one of Echinostomatidae were identified in the purging process.
The intensity of infection with O. viverrini worms varied in our patients. The worm
burden was significantly associated with observed hepato-biliary pathologies, i.e. study
participants diagnosed with common bile duct dilatation, liver fibrosis and intrahepatic
bile duct dilatation had 2.4 times, 3.1 times and 7.7 times higher worm burden than those
without such pathologies. Co-infections of O. viverrini and S. mekongi increased
consistently the risk for liver pathologies. Study participants infected with later coinfections
were at 2 and 6 times and 30 and 75 times higher risk of having the observed
liver fibrosis and hepatomegaly compared to infection with O. viverrini alone and noninfected
individuals, respectively in the ultrasound examination. The prevalence rates and intensity of infection with O. viverrini, and
associated multiparasitism with soil-transmitted helmints, food-borne trematodes and
S. mekongi, and the hepto-biliar morbidity related to these infections call for concerted
actions for control. Long-term and integrated efforts must improved access to preventive
and curative treatment courses in health facilities and the communities coupled with
health education and improved access to clean water and adequate sanitation
Yeast-based strategy for identification of 11β-HSD1 inhibitors
No full textGlucocorticoids are hormones with a vital role in regulation of metabolic and defence responses. Their metabolism plays an important role in the pathogenesis of obesity, a major risk factor for metabolic syndrome, a collection of disorders such as insulin resistance, dyslipidemia and hypertension.
At intracellular level the production of active glucocorticoids is regulated by two hydroxysteroid dehydrogenase enzyme isoforms 11β-HSD1 and 11β-HSD2, respectively. 11β-HSD2 is predominantly expressed in mineralocorticoid target tissues and acts as oxidase catalysing conversion of cortisol into cortisone. The isoform 11β-HSD1, expressed in a wide array of tissues and with highest levels in the liver, acts mainly as a reductase converting the cortisone into the biologically active hormone cortisol, in a NADPH dependent manner. Due to its implication in the metabolism of glucocorticoids, 11β-HSD1 has become a primary target for the treatment of metabolic syndrome.
In the last years many strategies have been developed for the screening of molecules with inhibitory effects against this target enzyme. All known approaches present unique features and are suitable for specific screening models. Nevertheless, due to the great therapeutic and economical interest around the treatment of metabolic syndrome, many research groups are constantly focused on the development of new and more successful strategies for identification of hits with improved pharmaceutical properties.
In this study an innovative synthetic biology platform for synthesis and screening of 11β-HSD1 inhibitors has been conceived and investigated. This strategy is based on the production of diverse chemical scaffolds in the yeast Saccharomyces cerevisiae, in which the molecules are directly screened through intracellular functional assays.
Providing all necessary genetic information, the biosynthetic pathway of plant triterpenoids, a big class of natural compounds with many beneficial effects on human health, was reconstructed in the baker’s yeast. Moreover, by applying DNA family shuffling methods, a library of chimeric triterpenoid synthase cDNAs was constructed. The chimeric sequences, potential carriers of new enzymatic functions, were assembled together with the wild-type molecules in expressible yeast artificial chromosomes (eYACs).
Furthermore, the construction of two yeast assays strains functionally co-expressing the murine glucocorticoid receptor (GR) and the human 11β-HSD1 enzyme is presented. In both developed strains, with different mechanisms, the reductase activity of the enzyme 11β-HSD1 on cortisone is connected with an easily detectable fluorescent signal. Cells that produce compounds with inhibitory activity against 11β-HSD1 can be identified through changes in fluorescence and isolated to further investigate the active molecules. The developed yeast-assays were validated using carbenoxolone, a known 11β-HSD1 inhibitor, and may represent useful tools for a first quick and easy screening of large number of membrane permeable putative inhibitory compounds
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The role of 11β-hydroxysteroid dehydrogenase type 1 in bile acid homeostasis
No full textBile acids (BAs) are important modulators of metabolic functions such as lipid, triglyceride and glucose homeostasis. Intrahepatic accumulation of BAs is known to cause liver injury in cholestatic conditions, where normal trans-hepatic BA flow is impaired due to pathological conditions or induced by toxic drugs. Therefore, it is important to understand the mechanisms of BA homeostasis regulation and to identify novel players and characterize their functions. The main goal of the present work was to investigate the impact of altered hepatic glucocorticoid activation by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on BA homeostasis and to unravel the mechanisms of adaptations in a scenario of impaired 11β-HSD1 function. In order to achieve this goal, we developed and validated an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the quantification of a total of 24 BAs, including 11 unconjugated, 6 glycine-conjugated and 7 taurine-conjugated BAs, in biological matrices (serum/plasma and tissues) and cell culture supernatants. This method was validated and applied in a side project in which potential time-dependent changes of BAs in plasma from sham-operated and uninephrectomized male Sprague-Dawley rats were investigated. Several primary and secondary BAs were transiently elevated one week after uninephrectomy, followed by normalization thereafter. Using liver microsomal preparations and recombinant enzyme we then tested whether 11β-HSD1, in addition to its well-known role in the conversion of inactive to active glucocorticoids, is able to reduce 7-oxo BAs. We found that human 11β-HSD1 reduces the secondary BA 7-oxolithocholic acid (7-oxoLCA) mainly to chenodeoxycholic acid (CDCA) and to lesser amount to ursodeoxycholic acid (UDCA). 11β-HSD1 exclusively catalyzed the oxoreduction of 7-oxoLCA, in contrast to its role in the interconversion of glucocorticoids. The enzyme also metabolized 7-oxoLCA-glycine and -taurine conjugates. Furthermore, we compared 7-oxoLCA metabolism by human 11β-HSD1 with that of other species, including canine, guinea-pig, rat, mouse and hamster and we observed species-specific differences. While recombinant mouse and rat 11β-HSD1 converted 7-oxoLCA to equivalent amounts of CDCA and UDCA, the hamster and canine enzymes were stereoselective, producing mainly CDCA similar to the human enzyme. Surprisingly, guinea-pig 11β-HSD1 did not reduce 7-oxoLCA. The analysis of circulating BA profiles of several species confirmed earlier observations by other investigators, that 7-oxoLCA and its glycine-conjugated (G-7-oxoLCA) metabolite are abundant BAs in guinea-pigs compared with other species. These findings suggest that the lack of 11β-HSD1 oxoreductase activity on 7-oxoLCA in guinea-pigs is responsible for its elevated circulating levels. Next, we hypothesized that 7-oxoLCA might be a biomarker of impaired 11β-HSD1 activity. Analysis of BAs in serum from liver-specific 11β-HSD1 deficient mice revealed 18-, 47- and 7-fold elevation of 7-oxoLCA, its taurine and glycine conjugates compared with wild-type mice, respectively. In addition, 7-oxoLCA and its taurine conjugate were 2- and 6-fold elevated in liver from liver-specific 11β-HSD1 deficient mice. Moreover, BA profiles in serum and liver of liver-specific 11β-HSD1 deficient mice indicated a disturbed BA homeostasis. Circulating and intrahepatic levels of several unconjugated BAs species were up to 16-fold significantly elevated in liver-specific 11β-HSD1 deficient compared with wild-type mice. To pinpoint the molecular mechanism of altered BAs profiles, gene expression analysis was performed. The results suggest FXR-dependent decrease of BA synthesis, a compensatory effect to counteract the intrahepatic accumulation of BAs. In addition, the enzymes responsible for BA conjugation with coenzyme A, an intermediate step in BAs amidation, named VLCS and VLCSH2 displayed significantly lower expression levels in liver from liver-specific 11β-HSD1 deficient compared with wild-type mice. The decreased BA conjugating machinery in the liver of liver-specific 11β-HSD1 deficient mice may account for the elevated intrahepatic levels of unconjugated BAs observed. Moreover, the expression of OATP4, a basolateral BA transporter responsible for the uptake of unconjugated BAs from the circulation into hepatocytes presented reduced expression levels and may account for the significant elevation of several circulating unconjugated BAs found in liver-specific 11β-HSD1 deficient mice.
In conclusion, we demonstrated an important role of 11β-HSD1 in the oxoreduction on 7-oxoLCA and provided evidences that 7-oxoLCA its taurine conjugate are functional biomarkers of impair 11β-HSD1 activity. Circulating concentrations of these 7-oxo BAs may find application in the assessment of the therapeutic efficacy of 11β-HSD1 inhibitors. Moreover, we described for the first time the impact of intrahepatic glucocorticoid regeneration deficiency on BA homeostasis in mice. Our findings indicate that 11β-HSD1 is an important modulator of BAs homeostasis, and potential disturbances of BA homeostasis must be taken into account when assessing the safety of 11β-HSD1 inhibitors, with particular attention to cholestatic patients and patients receiving combined therapeutic regimens with drugs known to induce liver injury
Community-directed intervention against liver fluke and soil-transmitted helminths in endemic areas of southern Laos
No full textBackground: Food-borne trematodiasis (FBT) and soil-transmitted helminth (STH) are neglected tropical diseases (NTDs) and threat human health in Southeast Asia. An estimate 67.3 million people are at risk of FBT caused by Opisthorchis viverrini (O. viverrini). Human infected with this parasite by consumption raw or insufficiently cooked fish dishes. Poor sanitation spreads the infection in environment. High burden of infection cause hepatobiliary diseases and with a longstanding of infection leads to develop cholangiocarcinoma (CCA). Liver fluke, O. viverrini, and STH are major public health problems in Laos. Over two million people are infected with O. viverrini mostly in central and southern Laos. An estimate 1,646,000 people are at risk for the STH. Hookworm is the most predominant species among the STH. Mass treatment alongside with health education is prioritized by Lao Ministry of Health for helminth control. However it is mainly implemented via vertical program that means leaving affected community having passive role for the helminth control. In addition this implementation requires substantial amount of human resource and fund to run the intervention which is challenging for Lao government to support for long-term intervention particularly intervention against liver fluke. In the work of this PhD thesis we developed, implemented and evaluated a community-directed intervention against the liver fluke and STH in southern Lao PDR. It has inspired by the CDTi of onchocerciasis in Western Africa.
Objectives:The main goal of this thesis is to develop an innovative approach, CDI, for the control of liver fluke and STHin southern Laos. Specific objectives were: 1.) to update the knowledge on helminth infection in the last four decades in Laos and the current helminth infection in liver fluke endemic areas in southern Laos; 2.) to understand helminth infections in relation to local community’s knowledge, attitudes and practices regarding worm infections; 3.) to deepen our understanding on consumption of raw fish dishes in relation to liver fluke infection in liver fluke endemic areas of southern Laos; 4.) to assess the community’s perception regarding the deworming intervention in endemic areas of S. mekongi and high prevalence of multiparasitism; 5.) to evaluate the effectiveness of the community-directed intervention against liver fluke and STHin southern Laos; and 6.) to identify factors associated with compliance to the intervention (CDI).
Methods: Five studies in this PhD thesis were community-based investigations and one was a literature review. A cross-sectional study designs was applied and using both quantitative and qualitative research techniques. Quantitative technique included stool examination to assess the prevalence and intensity of helminth infection, and structured interview with heads of households and household members. Qualitative methods comprised of semi-structured interviews, in-depth interviews, focus group discussions (FGD), and observations. Quantitative data were entered twice in Epidata software version 3.1 and analyzed in Stata software version 10.1. Conversations were transcribed from notes and tape-recorders and MAXQDA software version 10 was used for qualitative content analysis. For the literature review, data were obtained from international publications between 1970 and 2013 mainly searching through PubMed database via the website of University of Basel.
Results: Review on helminth infection in the last four decades of Lao PDR showed that currently ascariasis, trichuriasis, and hookworm infection rates are relatively low compared to the 1990s. But this not true for the mountainous and highland areas; hookworm is still a highly prevalent STH. O. viverrini infection rate remains high and even currently higher than before. The advance diagnosis using multiple stool sampling and multiple Kato Katz slides per a stool explains some of the increase. Multiparasitism together with liver flukes infections was observed. The habit of consumption of raw or insufficiently cooked fish dishes and open defecation is common practice in Laos thus it might keep infection and re-infection with O. viverrini in community. However possibilities to intervene on this habit are limited. Nowadays, in endemic area of S. mekongi the infection re-emerged, and children at 5 years of age were found already infected.
A baseline survey conducted in 10 villages of liver fluke endemic areas of Saravane district southern Laos pointed at very high infection prevalence of helminth infection but low level of awareness regarding worm infection. For instance, of 574 subjects the prevalence of O. viverrini, hookworm, Trichuris trichiura, Ascaris lumbricoides and Taenia sp. was 88.7%, 86.6%, 32.9%, 9.8%, and 11.5%, respectively. Most individuals were co-infected with O. viverrini and hookworm (77.3%). More men had multiple helminth infections than women. Of 130 heads of household, one third heard about liver fluke before, of which 59.2% associated it with eating raw fish dishes. Among the STH, roundworm was the most well-known (70.8%) but most people linked it with consumption of raw food (91.3%). Consumption of raw fish dishes was most commonly practiced (75.4%); few households possessed a latrine (16.1%); less than half mentioned health benefits from latrine use and personal hygiene. FGD participants had poor awareness on worm infections; more men liked eating raw fish than women; some disliked using latrine because they did not get used to it and due to its bad smell. Poor personal hygiene practices and village hygiene were observed.
Our result on consumption of raw fish dishes in relation to liver fluke infection in liver fluke endemic areas southern Laos was heterogeneous. The majority of FGD participants considered fish flesh that had been prepared with weaver ant extract (giving sour juice) and that then turned to white colour to be safe for consumption. Visual appearance, taste, smell and personal preference were given as reasons for consumption of raw fish dishes. Moreover, participants considered it a traditional way of food preparation, and practiced for generations in Laos. Ten different fish dishes that use raw or fermented fish were identified. All FGD participants reported to consume raw fish dishes.
In endemic areas of S. mekongiin southern Laos where also multiparasitism prevails, we found that opinion leaders and villagers were well aware of taking deworming during MDA in village. Leaders perceived the effectof MDA against severe schistosomiasis (big belly and patient ended up with vomit a lot of blood) and appreciated that it was provided free of charge in their village. They encouraged villagers to attend and take the drug. Anticipated adverse effect of praziquantel was a barrier for participation. Most leaders purchased deworming (except praziquantel) in a local pharmacy for deworming when MDA was absent in their villages (19/21). Most leaders (20/21) had a good knowledge on severe schistosomiasisthough only a few of them (5/21) described its cause correctly. They knew little about the disease consequences of liver fluke (3/21) and STH (4/21) infections but more about their causes. A high risk for worm infection was observed in community: consumption of raw or insufficiently cooked fish dishes (100%), frequent physical contacts with MekongRiver water (76.0%) and few latrines in village (14.5%).
In Saravane province, after implementing two rounds of CDI against liver fluke and STH we found that the prevalence of O. viverrini, hookworm, roundworm, and whipworm infection was reduced by 26.4%, 38.1%, 45.9%, and 30.3%, respectively. The frequency of multiparasitism was also reduced. Household heads had better knowledge on liver fluke, hookworm, and whipworm infection, means for prevention of liver fluke, and correct association between risk factors with hookworm and whipworm infection. Misconception on acquiring roundworm infection through eating any raw food was frequent. Few heads of households consumed raw fish dishes which was consistent with FGD participants discussed that after taking treatment they felt not eating raw fish dishes anymore and some were afraid of getting liver fluke again. Participants viewed that intervention was effective against liver fluke and other worm infection and prevented diseases. Community leaders had ownership in conducting the intervention.
The factor associated with the compliance to intervention (CDI)was assessed. We found that of 600 interviewees, 46.5% reported to have taken treatment during the mass treatment in village. Those who took treatment were mostly from poor households (p=0.013), aware of intervention (p<0.001), knew that intervention provided treatment for liver fluke (p<0.001) and abdominal pain (p=0.028) and saw the tapeworm in their stool (p=0.016). The majority of respondents heard about liver fluke and roundworm. The compliance with MDA was associated with poverty: very poor (OR=2.13, p=0.018) and poor (OR=2.07, p=0.022), knowing the effectiveness of intervention against liver fluke (OR=1.57, p=0.035) and recognizing about tapeworm infection (OR=2.95, p=0.037). CDDs performed their task quite well though supervision was rarely made by trained health center staff.
In conclusion: We conclude that beside the high prevalence of O. viverrini and STH, community leaders and community members have poor knowledge regarding worm infection and the role of MDA. Risk behaviour for worm infection is observed: eating raw or insufficiently cooked fish does exist due to people loved its taste, smell and look; perceived preparation technique is safe to eat and it is a traditional way, and practiced since generations; poor practice of hand-washing; barefoot walking; poor sanitation and less use latrine due to bad smell and they did not used to it. We also conclude that a new approach CDI is effective against worm infections and corrects community’s knowledge, attitudes and practicesregarding worm infections and mass treatment. Community leaders have ownership and capacity in conducting the CDI. Hence, it is possible to scale up this CDIto other liver fluke endemic areas of Saravane province and later to all southern Laos for the control of liver fluke and co-infected worms
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