ABSTRACT
BACKGROUND: Artemisinins, which are derived from plants, are subject to risk of supply interruption due to climatic changes. Consequently, an effort to identify a new synthetic antimalarial was initiated. A fixed-dose combination of arterolane maleate (AM), a new synthetic trioxolane, with piperaquine phosphate (PQP), a long half-life bisquinoline, was evaluated in patients with uncomplicatedPlasmodium falciparummalaria. METHODS: In this multicenter, randomized, double-blind, comparative, parallel-group trial, 1072 patients aged 12-65 years withP. falciparummonoinfection received either AM-PQP (714 patients) once daily or artemether-lumefantrine (A-L; 358 patients) twice daily for 3 days. All patients were followed up until day 42. RESULTS: Of the 714 patients in the AM-PQP group, 638 (89.4%) completed the study; of the 358 patients in the A-L group, 301(84.1%) completed the study. In both groups, the polymerase chain reaction corrected adequate clinical and parasitological response (PCR-corrected ACPR) on day 28 in intent-to-treat (ITT) and per-protocol (PP) populations was 92.86% and 92.46% and 99.25% and 99.07%, respectively. The corresponding figures on day 42 in the ITT and PP populations were 90.48% and 91.34%, respectively. After adjusting for survival ITT, the PCR-corrected ACPR on day 42 was >98% in both groups. The overall incidence of adverse events was comparable. CONCLUSIONS: AM-PQP showed comparable efficacy and safety to A-L in the treatment of uncomplicatedP. falciparummalaria in adolescent and adult patients. AM-PQP demonstrated high clinical and parasitological response rates as well as rapid parasite clearance. CLINICAL TRIALS REGISTRATION: India. CTRI/2009/091/000101.
Subject(s)
Antimalarials/administration & dosage , Artemisinins/administration & dosage , Ethanolamines/administration & dosage , Fluorenes/administration & dosage , Heterocyclic Compounds, 1-Ring/administration & dosage , Malaria, Falciparum/drug therapy , Malaria, Falciparum/parasitology , Peroxides/administration & dosage , Quinolines/administration & dosage , Spiro Compounds/administration & dosage , Adolescent , Adult , Africa/epidemiology , Aged , Antimalarials/therapeutic use , Artemether , Artemisinins/therapeutic use , Asia/epidemiology , Child , Double-Blind Method , Drug Therapy, Combination , Ethanolamines/therapeutic use , Female , Fluorenes/therapeutic use , Half-Life , Heterocyclic Compounds, 1-Ring/therapeutic use , Humans , India/epidemiology , Lumefantrine , Malaria, Falciparum/epidemiology , Male , Middle Aged , Peroxides/therapeutic use , Plasmodium falciparum/drug effects , Quinolines/therapeutic use , Spiro Compounds/therapeutic use , Young AdultABSTRACT
The recent emergence of artemisinin-resistant Plasmodium falciparum malaria in western Cambodia could threaten prospects for malaria elimination. Identification of the genetic basis of resistance would provide tools for molecular surveillance, aiding efforts to contain resistance. Clinical trials of artesunate efficacy were conducted in Bangladesh, in northwestern Thailand near the Myanmar border, and at two sites in western Cambodia. Parasites collected from trial participants were genotyped at 8,079 single nucleotide polymorphisms (SNPs) using a P. falciparum-specific SNP array. Parasite genotypes were examined for signatures of recent positive selection and association with parasite clearance phenotypes to identify regions of the genome associated with artemisinin resistance. Four SNPs on chromosomes 10 (one), 13 (two), and 14 (one) were significantly associated with delayed parasite clearance. The two SNPs on chromosome 13 are in a region of the genome that appears to be under strong recent positive selection in Cambodia. The SNPs on chromosomes 10 and 13 lie in or near genes involved in postreplication repair, a DNA damage-tolerance pathway. Replication and validation studies are needed to refine the location of loci responsible for artemisinin resistance and to understand the mechanism behind it; however, two SNPs on chromosomes 10 and 13 may be useful markers of delayed parasite clearance in surveillance for artemisinin resistance in Southeast Asia.
Subject(s)
Artemisinins/pharmacology , Drug Resistance/genetics , Genetic Loci/genetics , Plasmodium falciparum/genetics , Selection, Genetic , Asia, Southeastern , Genetic Markers/genetics , Genotype , Likelihood Functions , Odds Ratio , Oligonucleotide Array Sequence Analysis , Polymorphism, Single Nucleotide/genetics , Principal Component Analysis , Regression AnalysisABSTRACT
BACKGROUND: The emergence of artemisinin-resistant Plasmodium falciparum in Southeast Asia threatens malaria treatment efficacy. Mutations in a kelch protein encoded on P. falciparum chromosome 13 (K13) have been associated with resistance in vitro and in field samples from Cambodia. METHODS: P. falciparum infections from artesunate efficacy trials in Bangladesh, Cambodia, Laos, Myanmar, and Vietnam were genotyped at 33 716 genome-wide single-nucleotide polymorphisms (SNPs). Linear mixed models were used to test associations between parasite genotypes and parasite clearance half-lives following artesunate treatment. K13 mutations were tested for association with artemisinin resistance, and extended haplotypes on chromosome 13 were examined to determine whether mutations arose focally and spread or whether they emerged independently. RESULTS: The presence of nonreference K13 alleles was associated with prolonged parasite clearance half-life (P = 1.97 × 10(-12)). Parasites with a mutation in any of the K13 kelch domains displayed longer parasite clearance half-lives than parasites with wild-type alleles. Haplotype analysis revealed both population-specific emergence of mutations and independent emergence of the same mutation in different geographic areas. CONCLUSIONS: K13 appears to be a major determinant of artemisinin resistance throughout Southeast Asia. While we found some evidence of spreading resistance, there was no evidence of resistance moving westward from Cambodia into Myanmar.
Subject(s)
Antimalarials/pharmacology , Artemisinins/pharmacology , Drug Resistance , Malaria, Falciparum/parasitology , Mutation , Plasmodium falciparum/drug effects , Asia, Southeastern , Genotype , Humans , Plasmodium falciparum/genetics , Plasmodium falciparum/isolation & purification , Polymorphism, Single Nucleotide , Protozoan Proteins/geneticsABSTRACT
BACKGROUND: The WHO has reported that RDT and microscopy-confirmed malaria cases have declined in recent years. However, it is still unclear if this reflects a real decrease in incidence in Bangladesh, as particularly the hilly and forested areas of the Chittagong Hill Tract (CHT) Districts report more than 80% of all cases and deaths. surveillance and epidemiological data on malaria from the CHT are limited; existing data report Plasmodium falciparum and Plasmodium vivax as the dominant species. METHODS: A cross-sectional survey was conducted in the District of Bandarban, the southernmost of the three Hill Tracts Districts, to collect district-wide malaria prevalence data from one of the regions with the highest malaria endemicity in Bangladesh. A multistage cluster sampling technique was used to collect blood samples from febrile and afebrile participants and malaria microscopy and standardized nested PCR for diagnosis were performed. Demographic data, vital signs and splenomegaly were recorded. RESULTS: Malaria prevalence across all subdistricts in the monsoon season was 30.7% (95% CI: 28.3-33.2) and 14.2% (95% CI: 12.5-16.2) by PCR and microscopy, respectively. Plasmodium falciparum mono-infections accounted for 58.9%, P. vivax mono-infections for 13.6%, Plasmodium malariae for 1.8%, and Plasmodium ovale for 1.4% of all positive cases. In 24.4% of all cases mixed infections were identified by PCR. The proportion of asymptomatic infections among PCR-confirmed cases was 77.0%, oligosymptomatic and symptomatic cases accounted for only 19.8 and 3.2%, respectively. Significantly (p < 0.01) more asymptomatic cases were recorded among participants older than 15 years as compared to younger participants, whereas prevalence and parasite density were significantly (p < 0.01) higher in patients younger than 15 years. Spleen rate and malaria prevalence in two to nine year olds were 18.6 and 34.6%, respectively. No significant difference in malaria prevalence and parasite density was observed between dry and rainy season. CONCLUSIONS: A large proportion of asymptomatic plasmodial infections was found which likely act as a reservoir of transmission. This has major implications for ongoing malaria control programmes that are based on the treatment of symptomatic patients. These findings highlight the need for new intervention strategies targeting asymptomatic carriers.
Subject(s)
Asymptomatic Infections/epidemiology , Malaria/epidemiology , Plasmodium falciparum/isolation & purification , Adolescent , Adult , Bangladesh , Blood/parasitology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Malaria/blood , Malaria/complications , Malaria/parasitology , Male , Middle Aged , Plasmodium falciparum/genetics , Polymerase Chain Reaction , Prevalence , Seasons , Splenomegaly/epidemiology , Splenomegaly/parasitology , Young AdultABSTRACT
BACKGROUND: Spreading resistance of Plasmodium falciparum to existing drugs calls for the search for novel anti-malarial drugs and combinations for the treatment of falciparum malaria. METHODS: In vitro and ex vivo investigations were conducted with fresh P. falciparum field isolates and culture-adapted P. falciparum clones to evaluate the anti-malarial potential of mirincamycin, a lincosamide, alone and in combination with tafenoquine (TQ), dihydroartemisinin (DHA), and chloroquine (CQ). All samples were tested in a histidine-rich protein 2 (HRP2) drug susceptibility assay. RESULTS: Interaction analysis showed additive to synergistic interaction profiles with these potential partner drugs, with an overall geometric mean fractional inhibitory concentration at 50% inhibition (FIC50) of 0.78, 0.80 and 0.80 for mirincamycin with TQ, DHA, and CQ, respectively. Antagonism was not found in any of the tested field isolates or clones. The strongest tendency toward synergy (i.e. the lowest FIC) was seen with a combination ratio of 1:0.27 to 1:7.2 (mean 1:2.7) for the combination with tafenoquine. The optimal combination ratios for DHA and CQ were 1:444.4 to 1:36,000 (mean 1:10,755.5) and 1:2.7 to 1:216 (mean 1:64.5), respectively. No evidence of an activity correlation (i.e. potential cross-resistance) with DHA, mefloquine, quinine or chloroquine was seen whereas a significant correlation with the activity of clindamycin and azithromycin was detected. CONCLUSIONS: Mirincamycin combinations may be promising candidates for further clinical investigations in the therapy and prophylaxis of multidrug-resistant falciparum malaria or in combination with 4 or 8-aminoquinolines for the treatment and relapse prevention of vivax malaria.
Subject(s)
Antimalarials/pharmacology , Clindamycin/analogs & derivatives , Plasmodium falciparum/drug effects , Adolescent , Adult , Aged , Aminoquinolines/pharmacology , Artemisinins/pharmacology , Child , Chloroquine/pharmacology , Clindamycin/pharmacology , Drug Interactions , Female , Humans , Male , Middle Aged , Parasitic Sensitivity Tests , Plasmodium falciparum/isolation & purification , Young AdultABSTRACT
Although the prevalence of malaria remains high in parts of Bangladesh, there continues to be a substantial shortage of information regarding the less common malaria parasites such as Plasmodium malariae or Plasmodium knowlesi. Recent studies indicate that P. malariae may be extremely rare, and so far, there are no data on the presence (or absence) of P. knowlesi in southeastern Bangladesh. Genus- and species-specific nested polymerase chain reaction (PCR) analysis of the small subunit ribosomal RNA gene was performed to assess the presence and prevalence of P. malariae and P. knowlesi in 2,246 samples originating from asymptomatic and febrile participants of a cross-sectional and a febrile illnesses study in the Chittagong Hill Tracts in southeastern Bangladesh. P. malariae was detected in 60 samples (2.7%) corresponding to 8% of the 746 samples giving positive PCR results for Plasmodium sp., mainly because of the high prevalence (9.5%) among asymptomatic study participants testing positive for malaria. Symptomatic cases were more common (4.3% of all symptomatic malaria cases) during the dry season. Parasitemias were low (1,120-2,560/µl in symptomatic and 120-520/µl in asymptomatic carriers). Symptomatic patients presented mild to moderate symptoms like fever, chills, headache, dizziness, fatigue and myalgia.Although both the intermediate as well as the definite host are known to be endemic in southeastern Bangladesh, no evidence for the presence of P. knowlesi was found. We conclude that the role of P. malariae is highly underestimated in rural Bangladesh with major implications for malaria control and elimination strategies.
Subject(s)
Genetic Variation , Malaria/epidemiology , Plasmodium knowlesi/genetics , Plasmodium malariae/genetics , Adolescent , Adult , Bangladesh/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Malaria/parasitology , Male , Middle Aged , Phylogeny , Polymerase Chain Reaction , Prevalence , Seasons , Young AdultABSTRACT
Dirofilaria immitis is a parasite of domestic and wild canids and felids in tropical, subtropical and temperate regions throughout the world. The canine heartworm (D. immitis) is the causative agent of canine and feline cardiopulmonary dirofilariasis. This parasite is known to cause a zoonotic disease, namely human pulmonary dirofilariasis. D. immitis is known to be endemic in several South and Southeast Asian countries (e.g. India and Malaysia), but there has previously been no information about the presence of this pathogen in Bangladesh. We present a case of canine dirofilariasis caused by D. immitis in rural southeastern Bangladesh. A male filaroid nematode (95 mm in length and 1.94 mm in width) was identified in the heart of a dog. Species classification was performed by microscopy and molecular tools. Sequence analysis revealed a 100 % identity within the mitochondrial cytochrome c oxidase I (CO1) gene to two Chinese and one Australian D. immitis samples. Usually, dogs stay outside overnight with a high risk to get infected with D. immitis via nocturnal mosquito vectors, which may lead to high prevalences of this pathogen in the canine population and thus increase the risk of human infections with this neglected parasitic disease.
Subject(s)
Dirofilaria immitis/isolation & purification , Dirofilariasis/parasitology , Dog Diseases/parasitology , Animals , Bangladesh , Dirofilaria immitis/anatomy & histology , Dirofilaria immitis/classification , Dirofilaria immitis/genetics , Dogs , Electron Transport Complex IV/genetics , Heart/parasitology , Microscopy , Mitochondrial Proteins/genetics , Molecular Sequence Data , Sequence Analysis, DNAABSTRACT
A large variety of ectoparasites parasitizing on livestock, dogs, and rodents are documented throughout the world, of which several are proven vectors for major (including zoonotic) diseases affecting humans and/or livestock. However, there remains a significant lack of knowledge in regard to the ectoparasite fauna in remote regions of the developing world, such as southeastern Bangladesh, and an urgent need to investigate this fauna to improve diagnostic options. In the course of the present study, more than 5,300 ectoparasites were collected by flag dragging and handpicking of livestock, dogs, and rodents in the District of Bandarban (Chittagong Hill Tracts) in southeastern Bangladesh. Three tick species were identified: Haemaphysalis bispinosa (flagging, cattle, goats, and dogs), Rhipicephalus microplus (cattle, goats), and Rhipicephalus sanguineus (dogs, goats, and flagging). H. bispinosa was the dominant tick species on mammalian hosts as well as on vegetation. Furthermore, Ctenocephalides canis (dogs, goats) and Linognatus sp. (goat) were found. Overall, 73 rodents of eight different species (e.g., Mus musculus, Rattus sikkimensis, Bandicota bengalensis, and Niviventer sp.) hosted a variety of ectoparasites such as mites (Laelaps nuttali, Laelaps echidninus, Lyponissoides sp. and Ornithonyssus bacoti), fleas (Xenopsylla cheopis), and one myiasis-causing dipteran species. Monitoring the ectoparasite burden of livestock and other mammals is urgently needed in order to control ectoparasites associated with social and economic burden (e.g., reduced milk production, weight loss). Several zoonotic diseases can be transmitted by ectoparasites in this area, where the majority of the population live in basic housing conditions and in direct contact with livestock, dogs, and rodents.
Subject(s)
Arthropods/growth & development , Ectoparasitic Infestations/veterinary , Animals , Arthropods/classification , Bangladesh , Dogs , Livestock , Prevalence , RodentiaABSTRACT
Malaria is still a major threat in many parts of the world with resistance spreading to almost all classes of antimalarials. The limited arsenal of available antimalarial drugs emphasizes the urgent need for novel antimalarial compounds. Owing to the fact that novel leads from nature have traditionally played a pivotal role in the development of various classes of antimalarials, we investigated a set of eight naturally occurring dietary flavonoids and their analogues for their antiplasmodial activity on clinical field isolates in southeastern Bangladesh and culture-adapted chloroquine-sensitive and chloroquine-resistant parasite clones. Except for taxifolin, all the other flavonoids had 50% inhibitory concentrations below 14 µM, both in the field and laboratory-adapted parasites. Neither of the flavonoids showed any activity correlation with chloroquine. The quercetin analogue rutin (7.10 ± 10.32 µM) was the most active substance in field isolates as well as laboratory-adapted cultures (3.53 ± 13.34 µM in 3D7 and 10.38 ± 15.08 µM in K1), providing the first evidence of its activity against Plasmodium falciparum parasites. Thus, our results provide important evidence of the antimalarial activity of flavonoids in traditional use and thus warrant further investigation of these compounds as potential antiplasmodial agents.
Subject(s)
Antimalarials/chemistry , Antimalarials/pharmacology , Flavonols/chemistry , Flavonols/pharmacology , Malaria, Falciparum/parasitology , Plasmodium falciparum/drug effects , Adolescent , Adult , Aged , Animals , Bangladesh , Child , Female , Humans , Inhibitory Concentration 50 , Male , Middle Aged , Parasitic Sensitivity Tests , Plasmodium falciparum/isolation & purification , Young AdultABSTRACT
The use of direct nested PCR enables the detection of Plasmodium spp. from blood samples collected on filter papers without requiring the time-consuming procedures associated with DNA extraction. Direct PCR provides a rapid, highly sensitive, and cost-effective alternative to diagnosing malaria using filter paper samples and standard nested PCR.
Subject(s)
Blood/parasitology , Clinical Laboratory Techniques/methods , Malaria/diagnosis , Parasitology/methods , Plasmodium/isolation & purification , Polymerase Chain Reaction/methods , Specimen Handling/methods , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cost-Benefit Analysis , Desiccation , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Paper , Polymerase Chain Reaction/economics , Sensitivity and Specificity , Young AdultABSTRACT
BACKGROUND: In recent studies, the combination of azithromycin and artesunate has proven to be a promising alternative for the treatment of uncomplicated falciparum malaria. METHODS: We conducted a randomized, controlled clinical trial assessing the efficacy of azithromycin-artesunate combination therapy. The study was conducted involving 228 patients aged 8-65 years. Patients were randomized to 1 of 2 cohorts at a ratio of 2:1, receiving either azithromycin-artesunate once daily for 3 days (30 mg/kg per day of azithromycin plus 4 mg/kg per day of artesunate) or an adult dose of 80 mg of artemether plus 960 mg of lumefantrine (4 tablets Coartem or the equivalent for children weighing <35 kg) twice daily for 3 days. RESULTS: The 42-day cure rate by Kaplan-Meier analysis was 94.6% (95% confidence interval [CI], 89.38%-97.44%) in the azithromycin-artesunate arm and 97.0% (95% CI, 89.45%-99.40%) in the control arm. Fever clearance times and parasite clearance times did not show any differences between the 2 arms (P=.59 and .95, respectively). No serious adverse events were seen, but the percentage of patients who developed any adverse event was higher in the control group (P=.03). CONCLUSIONS: Our data suggest that azithromycin-artesunate is an efficacious and well-tolerated treatment for patients with uncomplicated falciparum malaria in Bangladesh.
Subject(s)
Antimalarials/therapeutic use , Artemisinins/administration & dosage , Azithromycin/administration & dosage , Malaria, Falciparum/drug therapy , Adolescent , Adult , Aged , Animals , Antimalarials/adverse effects , Artemether , Artemisinins/adverse effects , Artesunate , Azithromycin/adverse effects , Bangladesh , Child , Drug Therapy, Combination , Ethanolamines/administration & dosage , Female , Fluorenes/administration & dosage , Humans , Lumefantrine , Male , Middle Aged , Parasitemia/drug therapy , Time Factors , Treatment Outcome , Young AdultABSTRACT
We consider the NP-hard problem of MAP-inference for undirected discrete graphical models. We propose a polynomial time and practically efficient algorithm for finding a part of its optimal solution. Specifically, our algorithm marks some labels of the considered graphical model either as (i) optimal, meaning that they belong to all optimal solutions of the inference problem; (ii) non-optimal if they provably do not belong to any solution. With access to an exact solver of a linear programming relaxation to the MAP-inference problem, our algorithm marks the maximal possible (in a specified sense) number of labels. We also present a version of the algorithm, which has access to a suboptimal dual solver only and still can ensure the (non-)optimality for the marked labels, although the overall number of the marked labels may decrease. We propose an efficient implementation, which runs in time comparable to a single run of a suboptimal dual solver. Our method is well-scalable and shows state-of-the-art results on computational benchmarks from machine learning and computer vision.
ABSTRACT
We consider the energy minimization problem for undirected graphical models, also known as MAP-inference problem for Markov random fields which is NP-hard in general. We propose a novel polynomial time algorithm to obtain a part of its optimal non-relaxed integral solution. Our algorithm is initialized with variables taking integral values in the solution of a convex relaxation of the MAP-inference problem and iteratively prunes those, which do not satisfy our criterion for partial optimality. We show that our pruning strategy is in a certain sense theoretically optimal. Also empirically our method outperforms previous approaches in terms of the number of persistently labelled variables. The method is very general, as it is applicable to models with arbitrary factors of an arbitrary order and can employ any solver for the considered relaxed problem. Our method's runtime is determined by the runtime of the convex relaxation solver for the MAP-inference problem.
ABSTRACT
The existing research on pregnancy outcomes for women with intellectual and developmental disabilities (IDD) is sparse. This study analyzed the 2010 Healthcare Cost and Utilization Project Nationwide Inpatient Sample and compared deliveries among women with IDD (n = 340) to the general obstetric population. Women with IDD had longer hospital stays and were more likely to have Caesarean deliveries in contrast to other women. Rates of adverse pregnancy outcomes were elevated for women with IDD across a range of measures, including early labor, preterm birth, and preeclampsia, and their infants were more likely to have low birth weight, even after adjusting for age, race, ethnicity, and insurance type. Targeted interventions are needed to address these deleterious outcomes.
Subject(s)
Cesarean Section/statistics & numerical data , Developmental Disabilities/epidemiology , Intellectual Disability/epidemiology , Pregnancy Complications/epidemiology , Pregnancy Outcome/epidemiology , Adolescent , Adult , Female , Humans , Infant, Low Birth Weight , Pregnancy , Premature Birth/epidemiology , United States/epidemiology , Young AdultABSTRACT
In malaria-endemic regions any febrile case is likely to be classified as malaria based on presumptive diagnosis largely caused by a lack of diagnostic resources. A district-wide prevalence study assessing etiologies of fever in 659 patients recruited in rural and semi-urban areas of Bandarban district in southeastern Bangladesh revealed high proportions of seropositivity for selected infectious diseases (leptospirosis, typhoid fever) potentially being misdiagnosed as malaria because of similarities in the clinical presentation. In an area with point prevalences of more than 40% for malaria among fever cases, even higher seroprevalence rates of leptospirosis and typhoid fever provide evidence of a major persistent reservoir of these pathogens.
Subject(s)
Dengue/epidemiology , Disease Reservoirs , Endemic Diseases , Leptospirosis/epidemiology , Malaria/epidemiology , Typhoid Fever/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Bangladesh/epidemiology , Child , Child, Preschool , Coinfection , Cross-Sectional Studies , Dengue/diagnosis , Female , Humans , Infant , Leptospirosis/diagnosis , Malaria/diagnosis , Male , Middle Aged , Rural Population , Seroepidemiologic Studies , Typhoid Fever/diagnosis , Young AdultABSTRACT
Rodents are a key mammalian group highly successful in adapting to a variety of environments throughout the world and play an important role in many zoonotic cycles. Within this project, the gastrointestinal and extraintestinal parasite fauna of 76 rodents (Muroidea and Sciuridae) was determined in the District of Bandarban (Chittagong Hill Tracts) in Southeastern Bangladesh. Gastrointestinal and extraintestinal parasites were examined with macro- and microscopical tools (e.g. Ziehl-Neelsen Staining) at a field site in Bandarban. A wide variety of parasites were found in rodent hosts, including protozoa-Giardia sp. (n = 8), Cryptosporidium sp. (n = 1), Entamoeba sp. (n = 8), Trichomonadida (n = 4), Isospora sp. (n = 1), trematodes (Echinostoma sp.; n = 3), cestodes-Hymenolepis nana (n = 1), Hymenolepis diminuta (n = 3), Hymenolepis sp. (n = 2), Taenia taeniaeformis-Larven (n = 4), Catenotaenia sp. (n = 1), Taenia sp. (n = 1), nematodes-Heterakis spumosa (n = 4), Heterakis sp. (n = 1), Aspiculuris tetraptera (n = 2), Capillaria hepatica (n = 2), Capillaria sp. (n = 3), Syphacia sp. (n = 2), Strongyloides sp. (n = 10), Trichostrongylus sp. (n = 2) and Trichuris sp. (n = 1)-and acanthocephalans (Moniliformis moniliformis; n = 2). Several of the examined parasites are of zoonotic importance via direct or indirect transmission (e.g. C. hepatica) and may affect humans.
Subject(s)
Helminthiasis, Animal/parasitology , Helminths/isolation & purification , Rodent Diseases/parasitology , Rodentia/parasitology , Animals , Bangladesh , Helminths/classificationABSTRACT
In spite of the high prevalence of malaria in Bangladesh and other southern Asian countries, there remains a substantial shortage of knowledge about the less common human malaria parasites. Recent studies indicate that Plasmodium ovale is made up of two species, namely Plasmodium ovale wallikeri and Plasmodium ovale curtisi. Genus- and species-specific nested PCR analyses of the ssrRNA gene was used to detect P. ovale infections among 2,246 diagnostic samples. Plasmodium ovale infections were further differentiated by nested PCR of the potra gene and multilocus sequence analysis of the cox1, porbp2 and the ssrRNA genes. Both P. ovale curtisi and P. ovale wallikeri occur sympatrically in the Chittagong Hill Tracts, Bangladesh and all patients presented with a mild or asymptomatic symptom complex at the time of diagnosis. The pathogens can be differentiated by nested PCRs targeting the ssrRNA and potra genes, and display dimorphism in multilocus sequence analyses. We believe that we report the first evidence of sympatric P. ovale curtisi and P. ovale wallikeri in southern Asia within a relatively confined study area of less than 5,000 km(2). High rates of mixed infections, the emergence of "new" human malaria parasite species and the evidence of zoonotic capability call for optimised diagnostic strategies for a new era of eradication.
Subject(s)
Genetic Variation , Malaria/parasitology , Plasmodium ovale/classification , Plasmodium ovale/isolation & purification , Adolescent , Adult , Bangladesh , Child , Child, Preschool , Cluster Analysis , DNA, Protozoan/chemistry , DNA, Protozoan/genetics , Female , Humans , Male , Middle Aged , Molecular Sequence Data , Multilocus Sequence Typing , Phylogeny , Plasmodium ovale/genetics , Polymerase Chain Reaction , Protozoan Proteins/genetics , Sequence Analysis, DNA , Young AdultABSTRACT
OBJECTIVE: Recent reports indicate that first cases of genuine artemisinin resistance have already emerged along the Thai-Cambodian border. The main objective of this trial was to track the potential emergence of artemisinin resistance in Bangladesh, which in terms of drug resistance forms a gateway to the Indian subcontinent. METHODS: We conducted an open-label, randomized, controlled 42-day clinical trial in Southeastern Bangladesh to investigate the potential spread of clinical artemisinin resistance from Southeast Asia. A total of 126 uncomplicated falciparum malaria patients were randomized to one of 3 treatment arms (artesunate monotherapy with 2 or 4 mg/kg/day once daily or quinine plus doxycycline TID for 7 days). Only cases fulfilling a stringent set of criteria were considered as being artemisinin-resistant. FINDINGS: The 28-day and 42-day cure rates in the artesunate monotherapy (2 and 4 mg/kg) and quinine/doxycyline arms were 97.8% (95% confidence interval, CI: 87.8-99.8%), 100% (95% CI: 91.1-100%), and 100% (95% CI: 83.4-100%), respectively. One case of re-infection was seen in the artesunate high dose arm, and a single case of recrudescence was observed in the low dose group on day 26. No differences in median parasite and fever clearance times were found between the 2 artesunate arms (29.8 h and 17.9 h vs. 29.5 h and 19.1 h). Not a single case fulfilled our criteria of artemisinin resistance. Parasite clearance times were considerably shorter and ex vivo results indicate significantly higher susceptibility (50% inhibitory concentration for dihydroartemisinin was 1.10 nM; 95% CI: 0.95-1.28 nM) to artemisinins as compared to SE-Asia. CONCLUSION: There is currently no indication that artemisinin resistance has reached Bangladesh. However, the fact that resistance has recently been reported from nearby Myanmar indicates an urgent need for close monitoring of artemisinin resistance in the region. TRIAL REGISTRATION: ClinicalTrials.gov NCT00639873.
Subject(s)
Antimalarials/therapeutic use , Artemisinins/therapeutic use , Drug Resistance , Malaria, Falciparum/drug therapy , Plasmodium falciparum , Adolescent , Adult , Antimalarials/pharmacology , Artemisinins/pharmacology , Bangladesh , Child , Female , Humans , Male , Plasmodium falciparum/drug effects , Treatment Outcome , Young AdultABSTRACT
The authors report the first indigenous case of Plasmodium ovale infection from Bangladesh. The diagnosis was confirmed by PCR and sequence analysis. The patient had neither been outside of the country nor ever received blood transfusions. The authors concluded that there was evidence for a local transmission of P ovale malaria in Bangladesh. P ovale malaria should therefore always be considered a potential differential diagnosis in the indigenous population as well as travellers and migrants returning from South Asia, possibly up to years after their return.
Subject(s)
Malaria/epidemiology , Plasmodium ovale , Bangladesh/epidemiology , Child , Diagnosis, Differential , Female , Humans , Malaria/diagnosis , Malaria/parasitology , Parasitemia/diagnosis , Parasitemia/parasitologyABSTRACT
In spite of the high prevalence of malaria in Southeastern Bangladesh, there remains a significant shortage of information regarding the presence of three of five human malaria parasites: Plasmodium ovale, P. malariae, and P. knowlesi. The presence of P. ovale and P. knowlesi has previously never been reported from Bangladesh. We used a genus- and species-specific nested polymerase chain reaction, targeting highly conserved regions of the small subunit ribosomal RNA (SSU rRNA) gene, to investigate the presence of malaria parasites in a total number of 379 patient samples in a survey of patients with febrile illnesses in the Chittagong Hill Tracts in Southeastern Bangladesh. We identified the first cases of P. ovale in Bangladesh. They were confirmed by sequence analysis; 189 of 379 samples (49.9%; 95% confidence interval = 44.9-54.9%) were positive for Plasmodium sp. by PCR. P. falciparum monoinfections accounted for 68.3% (61.3-74.5%), followed by P. vivax (15.3%; 10.9-21.2%), P. malariae (1.6%; 0.5-4.6%), P. ovale (1.6%; 0.5-4.6%), and mixed infections (13.2%; 9.1-18.8%). We found no evidence of P. knowlesi in this region.