Publications by authors named "Peter Starzengruber"

27 Publications

  • Page 1 of 1

Clinical Usefulness of Susceptibility Breakpoints for Yeasts in the Treatment of Candidemia: A Noninterventional Study.

J Fungi (Basel) 2020 Jun 2;6(2). Epub 2020 Jun 2.

Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria.

This prospective noninterventional study evaluated whether antifungal susceptibility data (MIC) provided for clinical isolates on the basis of recently established breakpoints are taken into account by clinicians to guide their treatment decision making process, and assessed the response in MIC- and non-MIC-based treatment groups. During a six month period, the usage of systemic antifungals was recorded in detail and compared with mycological data ( species and MICs) in candidemia patients. Patients were assigned to a susceptible or resistant infection group based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints; treatment decisions were under the professional discretion of the treating physicians. 123 patients were evaluated with accounting for 59%, for 19%, for 15%, for 4% and for 3%. Antifungal treatment correlated with species and MICs in 80% ( = 99 patients), high MICs and species-dependent guideline recommendations were ignored in 20% ( = 24 patients); the overall outcome of candidemia cases in our study population was excellent, as by day 14, all patients were cleared from fungal blood stream infection (mean 5.6 days, range 2-12). The current variability in antifungal usage and the delay in initiating appropriate therapy indicate a need for antifungal stewardship to improve the management of invasive fungal infections.
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http://dx.doi.org/10.3390/jof6020076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345773PMC
June 2020

Pharyngeal carriage rates of Neisseria meningitidis in health care professionals at a tertiary university pediatric hospital.

Eur J Clin Microbiol Infect Dis 2020 Sep 24;39(9):1703-1709. Epub 2020 Apr 24.

Department of Pediatrics and Adolescent Medicine, Division of Neonatology, Pediatric Intensive Care Medicine and Neuropediatrics, Medical University of Vienna, Vienna, Austria.

Pharyngeal carriage is the reservoir for Neisseria meningitidis in the population and the first step in disease transmission. Especially in young infants and adolescents, N. meningitidis can cause serious invasive infection with high fatality rates and high rates of long-term sequelae among survivors. The aim of this study was to determine N. meningitidis colonization rates in asymptomatic health care professionals at a tertiary university pediatric hospital and to identify risk factors for carriage. This cross-sectional meningococcal carriage survey was conducted between April and October 2018 at the Medical University of Vienna. Individuals working as nurses, pediatricians, or medical students were enrolled. Oropharyngeal swabs were directly plated onto selective agar plates and conventional culture was used for bacterial identification. Meningococcal isolates were further characterized using whole-genome sequencing. A total of 437 oropharyngeal specimens were collected. Overall, meningococcal carriage prevalence was 1.14% (5/437), with 0.7% (3/437) for capsular genotype B, and 0.5% (2/437) for capsular genotype W. Mean age of carriers was significantly lower than of non-carriers (24.2 vs. 35.8; p = 0.004). The highest carriage rate of 4.4% (4/91) was found in the age group 18-25. Carriage was negatively associated with age and timespan working in pediatrics. This is the first study evaluating the prevalence of Neisseria meningitidis carriage in health care professionals working in Pediatrics and Adolescent Medicine. Carriage was in general lower than expected for all age groups, implicating a low risk of meningococcal transmission via this population.
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http://dx.doi.org/10.1007/s10096-020-03894-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427699PMC
September 2020

Molecular epidemiology of multidrug-resistant clinical isolates of Acinetobacter baumannii : A 10-year analysis in a large tertiary care university hospital in central Europe with international admissions.

Wien Klin Wochenschr 2017 Nov 3;129(21-22):816-822. Epub 2017 Aug 3.

Department of Infection Control and Hospital Epidemiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Background: Over the last 10 years, multidrug resistant Acinetobacter baumannii has been spreading worldwide as emerging microorganisms that negatively impact on the outcome of in-hospital patients.

Methods: Between 2007 and 2016, all isolates of patients of the Vienna General Hospital (VGH), tested positive for multidrug resistant Acinetobacter baumannii (MDR A. baumannii) strains, were investigated with respect to their genetic relationship. Patient medical histories were reviewed in order to collect discriminating factors related to MDR A. baumannii colonization or infection.

Results: A total of 79 isolates of 76 patients were obtained. For 44 of them (55.7%) the first diagnosis ward was an intensive care unit (ICU). A total of 10 genotype clusters were identified and 35 cases (44.3%) of in-hospital acquisition in our institution could be detected. Multidrug resistant Acinetobacter baumannii isolates were acquired before admission to our hospital in 44 cases (55.7%) and in 31 (70.5%) they belonged to patients who had previous exposure to the healthcare setting of high prevalence countries for MDR A. baumannii.

Conclusion: Patients admitted to our hospital with a previous healthcare contact in a high prevalence country for multidrug resistant Acinetobacter baumannii should be screened before admission to high-risk wards. Isolation of these patients until microbiological results could reduce negative outcome in these wards.
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http://dx.doi.org/10.1007/s00508-017-1242-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676840PMC
November 2017

A Phase 3, Double-Blind, Randomized Study of Arterolane Maleate-Piperaquine Phosphate vs Artemether-Lumefantrine for Falciparum Malaria in Adolescent and Adult Patients in Asia and Africa.

Clin Infect Dis 2016 Apr 21;62(8):964-971. Epub 2016 Feb 21.

Medical Affairs & Clinical Research, Sun Pharmaceutical Industries Limited (erstwhile Ranbaxy Laboratories Ltd), Gurgaon, Haryana, India.

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.
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http://dx.doi.org/10.1093/cid/ciw029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803108PMC
April 2016

A national point prevalence study on healthcare-associated infections and antimicrobial use in Austria.

Wien Klin Wochenschr 2016 Feb 27;128(3-4):89-94. Epub 2016 Jan 27.

Department of Hospital Epidemiology and Infection Control, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Background: The first point prevalence survey performed in Austria had the aim to assess the magnitude of healthcare-associated infections and antimicrobials use in the country.

Methods: A multicentre study was carried out from May until June 2012 in nine acute care hospitals with a mean bed number of 620. Data from 4321 patients' clinical charts were reviewed.

Results: The overall healthcare-associated infections prevalence was 6.2% (268/4321) with the highest rate in intensive care departments (20.9%; 49/234). In medical and surgical departments the healthcare-associated infections prevalence was 5.4% (95/1745) and 6.6% (105/1586), respectively. The most frequent healthcare-associated infections were: urinary tract infections (21.3%; 61/287), pneumonia (20.6%; 59/287) and surgical site infections (17.4%; 50/287). The most common isolated microorganisms were: Escherichia coli (14.8%; 26/176), Enterococcus species (13.1%; 23/176) and Pseudomonas aeruginosa (11.4%; 20/176). Thirty-three per cent (1425/4321) of the patients received antimicrobials because of community-acquired infections treatment (14.2%; 615/4321), healthcare-associated infections treatment (6.4%; 278/4321), and surgical (8.2%; 354/4321) and medical prophylaxis (3.2%; 138/4321). Surgical prophylaxis was the indication for 22.0% (394/1792) of the overall prescriptions and was prolonged for more than 1 day in 77.2% (304/394) of the cases.

Conclusion: The national Austrian survey proved the feasibility of a nation-wide network of surveillance of both healthcare-associated infections and antimicrobial use that will be repeated in the future. Healthcare-associated infections and antimicrobial use have been confirmed to be a grave health problem. The excessive prolongation of perioperative prophylaxis in Austria needs to be limited.
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http://dx.doi.org/10.1007/s00508-015-0947-8DOI Listing
February 2016

Case report: spontaneous rupture of spleen in patient with Plasmodium ovale malaria.

Wien Klin Wochenschr 2016 Jan 5;128(1-2):74-7. Epub 2015 Nov 5.

Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Malaria may lead to spontaneous splenic rupture as a rare but potentially lethal complication. Most frequently, this has been reported in patients infected with Plasmodium falciparum and Plasmodium vivax, while other parasitic agents are less likely to be the cause.We report a 29-year-old British Caucasian, who after returning from a business trip in Democratic Republic Congo was diagnosed with tertian malaria caused by Plasmodium ovale.During his in-patient stay, the patient suffered a splenic rupture requiring immediate surgical intervention and splenectomy. Following this surgical intervention, there was an uneventful recovery, and the patient was discharged in a good general condition.
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http://dx.doi.org/10.1007/s00508-015-0888-2DOI Listing
January 2016

Antibacterial activity of a sterile antimicrobial polyisoprene surgical glove against transient flora following a 2-hours simulated use.

BMC Surg 2015 Jul 4;15:81. Epub 2015 Jul 4.

Institute for Skin Integrity and Infection Prevention, School of Human & Health Sciences, R1/29 Ramsden Building, University of Huddersfield, Huddersfield, HD1 3DH, UK.

Background: A surgical glove will protect surgeons and patients only if the glove's integrity remains intact. However, several studies have demonstrated that undetected micro-perforations of surgical gloves are common. Because of the possibility of surgical glove puncture, an antimicrobial surgical glove was developed. The aim of this laboratory based experimental study was to assess the antibacterial efficacy of the interior chlorhexidine-gluconate (CHG)-coat of an antimicrobial synthetic polyisoprene surgical glove by using a standardized microbiological challenge.

Methods: Sixteen healthy adult participants donned one antimicrobial surgical glove and one non-antimicrobial surgical glove randomly allocated to their dominant and non-dominant hand following a crossover design. During a 2-h wear time, participants performed standardized finger and hand movements. Thereafter, the interior surface of excised fingers of the removed gloves was challenged with 8.00 log10 cfu/mL S. aureus (ATCC 6538) or K. pneumoniae (ATCC 4352), respectively. The main outcome measure was the viable mean log10 cfu counts of the two glove groups after 5 min contact with the interior glove's surface.

Results: When comparing an antimicrobial glove against an untreated reference glove after 2-h simulated use wear-time, a mean reduction factor of 6.24 log10 (S. aureus) and 6.22 log10 (K. pneumoniae) was achieved after 5 min contact.

Conclusion: These results demonstrate that wearing antibacterial gloves on hands does not negatively impact their antibacterial activity after 2-h of wear. This may have a potential benefit for patient safety in case of glove puncture during surgical procedures.
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http://dx.doi.org/10.1186/s12893-015-0058-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490737PMC
July 2015

The strength of coughing may forecast the likelihood of spread of multi-drug resistant microorganisms from the respiratory tract of colonized patients.

Antimicrob Resist Infect Control 2014 12;3(1):38. Epub 2014 Dec 12.

Department of Hospital Hygiene and Infection Control, Vienna General Hospital, Medical University Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Background: Current recommendations indicate that patients who are coughing and have multidrug resistant microorganisms (MDROs) in their sputum are considered to be shedders and should be cared for in single room isolation at least until symptoms resolve. Airborne spread and subsequent contamination of surfaces adjacent to patients may contribute to transmission. Hence, isolation measures for patients colonized or infected with MDRO at their respiratory tract are intended to interrupt such transmission. However, the potential for microbial shedding in patients with MDRO-positive microbiological reports from their respiratory tract and factors justifying the need for single room isolation are viewed controversially.

Methods: Cough aerosol produced by patients colonized with MDROs was measured for viable counts. Descriptive analysis together with logistic regression analysis was performed to assess the impact of strength of cough on growth of MDRO on culture plates.

Results: In 18% (23/128) MDRO were transmitted. Multivariate analysis revealed that strength of cough significantly predicts the yield of MDRO on culture plates (P = 0.012).

Conclusion: Based on these results it can be concluded that risk stratification for decision of single room isolation of patients colonized or infected with MDROs at their respiratory tract may also take the severity of cough into consideration. However, more work is required in order to assess the severity of cough objectively.
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http://dx.doi.org/10.1186/s13756-014-0038-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271473PMC
December 2014

Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia.

J Infect Dis 2015 Mar 1;211(5):670-9. Epub 2014 Sep 1.

Mahidol-Oxford Tropical Medicine Research Unit Shoklo Malaria Research Unit Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.

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.
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http://dx.doi.org/10.1093/infdis/jiu491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334802PMC
March 2015

Mirincamycin, an old candidate for malaria combination treatment and prophylaxis in the 21st century: in vitro interaction profiles with potential partner drugs in continuous culture and field isolates.

Malar J 2014 Jun 10;13:228. Epub 2014 Jun 10.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1186/1475-2875-13-228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059879PMC
June 2014

Severe Clostridium difficile infection: incidence and risk factors at a tertiary care university hospital in Vienna, Austria.

Wien Klin Wochenschr 2014 Jul 6;126(13-14):427-30. Epub 2014 Jun 6.

Department of Hospital Hygiene and Infection Control, Vienna General Hospital, Medical University Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Background: Clostridium difficile infection (CDI) is the major cause of hospital-acquired bacterial diarrhoea. The incidence of CDI has been increasing in Canada, the US and Europe and severe cases are becoming more common.

Methods: A retrospective cohort study investigating all patients with an episode of CDI present at the Vienna University Hospital between 01 January 2012 and 31 December 2012 was conducted. All microbiologically confirmed C. difficile toxin positive cases were included, ribotyped and analysed regarding their clinical course.

Results: A total of 278 patients with CDI were recorded, with an overall CDI incidence of 5.23 per 10,000 patients-days. Around 84,5 % (235/278) of CDI cases would have been classified as severe CDI according to European Society of Clinical Microbiology and Infectious Diseases (ESCMID) if all criteria were used. According to Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America (SHEA/IDSA) guidelines only 16.5 % (46/278) could be classified as severe; with a severe CDI incidence of 4.41 and 0.86 per 10,000 patient-days, respectively. Multivariate analysis showed only a co-morbidity index of ≥ 3 (p = 0.013) as independent risk factor for severe CDI. No link between ribotype 027 and severity or clustering was observed in our study population.

Conclusions: Special attention in terms of restrictive antibiotic prescription should be given to patients having a Charlson co-morbidity ≥ 3 at the time of hospital admission. SHEA/IDSA guidelines were more accurate than ESCMID criteria in predicting severe CDI in our collective, of mostly severely ill patients, in a tertiary care hospital setting.
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http://dx.doi.org/10.1007/s00508-014-0549-xDOI Listing
July 2014

High prevalence and genetic diversity of Plasmodium malariae and no evidence of Plasmodium knowlesi in Bangladesh.

Parasitol Res 2014 Apr 28;113(4):1537-43. Epub 2014 Feb 28.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Kinderspitalgasse 15, 1090, Vienna, Austria.

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.
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http://dx.doi.org/10.1007/s00436-014-3798-8DOI Listing
April 2014

Evidence of a major reservoir of non-malarial febrile diseases in malaria-endemic regions of Bangladesh.

Am J Trop Med Hyg 2014 Feb 13;90(2):377-82. Epub 2014 Jan 13.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria; MARIB, Malaria Research Initiative Bandarban, Bandarban, Bangladesh; Institute of Parasitology, Department of Pathobiology, University of Veterinary Medicine Vienna; ICDDR,B, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.

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.
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http://dx.doi.org/10.4269/ajtmh.13-0487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919252PMC
February 2014

High prevalence of asymptomatic malaria in south-eastern Bangladesh.

Malar J 2014 Jan 9;13:16. Epub 2014 Jan 9.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Kinderspitalgasse 15, Vienna 1090, Austria.

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.
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http://dx.doi.org/10.1186/1475-2875-13-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896725PMC
January 2014

Current status of artemisinin-resistant falciparum malaria in South Asia: a randomized controlled artesunate monotherapy trial in Bangladesh.

PLoS One 2012 18;7(12):e52236. Epub 2012 Dec 18.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0052236PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525560PMC
June 2013

Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia.

Proc Natl Acad Sci U S A 2013 Jan 17;110(1):240-5. Epub 2012 Dec 17.

Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

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.
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http://dx.doi.org/10.1073/pnas.1211205110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538248PMC
January 2013

Plasmodium ovale in Bangladesh: genetic diversity and the first known evidence of the sympatric distribution of Plasmodium ovale curtisi and Plasmodium ovale wallikeri in southern Asia.

Int J Parasitol 2012 Jun 23;42(7):693-9. Epub 2012 May 23.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Kinderspitalgasse 15, 1090 Vienna, Austria.

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.
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http://dx.doi.org/10.1016/j.ijpara.2012.04.015DOI Listing
June 2012

Antiplasmodial activity of flavonol quercetin and its analogues in Plasmodium falciparum: evidence from clinical isolates in Bangladesh and standardized parasite clones.

Parasitol Res 2012 Jun 4;110(6):2289-95. Epub 2012 Jan 4.

Institute of Medical Chemistry, Department of Biochemistry and Genetics, Medical University of Vienna, Waehringer Strasse 10, Vienna, 1090, Austria.

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.
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http://dx.doi.org/10.1007/s00436-011-2763-zDOI Listing
June 2012

Novel nested direct PCR technique for malaria diagnosis using filter paper samples.

J Clin Microbiol 2011 Apr 26;49(4):1628-30. Epub 2011 Jan 26.

Department of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Kinderspitalgasse 15, A-1090 Vienna, Austria.

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.
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http://dx.doi.org/10.1128/JCM.01792-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122810PMC
April 2011

Indigenous Plasmodium ovale malaria in Bangladesh.

Am J Trop Med Hyg 2010 Jul;83(1):75-8

Department of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.4269/ajtmh.2010.09-0796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912579PMC
July 2010

Azithromycin combination therapy for the treatment of uncomplicated falciparum malaria in Bangladesh: an open-label randomized, controlled clinical trial.

J Infect Dis 2010 Aug;202(3):392-8

Department of Specific Prophylaxes and Tropical Medicine, Medical University of Vienna, Austria.

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.
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http://dx.doi.org/10.1086/653710DOI Listing
August 2010

The first case of Plasmodium ovale malaria from Bangladesh.

BMJ Case Rep 2010 Sep 29;2010. Epub 2010 Sep 29.

Department of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1136/bcr.03.2010.2865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3029534PMC
September 2010

Interaction between lumefantrine and monodesbutyl-benflumetol in Plasmodium falciparum in vitro.

Wien Klin Wochenschr 2008 ;120(19-20 Suppl 4):85-9

Institute of Specific Prophylaxis and Tropical Medicine, Centre for Physiology and Pathophysiology, Medical University of Vienna, Austria.

The pharmacodynamic interaction between lumefantrine and its monodesbutyl analogue (DBB) has been investigated in 35 fresh isolates of Plasmodium falciparum. Both compounds showed highly significant activity correlation. The geometric mean values for complete inhibition of schizont maturation (GMCOC) were 536,8 nM for lumefantrine, 246.0 nM for DBB, 235,5 nM for LUM-DBB 999:1, and 155,2 nM for LUM-DBB 995:5, with significant activity differences between lumefantrine and DBB as well as the LUM-DBB combinations. For the combination of lumefantrine and DBB 995:5 the sums of the fractional inhibitory concentrations according to Berenbaum (SFIC) indicated marked synergism, the intensity of interaction rising with the effective inhibitory concentrations.
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http://dx.doi.org/10.1007/s00508-008-1080-8DOI Listing
July 2009

Synergism between monodesbutyl-benflumetol and artemisinin in Plasmodium falciparum in vitro.

Wien Klin Wochenschr 2008 ;120(19-20 Suppl 4):80-4

Institute of Specific Prophylaxis and Tropical Medicine, Centre for Physiology and Pathophysiology, Medical University of Vienna, Austria.

The sensitivity to artemisinin, monodesbutyl-benflumetol (DBB) and a 1:1 m/m combination of the two compounds was successfully investigated on 34 fresh isolates of Plasmodium falciparum. On a molar basis the combination was most active, followed by DBB and artemisinin. The geometric mean concentrations effecting full inhibition (GMCOC) were 49.25 nM for the combination, 279.12 nM for DBB, and 494.05 for artemisinin. The difference between the efficacy of the combination and that of its components was highly significant. Interaction between artemisinin and DBB showed moderate synergism at the EC(50) and strong synergism at EC(90) and EC(99). The individual parasite isolates showed a significant inverse correlation between the ECs and the degree of synergism. Positive specific pharmacodynamic interaction was therefore most marked in isolates with reduced sensitivity against artemisinin and DBB.
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http://dx.doi.org/10.1007/s00508-008-1034-1DOI Listing
July 2009

[In vitro interaction studies of azithromycin and dihydroartemisinin in Plasmodium falciparum isolates from Bangladesh].

Wien Klin Wochenschr 2007 ;119(19-20 Suppl 3):71-5

Department of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Austria.

In recent clinical trials acithromycin in combination with artemisinin derivatives proved to be a promising combination therapy with indifferent to synergistic interaction. The aim of the present study was the assessment of optimal combination ratios for dihydroartemisinin and azithromycin for the treatment of uncomplicated falciparum malaria. The study was conducted in Bandarban, in Southeastern Bangladesh. Plasmodium falciparum isolates collected as part of a clinical trial were cultured for 72 hours. Samples were analyzed using the HRP2 drug sensitivity assay in fixed combinations and checkerboard assays. An indifferent mode of interaction was found for the 1:500 combination of dihydroartemisinine and azithromycin. The sum fractional inhibitory concentrations (SFICs) at IC95 ranged from 0.89 to 1.16 for combination ratios of 1:500 and 1:5000, respectively. A trend towards lower SFICs was observed with rising inhibitory concentrations (i.e. at IC90 and IC95). Correlation analysis suggests a different mode of action for azithromycin as compared to traditional antimalarials.
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http://dx.doi.org/10.1007/s00508-007-0863-7DOI Listing
February 2010

In vitro interaction of dihydroartemisin and lumefantrine in clinical field isolates from Bangladesh.

Wien Klin Wochenschr 2007 ;119(19-20 Suppl 3):67-70

Department of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.

The combination of artemether and lumefantrine was introduced in 2005 as the official first line therapy for uncomplicated falciparum malaria in Bangladesh. Fresh P. falciparum samples from patients with acute uncomplicated falciparum malaria who presented to the field site at the Bandarban Sadar Hospital in Bangladesh were tested in checkerboard in vitro drug sensitivity assays to assess the interaction between dihydroartemisinin (DHA) and lumefantrine (LUM). Clearly synergistic interactions with an overall mean FIC(50) of 0.52 and individual mean FICs between 0.26 and 0.85 were found. Lowest FICs were 0.41, 0.18, 0.22, 0.15 and 0.11 at different combination ratios. The optimal combination ratio of the drug combination indicated by the lowest mean FIC average was found to be 1:150 DHA:LUM. Although activity correlations between DHA and lumefantrine were significant, indicating possible cross sensitivity patterns, our data confirm that artemether-lumefantrine is a highly synergistic drug combination.
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http://dx.doi.org/10.1007/s00508-007-0862-8DOI Listing
February 2010

Specific pharmacokinetic interaction between lumefantrine and monodesbutyl-benflumetol in Plasmodium falciparum.

Wien Klin Wochenschr 2007 ;119(19-20 Suppl 3):60-6

Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.

The blood schizontocidal activity of lumefantrine, monodesbutyl-benflumetol (DBB) and a 999:1 combination of both compounds has been investigated in 26 fresh isolates of Plasmodium falciparum from northwestern Thailand, using the WHO standard protocol Mark II for determining the inhibition of schizont maturation. The geometric mean cut-off concentrations of schizont maturation (GMCOC) were 943.2 nM for lumefantrine, 146.3 nM for DBB and 182.2 nM for the 999:1 combination of lumefantrine and DBB. The EC(50) values were 27.3 nM for lumefantrine, 5.7 nM for DBB, and 16.5 nM for the combination, and the EC(90) values 163.1 nM for lumefantrine, 44.1 nM for DBB, and 78.3 nM for the combination. Despite the very low concentration in the combination, DBB exerted significant synergistic activity with lumefantrine that was strongest at the EC(90) and EC(99) levels. Correlation analysis indicates that DBB is the leading determinant for the activity of the combination.
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http://dx.doi.org/10.1007/s00508-007-0861-9DOI Listing
February 2010
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