Dynamics of plasmodium falciparum selection after Artemether-Lumefantrine treatment in Africa

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Plasmodium falciparum drug resistance phenotype as assessed by patient antimalarial drug levels and Its association With pfmdr1 polymorphisms

Background. Multidrug-resistant Plasmodium falciparum is a major threat to global malaria control. Parasites develop resistance by gradually acquiring genetic polymorphisms that decrease drug susceptibility. The aim of this study was to investigate the extent to which parasites with different genetic characteristics are able to withstand individual drug blood concentrations. Methods. We analyzed 2 clinical trials that assessed the efficacy and effectiveness of artemether-lumefantrine. As a proof of concept, we used measured day 7 lumefantrine concentrations to estimate the concentrations at which reinfections multiplied. P. falciparum multidrug resistance gene 1 (pfmdr1) genotypes of these parasites were then correlated to drug susceptibility. Results. Reinfecting parasites with the pfmdr1 N86/184F/D1246 haplotype were able to withstand lumefantrine blood concentrations 15-fold higher than those with the 86Y/Y184/1246Y haplotype. Conclusions. By estimating drug concentrations, we were able to quantify the contribution of pfmdr1 single-nucleotide polymorphisms to reduced lumefantrine susceptibility. The method can be applied to all long-half-life antimalarial drugs, enables early detection of P. falciparum with reduced drug susceptibility in vivo, and represents a novel way for unveiling molecular markers of antimalarial drug resistance.Swedish Development Cooperation Agency-Department for Research Cooperation (SIDA-SAREC) [SWE 2004-3850, Bil-Tz 16/9875007059, SWE-2009-165]; World Health Organization MIM-TDR [[A60100] MAL IRM 06 03]; Goljes Foundation; Swedish medical research council [K2010-56X-21457-01-3]; Wellcome Trust of Great Britai

Using Constructed Wetlands to Remove Pathogenic Parasites and Fecal Coliforms from Wastewater in Dar es Salaam and Iringa, Tanzania

Wastewater treatment is a widely used health protection measure that can be applied to control the transmission of wastewater-related infectious diseases to communities exposed to wastewater. This study determined the efficiency of three full-scale constructed wetlands (CWs) in removing pathogenic parasites and fecal coliform (FC) bacteria from wastewater. Wastewater samples were collected from three CW systems located in the Dar es Salaam and Iringa regions of Tanzania. The modified Bailenger and modified Ziehl-Neelsen stain techniques were used to detect and quantify parasites. The membrane filtration method was used to detect and quantify FC bacteria. Data were analysed using IBM SPSS version 20. Helminth (Ascaris lumbricoides, hookworm, and Taenia spp.) eggs were completely removed by two CW systems. In all the systems, the removal of protozoa ranged from 99.8% to 100%. The mean concentrations of FCs in effluents ranged from 5 to 6 log units/100 mL. Effluents of all CW systems met the recommended parasitological quality requirements of the World Health Organization for the safe reuse of wastewater. FC effluents concentrations did not meet the local discharge standards of the Tanzania Bureau of Standards. Therefore, improvement to the CWs’ design, operation, and maintenance are required for the efficient removal of bacteria. Keywords: helminth, protozoa, fecal coliform, wastewater treatment, constructed wetlan

Stroke in Patients with Schistosomiasis: Review of Cases in Literature

Introduction. Cerebral vascular comorbidities may occur in patients with schistosomiasis, as described in case reports. Aim and Methods. We have summarized general clinical and neurological features in patients with stroke associated with schistosomiasis, through a review of case reports in the literature. Investigation Outcomes. A total of eight case reports were retrieved. The mean age of patients was 36.42 +/- 16.7 (19 to 56 years), four females, three males, and one anonymous sex. Eosinophilia was the most frequent feature at presentation, followed by cardiac abnormalities, confusion, fever, ataxia, hemiplegia, headache, urticaria, dysphasia, and memory impairment. Patients usually present with watershed infarction or intracranial vasculitis. In one case, extracranial carotid arteries presented with inflammation and stenosis. The patient's serology was positive on admission in five cases. Full neurological recovery was reported in three cases, and partial improvement in another three. In two cases, information on neurological outcomes was incomplete. Stroke in schistosomiasis can be caused by haemodynamic impairment, direct lesion to the arterial wall, vasa vasorum obliterative endarteritis, contiguity with a focus of inflamed tissue, or inflammatory intimal damage. Schistosomiasis needs to be included in the differential diagnosis of stroke in people living or coming back from endemic areas. Conclusions. Further studies addressing the noncommunicable comorbidity issues related to this condition are needed

Aetiology of acute febrile episodes in children attending Korogwe District Hospital in north-eastern Tanzania

Introduction: Although the burden of malaria in many parts of Tanzania has declined, the proportion of children with fever has not changed. This situation underscores the need to explore the possible causes of febrile episodes in patients presenting with symptoms at the Korogwe District Hospital (KDH). Methods: A hospital based cross-sectional study was conducted at KDH, north-eastern Tanzania. Patients aged 2 to 59 months presenting at the outpatient department with an acute medical condition and fever (measured axillary temperature ≥37.5°C) were enrolled. Blood samples were examined for malaria parasites, human immunodeficiency virus (HIV) and bacterial infections. A urine culture was performed in selected cases to test for bacterial infection and a chest radiograph was requested if pneumonia was suspected. Diagnosis was based on both clinical and laboratory investigations. Results: A total of 867 patients with a median age of 15.1 months (Interquartile range 8.6-29.9) were enrolled from January 2013 to October 2013. Respiratory tract infections were the leading clinical diagnosis with 406/867 (46.8%) of patients diagnosed with upper respiratory tract infection and 130/867 (15.0%) with pneumonia. Gastroenteritis was diagnosed in 184/867 (21.2%) of patients. Malaria infection was confirmed in 72/867 (8.3%) of patients. Bacterial infection in blood and urine accounted for 26/808 (3.2%) infections in the former, and 66/373 (17.7%) infections in the latter. HIV infection was confirmed in 10/824 (1.2%) of patients. Respiratory tract infections and gastroenteritis were frequent in patients under 36 months of age (87.3% and 91.3% respectively). Co-infections were seen in 221/867 (25.5%) of patients. The cause of fever was not identified in 65/867 (7.5%) of these patients. Conclusions: The different proportions of infections found among febrile children reflect the causes of fever in the study area. These findings indicate the need to optimise patient management by developing malaria and non-malaria febrile illnesses management protocols. © 2014 Mahende et al

Malaria diagnosis and treatment practices following introduction of rapid diagnostic tests in Kibaha District, Coast Region, Tanzania

Background: The success of the universal parasite-based malaria testing policy for fever patients attending primary health care (PHC) facilities in Tanzania will depend highly on health workers\u27 perceptions and practices. The aim of this study was, therefore, to assess the present use of malaria diagnostics (rapid diagnostic tests (RDTs) and microscopy), prescription behaviour and factors affecting adherence to test results at PHC facilities in Kibaha District, Coast Region, Tanzania. Methods: Exit interviews were conducted with fever patients at PHC facilities and information on diagnostic test performed and treatment prescribed were recorded. Interviews with prescribers to assess their understanding, perceptions and practices related to RDTs were conducted, and health facility inventory performed to assess availability of staff, diagnostics and anti-malarial drugs. Results: The survey was undertaken at ten governmental PHC facilities, eight of which had functional diagnostics. Twenty health workers were interviewed and 195 exit interviews were conducted with patients at the PHC facilities. Of the 168 patients seen at facilities with available diagnostics, 105 (63%) were tested for malaria, 31 (30%) of whom tested positive. Anti-malarial drugs were prescribed to all patients with positive test results, 14% of patients with negative results and 28% of patients not tested for malaria. Antibiotics were more likely to be prescribed to patients with negative test results compared to patients with positive results (81 vs 39%, p \u3c 0.01) and among non-tested compared to those tested for malaria (84 vs 69%, p = 0.01). Stock-outs of RDTs and staff shortage accounted for the low testing rate, and health worker perceptions were the main reason for non-adherence to test results. Conclusions: Anti-malarial prescription to patients with negative test results and those not tested is still practiced in Tanzania despite the universal malaria testing policy of fever patients. The use of malaria diagnostics was also associated with higher prescription of antibiotics among patients with negative results. Strategies to address health system factors and health worker perceptions associated with these practices are needed. © 2013 Mubi et al.; licensee BioMed Central Ltd

Variant merozoite protein expression is associated with erythrocyte invasion phenotypes in Plasmodium falciparum isolates from Tanzania

[No abstract available

Usefulness of Plasmodium falciparum-specific rapid diagnostic tests for assessment of parasite clearance and detection of recurrent infections after artemisinin-based combination therapy

Background: Rapid diagnostic test (RDT) is an important tool for parasite-based malaria diagnosis. High specificity of RDTs to distinguish an active Plasmodium falciparum infection from residual antigens from a previous infection is crucial in endemic areas where residents are repeatedly exposed to malaria. The efficiency of two RDTs based on histidine-rich protein 2 (HRP2) and lactate dehydrogenase (LDH) antigens were studied and compared with two microscopy techniques (Giemsa and acridine orange-stained blood smears) and real-time polymerase chain reaction (PCR) for assessment of initial clearance and detection of recurrent P. falciparum infections after artemisinin-based combination therapy (ACT) in a moderately high endemic area of rural Tanzania. Methods: In this exploratory study 53 children \u3c five years with uncomplicated P. falciparum malaria infection were followed up on nine occasions, i.e., day 1, 2, 3, 7, 14, 21, 28, 35 and 42, after initiation of artemether-lumefantrine treatment. At each visit capillary blood samples was collected for the HRP2 and LDH-based RDTs, Giemsa and acridine orange-stained blood smears for microscopy and real-time PCR. Assessment of clearance times and detection of recurrent P. falciparum infections were done for all diagnostic methods. Results: The median clearance times were 28 (range seven to \u3e42) and seven (two to 14) days for HRP2 and LDH-based RDTs, two (one to seven) and two (one to 14) days for Giemsa and acridine orange-stained blood smear and two (one to 28) days for real-time PCR. RDT specificity against Giemsa-stained blood smear microscopy was 21% for HRP2 on day 14, reaching 87% on day 42, and ≥96% from day 14 to 42 for LDH. There was no significant correlation between parasite density at enrolment and duration of HRP2 positivity (r = 0.13, p = 0.34). Recurrent malaria infections occurred in ten (19%) children. The HRP2 and LDH-based RDTs did not detect eight and two of the recurrent infections, respectively. Conclusion: The LDH-based RDT was superior to HRP2-based for monitoring of treatment outcome and detection of recurrent infections after ACT in this moderately high transmission setting. The results may have implications for the choice of RDT devices in similar transmission settings for improved malaria case management. Trial registration. Clinicaltrials.gov, NCT01843764. © 2013 Aydin-Schmidt et al.; licensee BioMed Central Ltd

Oral candida infection among HIV patients at Kilimanjaro Christian Medical Centre in northern, Tanzania

Background: Oral candidiasis has been a global health challenge especially in immunocompromised patients particularly with HIV infection. Though the incidence and prevalence of opportunistic infections have been reduced due to the use of anti-retroviral therapy (ART), oral candidiasis remains the most frequently HIV-associated oral lesion in Tanzania. This study aimed at determining the prevalence of oral candida infection in HIV positive patients and investigate the relationship between oral manifestations and the level of immunosuppression. Method: This study was carried out at Kilimanjaro Christian Medical Centre in Moshi, Tanzania. The study included 314 HIV patients with complete clinical results records who were diagnosed with HIV and who were on ARV and attending the hospital for care and treatment. Results: Prevalence of oral candida was 42.0% (132/314). Age group 6-27 years accounted for half of the infections (49/98).  A significantly higher prevalence of candida infection  (66.7%; 24/36) was obseved among patients with <200 cells/µl than in those with 200-500 cells/µl or >500 cells/µl (Chi-square χ2=14.9, p=0.001). The mean CD4+T-cell counts in HIV patients infected with oral candida was lower (523±35) than patients without oral candida infection (645±31 cells/µl), (ANOVA, p= 0.009). The mean CD4+ T-cell count among HIV patients on ART and those not on ART was not statistically different. Conclusion: The prevalence of oral candida infection was significantly higher in patients with CD4+ cell counts less than 200 cells/µl

Non-falciparum Malaria in Africa and Learning From Plasmodium vivax in Asia

To the Editor—We read with interest Groger and colleagues’ prospective study of Plasmodium ovale relapses in Gabon [1]. Their work is timely given non-falciparum malaria’s increasing prom-inence in Africa and the potential role of hypnozoite-induced relapses in this trend. Despite declines in Plasmodium falciparum transmission, molecular sur-veys have shown a 6-fold increase in the odds of P.  ovale infection in Tanzania from 2010 to 2016 [2], and a similar trend in the Democratic Republic of Congo, where the species’ prevalence increased from 0.4 to 8.3% in national surveys con-ducted in 2007 and 2013 [3, 4]. Successful interventions against P.  falciparum in Zanzibar [5] and Uganda [6] have not had the same effect on non-falciparum species. Clearly, P.  ovale is becoming an increasingly important malaria in Africa