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

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

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

Plasmodium falciparum Drug Resistance Genes pfmdr1 and pfcrt In Vivo Co-Expression During Artemether-Lumefantrine Therapy

Background: Artemisinin-based combination therapies (ACTs) are the global mainstay treatment of uncomplicated Plasmodium falciparum infections. PfMDR1 and PfCRT are two transmembrane transporters, associated with sensitivity to several antimalarials, found in the parasite food vacuole. Herein, we explore if their relatedness extends to overlapping patterns of gene transcriptional activity before and during ACT administration.Methods: In a clinical trial performed in Tanzania, we explored the pfmdr1 and pfcrt transcription levels from 48 patients with uncomplicated P. falciparum malaria infections who underwent treatment with artemether-lumefantrine (AL). Samples analyzed were collected before treatment initiation and during the first 24 h of treatment. The frequency of PfMDR1 N86Y and PfCRT K76T was determined through PCR-RFLP or direct amplicon sequencing. Gene expression was analyzed by real-time quantitative PCR.Results: A wide range of pre-treatment expression levels was observed for both genes, approximately 10-fold for pfcrt and 50-fold for pfmdr1. In addition, a significant positive correlation demonstrates pfmdr1 and pfcrt co-expression. After AL treatment initiation, pfmdr1 and pfcrt maintained the positive co-expression correlation, with mild downregulation throughout the 24 h post-treatment. Additionally, a trend was observed for PfMDR1 N86 alleles and higher expression before treatment initiation.Conclusion: pfmdr1 and pfcrt showed significant co-expression patterns in vivo, which were generally maintained during ACT treatment. This observation points to relevant related roles in the normal parasite physiology, which seem essential to be maintained when the parasite is exposed to drug stress. In addition, keeping the simultaneous expression of both transporters might be advantageous for responding to the drug action

Alternatively spliced transcripts and novel pseudogenes of the Plasmodium falciparum resistance-associated locus pfcrt detected in East African malaria patients.

OBJECTIVES: Polymorphisms in the lysosomal transporter encoded by the pfcrt gene directly impact on Plasmodium falciparum susceptibility to aminoquinolines. The Lys76Thr mutation is the critical change conferring chloroquine resistance in vitro and in vivo, but always occurs with additional non-synonymous changes in the pfcrt coding sequence. We sought to better describe pfcrt polymorphisms distal to codon 76. METHODS: Small-volume samples (≤ 500 μL) of parasite-infected blood collected directly from malaria patients presenting for treatment in Sudan and Tanzania were immediately preserved for RNA extraction. The pfcrt locus was amplified from cDNA preparations by nested PCR and sequenced directly to derive full-length mRNA sequences. RESULTS: In one of two sites in Sudan, two patients were found with an unorthodox spliced form of pfcrt mRNA in which two exons were skipped, but it was not possible to test for the presence of the putative protein products of these aberrant transcripts. Genomic DNA sequencing from dried blood spots collected in parallel confirmed the presence of spliced pfcrt pseudogenes in a minority of parasite isolates. Full-length cDNA from conventionally spliced mRNA molecules in all study sites demonstrated the existence of a variety of pfcrt haplotypes in East Africa, and thus provides evidence of intragenic recombination. CONCLUSIONS: The presence of pseudogenes, although unlikely to have any direct public health impact, may confound results obtained from simple genotyping methods that consider only codon 76 and the adjacent residues of pfcrt

Evaluating malaria prevalence and land cover across varying transmission intensity in Tanzania using a cross-sectional survey of school-aged children

BACKGROUND: Transmission of malaria in sub-Saharan Africa has become increasingly stratified following decades of malaria control interventions. The extent to which environmental and land cover risk factors for malaria may differ across distinct strata of transmission intensity is not well known and could provide actionable targets to maximize the success of malaria control efforts. METHODS: This study used cross-sectional malaria survey data from a nationally representative cohort of school-aged children in Tanzania, and satellite-derived measures for environmental features and land cover. Hierarchical logistic regression models were applied to evaluate associations between land cover and malaria prevalence within three distinct strata of transmission intensity: low and unstable, moderate and seasonal, and high and perennial. RESULTS: In areas with low malaria transmission, each 10-percentage point increase in cropland cover was associated with an increase in malaria prevalence odds of 2.44 (95% UI: 1.27, 5.11). However, at moderate and higher levels of transmission intensity, no association between cropland cover and malaria prevalence was detected. Small associations were observed between greater grassland cover and greater malaria prevalence in high intensity settings (prevalence odds ratio (POR): 1.10, 95% UI: 1.00, 1.21), and between greater forest cover and reduced malaria prevalence in low transmission areas (POR: 0.74, 95% UI: 0.51, 1.03), however the uncertainty intervals of both estimates included the null. CONCLUSIONS: The intensity of malaria transmission appears to modify relationships between land cover and malaria prevalence among school-aged children in Tanzania. In particular, greater cropland cover was positively associated with increased malaria prevalence in areas with low transmission intensity and presents an actionable target for environmental vector control interventions to complement current malaria control activities. As areas are nearing malaria elimination, it is important to re-evaluate environmental risk factors and employ appropriate interventions to effectively address low-level malaria transmission

Impact of laboratory diagnosis for improving the management of uncomplicated malaria at peripheral health care settings in Coast region, Tanzania

Malaria is a disease caused by parasites of the genus Plasmodium. Five species cause human disease, but the most common in tropical areas, and the cause of severe disease is Plasmodium falciparum. Control of morbidity and mortality is mainly achieved through appropriate malaria case management, which includes prompt diagnosis and treatment with effective antimalarial drugs. While definitive diagnosis of malaria is made by demonstration of parasites in the patient blood through microscopic examination of giemsa stained blood smears, in most clinical settings in Africa, diagnosis is limited by lack of facilities and personnel. The availability of malaria rapid diagnostic tests (RDTs) offers an opportunity to extend diagnostic services to areas previously not covered by conventional microscopy services. Two intervention trials were conducted, one at primary health care (PHC) facilities using microscopy, and the other at community level, through community health workers (CHWs), using rapid diagnostic tests (RDTs) for malaria diagnosis, and the impact of the interventions on antimalarial drugs prescription practices, antibiotic prescriptions and health outcome was investigated (Study I and II). A descriptive, cross sectional study was conducted to assess health workers diagnostic and prescription practices following introduction of RDTs for universal testing of malaria at PHC level in Tanzania (Study III). An exploratory study was also carried out to assess the usefulness of Histidine rich protein 2 (HRP2) and lactate dehydrogenase (LDH) based RDTs for treatment monitoring and detection of recurrent infection following artemisinin-based combination therapy (ACT) during a 42 day follow up period (Study IV). The use of parasite-based diagnostics significantly reduced antimalarial prescriptions at health facility and community level without affecting the health outcome of patients not treated with antimalarials (study I and II). The prescriptions of antimalarial drugs were 61% at intervention health facilities, whereas in the clinical and control arms the prescription rates remained high, 95% and 99%, respectively (study I). Similarly, 53% of patients tested with RDT at community level were provided antimalarial drugs compared to 96% among patients treated based on clinical diagnosis only (Study II). The availability of parasite-based diagnostics and antimalarial drugs within the community allowed early access to treatment as 67% of patients consulted CHWs within 24 hours of onset of fever (Study II). The rate of non adherence to test results was low in both study I and II. Study III observed low use of parasite-based diagnostics among fever patients (63%), low non adherence to test results (14%), substantial prescription of antimalarial drugs to non-tested patients (28%) and high prescriptions of antibiotics among patients with negative RDT results (81%), as well as frequent stock outs of both RDTs and ACTs. HRP2 based tests performed poorly when compared to LDH based tests for treatment monitoring, with median clearance times of 28 (7-42) and 7 (2-14) days respectively (Study IV). HRP2 based tests were unable to detect 8/10 recurrent infections during follow up compared to only two recurrent infections missed by LDH based tests. These studies lead to a conclusion that the availability of parasite-based diagnostics helps to restrict treatment with antimalarial drugs to patients with malaria. However, non adherence to malaria test results could undermine the potential of RDTs, and in-depth studies should be conducted to identify its causes. As the relative contribution of malaria as a cause of fever is declining in Tanzania, there is need to improve the overall management of non-malarial fevers. The longer the persistence of HRP2 antigen in blood makes HRP2 based tests not suitable for treatment monitoring and detection of recurrent infection calling for alternative diagnostic strategies for this purpose