History of malaria research and its contribution to the malaria control success in Suriname: a review

Suriname has cleared malaria from its capital city and coastal areas mainly through the successful use of chloroquine and DDT (dichloro-diphenyl-trichloroethane) during the Global Malaria Eradication programme that started in 1955. Nonetheless, malaria transmission rates remained high in the interior of the country for a long time. An impressive decline in malaria cases was achieved in the past few years, from 14,403 registered cases in 2003 to 1,371 in 2009. The introduction of artemisinin-based combination therapy (ACT) in 2004 has further fuelled the decrease in the number of infections with Plasmodium falciparum. The only population group still heavily burdened with malaria is gold mining industry workers. Interestingly, an important part of malaria cases diagnosed and treated in Suriname originate from border regions. Therefore, practical initiatives of combined efforts between neighbouring countries must be scaled up in order to effectively attack these specific areas. Furthermore, it is of vital importance to keep investing into the malaria control programme and public awareness campaigns. Especially the correct use of ACT must be promoted in order to prevent the emergence of resistance. However, effective preventive measures and adequate therapeutic options are on their own not enough to control, let alone eliminate malaria. Changing personal and social behaviour of people is particularly difficult, but crucial in making the current success sustainable. With this in mind, research on successfully implemented interventions, focusing on behavioural modifications and methods of measuring their effectiveness, must be expanded

Is flow cytometry better in counting malaria pigment-containing leukocytes compared to microscopy?

<p>Abstract</p> <p>Background</p> <p>Detection of malaria pigment (or haemozoin; Hz)-containing leukocytes may have prognostic relevance in malaria; however, studies reported conflicting results, with microscopic counts suggestive of being inaccurate and imprecise.</p> <p>Methods</p> <p>Numbers of Hz-containing leukocytes from a malaria patient obtained with a flow cytometer counting 50.000 gated events were compared with thin film microscopy as applied under field conditions.</p> <p>Results</p> <p>Flow cytometry identified 5.8% Hz-containing monocytes and 1.8% Hz-containing neutrophils. The microscopic examination yielded 10% and 13% of Hz-containing monocytes, as well as 0% and 0.5% of Hz-containing neutrophils for observers one and two, respectively.</p> <p>Conclusion</p> <p>Novel, robust and affordable cytometric methods should be evaluated in the field as they may assist in utilizing Hz-containing cells as clinically useful parameter.</p

Factors associated with retention to care in an HIV clinic in Gabon, Central Africa

BACKGROUND: Retention to HIV care is vital for patients' survival, to prevent onward transmission and emergence of drug resistance. Travelling to receive care might influence adherence. Data on the functioning of and retention to HIV care in the Central African region are limited. METHODS: This retrospective study reports outcomes and factors associated with retention to HIV care at a primary HIV clinic in Lambaréné, Gabon. Adult patients who presented to this clinic between January 2010 and January 2012 were included. Outcomes were retention in care (defined as documented show-up for clinical visits, regardless of delay) or LTFU (defined as a patient not retained in care; on ART or ART naïve, not returning to care during the study period with a patient delay for scheduled visits of more than 6 months), and mortality. Cox regression analysis was used to assess factors associated with respective outcomes. Qualitative data on reasons for LTFU were obtained from focus-group discussions. RESULTS: Of 223 patients included, 67.3% were female. The mean age was 40.5 (standard deviation 11.4) years and the median CD4 count 275 (interquartile range 100.5-449.5) cells/μL. In total, 34.1% were lost to follow up and 8.1% died. Documented tuberculosis was associated with increased risk of being LTFU (adjusted hazard ratio (aHR) 1.80, 95% confidence interval (95% CI) 1.05-3.11, P = 0.03), whereas early starting anti-retroviral therapy (ART) was associated with a decreased risk of LTFU (aHR 0.43, 95%CI 0.24-0.76, P = 0.004), as was confirmed by qualitative data. CONCLUSIONS: Retention to HIV care in a primary clinic in Gabon is relatively poor and interventions to address this should be prioritized in the HIV program. Early initiation of ART might improve retention in care

The influence of pregnancy on the pharmacokinetic properties of artemisinin combination therapy (ACT): a systematic review

Pregnancy has been reported to alter the pharmacokinetic properties of anti-malarial drugs, including the different components of artemisinin-based combination therapy (ACT). However, small sample sizes make it difficult to draw strong conclusions based on individual pharmacokinetic studies. The aim of this review is to summarize the evidence of the influence of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations. A PROSPERO-registered systematic review to identify clinical trials that investigated the influence of pregnancy on the pharmacokinetic properties of different forms of ACT was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2015. The following components of ACT that are currently recommend by the World Health Organization as first-line treatment of malaria in pregnancy were reviewed: artemisinin, artesunate, dihydroartemisinin, lumefantrine, amodiaquine, mefloquine, sulfadoxine, pyrimethamine, piperaquine, atovaquone and proguanil. The literature search identified 121 reports, 27 original studies were included. 829 pregnant women were included in the analysis. Comparison of the available studies showed lower maximum concentrations (Cmax) and exposure (AUC) of dihydroartemisinin, the active metabolite of all artemisinin derivatives, after oral administration of artemether, artesunate and dihydroartemisinin in pregnant women. Low day 7 concentrations were commonly seen in lumefantrine studies, indicating a low exposure and possibly reduced efficacy. The influence of pregnancy on amodiaquine and piperaquine seemed not to be clinically relevant. Sulfadoxine plasma concentration was significantly reduced and clearance rates were higher in pregnancy, while pyrimethamine and mefloquine need more research as no general conclusion can be drawn based on the available evidence. For atovaquone, the available data showed a lower maximum concentration and exposure. Finally, the maximum concentration of cycloguanil, the active metabolite of proguanil, was significantly lower, possibly compromising the efficacy. These findings suggest that reassessment of the dose of the artemisinin derivate and some components of ACT are necessary to ensure the highest possible efficacy of malaria treatment in pregnant women. However, for most components of ACT, data were insufficient and extensive research with larger sample sizes will be necessary to identify the exact influences of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations. In addition, different clinical studies used diverse study designs with various reported relevant outcomes. Future pharmacokinetic studies could benefit from more uniform designs, in order to increase quality, robustness and effectiveness. CRD42015023756 (PROSPERO

New imaging approaches for improving diagnosis of childhood tuberculosis

In South Africa (SA), childhood tuberculosis (TB) still accounts for considerable morbidity and mortality. The incidence of TB disease and risk of progression to severe or disseminated forms are especially high in young children or those with HIV infection. Childhood TB presents most commonly as primary TB, often with non specific signs and symptoms; TB may also present as acute pneumonia. The clinical diagnosis can therefore be challenging. Furthermore, due to difficulty in obtaining good-quality specimens and the paucibacillary nature of childhood TB, microbiological confirmation is only achieved in a minority of children, especially in settings where there is limited capacity for microbiological confirmation

Assessing anti-malarial drug effects ex vivo using the haemozoin detection assay

© 2015 Rebelo et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: In vitro sensitivity assays are crucial to detect and monitor drug resistance. Plasmodium falciparum has developed resistance to almost all anti-malarial drugs. Although different in vitro drug assays are available, some of their inherent characteristics limit their application, especially in the field. A recently developed approach based on the flow cytometric detection of haemozoin (Hz) allowed reagent-free monitoring of parasite maturation and detection of drug effects in culture-adapted parasites. In this study, the set-up, performance and usefulness of this novel assay were investigated under field conditions in Gabon. Methods: An existing flow cytometer (Cyflow Blue) was modified on site to detect light depolarization caused by Hz. Blood from malaria patients was incubated for 72 hrs with increasing concentrations of chloroquine, artesunate and artemisinin. The percentage of depolarizing red blood cells (RBC) was used as maturation indicator and measured at 24, 48 and 72 hrs of incubation to determine parasite growth and drug effects. Results: The flow cytometer was easily adapted on site to detect light depolarization caused by Hz. Analysis of ex vivo cultures of parasites, obtained from blood samples of malaria patients, showed four different growth profiles. In 39/46 samples, 50% inhibitory concentrations (IC50) were successfully determined. IC50 values for chloroquine were higher than 200 nM in 70% of the samples, indicating the presence of chloroquine-resistant parasites. For artesunate and artemisinin, IC50 values ranged from 0.9 to 60 nM and from 2.2 nM to 124 nM, respectively, indicating fully sensitive parasites. Conclusion: Flow cytometric detection of Hz allowed the detection of drug effects in blood samples from malaria patients, without using additional reagents or complex protocols. Adjustment of the initial parasitaemia was not required, which greatly simplifies the protocol, although it may lead to different IC50 values. Further investigation of set-up conditions of the Hz assay, as well as future studies in various settings should be performed to further determine the usefulness of this assay as a tool for rapid resistance testing in malaria-endemic countries.This work was supported by the Luso-American Foundation (FLAD-LACR grant: B-A.V-109-09/07). MR acknowledges Fundação para a Ciência e a Tecnologia for doctoral grant (SFRH/BD/84530/2012) and Fundação Calouste Gulbenkian for the Award CAML/Gulbenkian for Travel ACGT fellowship.info:eu-repo/semantics/publishedVersio

Molecular surveillance of mutations in the cytochrome b gene of Plasmodium falciparum in Gabon and Ethiopia

BACKGROUND: Atovaquone is part of the antimalarial drug combination atovaquone-proguanil (Malarone(®)) and inhibits the cytochrome bc(1 )complex of the electron transport chain in Plasmodium spp. Molecular modelling showed that amino acid mutations are clustered around a putative atovaquone-binding site resulting in a reduced binding affinity of atovaquone for plasmodial cytochrome b, thus resulting in drug resistance. METHODS: The prevalence of cytochrome b point mutations possibly conferring atovaquone resistance in Plasmodium falciparum isolates in atovaquone treatment-naïve patient cohorts from Lambaréné, Gabon and from South Western Ethiopia was assessed. RESULTS: Four/40 (10%) mutant types (four different single polymorphisms, one leading to an amino acid change from M to I in a single case) in Gabonese isolates, but all 141/141 isolates were wild type in Ethiopia were found. CONCLUSION: In the absence of drug pressure, spontaneous and possibly resistance-conferring mutations are rare

Assessing the Consequences of Stigma for Tuberculosis Patients in Urban Zambia

Assessing the consequences of stigma for tuberculosis patients in urban zambia Cremers, A.L.; de Laat, M.M.; Kapata, N.; Gerrets, R.P.M.; Klipstein-Grobusch, K.; Grobusch, M.P. Published in: PLoS ONE DOI: 10.1371/journal.pone.0119861 Link to publication Citation for published version (APA): Cremers, A. L., de Laat, M. M., Kapata, N., Gerrets, R., Klipstein-Grobusch, K., &amp; Grobusch, M. P. (2015). Assessing the consequences of stigma for tuberculosis patients in urban zambia. PLoS ONE, 10(3), [e0119861]. https://doi.org/10.1371/journal.pone.0119861 General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract Background Stigma is one of the many factors hindering tuberculosis (TB) control by negatively affecting hospital delay and treatment compliance. In Zambia, the morbidity and mortality due to TB remains high, despite extended public health attempts to control the epidemic and to diminish stigma. Study Aim To enhance understanding of TB-related stigmatizing perceptions and to describe TB patients&apos; experiences of stigma in order to point out recommendations to improve TB policy. Methods We conducted a mixed method study at Kanyama clinic and surrounding areas, in Lusaka, Zambia; structured interviews with 300 TB patients, multiple in-depth interviews with 30 TB patients and 10 biomedical health workers, 3 focus group discussions with TB patients and treatment supporters, complemented by participant observation and policy analysis of the TB control program. Predictors of stigma were identified by use of multivariate regression analyses; qualitative analysis of the in-depth interviews, focus group discussions and participant observation was used for triangulation of the study findings. Results We focused on the 138/300 patients that described TB-related perceptions and attitudes, of whom 113 (82%) reported stigma. Data Availability Statement: All relevant data from the TBAC study are contained within the paper. Additional data will be made available by our first author. The original data contain information which may lead to the identification of study subjects and in order to protect their privacy, a request to gain access to the original data is needed. Funding: No specific funding was received for this study other than the personal grants for ALC specified below. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. both among children and adults and included low self-esteem, insults, ridicule, discrimination, social exclusion, and isolation leading to a decreased quality of life and social status, non-disclosure, and/or difficulties with treatment compliance and adherence. Women had significantly more stigma-related problems than men. Conclusions The findings illustrate that many TB patients faced stigma-related issues, often hindering effective TB control and suggesting that current efforts to reduce stigma are not yet optimal. The content and implementation of sensitization programs should be improved and more emphasis needs to be placed on women and children. Introduction Alongside biological, economic, and cultural barriers to effective tuberculosis (TB) control, stigma constitutes one of the major social factors causing hospital delay and hindering compliance among TB patients The importance of addressing stigma related to TB is illustrated by the fact that this disease is one of the major causes of death worldwide. Zambia ranks 29 th among the world&apos;s top TB countries identified by the World Health Organisation (WHO) having 427/100.000 incident TB cases in the year 2012. HIV co-infection rate is 61% and MDR-TB prevails in 0.3% of new Consequences of Stigma for Tuberculosis Patients in Urban Zambia PLOS ONE

Methaemoglobin and COHb in patients with malaria

Background Haemolytic conditions may contribute to disease pathogenesis and severe clinical manifestations through the liberation of free haemoglobin (Hb) and production of toxic free haem. Thus, free Hb and haem should be associated with altered MetHb and COHb levels in malaria as in other conditions. Methods This study comprises data collected at three different sites: (i) a retrospective analysis of the first arterial blood gas result (ABGS) of any patient during 2010 at the University Hospital in Lisbon; (ii) a retrospective analysis of ABGS from patients with severe malaria admitted to the intensive care unit in Berlin, Germany; and (iii) a prospective study of non-invasive MetHb measurements in children with and without malaria in Lambaréné, Gabon. Results In Lisbon, the mean MetHb level was 1.4% (SD: 0.5) in a total of 17,834 ABGS. Only 11 of 98 samples with a MetHb level of >3.0 referred to infections. COHb levels showed no particular association with clinical conditions, including sepsis. In 13 patients with severe malaria in Berlin, the mean MetHb levels on admission was 1.29%, with 1.36% for cerebral malaria and 1.14% for non-cerebral malaria (P > 0.05). All COHb measurements were below 2.3%. In Lambaréné, Gabon, 132 healthy children had a mean MetHb level of 1.57%, as compared to 150 children with malaria, with a value of 1.77% and 2.05% in uncomplicated and complicated cases, respectively (P < 0.01). Conclusions The data appears consistent with the methaemoglobin/haem hypothesis in malaria and sepsis pathogenesis. However, although MetHb was significantly different between healthy controls and children with malaria in Africa, the difference was rather small, also when compared to previous studies. Still, non-invasive bedside MetHb testing may warrant further evaluation as it could be a simple adjuvant tool for prognosis in resource poor settings

Discontinuing atovaquone/proguanil prophylaxis ad-hoc post-exposure and during-travel dose-sparing prophylactic regimens against P. falciparum malaria: an update with pointers for future research

© 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Background: Atovaquone/proguanil (AP) is a highly effective malaria chemoprophylaxis combination. According to current guidelines, AP is taken once daily during, and continued for seven days post exposure. A systematic review by Savelkoel et al. summarised data up to 2017 on abbreviated AP regimens, and concluded that discontinuing AP upon return may be effective, although the available data was insufficient to modify current recommendations. The same applies to other studies evaluating during-travel dose-sparing regimens. Methods: A literature search in Pubmed and Embase was performed including search terms related to AP prophylaxis and pharmacokinetics to search for recent studies on abbreviated AP regimens published since 2017. Results: Since the 2017 review, no new studies assessing discontinuing AP ad-hoc post-exposure prophylaxis have been published. Two new studies were identified assessing other abbreviated AP regimens; one investigated a twice-weekly AP regimen in 32 travellers, and one a three-day AP course in therapeutic dose (1000/400 mg) prior to exposure in 215 travellers. No malaria cases were detected in the study participants adhering to these regimens. Conclusions: Further research would be needed if the research question is considered of sufficient importance to facilitate evidence-based decision-making to modify current guidelines, as efficacy studies in travellers are fraught with confounders. We recommend human challenge trials to study abbreviated AP regimens pertaining to malaria chemoprophylaxis as they allow for rational, subject number, time- and cost-saving trial designs.info:eu-repo/semantics/publishedVersio