10 research outputs found
Space optimization for objects layout
No full textThis thesis was scanned from the print manuscript for digital preservation and is copyright the author.
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WAsP model performance verification using lidar data
No full text© 2015, The Author(s).This study describes the verification of Wind Atlas Analysis and Application program (WAsP) modelled average wind speeds in a complex terrain. WAsP model was run using data collected at 3 masts: Kalkumpei, Nyiru and Sirima using cup anemometers and wind vanes for the entire 2009 calendar year and verified using data collected by WindTracer LIDAR (light detection and ranging) for 2 weeks from 11th to 24th July 2009. Evaluating WAsP mean wind speed map using LIDAR data showed that Nyiru station provides the best data to model mean wind speed over the wind farm domain with a mean difference of 0.16 m/s, root mean square error of 0.85 m/s and Index of Agreement of 0.61. Construction of a 310 MW windfarm has commenced at this site. Once completed, the windfarm will be operating 365 vestas V52-850kW turbines
Understanding the Materno-Fetal Interface During Microbial Infections
No full textThis eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
Rapid malaria diagnostic tests vs. clinical management of malaria in rural Burkina Faso: safety and effect on clinical decisions. A randomized trial
Get PDFOBJECTIVES: To assess if the clinical outcome of patients treated after performing a Rapid Diagnostic Test for malaria (RDT) is at least equivalent to that of controls (treated presumptively without test) and to determine the impact of the introduction of a malaria RDT on clinical decisions. METHODS: Randomized, multi-centre, open clinical trial in two arms in 2006 at the end of the dry and of the rainy season in 10 peripheral health centres in Burkina Faso: one arm with use of RDT before treatment decision, one arm managed clinically. Primary endpoint: persistence of fever at day 4. Secondary endpoints: frequency of malaria treatment and of antibiotic treatment. RESULTS: A total of 852 febrile patients were recruited in the dry season and 1317 febrile patients in the rainy season, and randomized either to be submitted to RDT (P_RTD) or to be managed presumptively (P_CLIN). In both seasons, no significant difference was found between the two randomized groups in the frequency of antimalarial treatment, nor of antibiotic prescription. In the dry season, 80.8% and 79.8% of patients with a negative RDT were nevertheless diagnosed and treated for malaria, and so were 85.0% and 82.6% negative patients in the rainy season. In the rainy season only, both diagnosis and treatment of other conditions were significantly less frequent in RDT positive vs. negative patients (48.3% vs. 61.4% and 46.2% vs. 59.9%, P = 0.00 and 0.00, respectively). CONCLUSION: Our study was inconclusive on RDT safety (clinical outcome in the two randomized groups), because of an exceedingly and unexpectedly low compliance with the negative test result. Further research is needed on best strategies to promote adherence and on the safety of a test based strategy compared with the current, presumptive treatment strategy
Author response: Major transcriptional changes observed in the Fulani, an ethnic group less susceptible to malaria
No full textRational deployment of antimalarial drugs in Africa: should first-line combination drugs be reserved for paediatric malaria cases?
Get PDFArtemisinin-based combination therapy is exerting novel selective pressure upon populations of Plasmodium falciparum across Africa. Levels of resistance to non-artemisinin partner drugs differ among parasite populations, and so the artemisinins are not uniformly protected from developing resistance, already present in South East Asia. Here, we consider strategies for prolonging the period of high level efficacy of combination therapy for two particular endemicities common in Africa. Under high intensity transmission, two alternating first-line combinations, ideally with antagonistic selective effects on the parasite genome, are advocated for paediatric malaria cases. This leaves second-line and other therapies for adult cases, and for intermittent preventive therapy. The drug portfolio would be selected to protect the 'premier' combination regimen from selection for resistance, while maximising impact on severe disease and mortality in children. In endemic areas subject to low, seasonal transmission of Plasmodium falciparum, such a strategy may deliver little benefit, as children represent a minority of cases. Nevertheless, the deployment of other drug-based interventions in low transmission and highly seasonal areas, such as mass drug administration aimed to interrupt malaria transmission, or intermittent preventive therapy, does provide an opportunity to diversify drug pressure. We thus propose an integrated approach to drug deployment, which minimises direct selective pressure on parasite populations from any one drug component. This approach is suitable for qualitatively and quantitatively different burdens of malaria, and should be supported by a programme of routine surveillance for emerging resistanc
Fabrication and Characterization of Polylactic Acid (PLA) Microporous Film Coated with Gelatin and Chromolaena Odorate Leaf Extract for Wound Dressing Application
Get PDFThe infection of the skin wound is the cause of pain and difficult recovery. This work has developed wound dressing from microporous PLA film-coated gelatin from marrow bone and jellyfish with blended Chromolaena odorata leaf extract at low concentration to stimulate skin cell growth. The microporous PLA film was produced by solution method with different ratios between dichloromethane (CH2Cl2) and tetrahydrofuran (THF) at 25:35, 25:50, and 25:65, respectively. The optical microscope and scanning electron microscope (SEM) were used to analyze the pore size of microporous PLA film and its physical characteristics after coating with different gelatins by dip coating process. The wound dressing film was determined for cell viability after testing with NIH/3T3 and HaCaT in the culture cell plate. The testing method was followed by a 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay to measure cell stimulation and cell viability using a UV absorption technique after staining. The result shows that our wound dressing can stimulate both NIH/3T3 and HaCaT keratinocytes but with different characteristics due to the different releasing characters of gelatins and different responses of cell types depending on C. odorata leaf extract concentration. The microporous PLA film-coated gelatin from jellyfish revealed better skin cell growth in both NIH/3T3 and HaCaT keratinocytes than that of coated gelatin from marrow bone because of the continuous releasing rate after contact with water of gelatin from jellyfish. Moreover, C. odorata leaf extract which was used for reducing the inflammation of the cellular injury displayed toxic HaCaT keratinocyte at high concentrations but it did not affect the NIH/3T3 toxicity. Interestingly, it can stimulate the cell viability of NIH/3T3 until 3 mg/mL of C. odorata leaf extract concentration and displays constant cell viability afterward
Exploring the context and potential benefits of implementing an Intermittent Preventive Treatment for malaria in infants (IPTi) in Papua New Guinea
Get PDFSummary: Background
Intermittent preventive treatment (IPTi) is an intervention aiming to reduce the
risk of malaria in infants. Its concept is to deliver a full treatment course of
antimalarial drugs to infants, three or four times during the first year of life,
following the expanded program of immunization (EPI) schedule and regardless
of clinical malaria episodes.
Mainly Sulphadoxine/pyrimthamine (SP) was studied and demonstrated to
reduce the risk of malaria by 30% in Africa, where Plasmodium falciparum (Pf) is
the predominant species. No study has been carried out in regions of the world
with a significant burden of non-Pf infections. There is therefore a need to
investigate the potential benefits of IPTi in areas, such as Papua New Guinea
(PNG), highly endemic for Plasmodium vivax (Pv) malaria.
Apart from efficacy, which is the corner stone of an intervention, it is essential to
have a clear picture of the context in which such an intervention might be
implemented. Indeed, determinants of effectiveness such as the malaria context
(epidemiology and case management), the acceptability and the access to the
intervention need to be investigated prior to the implementation of IPTi.
The present study investigates the efficacy of IPTi in PNG as well as some key
aspects of infant’s health in PNG that might help to understand the context in
which IPTi could be implemented.
Methods
Randomized controlled trial investigating the protective efficacy of 4 doses of SP
associated to 3 days of artesunate (SP-AS3) or 3 days of amodiaquine (SP-AQ3)
given at 3-month intervals during the first year of life. Most of infants were
followed-up for an additional 12 months. The study took place in Madang and
Maprik (PNG) from 2006 to 2010, but only the Madang cohort was used for the
IPTi efficacy analyses.
Making use of the morbidity passive case detection of the trial, the following
aspects of infant’s health in PNG were investigated:
· Effectiveness of treating infants with a unified treatment
(artemther/lumefantrine, AL) for Pf & Pv malaria based on the result of the
rapid diagnostic test (RDT)
· The incidence of common illnesses based on RDT and syndromic
definitions of diseases and the impact of IPTi on them.
· The performances of the integrated management childhood illness (IMCI)
supplemented with RDT & IPTi for the management of common
syndromes/diseases in PNG.
The acceptability of IPTi was also assed alongside the drug trial.
Findings
1605 infants 3 months old were enrolled in the IPTi trial, 1125 in Madang and 480
in Maprik. The intention-to-treat relative risk (RR) at 15 months of age (Madang
site only) was 0.72 (95%CI, 0.57 - 0.90) on all malaria episodes with SP-AQ3 and
0.88 (95%CI, 0.70 - 1.10) with SP-AS3, overall p=0.017. Using SP-AQ3, the RR
was 0.63 (95%CI, 0.45 - 0.88) on Pf and 0.78 (95%CI, 0.60 - 1.01) on Pv. No
difference was observed in the incidence of overall morbidity, severe diseases
and non-malarial illnesses between the placebo and IPTI intervention arms.
Fewer deaths were observed in the treatment arms compared to placebo:
placebo=8, SP-AQ3=1 and SP-AS3=3.
7223 fever episodes occurred (in Madang and Maprik) during the study and 5670
had a negative RDT result. Out of them, 133 (3.4%) re-attended the clinic within
7 days for fever, and 1 died of lower respiratory tract infection (LRTI). 23 (0.6%)
infants re-presented with a severe illness (4 with positive BS and/or RDT). 1728
children with positive RDT results were treated with artemether/lumefantrine (AL).
30 (1.7%) re-attended within 7 days for fever, none died.
Out of the total cohort, incidence rates (episodes/child/year) for common
syndromes/diseases were: 0.85 (95%CI, 0.81-0.90) for LRTI, 0.72 (95%CI, 0.65-
0.93) for gastroenteritis (GI), 0.62 for malaria (95%CI, 0.58 - 0.66) and 0.08
(95%CI, 0.07-0.09) for otitis.
The introduction of RDT led to a high accuracy of “on site” malaria diagnosis (К
=0.99). On the opposite, the clinical diagnosis accuracy for others syndromes
was poor: К=0.47 for LRTI, К=0.52 for GI and К= 0.52 for otitis.
25% of illness episodes were inappropriately treated: 6% did not receive
antibiotics when they should have and 19% received antibiotics when they should
not have (according to recommendations). The prescription’s rate of antibiotics
was 56% when the RDT for malaria was negative and 16% when the RDT was
positive (p<0.001). The acceptability of IPTi appears to be good in Melanesian
populations.
Conclusion
The use of RDT and artemether/lumefantrine is a safe and effective strategy for
the management of malaria cases in PNG and could be implemented very easily.
IPTi has demonstrated its efficacy to reduce both Pf and Pv episodes. However,
the apparent absence of benefit on the overall morbidity and on severe illnesses
is a concern and mitigates the interest of implementing this intervention in PNG.
Furthermore, other factors such as a low EPI coverage and rapidly changing
malaria endemicity due to the recent introduction in PNG of insecticide treated
nets (ITN) and artemisinin combination therapies (ACT) are likely to jeopardize
the potential benefits of IPTi in PNG. ---------- Zusammenfassung:
Hintergrund
Intermittent preventive treatment in infants (IPTi) ist eine Intervention mit dem
Ziel, das Risiko von Malaria bei Kleinkindern zu reduzieren. Sein Konzept ist den
Säuglingen Behandlung mit Malariamedikamenten, drei oder viermal während
des ersten Lebensjahres, nach dem Zeitplan des Erweitertens Programms der
Immunisierung (EPI) und unabhängig von klinischen Malaria Episoden.
Haupsächlich Sulfadoxin/pyrimthamine (SP) wurde studiert und zeigte, dass das
Risiko von Malaria um 30% in Afrika reduziert wurde, wo Plasmodium falciparum
(Pf) die vorherrschende Spezies ist. Keine Studie wurde in den Regionen der
Welt mit einer signifikanten Belastung durch nicht-Pf-Infektionen durchgeführt. Es
besteht daher ein Bedarf, die potenziellen Vorteile der IPTi in Bereichen wie
Papua-Neuguinea (PNG), hoch endemisch für Plasmodium vivax (Pv) Malaria,
zu untersuchen.
Abgesehen von Wirksamkeit, die der Grundstein für eine Intervention ist, ist es
wichtig, ein klares Bild des Kontextes zu haben, in dem ein solcher Eingriff
durchgeführt werden könnte. Tatsächlich, Determinante der Wirksamkeit wie der
Malariakontext (Epidemiologie und Case Management), die Akzeptanz und der
Zugang auf die Intervention, muss vor der Durchführung von IPTi untersucht
werden.
Die vorliegende Studie untersucht die Wirksamkeit von IPTi in PNG sowie einige
der wichtigsten Aspekte der kindlichen Gesundheit von Kleinkindern in PNG, die
helfen könnten, den Kontext, in dem IPTi implementiert werden könnte, zu
verstehen.
Methoden
Randomisierte kontrollierte Studie, die die schützende Wirkung untersucht von
vier Dosen von SP und 3 Tagen von Artesunat (SP-AS3) oder 3 Tage von
Amodiaquin (SP-AQ3) in 3-monatigen Abständen, gegeben während des ersten
Lebensyahres. Die meisten Kinder wurden für weitere 12 Monate beobachtet.
Die Studie fand in Madang und Maprik (PNG) von 2006 bis 2010 statt, aber nur
die Madang Kohorte wurde für die IPTi Wirksamkeit Analyse verwendet.
Folgende Aspekte der Gesundheit der Kleinkinder in PNG wurden untersucht,
indem die passiven Fälle der Studie registriert wurden:
• Wirksamkeit der Behandlung von Säuglingen mit einer einheitlichen
Behandlung (artemther / Lumefantrin, AL) für Pf & Pv Malaria, dem Ergebnis des
rapid diagnostic test (RDT) nach.
• Die Inzidenz von gewöhnlichen Krankheiten nach RDT und syndromalen
Definitionen von Krankheiten und die Auswirkungen von IPTi auf ihnen.
• Die Leistungen des integrierten Managementsystems Kinderkrankheiten (IMCI)
ergänzt mit RDT & IPTi für die Bewirtschaftung der gewöhnlichen Syndrome / in
PNG.
Die Akzeptanz von IPTi wurde während dieser Studie bestimmt .
Resultate
1605 3-Monate alt Säuglinge wurden in die IPTi Studie eingezogen, 1125 in
Madang und 480 in Maprik. Intention-to-treat relative Risiko (RR) bei 15 Monaten
alt betrug 0.72 (95% CI, 0.57 bis 0.90) auf allen Malariaepisoden mit SP-AQ3
und 0.88 (95% CI, 0.70 bis 1.10) mit SP-AS3, Insgesamt p = 0.017. Mit SP-AQ3
wurde das RR 0.63 (95% CI, 0.45 bis 0.88) auf Pf und 0.78 (95% CI, 0.60 bis
1.01) auf Pv. Es wurde kein Unterschied in der Inzidenz von insgesamter
Morbidität, schwere Erkrankungen und nicht-Malaria-Erkrankungen zwischen der
Placebo-und IPTi Intervention Arme beobachtet. Nur wenige Todesfälle wurden
in den Behandlungsgruppen im Vergleich zu Placebo beobachtet: Placebo = 8,
SP-AQ3 = 1 und SP-AS3 = 3 ist.
7223 Fieberepisode (in Madang und Maprik) sind während der Studie
aufgetreten und 5670 hatten einen negativen RDT. Aus ihnen, 133 (3.4%)
besuchten die Klinik innerhalb von 7 Tagen bei Fieber wieder und 1 starb an
unteren Atemwegeinfektion (LRTI). 23 (0.6%) Säuglinge kamen erneut mit einer
schweren Krankheit (4 mit positiven BS und / oder RDT). 1728 Kinder mit
positiven RDT Ergebnissen wurden mit Artemether / Lumefantrin (AL) behandelt.
30 (1.7%) besuchten die klinik innerhalb von 7 Tagen bei Fieber wieder, keiner
starb.
Von der insgesamten Kohorte waren Inzidenzraten (Episode / Kind / Jahr) für
gemeinsame Syndrome / Krankenheiten : 0.85 (95% CI, 0.81-0.90) für LRTI, 0.72
(95% CI, 0.65-0.93) für Gastroenteritis (GI), 0.62 f!ur malaria (95%CI, 0.58 - 0.66)
und 0.08 (95% CI, 0.07-0.09) für Otitis.
Die Einführung von RDT führte zu einer hohen Genauigkeit von "on site"
Malaria-Diagnose (К = 0.99). Im gegenteil, war die Genauigkeit klinischer
Diagnose für andere Syndrome schlecht : К = 0.47 für LRTI, К = 0.52 für GI und
К = 0.52 für Otitis.
25% der Krankheitsepisoden wurden unsachgemäß behandelt: 6% erhielten
keine Antibiotica, wenn sie sie haben sollten und 19% erhielten Antibiotika, wenn
sie sie nicht haben sollten (den Empfehlungen nach). Die Verschreibung von
Antibiotika war 56% wenn der RDT für Malaria negative war und 16% wenn der
RDT postiv war (p <0.001). Die Akzeptanz für IPTi scheint in melanesischen
Bevölkerung gut zu sein.
Schlussvolgernd
Die Verwendung von RDT und Artemether / Lumefantrin ist eine sichere und
wirksame Strategie für die Verwaltung der Malariafälle in PNG und könnte sehr
leicht realisiert werden. IPTi hat seine Wirksamkeit demonstriet, sowohl Pf und
Pv Episoden zu reduzieren. Allerdings ist die offensichtliche Abwesenheit von
Vorteilen auf die gesamte Morbidität und auf schwere Krankheiten ein Anliegen,
und mildert das Interesse der Durchführung dieser Intervention in PNG. Darüber
hinaus gibt es andere Faktoren, wie eine niedrige EPI Berichterstattung und die
sich rasch verändernde Malaria endemizität durch die kürzliche Einführung in
PNG von Insektiziden behandelte Moskitonetze (ITN) und Artemisinin-
Kombinationstherapien (ACT), die die potenziellen Vorteile der IPTi in PNG
gefährden könnten
Assessing malaria attributed mortality in west and southern Africa
Get PDFMalaria has persistently remained a serious health and socio-economic problem in developing nations particularly in Sub-Saharan Africa (SSA). There are approximately 500 million cases of malaria each year and close to one million deaths occurring mainly among children under five years. Developing countries spend a reasonable proportion of their gross domestic product (GDP) on malaria which in the end hinders their levels of development.
World Health Organizations (WHO) and partners through the Roll Back Malaria initiative (RBM) have targeted vector control, health promotion and case management (using rapid diagnostic tests and treatment with Artemisinin combination therapy) in order reduce malaria morbidity and mortality cases. Since 2002, funds for promoting malaria control activities have increased exponentially in SSA. Major donors include presidential malaria initiative (PMI) and Global fund to fight AIDS, tuberculosis and malaria (GFATM). Countries which have scaled up the recommended malaria control strategies such as insecticides-treat net (ITN) and treatment of confirmed cases have reported a decline in both morbidity and mortality especially among children. However, these statistics are based on health facilities data and yet in most developing countries many deaths occur at home and are never recorded due to inefficient vital registration systems. Monitoring the progress of such interventions requires reliable sources of data on both the transmission and infection outcome.
In malaria endemic areas, people acquire natural immunity during the early years of their life after getting exposed to repeated infections. This is observed from the reductions in the number of severe malaria-related morbidity and mortality cases especially in children >5 years. Due to the current undertakings that are aimed at reducing malaria exposure, there are concerns about shifting the disease burden to older children but the required to data to monitor this are not readily available in SSA. Low income countries have resorted to health and demographic surveillance systems (HDSS) to monitor routinely population changes and health outcomes within a defined geographical area.
In 2000, the INDEPTH, a network of HDSS integrated the Malaria Transmission Intensity and Mortality Burden Across Africa (MTIMBA) project into selected sites’ routine activities in order to assess the transmission-malaria mortality relationship taking into account the current interventions. Mortality data and other demographic characteristics were extracted from routinely collected HDSS databases. The entomological data were collected every fortnight from randomly sampled compounds over the 3 years MTIMBA period.
The MTIMBA project generated large geostatistical data that are correlated in space and time. Furthermore, the project captured longitudinal mosquito data that were characterized by many zeros especially during the dry periods. The zeros are due empty traps from a compound or when all the captured mosquitoes are not infectious. Appropriate data analysis therefore should apply models that account for spatial-temporal correlation and the excess zeros in order to avoid over or underestimation of parameters. Zero-inflated geostatistical models account for spatial-temporal correlation by introducing location-specific and time interval random effects which creates more parameters to estimate. Bayesian models implemented via Markov chain Monte Carlo simulation (MCMC) addresses fit of highly parameterized models.
This work applied zero-inflated Bayesian models to estimate malaria attributable mortality across all age-groups using large, correlated and sparse data collected from Navrongo and Manhiça HDSS between 2001 and 2004. The contributions of this thesis were (i) the description of the HDSS data characteristics and relevant methods for analysis; (ii) the spatially explicit estimates of malaria transmission intensity at monthly intervals; and (iii) the relationship between all-cause mortality and malaria transmission intensity across all age categories.
Chapter 2 described the characteristics of the MTIMBA data. These are large geostatistical, temporal, seasonal and zero-inflated data. The mortality and mosquito data were misaligned because they were captured at different compounds and time periods. Zero-inflated Bayesian spatio-temporal models are the state-of-art in handling such data. The rigorous statistical process was demonstrated by modelling sporozoite rate (SR) data from Manhiça HDSS. The analysis of the MTIMBA data was used as an avenue for building SSA capacity through course work, seminars and mentorship. Site-specific analyses are still on-going. However, the project generated data that is relevant for assessing within and between site malaria transmission heterogeneity.
The Navrongo malaria exposure surfaces described in chapter 3 were obtained from zero-inflated geostatistical models fitting separately the binomial SR data and negative binomial count data by mosquito species. All the models included space and time correlation in addition to the Climate, environmental and seasonality covariates. The entomological inoculation rate (EIR) estimates were derived as a product of predicted man biting rate and SR. Observed EIR in this district was >100 infective bites/person/year. Distance to water to bodies, day temperatures and vegetation were the main predictors of mosquito densities for the two species. The EIR maps clearly indicated that the temporal heterogeneity was stronger than the spatial variation in this area. The same situation was also observed from the analyses of the two MTIMBA sites of Rufiji (Tanzania) and Kisumu (Kenya).
Monthly malaria exposure surfaces (chapter 3) were linked to the nearest compounds where mortality was observed as described in chapter 4. Time to death data were split at monthly intervals in order to generate Bernoulli and binomial data that were modelled via logistic regression formulations. Spatio-temporal models were fitted to obtain age-specific mortality risk estimates. The model considered 2 covariates; natural logarithm transformed EIR estimates with their measurement errors and age. ITN variable was only included in neonates, post-neonates and child models. The analysis showed a positive log-linear relationship between all-cause mortality and malaria exposure in all the age groups but the association was only important among children (1-4 years) and people >= 60 years. ITN use showed a protective effect among all the under five children, confirming what was observed in Rufiji and Kisumu HDSS.
The methods used in estimating malaria exposure surfaces and mortality risks in chapters 3 and 4 were extended to Manhiça HDSS (Mozambique) data to describe the mortality-malaria transmission relationship for this area (chapter 5). The spatio-temporal age-specific models considered EIR estimates with their measurement errors (to account for the predictive uncertainty) and age as model covariates.
The distance to the nearest water bodies was the only important common predictor of An. funestus and An. gambiae mosquito densities. Malaria transmission intensity declined consistently in this area. The Model-based results indicated a positive log-linear relationship between all-cause mortality and malaria exposure across all age groups namely; the neonates (0-28 days), post-neonates (1-11months), children (1-4years), young people (5-14 years), adults (15- 59years) and old age (>=60 years).
This work contributes to further understand of malaria-mortality relationships. A positive association between mortality and malaria exposure among the under fives is consistent with what was reported from the MTIMBA sites of Rufiji and Kisumu. Completion of the remaining site-specific analyses followed by a meta-analysis will make a great contribution to malaria epidemiology. Further work however, should consider cohort analysis in order to ascertain whether malaria control interventions have caused a shift in the age of acquired immunity
