Malaria diagnostic testing and treatment practices in three different Plasmodium falciparum transmission settings in Tanzania: before and after a government policy change

BACKGROUND: Patterns of decreasing malaria transmission intensity make presumptive treatment of malaria an unjustifiable approach in many African settings. The controlled use of anti-malarials after laboratory confirmed diagnosis is preferable in low endemic areas. Diagnosis may be facilitated by malaria rapid diagnostic tests (RDTs). In this study, the impact of a government policy change, comprising the provision of RDTs and advice to restrict anti-malarial treatment to RDT-positive individuals, was assessed by describing diagnostic behaviour and treatment decision-making in febrile outpatients <10 years of age in three hospitals in the Kagera and Mwanza Region in northern Tanzania. METHODS: Prospective data from Biharamulo and Rubya Designated District Hospital (DDH) were collected before and after policy change, in Sumve DDH no new policy was implemented. Diagnosis of malaria was confirmed by RDT; transmission intensity was evaluated by a serological marker of malaria exposure in hospital attendees. RESULTS: Prior to policy change, there was no evident association between the actual level of transmission intensity and drug-prescribing behaviour. After policy change, there was a substantial decrease in anti-malarial prescription and an increase in prescription of antibiotics. The proportion of parasite-negative individuals who received anti-malarials decreased from 89.1% (244/274) to 38.7% (46/119) in Biharamulo and from 76.9% (190/247) to 10.0% (48/479) in Rubya after policy change. CONCLUSION: This study shows that an official policy change, where RDTs were provided and healthcare providers were advised to adhere to RDT results in prescribing drugs can be followed by more rational drug-prescribing behaviour. The current findings are promising for improving treatment policy in Tanzanian hospitals

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Mimi Debruyn De wondere wereld van een 18de-eeuws receptenboek voor Kunst-Schilders, Vernissers, Vergulders en Marmelaers. [The wondrous world of an 18th century book of recipes for painters, varnishers, gilders and marblers.]In 1777 publiceerden de gebroeders Gimblet in Gent een receptenboek voor de kunst- en decoratieschilders van hun tijd. Dit encyclopedisch kookboek viel onder de aandacht van Mimi Debruyn, die er enthousiast in grasduinde op zoek naar wetenswaardigheden over de materialen en technieken van de toenmalige exterieurafwerking en binneninrichting.Ilse Boeren, Kris Vandekerkhove, Sara Adriaenssens, Dries Tys, Koen Deforce, Kristof Haneca en Jan Bastiaens - Relicten van houtskoolmeilers in het Zoerselbos. [Remnants of charcoal kilns in the old woodland Zoerselbos.]Thans één van de meest waardevolle bosgebieden in Vlaanderen was het Zoerselbos, tot het begin van de 19de eeuw, het tafereel van een belangrijke economische activiteit: de productie van houtskool. De overblijfselen hiervan recent en bij toeval ontdekt zijn slechts voor een geoefend oog zichtbaar en in Vlaanderen nauwelijks gekend. In opdracht van het agentschap Ruimte en Erfgoed trok een team van wetenschappers op verder onderzoek uit en werden de meilers in het Zoerselbos geïnventariseerd, onderzocht en geëvalueerd met het oog op hun behoud voor de toekomst.Guido Cuyt Archeologisch onderzoek door vrijwilligers in Vlaanderen. [Archaeological research by voluntary workers in Flanders.]De directeur van de Nationale Dienst voor Opgravingen wist het 30 jaar geleden al: Er zijn maar twee soorten archeologen, namelijk goeie en slechte. En beide soorten vind je zowel bij de beroeps- als bij de amateurarcheologen. De amateurarcheoloog, vroeger verguisd en later geherwaardeerd, dreigt de dag van vandaag opnieuw verdrongen te worden. Is er nog een toekomst? Guido Cuyt - zelf een gepassioneerd amateurarcheoloog - schetst de evolutie van de amateurarcheologie in Vlaanderen en pleit meteen ook voor bezinning en herprofilering.Lieve Viaene-Awouters Heraldiek in Vlaanderen. Dertig jaar Vlaamse Heraldische Raad. [Heraldry in Flanders. Thirty years of Flemisch Heraldic Council.]Wapenborden en heraldische voorstellingen zijn sinds de vroege middeleeuwen in Vlaanderen van grote historische betekenis. Al 30 jaar waakt een raad van deskundigen over het historisch en heraldisch verantwoord toekennen van nieuwe wapens en over hun uniform gebruik. De raad formuleert tevens adviezen ten behoeve van de bevoegde minister en probeert een antwoord te bieden op de wildgroei aan logos die hand over hand toeneemt. Een overzicht van drie decennia Vlaamse Heraldische Raad door Lieve Viaene-Awouters.Summar

Safety of single low-dose primaquine in glucose-6-phosphate dehydrogenase deficient falciparum-infected African males: Two open-label, randomized, safety trials.

BACKGROUND: Primaquine (PQ) actively clears mature Plasmodium falciparum gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals can cause hemolysis. We assessed the safety of low-dose PQ in combination with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in G6PDd African males with asymptomatic P. falciparum malaria. METHODS AND FINDINGS: In Burkina Faso, G6PDd adult males were randomized to treatment with AL alone (n = 10) or with PQ at 0.25 (n = 20) or 0.40 mg/kg (n = 20) dosage; G6PD-normal males received AL plus 0.25 (n = 10) or 0.40 mg/kg (n = 10) PQ. In The Gambia, G6PDd adult males and boys received DP alone (n = 10) or with 0.25 mg/kg PQ (n = 20); G6PD-normal males received DP plus 0.25 (n = 10) or 0.40 mg/kg (n = 10) PQ. The primary study endpoint was change in hemoglobin concentration during the 28-day follow-up. Cytochrome P-450 isoenzyme 2D6 (CYP2D6) metabolizer status, gametocyte carriage, haptoglobin, lactate dehydrogenase levels and reticulocyte counts were also determined. In Burkina Faso, the mean maximum absolute change in hemoglobin was -2.13 g/dL (95% confidence interval [CI], -2.78, -1.49) in G6PDd individuals randomized to 0.25 PQ mg/kg and -2.29 g/dL (95% CI, -2.79, -1.79) in those receiving 0.40 PQ mg/kg. In The Gambia, the mean maximum absolute change in hemoglobin concentration was -1.83 g/dL (95% CI, -2.19, -1.47) in G6PDd individuals receiving 0.25 PQ mg/kg. After adjustment for baseline concentrations, hemoglobin reductions in G6PDd individuals in Burkina Faso were more pronounced compared to those in G6PD-normal individuals receiving the same PQ doses (P = 0.062 and P = 0.022, respectively). Hemoglobin levels normalized during follow-up. Abnormal haptoglobin and lactate dehydrogenase levels provided additional evidence of mild transient hemolysis post-PQ. CONCLUSIONS: Single low-dose PQ in combination with AL and DP was associated with mild and transient reductions in hemoglobin. None of the study participants developed moderate or severe anemia; there were no severe adverse events. This indicates that single low-dose PQ is safe in G6PDd African males when used with artemisinin-based combination therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02174900 Clinicaltrials.gov NCT02654730

Scale-up of Malaria Rapid Diagnostic Tests and Artemisinin-Based Combination Therapy: Challenges and Perspectives in Sub-Saharan Africa.

Guido Bastiaens and colleagues describe barriers to achieving scale-up and appropriate use of rapid diagnostic tests and artemisinin-based combination therapy for malaria in sub-Saharan Africa. Please see later in the article for the Editors' Summary

Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis

Background Since the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy. Methods An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected. Results In 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08–0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes. Conclusion Primaquine’s transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP

Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis.

BACKGROUND: Since the World Health Organization recommended single low-dose (0.25 mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant Plasmodium falciparum, several single-site studies have been conducted to assess efficacy. METHODS: An individual patient meta-analysis to assess gametocytocidal and transmission-blocking efficacy of PQ in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (1) gametocyte carriage in the first 2 weeks post treatment; and (2) the probability of infecting at least 1 mosquito or of a mosquito becoming infected. RESULTS: In 2574 participants from 14 studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytemia on day 0 (odds ratio [OR],?0.22; 95% confidence interval [CI], .17-.28 and OR,?0.12; 95% CI, .08-.16, respectively). Rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (P?=?.010 for day 7). Addition of 0.25 mg/kg PQ was associated with near complete prevention of transmission to mosquitoes. CONCLUSIONS: Transmission blocking is achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP

Serologic Markers of Previous Malaria Exposure and Functional Antibodies Inhibiting Parasite Growth Are Associated With Parasite Kinetics Following a Plasmodium falciparum Controlled Human Infection.

BACKGROUND: We assessed the impact of exposure to Plasmodium falciparum on parasite kinetics, clinical symptoms, and functional immunity after controlled human malaria infection (CHMI) in 2 cohorts with different levels of previous malarial exposure. METHODS: Nine adult males with high (sero-high) and 10 with low (sero-low) previous exposure received 3200 P. falciparum sporozoites (PfSPZ) of PfSPZ Challenge by direct venous inoculation and were followed for 35 days for parasitemia by thick blood smear (TBS) and quantitative polymerase chain reaction. Endpoints were time to parasitemia, adverse events, and immune responses. RESULTS: Ten of 10 (100%) volunteers in the sero-low and 7 of 9 (77.8%) in the sero-high group developed parasitemia detected by TBS in the first 28 days (P = .125). The median time to parasitemia was significantly shorter in the sero-low group than the sero-high group (9 days [interquartile range {IQR} 7.5-11.0] vs 11.0 days [IQR 7.5-18.0], respectively; log-rank test, P = .005). Antibody recognition of sporozoites was significantly higher in the sero-high (median, 17.93 [IQR 12.95-24] arbitrary units [AU]) than the sero-low volunteers (median, 10.54 [IQR, 8.36-12.12] AU) (P = .006). Growth inhibitory activity was significantly higher in the sero-high (median, 21.8% [IQR, 8.15%-29.65%]) than in the sero-low group (median, 8.3% [IQR, 5.6%-10.23%]) (P = .025). CONCLUSIONS: CHMI was safe and well tolerated in this population. Individuals with serological evidence of higher malaria exposure were able to better control infection and had higher parasite growth inhibitory activity. CLINICAL TRIALS REGISTRATION: NCT03496454

Het archeologisch onderzoek in Raversijde (Oostende) in de periode 1992-2005

Raversijde - sinds 1970 deel van de stad Oostende, voordien Middelkerke - gaat terug tot een laatmiddeleeuwse vissersnederzetting met de naam Walraversijde. Deze vissersnederzetting was gesitueerd nabij de huidige grens Middelkerke/Oostende in een zone die zich grotendeels binnen het huidige provinciedomein Raversijde bevindt, maar zich ook nog in belangrijke mate uitstrekt tot op het strand ter hoogte van dit domein.In deze publicatie over archeologisch onderzoek in Raversijde komen de opgravingscampagnes op het grondgebied van het provinciedomein Raversijde uit de periode 1992-1998 uitvoerig aan bod. Daarnaast worden een aantal markante opgravingsresultaten van na 1998 belicht: het muntdepot dat op het einde van 1999 werd aangetroffen, de in 2003 aangesneden zone met begravingen en de in 2005 geïdentificeerde Romeinse dijk.Dit 8ste deel van de Relicta Monografieën behandelt chronologisch de resten en sporen uit de prehistorie, de Romeinse periode, de late middeleeuwen en de vroeg-moderne tijden. Deze publicatie is in de eerste plaats een opgravingsverslag: ze beschrijft, analyseert en interpreteert de belangrijkste sporen samen met een selectie van de aangetroffen mobiele resten en de resultaten van natuurwetenschappelijk onderzoek

G6PD polymorphisms and hemolysis after antimalarial treatment with low single-dose primaquine: a pooled analysis of six African clinical trials

Primaquine (PQ) is an antimalarial drug with the potential to reduce malaria transmission due to its capacity to clear mature Plasmodium falciparum gametocytes in the human host. However, the large-scale roll-out of PQ has to be counterbalanced by the additional risk of drug-induced hemolysis in individuals suffering from Glucose-6-phospate dehydrogenase (G6PD) deficiency, a genetic condition determined by polymorphisms on the X-linked G6PD gene. Most studies on G6PD deficiency and PQ-associated hemolysis focused on the G6PD A- variant, a combination of the two single nucleotide changes G202A (rs1050828) and A376G (rs1050829), although other polymorphisms may play a role. In this study, we tested the association of 20 G6PD single nucleotide polymorphisms (SNPs) with hemolysis measured seven days after low single dose of PQ given at the dose of 0.1 mg/kg to 0.75 mg/kg in 957 individuals from 6 previously published clinical trials investigating the safety and efficacy of this drug spanning five African countries. After adjusting for inter-study effects, age, gender, baseline hemoglobin level, PQ dose, and parasitemia at screening, our analysis showed putative association signals from the common G6PD mutation, A376G [−log (p-value) = 2.44] and two less-known SNPs, rs2230037 [−log (p-value] = 2.60), and rs28470352 [−log (p-value) = 2.15]; A376G and rs2230037 were in very strong linkage disequilibrium with each other (R = 0.978). However, when the effects of these SNPs were included in the same regression model, the subsequent associations were in the borderline of statistical significance. In conclusion, whilst a role for the A- variant is well established, we did not observe an important additional role for other G6PD polymorphisms in determining post-treatment hemolysis in individuals treated with low single-dose PQ. 10 10 10

The Penn State Worry Questionnaire – Past Day: Development and validation of a measure assessing daily levels of worry

Based on the widely used Penn State Worry Questionnaire for trait worry, a scale was developed to measure the level of worry experienced during the past 24 h. This instrument, the Penn State Worry Questionnaire-Past Day (PSWQ-PD), was administered to a student sample and two clinical samples. The PSWQ-PD demonstrated high internal consistency, good convergent validity and adequate test-retest reliability. A confirmatory factor analysis revealed that a unifactorial solution provided the best fit. Moreover, it was shown that the PSWQ-PD is a more state-like worry measure than the original PSWQ. The PSWQ-PD is a promising, brief tool for daily worry assessment, which is apt for frequent administration. © Springer Science+Business Media, LLC 2011.status: publishe