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Michele Van Vugt

ABSTRACT. Larval source management (LSM) could reduce malaria transmission when executed alongside core vector control strategies. Involving communities in LSM could increase intervention coverage, reduce operational costs, and promote... more
ABSTRACT. Larval source management (LSM) could reduce malaria transmission when executed alongside core vector control strategies. Involving communities in LSM could increase intervention coverage, reduce operational costs, and promote sustainability via community buy-in. We assessed the effectiveness of community-led LSM to reduce anopheline larval densities in 26 villages along the perimeter of Majete Wildlife Reserve in southern Malawi. The communities formed LSM committees which coordinated LSM activities in their villages following specialized training. Effectiveness of larviciding by LSM committees was assessed via pre- and post-spray larval sampling. The effect of community-led LSM on anopheline larval densities in intervention villages was assessed via comparisons with densities in non-LSM villages over a period of 14 months. Surveys involving 502 respondents were undertaken in intervention villages to explore community motivation and participation, and factors influencing t...
Additional file 8. Appendix 8: MMP focal area C weather data.
Additional file 10. Appendix 10: Malaria, ARIs, and diarrhoea events by month.
Additional file 3. Appendix 3: Malaria events.
Background:Monitoring malaria transmission is a critical component of efforts to achieve targets for elimination and eradication. Two commonly monitored metrics of transmission intensity are parasite prevalence (PR) and the entomological... more
Background:Monitoring malaria transmission is a critical component of efforts to achieve targets for elimination and eradication. Two commonly monitored metrics of transmission intensity are parasite prevalence (PR) and the entomological inoculation rate (EIR). Comparing the spatial and temporal variations in the PR and EIR of a given geographical region and modelling the relationship between the two metrics may provide a fuller picture of the malaria epidemiology of the region to inform control activities.Methods:Using geostatistical methods, we compare the spatial and temporal patterns of Plasmodium falciparum EIR and PR using data collected over 38 months in a rural area of Malawi. We then quantify the relationship between EIR and PR by using empirical and mechanistic statistical models.Results:Hotspots identified through the EIR and PR partly overlapped during high transmission seasons but not during low transmission seasons. The estimated relationship showed a 1-month delayed e...
Background Current standard interventions are not universally sufficient for malaria elimination. The effects of community-based house improvement (HI) and larval source management (LSM) as supplementary interventions to the Malawi... more
Background Current standard interventions are not universally sufficient for malaria elimination. The effects of community-based house improvement (HI) and larval source management (LSM) as supplementary interventions to the Malawi National Malaria Control Programme (NMCP) interventions were assessed in the context of an intensive community engagement programme. Methods The study was a two-by-two factorial, cluster-randomized controlled trial in Malawi. Village clusters were randomly assigned to four arms: a control arm; HI; LSM; and HI + LSM. Malawi NMCP interventions and community engagement were used in all arms. Household-level, cross-sectional surveys were conducted on a rolling, 2-monthly basis to measure parasitological and entomological outcomes over 3 years, beginning with one baseline year. The primary outcome was the entomological inoculation rate (EIR). Secondary outcomes included mosquito density, Plasmodium falciparum prevalence, and haemoglobin levels. All outcomes we...
The World Health Organization recommends malaria to be confirmed by either microscopy or a rapid diagnostic test (RDT) before treatment. The correct use of RDTs in resource-limited settings facilitates basing treatment onto a confirmed... more
The World Health Organization recommends malaria to be confirmed by either microscopy or a rapid diagnostic test (RDT) before treatment. The correct use of RDTs in resource-limited settings facilitates basing treatment onto a confirmed diagnosis; contributes to speeding up considering a correct alternative diagnosis, and prevents overprescription of anti-malarial drugs, reduces costs and avoids unnecessary exposure to adverse drug effects. This review aims to evaluate health workers' compliance to RDT results and factors contributing to compliance. A PROSPERO-registered systematic review was conducted to evaluate health workers' compliance to RDTs in sub-Saharan Africa, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies published up to November 2015 were searched without language restrictions in Medline/Ovid, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African I...
There is broad consensus that successful and sustained larval source management (LSM) interventions, including bio-larviciding campaigns, require embeddedness in local community institutions. Ideally, these community structures should... more
There is broad consensus that successful and sustained larval source management (LSM) interventions, including bio-larviciding campaigns, require embeddedness in local community institutions. Ideally, these community structures should also be capable of mobilizing local resources to (co-)finance interventions. To date, farmer cooperatives, especially cooperatives of rice growers whose economic activity facilitates mosquito breeding, have remained under the radar in designing community-based bio-larviciding campaigns. This study explores the potential of rice farmer cooperatives in Bugesera district, Rwanda, to take up the aforementioned roles. To this purpose, we surveyed 320 randomly selected rice farmers who belonged to one of four rice cooperatives in the area and elicited their willingness-to-pay (WTP) for application of Bti, a popular bio-larvicide, in their rice paddies. Results from a (non-incentivized) bidding game procedure, which tested two alternative contribution schemes...
Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria... more
Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. Results A total of 70,22...
Factors impeding the acceptability and use of malaria preventive measures: implications for stern Rwanda care seeking is a critical step in the development of effective, targeted interventions aiming to further reduce malaria
The artemisinin derivatives are the most potent antimalarials. They are rapidly absorbed orally, parenterally and intra-rectally. The latter mode of administration is particularly interesting in rural tropics. Preliminary studies have... more
The artemisinin derivatives are the most potent antimalarials. They are rapidly absorbed orally, parenterally and intra-rectally. The latter mode of administration is particularly interesting in rural tropics. Preliminary studies have shown that artemisinin and its derivatives artesunate and artemether are effective when given intrarectally. More studies are needed to establish the optimum regimen.
Worsening drug resistance in Plasmodium falciparum malaria is a major threat to health in tropical countries. We did a prospective study of malaria incidence and treatment in an area of highly multidrug-resistant P. falciparum malaria. We... more
Worsening drug resistance in Plasmodium falciparum malaria is a major threat to health in tropical countries. We did a prospective study of malaria incidence and treatment in an area of highly multidrug-resistant P. falciparum malaria. We assessed incidence of P. falciparum malaria and the in-vivo responses to mefloquine treatment over 13 years in two large camps for displaced Karen people on the northwest border of Thailand. During this time, the standard mefloquine dose was first increased, and then combined artesunate and mefloquine was introduced as first-line treatment for uncomplicated P. falciparum malaria. Early detection and treatment controlled P. falciparum malaria initially while mefloquine was effective (cure rate with mefloquine [15 mg/kg] and sulphadoxine-pyrimethamine in 1985, 98% [95% CI 97-100]), but as mefloquine resistance developed, the cure rate fell (71% [67-77] in 1990). A similar pattern was seen for high-dose (25 mg/kg) mefloquine monotherapy from 1990-94. Since the general deployment of the artesunate-mefloquine combination in 1994, the cure rate increased again to almost 100% from 1998 onwards, and there has been a sustained decline in the incidence of P. falciparum malaria in the study area. In-vitro susceptibility of P. falciparum to mefloquine has improved significantly (p=0.003). In this area of low malaria transmission, early diagnosis and treatment with combined artesunate and mefloquine has reduced the incidence of P. falciparum malaria and halted the progression of mefloquine resistance. We recommend that antimalarial drugs should be combined with artemisinin or a derivative to protect them against resistance.
Larval source management (LSM) programs for control of malaria vectors are often vertically organized, while there is much potential for involving local communities in program implementation. To address this, we evaluated the... more
Larval source management (LSM) programs for control of malaria vectors are often vertically organized, while there is much potential for involving local communities in program implementation. To address this, we evaluated the entomological impact of community-based application of Bacillus thuringiensis var. israelensis (Bti) in a rice irrigation scheme in Ruhuha, Rwanda. A non-randomized trial with control compared a Bti implementation program that was supervised by the project team (ES) with a program that was led and carried out by local rice farming communities (CB). One other area served as a control to assess mosquito populations without Bti application. Entomological surveys were carried out every two weeks and assessed the presence and abundance of the larval, pupal, and adult stages of Anopheles mosquitoes. In ES, the per round reduction in Anopheles larval habitats was estimated at 49%. This reduction was less in CB (28%) and control (22%) although the per round reduction i...
Background Malaria, acute respiratory infections (ARIs) and diarrhoea are the leading causes of morbidity and mortality among children under 5 years old. Estimates of the malaria incidence are available from a previous study conducted in... more
Background Malaria, acute respiratory infections (ARIs) and diarrhoea are the leading causes of morbidity and mortality among children under 5 years old. Estimates of the malaria incidence are available from a previous study conducted in southern Malawi in the absence of community-led malaria control strategies; however, the incidence of the other diseases is lacking, owing to understudying and competing disease priorities. Extensive malaria control measures through a community participation strategy were implemented in Chikwawa, southern Malawi from May 2016 to reduce parasite prevalence and incidence. This study assessed the incidence of clinical malaria, ARIs and acute diarrhoea among under-five children in a rural community involved in malaria control through community participation. Methods A prospective cohort study was conducted from September 2017 to May 2019 in Chikwawa district, southern Malawi. Children aged 6–48 months were recruited from a series of repeated cross-secti...
Community mobilization for malaria elimination: application of an open space methodology in
Background To further reduce malaria burden, identification of areas with highest burden for targeted interventions needs to occur. Routine health information has the potential to indicate where and when clinical malaria occurs the most.... more
Background To further reduce malaria burden, identification of areas with highest burden for targeted interventions needs to occur. Routine health information has the potential to indicate where and when clinical malaria occurs the most. Developing countries mostly use paper-based data systems however they are error-prone as they require manual aggregation, tallying and transferring of data. Piloting was done using electronic data capture (EDC) with a cheap and user friendly software in rural Malawian primary healthcare setting to improve the quality of health records. Methods Audit and feedback tools from the Joanna Briggs Institute (Practical Application of Clinical Evidence System and Getting Research into Practice) were used in four primary healthcare facilities. Using this approach, the best available evidence for a malaria information system (MIS) was identified. Baseline audit of the existing MIS was conducted in the facilities based on available best practice for MIS; this i...
The efficacy of chloroquine (25 mg base/kg over 3 days) in Plasmodium vivax malaria was evaluated in 1995/ 96 in 342 patients living in an endemic area on the western border of Thailand. Clearance of fever and parasites was obtained... more
The efficacy of chloroquine (25 mg base/kg over 3 days) in Plasmodium vivax malaria was evaluated in 1995/ 96 in 342 patients living in an endemic area on the western border of Thailand. Clearance of fever and parasites was obtained within 2 days in >95% of the patients, and all were aparasitaemic by day 4. Reappearance of P. vivax occurred
Following a marked decline in the efficacy in vivo of mefloquine between 1990 and 1994, a combination of artesunate (4 mg/kg/d for 3 d) and mefloquine (25 mg/kg) has been used as first line treatment of uncomplicated falciparum malaria in... more
Following a marked decline in the efficacy in vivo of mefloquine between 1990 and 1994, a combination of artesunate (4 mg/kg/d for 3 d) and mefloquine (25 mg/kg) has been used as first line treatment of uncomplicated falciparum malaria in camps for displaced persons located along the north-western border of Thailand. Antimalarial drug susceptibility of fresh isolates of Plasmodium falciparum
In areas where multidrug-resistant Plasmodium falciparum (MDR-Pf) is prevalent, only quinine is known to be safe and effective in pregnant women. On the western border of Thailand, 7 days of supervised quinine (30 mg/kg daily) cures... more
In areas where multidrug-resistant Plasmodium falciparum (MDR-Pf) is prevalent, only quinine is known to be safe and effective in pregnant women. On the western border of Thailand, 7 days of supervised quinine (30 mg/kg daily) cures two-thirds of P. falciparum-infected women in the 2nd and 3rd trimesters of pregnancy. Artesunate is effective against MDR-Pf and the limited data on its
Introduction: Maternal mortality is high in developing countries, but there are few data in high-risk groups such as migrants and refugees in malaria-endemic areas. Trends in maternal mortality were followed over 25 years in antenatal... more
Introduction: Maternal mortality is high in developing countries, but there are few data in high-risk groups such as migrants and refugees in malaria-endemic areas. Trends in maternal mortality were followed over 25 years in antenatal clinics prospectively established in an area with low seasonal transmission on the north-western border of Thailand. Methods and Findings: All medical records from women who attended the Shoklo Malaria Research Unit antenatal clinics from 12 May 1986 to 31 December 2010 were reviewed, and maternal death records were analyzed for causality. There were 71 pregnancy-related deaths recorded amongst 50,981 women who attended antenatal care at least once. Three were suicide and excluded from the analysis as incidental deaths. The estimated maternal mortality ratio (MMR) overall was 184 (95%CI 150–230) per 100,000 live births. In camps for displaced persons there has been a six-fold decline in the MMR from 499 (95%CI 200–780) in 1986–90 to 79 (40–170) in 2006...
On 20 November 2019, Lassa fever was diagnosed in a physician repatriated from Sierra Leone to the Netherlands. A second physician with suspected Lassa fever, repatriated a few days later from the same healthcare facility, was confirmed... more
On 20 November 2019, Lassa fever was diagnosed in a physician repatriated from Sierra Leone to the Netherlands. A second physician with suspected Lassa fever, repatriated a few days later from the same healthcare facility, was confirmed infected with Lassa virus on 21 November. Comprehensive contact monitoring involving high- and low-risk contacts proved to be feasible and follow-up of the contacts did not reveal any case of secondary transmission in the Netherlands.
IntroductionHepatitis B virus (HBV) remains a public health threat and the main route of transmission is from mother to child (MTCT). Tenofovir disoproxil fumarate (TDF) treatment can reduce MTCT of HBV although the optimal timing to... more
IntroductionHepatitis B virus (HBV) remains a public health threat and the main route of transmission is from mother to child (MTCT). Tenofovir disoproxil fumarate (TDF) treatment can reduce MTCT of HBV although the optimal timing to attain undetectable HBV DNA concentrations at delivery is unknown. This protocol describes the procedures following early initiation of maternal TDF prior to 20 weeks gestation to determine efficacy, safety and feasibility of this approach in a limited-resource setting.Methods and analysesOne hundred and seventy pregnant women from the Thailand–Myanmar border between 12 and <20 weeks gestational age will be enrolled into a one-arm, open-label, TDF treatment study with cessation of TDF 1 month after delivery. Sampling occurs monthly prenatal, at birth and at 1, 2, 4 and 6 months post partum. Measurement of tenofovir concentrations in maternal and cord plasma is anticipated in 10–15 women who have detectable HBV DNA at delivery and matched to 20–30 wom...
Background Reducing the burden of malaria highly depends on access to prompt and effective malaria diagnosis and treatment. The aim of this study was to identify challenges affecting prompt access to effective uncomplicated malaria case... more
Background Reducing the burden of malaria highly depends on access to prompt and effective malaria diagnosis and treatment. The aim of this study was to identify challenges affecting prompt access to effective uncomplicated malaria case management in children below 10 years old in rural primary health care facilities in Malawi. Methods A cross sectional health facility survey was conducted in six primary health facilities in Chikhwawa district, Malawi. Officers-in-charge of health facilities were interviewed on availability of staff, supplies and drugs. All consecutive children presenting at the facility with fever or suspected malaria, aged 6 months to 10 years old, were eligible to participate in exit interviews. Exit interviews with participants’ guardians assessed duration of illness, demographic information and distance travelled. Adherence to recommended malaria case management guidelines included performing malaria rapid diagnostic tests (mRDTs) in children with fever or susp...
An open, randomized comparison of artemether-benflumetol (CGP 56 697; Novartis) with artesunate-mefloquine was conducted in 617 patients with acute uncomplicated multidrug-resistant falciparum malaria on the western border of Thailand.... more
An open, randomized comparison of artemether-benflumetol (CGP 56 697; Novartis) with artesunate-mefloquine was conducted in 617 patients with acute uncomplicated multidrug-resistant falciparum malaria on the western border of Thailand. Both treatments rapidly and reliably cleared fever and parasitemia, and there was no significant difference in the initial therapeutic response parameters. Parasite genotyping was used to distinguish recrudescences from new infections. The 63-day cure rate for artesunate-mefloquine (94%) was significantly higher than the cure rate for artemether-benflumetol (81%) (P < 0.001). Both regimens were well tolerated. Nausea, vomiting, dizziness, sleep disorders, and other neurological side effects were between two and four times more common in the artesunate-mefloquine group than in the artemether-benflumetol group (P < 0.001). Artemether-benflumetol is effective and very well tolerated in the treatment of multidrug-resistant falciparum malaria. A high...
Increased engagement of communities has been emphasized in global plans for malaria control and elimination. Three interventions to reinforce and complement national malaria control recommendations were developed and applied within the... more
Increased engagement of communities has been emphasized in global plans for malaria control and elimination. Three interventions to reinforce and complement national malaria control recommendations were developed and applied within the context of a broad-based development initiative, targeting a rural population surrounding a wildlife reserve. The interventions, which were part of a 2-year research trial, and assigned to the village level, were implemented through trained local volunteers, or 'health animators', who educated the community and facilitated collective action. Community workshops on malaria were designed to increase uptake of national recommendations; a manual was developed, and training of health animators conducted, with educational content and analytical tools for a series of fortnightly community workshops in annual cycles at village level. The roll-back malaria principle of diagnosis, treatment and use of long-lasting insecticidal nets was a central compone...
Malaria remains a global burden contributing to morbidity and mortality especially in children under 5 years of age. Despite the progress achieved towards malaria burden reduction, achieving elimination in more countries remains a... more
Malaria remains a global burden contributing to morbidity and mortality especially in children under 5 years of age. Despite the progress achieved towards malaria burden reduction, achieving elimination in more countries remains a challenge. This article aims to review the prevention and control strategies for malaria, to assess their impact towards reducing the disease burden and to highlight the best practices observed. Use of long-lasting insecticide-treated nets and indoor residual spraying has resulted a decline in the incidence and prevalence of malaria in Sub-Saharan Africa. Other strategies such as larval source management have been shown to reduce mosquito density but require further evaluation. New methods under development such as house improvement have demonstrated to minimize disease burden but require further evidence on efficacy. Development of the RTS,S/AS01 malaria vaccine that provides protection in under-five children has provided further progress in efforts of ma...
The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in... more
The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations. A search in PubMed, Embase, ClinicalTrials.gov, Google Scholar, conference proceedings, and the WorldWide Antimalarial Resistance Network (WWARN) pharmacology database identified 31 relevant clinical studies published between 1 January 1990 and 31 December 2012, with 4,546 patients in whom lumefantrine concentrations were measured. Under the auspices of WWARN, relevant individual concentration-time data, clinical covariates, and outcome data f...
Interventions to reduce malaria burden are effective if communities use them appropriately and consistently. Several tools have been suggested to promote uptake and use of malaria control interventions. Community workshops on malaria,... more
Interventions to reduce malaria burden are effective if communities use them appropriately and consistently. Several tools have been suggested to promote uptake and use of malaria control interventions. Community workshops on malaria, using the 'Health Animator' approach, are a potential behaviour change strategy for malaria control. The strategy aims to influence a change in mind-set of vulnerable populations to encourage self-reliance, using community volunteers known as Health Animators. The aim of the paper is to describe the process of implementing community workshops on malaria by Health Animators to improve uptake and use of malaria control interventions in rural Malawi. This is a descriptive study reporting feasibility, acceptability, appropriateness and fidelity of using Health Animator-led community workshops for malaria control. Quantitative data were collected from self-reporting and researcher evaluation forms. Qualitative assessments were done with Health Anima...
We evaluated existing data on the prophylactic efficacy of atovaquone-proguanil (AP) in order to determine whether prophylaxis in travellers can be discontinued on the day of return from a malaria-endemic area instead of seven days after... more
We evaluated existing data on the prophylactic efficacy of atovaquone-proguanil (AP) in order to determine whether prophylaxis in travellers can be discontinued on the day of return from a malaria-endemic area instead of seven days after return as per currently recommended post-travel schedule. PubMed and Embase databases were searched to identify relevant studies. This PROSPERO-registered systematic review followed PRISMA guidelines. The search strategy included terms or synonyms relevant to AP combined with terms to identify articles relating to prophylactic use of AP and inhibitory and half-life properties of AP. Studies considered for inclusion were: randomized controlled trials, cohort studies, quasi-experimental studies, open-label trials, patient-control studies, cross-sectional studies; as well as case-series and non-clinical studies. Data on study design, characteristics of participants, interventions, and outcomes were extracted. Primary outcomes considered relevant were p...
AbstractThe serum lipid profile in malaria patients has been found to differ from that of healthy controls. We investigated serum lipid profile changes in malaria patients over time compared with patients with other febrile diseases. In... more
AbstractThe serum lipid profile in malaria patients has been found to differ from that of healthy controls. We investigated serum lipid profile changes in malaria patients over time compared with patients with other febrile diseases. In total, 217 patients were included in the study (111 malaria patients and 106 symptomatic controls, defined as malaria-negative febrile patients). Serum lipid levels (mmol/L) were significantly lower in malaria patients compared with those with other febrile diseases (total cholesterol [TC] = 3.26 [standard deviation = 0.94] versus 3.97 [1.22; P < 0.001]; high-density lipoprotein cholesterol [HDL-C] = 0.43 [0.47] versus 1.05 [0.67; P < 0.001], low-density lipoprotein cholesterol [LDL-C] = 2.05 [0.76] versus 2.42 [0.90; P < 0.001]. Triglycerides (TGs) levels were higher in malaria patients (1.81 [1.02] versus 1.11 [0.82; P < 0.001]). No significant differences were found for apolipoprotein A1, apolipoprotein B, and lipoprotein(a). Cholester...
Immunocompromised and chronically ill travellers (ICCITs) are susceptible to travel related diseases. In ICCITs, pre-travel care regarding vaccinations and prophylactics is complex. We evaluated the protection level by preventive measures... more
Immunocompromised and chronically ill travellers (ICCITs) are susceptible to travel related diseases. In ICCITs, pre-travel care regarding vaccinations and prophylactics is complex. We evaluated the protection level by preventive measures in ICCITs by analysing rates of vaccination protection, antibody titres, and the prescription of standby antibiotics. We analysed, and reported according to STROBE guidelines, pre-travel care data for ICCITs visiting the medical pre-travel clinic at the Academic Medical Centre, The Netherlands from 2011 to 2016. We analysed 2104 visits of 1826 ICCITs. Mean age was 46.6 years and mean travel duration 34.5 days. ICCITs on immunosuppressive treatment (29.7%), HIV (17.2%) or diabetes mellitus (10.2%) comprised the largest groups. Most frequently visited countries were Suriname, Indonesia, and Ghana. Most vaccination rates were >90%. Of travellers in high need of hepatitis A and B protection, 56.6 and 75.7%, underwent titre assessments, respectively....
area was shielded to avoid exposure to the light. Only one session was performed. Five days after treatment, the tumors exhibited a black-colored appearance suggesting necrosis (Fig. 1b). Indeed, a biopsy specimen from one tumor showed... more
area was shielded to avoid exposure to the light. Only one session was performed. Five days after treatment, the tumors exhibited a black-colored appearance suggesting necrosis (Fig. 1b). Indeed, a biopsy specimen from one tumor showed massive necrosis in the dermis (Fig. 2b). Notably, the lesions showed significant improvement after 3 months of treatment, leaving a fibrous scar (Fig. 1c). The patient did not show any adverse events throughout treatment. ALA-PDT has recently been used in CTCL with good results. ALA is known to induce synthesis of the endogenous photosensitizer, protoporphyrin IX, in tumor cells. Protoporphyrin IX leads to cell damage and necrosis after photoactivation under visible light. PDT uses visible light, which is considered too weak to penetrate deep into the skin. ALA is usually applied topically to the lesion, and PDT sessions are repeated for skin tumors, including actinic keratosis and basal cell carcinoma. Several case reports and studies have proven the effectiveness of PDT in CTCL. Most of those cases were treated with PDT for patch or plaque lesions in which the tumor cells were localized within the upper dermal lesion. In the present case, we applied ALA intradermally to the tumor lesions, and a single session resulted in excellent improvement. This was most likely because intradermal application of ALA efficiently induced cytotoxic effects under visible light activation. Based on our experience, we recommend applying ALA intradermally to supply deep dermal lesions. Our report provides further evidence that ALA-PDT can offer an alternative treatment in complex cases that are resistant to conventional therapies, and also suggests that this therapy can be useful even for tumor lesions of CTCL.
Malaria is a notifiable disease in the Netherlands, a non-endemic country. Imported malaria infections occur regularly among travellers, migrants and visitors. Surveillance data were analysed from 2008 to 2015. Trends in amounts of... more
Malaria is a notifiable disease in the Netherlands, a non-endemic country. Imported malaria infections occur regularly among travellers, migrants and visitors. Surveillance data were analysed from 2008 to 2015. Trends in amounts of notifications among risk groups were analysed using Poisson regression. For asylum seekers, yearly incidence was calculated per region of origin, using national asylum request statistics as denominator data. For tourists, denominator data were used from travel statistics to estimate incidence per travel region up to 2012. A modest increase in overall imported malaria notifications occurred in 2008-2015 (from 222 in 2008 to 344 in 2015). Notably, in 2014 and 2015 sharp increases were seen in malaria among travellers visiting friends and relatives (VFR), and in asylum seekers. Of all Plasmodium falciparum infections, most (1254/1337; 93.8%) were imported from Africa; 1037/1337 (77.6%) were imported from Central and West Africa. Malaria in VFR was mostly cau...

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Worsening drug resistance in Plasmodium falciparum malaria is a major threat to health in tropical countries. We did a prospective study of malaria incidence and treatment in an area of highly multidrug-resistant P. falciparum malaria. We... more
Worsening drug resistance in Plasmodium falciparum malaria is a major threat to health in tropical countries. We did a prospective study of malaria incidence and treatment in an area of highly multidrug-resistant P. falciparum malaria. We assessed incidence of P. falciparum malaria and the in-vivo responses to mefloquine treatment over 13 years in two large camps for displaced Karen people on the northwest border of Thailand. During this time, the standard mefloquine dose was first increased, and then combined artesunate and mefloquine was introduced as first-line treatment for uncomplicated P. falciparum malaria. Early detection and treatment controlled P. falciparum malaria initially while mefloquine was effective (cure rate with mefloquine [15 mg/kg] and sulphadoxine-pyrimethamine in 1985, 98% [95% CI 97-100]), but as mefloquine resistance developed, the cure rate fell (71% [67-77] in 1990). A similar pattern was seen for high-dose (25 mg/kg) mefloquine monotherapy from 1990-94. Since the general deployment of the artesunate-mefloquine combination in 1994, the cure rate increased again to almost 100% from 1998 onwards, and there has been a sustained decline in the incidence of P. falciparum malaria in the study area. In-vitro susceptibility of P. falciparum to mefloquine has improved significantly (p=0.003). In this area of low malaria transmission, early diagnosis and treatment with combined artesunate and mefloquine has reduced the incidence of P. falciparum malaria and halted the progression of mefloquine resistance. We recommend that antimalarial drugs should be combined with artemisinin or a derivative to protect them against resistance.