To explore clinical and virological characteristics and describe the epidemiology of dengue in patients who presented with acute undifferentiated fever (AUF) at primary health centers (PHC) in Binh Thuan Province, Vietnam.A prospective observational study was conducted from 2001 to 2006 to study the aetiology in AUF patients. Demographic and clinical information was obtained, and dengue polymerase chain reaction (RT-PCR) and serology were performed on a random selection of patients.Three hundred fifty-one serologically confirmed dengue patients including 68 primary and 283 secondary infections were included in this study. In 25% (86/351) dengue virus (DENV) was detected by RT-PCR among which 32 DENV-1, 16 DENV-2, 1 DENV-3 and 37 DENV-4 were identified. The predominant dengue serotype varied by year with seasonal fluctuation: DENV-4 in 2001-2002, DENV-1 and DENV-2 from 2003 to 2006. Primary dengue was more common in children. Higher viraemia levels (P=0.010) were found in primary infections compared to secondary infections. DENV-1 infected patients had higher viraemia levels than DENV-2 (P=0.003) and DENV-4 (P<0.001) infected patients. Clinical symptoms were often seen in adults. Few differences in clinical symptoms were found between primary and secondary infection and no significant differences in clinical symptoms between the serotypes were observed.Our data provide insight in the epidemiology, clinical profile and virological features of mild symptomatic dengue patients who presented to PHC with AUF in Vietnam.
To describe an analysis of the patients seen at the Outpatient Department (OPD) for Tropical Diseases in the Academic Medical Centre, Amsterdam, during 1996 and 1997.Descriptive cross-sectional study.From our database of OPD-patients the following data were analysed: age, country of birth, travel destination and most frequent complaints at presentation. These were further analysed in relation to travel destination, diagnosis and need of admission.In 1996 and 1997 1763 patients visited the OPD. Abdominal complaints, fever, general malaise and skin diseases were the main problems. Abdominal complaints were more often acquired in Asia, fever in sub-Saharan Africa and skin problems in South America. General malaise was not related to a specific travel destination. Abdominal complaints, fever and general malaise were more often caused by parasites, and skin problems by bacteria. Plasmodia were the most frequently encountered microbial cause. Malaria was found in 1 out of every 3 Dutch, and 9 out of every 10 Ghanaian patients with fever from Africa.The analysis of the database yielded useful information regarding patients with import diseases in the Netherlands and with respect to travellers to tropical areas.
The tensile yield behaviour of an aliphatic polyketone is studied in relation to the molecular relaxation processes present in the polymer. Dynamic mechanical thermal analysis reveals the presence of three molecular relaxation mechanisms; the crystalline a-, and the amorphous b- and, g-process. The tensile yield behaviour, measured over a large range of temperature and strain rate, also gives evidence of these three relaxation mechanisms. The increase of the water content from 0.5 to 2.3 wt% leads to a selective change in the b-contribution, whereas the a- and g-processes show little to no change. With respect to the tensile yield behaviour this leads to a reduction of the yield stress at high strain rates and/or low temperatures. q 1999 Elsevier Science Ltd. All rights reserved.
ABSTRACT Recently, there has been a renewed interest in the development of new drugs for the treatment of leishmaniasis. This has spurred the need for pharmacodynamic markers to monitor and compare therapies specifically for visceral leishmaniasis, in which the primary recrudescence of parasites is a particularly long-term event that remains difficult to predict. We performed a systematic review of studies evaluating biomarkers in human patients with visceral, cutaneous, and post-kala-azar dermal leishmaniasis, which yielded a total of 170 studies in which 53 potential pharmacodynamic biomarkers were identified. In conclusion, the large majority of these biomarkers constituted universal indirect markers of activation and subsequent waning of cellular immunity and therefore lacked specificity. Macrophage-related markers demonstrate favorable sensitivity and times to normalcy, but more evidence is required to establish a link between these markers and clinical outcome. Most promising are the markers directly related to the parasite burden, but future effort should be focused on optimization of molecular or antigenic targets to increase the sensitivity of these markers. In general, future research should focus on the longitudinal evaluation of the pharmacodynamic biomarkers during treatment, with an emphasis on the correlation of studied biomarkers and clinical parameters.
BackgroundTreatment of HIV/malaria-coinfected patients with antiretroviral therapy (ART) and artemisinin-based combination therapy has potential for drug interactions. We investigated the pharmacokinetics of artemether, dihydroartemisinin and lumefantrine after administration of a single dose of 80/480 mg of artemether/lumefantrine to HIV-infected adults, taken with and without lopinavir/ritonavir.
African tick-bite fever (ATBF) is frequently diagnosed in The Netherlands in travelers returning from South Africa. It is caused by Rickettsia africae and diagnosis is based on travel history and clinical presentation and usually confirmed by detecting serum antibodies against rickettsiae of the spotted fever group. However, these typically occur late in the course of the disease, and a mild clinical course or early antibiotic treatment can diminish antibody production.Four travelers presented with (sub)febrile temperatures and eschar(s), several days after returning from South Africa. R. africae DNA was amplified and sequenced from skin biopsies of the eschars of all patients. Initial immunofluorescence assays yielded no immunoglobulin M (IgM)/IgG antibodies directed against spotted fever group rickettsiae; however, serology in the convalescent phase-several weeks after the patients had fully recovered-was positive.ATBF should be considered in travelers returning from South Africa to The Netherlands with febrile illness and (multiple) skin lesions. The diagnosis can be confirmed by (paired) serology; however, polymerase chain reaction and sequencing on skin biopsies could be a (faster and more accurate) confirmatory test. Advantages of molecular methods over serology are species identification and high sensitivity early in the course of the disease.
Early diagnosis and treatment of malaria (EDTM) is a key component of malaria control. The success of EDTM depends on health seeking behaviour and the quality of the health service. This study assessed self-diagnosis, treatment and treatment delay after the introduction of EDTM in 1993. In southern Vietnam EDTM comprises microscopic diagnosis and free treatment with artemisinin derivatives at public health facilities. Until 2001, 1698 questionnaires had been completed by patients participating in randomized treatment trials of uncomplicated malaria. The presumptive self diagnosis 'malaria' increased from 68% in 1993 to 100% in 2001 and self-treatment decreased, from 74% to 8% in 2000 and 24% in 2001. The median (maximum) delay between first symptoms and seeking treatment at a public health facility decreased from 3 (23) to 1.3 (3) days (P<0.001) Concomitant was a significant decline of reported incidence of malaria-associated mortality, severe malaria and uncomplicated malaria. If offered an attractive package of EDTM, patients become sensitized to the possibility of malaria and less likely to self-treat. EDTM should be provided as soon as possible to all symptomatic patients, aiming at reducing treatment delay to a maximum of 2 days.
Malaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax. A systematic review identified P. vivax efficacy studies of chloroquine with or without primaquine published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology, and the haematological response versus time was quantified using a multivariable linear mixed effects model with non-linear terms for time. Mean differences in haemoglobin between treatment groups at day of nadir and day 42 were estimated from this model. In total, 3421 patients from 29 studies were included: 1692 (49.5%) with normal G6PD status, 1701 (49.7%) with unknown status and 28 (0.8%) deficient or borderline individuals. Of 1975 patients treated with chloroquine alone, the mean haemoglobin fell from 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/dL [12.60, 13.17] on day 42. In comparison to chloroquine alone, the mean haemoglobin in 1446 patients treated with chloroquine plus primaquine was − 0.13 g/dL [− 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p < 0.001). On day 42, patients with recurrent parasitaemia had a mean haemoglobin concentration − 0.72 g/dL [− 0.90, − 0.54] lower than patients without recurrence (p < 0.001). Seven days after starting primaquine, G6PD normal patients had a 0.3% (1/389) risk of clinically significant haemolysis (fall in haemoglobin > 25% to < 7 g/dL) and a 1% (4/389) risk of a fall in haemoglobin > 5 g/dL. Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia. Its widespread implementation will require accurate diagnosis of G6PD deficiency to reduce the risk of drug-induced haemolysis in vulnerable individuals. This trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016.
De Vries PJ, Hoekstra JBL, de Hooge P, van Hattum J. Portal venous flow and follow-up in patients with liver disease and healthy subjects. Assessments with duplex Doppler. Scand J Gastroenterol 1994;29:172-177.The evolution of portal venous flow in non-end-stage chronic liver disease with portal hypertension was assessed in 59 patients and compared with that in 55 control subjects and by means of duplex Doppler measurements by a single observer. All patients were prospectively followed up, and a repeated measurement was performed in a subgroup of 23 patients. The mean (±SD) portal venous diameter and velocity of patients versus controls were 11.2 (±2.0) mm versus 10.1 (±1.4) mm (p < 0.0005) and 11.0 (±4.2) cm/sec versus 13.9 (±4.1) cm/sec (p < 0.0005). The portal venous flow did not differ: 671 (±291) ml/rnin versus 652 (±203) ml/min. Diagnosis, Child class, and grade of varices did not influence the portal flow. Patients were followed up during a median (±SD) time of 47 (±17) months. Nineteen (32%) patients died, and 14 (23%) had a variceal hemorrhage. Survival and hemorrhage were not correlated with the portal venous flow. Subsequent measurements in 23 patients showed a significant decrease in portal venous flow in 5 patients who died during follow-up. This was not found in the patients who survived. It is concluded that portal venous flow in chronic liver disease with portal hypertension is stable for a long time in the evolution of chronic liver disease. The existence of a 'portostat' is postulated. Only in the terminal stage of liver disease can a reduction of the portal venous flow be detected.
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