[Splenomegaly in an Eritrean refugee: the hyper-reactive malaria splenomegaly syndrome.] / Splenomegalie bij een Eritrese vluchteling.

BACKGROUND: Hyper-reactive malaria splenomegaly (HMS) is a rare and potentially severe complication of malaria. It is likely that the incidence of patients with HMS will rise in the Netherlands due to the recent increase in asylum-seekers from Sub-Saharan Africa. It can be difficult to diagnose this disease, as this case shows. CASE DESCRIPTION: A 31-year-old male from Eritrea was admitted with fever and dyspnea, caused by an influenza A-infection. The patient also presented with cachexia, pronounced hepatosplenomegaly and pancytopenia. Microscopic diagnostic analysis for malaria was negative. HMS was eventually diagnosed through high-sensitivity qPCR for malaria, which showed the presence of a very low level of Plasmodium falciparum parasitemia; furthermore, IgM levels were high and malaria serology was strongly positive. CONCLUSION: HMS should be considered in patients from malaria-endemic areas presenting with splenomegaly and pancytopenia. Because standard diagnostics for malaria are often negative in this population, malaria serology and sensitive qPCR play an important diagnostic role.

Persisting arthralgia due to Mayaro virus infection in a traveler from Brazil: is there a risk for attendants to the 2014 FIFA World Cup?

The 2014 FIFA World Cup and the 2016 Olympic Games will attract large groups of visitors to Brazil. These visitors will be at risk for different arboviral infections, some of which not well known outside endemic areas. We report a case of a 52-year-old Dutch woman who presented with persistent arthralgia due to a Mayaro virus (MAYV) infection which she contracted in the Amazon basin in Brazil. MAYV is a mosquito-borne alphavirus which primarily circulates in humid tropical forests of South America. Infections are rarely reported in travelers and are characterized by an acute febrile illness which is often followed by a prolonged and sometimes incapacitating polyarthralgia. Both travelers and physicians should be aware of the risk of these arboviral infections and the importance of mosquito bite prevention should be stressed.

Audit of antibiotic prescribing in two governmental teaching hospitals in Indonesia.

This article estimates the magnitude and quality of antibiotic prescribing in Indonesian hospitals and aims to identify demographic, socio-economic, disease-related and healthcare-related determinants of use. An audit on antibiotic use of patients hospitalized for 5 days or more was conducted in two teaching hospitals (A and B) in Java. Data were collected by review of records on the day of discharge. The method was validated through concurrent data collection in Hospital A. Multivariate logistic regression analysis was performed to determine variables to explain antibiotic prescribing. Prescriptions were assessed by three reviewers using standardized criteria. A high proportion (84%) of 999 patients (499 in Hospital A and 500 in Hospital B) received an antibiotic. Prescriptions could be categorized as therapeutic (53%) or prophylactic (15%), but for 32% the indication was unclear. Aminopenicillins accounted for 54%, and cephalosporins (mostly third generation) for 17%. The average level of antibiotic use amounted to 39 DDD/100 patient-days. Validation revealed that 30% of the volume could be underestimated due to incompleteness of the records. Predictors of antibiotic use were diagnosis of infection, stay in surgical or paediatric departments, low-cost nursing care, and urban residence. Only 21% of prescriptions were considered to be definitely appropriate; 15% were inappropriate regarding choice, dosage or duration, and 42% of prescriptions, many for surgical prophylaxis and fever without diagnosis of infection, were deemed to be unnecessary. Agreement among assessors was low (kappa coefficients 0.13-0.14). Despite methodological limitations, recommendations could be made to address the need for improving diagnosis, treatment and drug delivery processes in this setting.

Preventing nosocomial infections: improving compliance with standard precautions in an Indonesian teaching hospital.

Standard precautions can prevent transmission of micro-organisms. This study investigated hand hygiene, handling of needles and use of personal protective equipment in an Indonesian teaching hospital, and performed a multi-faceted intervention study to improve compliance. An intervention was performed in an internal medicine ward and a paediatric ward, consisting of development of a protocol for standard precautions, installation of washstands, educational activities and performance feedback. Before, during and after the intervention, observers monitored compliance with hand hygiene, safe handling of needles and use of gloves, gowns and masks. A gynaecology ward served as the control. Unobtrusive observations were performed to check for an influence of the observers on the overt observations. In total, 7,160 activities were observed. Compliance with hand hygiene increased from 46% to 77% in the internal medicine ward and from 22% to 62% in the paediatric ward. Before the intervention, no safe recapping of needles was recorded in either ward. After the intervention, 20% of needles were recapped safely. Inappropriate gown use decreased in the internal medicine ward. There were no significant changes in use of gloves and masks. There may have been an effect of the overt observations in the paediatric ward, but there was no effect in the internal medicine ward. There were no significant changes in the control ward, except for a decrease in the use of gloves. In conclusion, compliance with hand hygiene procedures improved significantly due to an intervention project focused on education and improved facilities. Compliance with safe handling of needles improved slightly due to introduction of the one-handed method for safe recapping of used needles.

Extranodal marginal zone (MALT) lymphoma in common variable immunodeficiency.

We describe two patients with common variable immunodeficiency (CVID) who developed extranodal marginal zone lymphoma (formerly described as mucosa-associated lymphoid tissue lymphoma or MALT lymphoma). One patient, with documented pernicious anaemia and chronic atrophic gastritis with metaplasia, developed a Helicobacter pylori-positive extranodal marginal zone lymphoma in the stomach. Three triple regimens of antibiotics were necessary to eliminate the H. pylori, after which the lymphoma completely regressed. Patient B had an H. pylori-negative extranodal marginal zone lymphoma of the parotid gland, which remarkably regressed after treatment with clarithromycin. Reviewing the literature, we found eight cases of extranodal marginal zone lymphoma complicating CVID, but probably many more cases labelled as non-Hodgkin's lymphoma are hidden in the literature. Until more data are available on the predictive value of noninvasive screening for pathology of the stomach, we recommend endoscopy to assess the gastric status in CVID patients in order to detect these malignancies at an early stage. Elimination of H. pylori infection is the treatment of choice in Helicobacter-positive extranodal marginal zone lymphoma. The possibility of elimination failure, most probably due to frequent and prolonged exposure to antibiotics in this patient group, should be taken into account. Treatment with antibiotics in Helicobacter-negative extranodal marginal zone lymphoma must be considered.

Graves' disease during immune reconstitution in HIV-infected patients treated with HAART.

Autoimmune phenomena after immune recovery due to HAART are not frequently described. Recently we found 3 patients with Graves' disease after starting HAART, outnumbering the expected incidence; 13 patients have been reported in the literature up to the present time.A probable relation between immune restoration and development of Graves' disease might be suspected.

HLA-DRB1*12 is associated with protection against complicated typhoid fever, independent of tumour necrosis factor alpha.

We investigated whether HLA-DR2 or -DR12 alleles in 63 Javanese patients with complicated or non-complicated typhoid fever were associated with severity of disease. No association was observed between HLA type and susceptibility to disease. However, in patients we did find a negative association of DR12 (DRB1*12021) with complicated typhoid fever (P = 0.05; OR = 0.3; 95% CI: 0.1-1.0). No effect of DR2 (DRB1*1502) on outcome (P = 0.46; OR = 1.5; 95% CI: 0.5-4.5) was demonstrated. The odds ratio for DR12 remained unchanged after adjusting for DR2. Tumour necrosis factor alpha (TNF-alpha) production capacity in lipopolysaccharide (LPS)-stimulated whole blood culture, as measured by non-equilibrium radioimmunoassay, was significantly lower in complicated than in non-complicated cases (P = 0.02), confirming previous data. No significant correlation of either DR12 (P = 0.47) or DR2 (P = 0.89) was found with TNF-alpha production capacity. Apparently, protection against complications by DR12 is attributable to other mechanisms.

Poor food hygiene and housing as risk factors for typhoid fever in Semarang, Indonesia.

To identify risk factors for typhoid fever in Semarang city and its surroundings, 75 culture-proven typhoid fever patients discharged 2 weeks earlier from hospital and 75 controls were studied. Control subjects were neighbours of cases with no history of typhoid fever, not family members, randomly selected and matched for gender and age. Both cases and controls were interviewed at home by the same trained interviewer using a standardized questionnaire. A structured observation of their living environment inside and outside the house was performed during the visit and home drinking water samples were tested bacteriologically. Univariate analysis showed the following risk factors for typhoid fever: never or rarely washing hands before eating (OR = 3.28; 95% CI = 1.41-7.65); eating outdoors at least once a week (OR = 3.00; 95% CI = 1.09-8.25); eating outdoors at a street food stall or mobile food vendor (OR = 3.86; 95% CI = 1.30-11.48); consuming ice cubes in beverage in the 2-week period before getting ill (OR = 3.00, 95% CI = 1.09-8.25) and buying ice cubes from a street vendor (OR = 5.82; 95% CI = 1.69-20.12). Water quality and living environment of cases were worse than that of controls, e.g. cases less often used clean water for taking a bath (OR = 6.50; 95% CI = 1.47-28.80), for brushing teeth (OR = 4.33; 95% CI = 1.25-15.20) and for drinking (OR = 3.67; 95% CI = 1.02-13.14). Cases tended to live in houses without water supply from the municipal network (OR=11.00; 95% CI = 1.42-85.2), with open sewers (OR = 2.80; 95% CI = 1.0-7.77) and without tiles in the kitchen (OR = 2.67; 95% CI = 1.04-6.81). Multivariate analysis showed that living in a house without water supply from the municipal network (OR = 29.18; 95% CI = 2.12-400.8) and with open sewers (OR = 7.19; 95% CI = 1.33-38.82) was associated with typhoid fever. Never or rarely washing hands before eating (OR = 3.97; 95% CI = 1.22-12.93) and being unemployed or having a part-time job (OR = 31.3; 95% CI = 3.08-317.4) also were risk factors. In this population typhoid fever was associated with poor housing and inadequate food and personal hygiene.

[Periodically leaking capillaries]. / Periodiek lekkende haarvaten.

The systemic capillary leak syndrome (Clarkson's syndrome) is a rare idiopathic disorder, characterized by recurrent episodes of hypovolaemic shock, haemoconcentration and hypoalbuminaemia due to a sudden shift of fluid and macromolecules from the intravascular to the interstitial space. A young man is presented in whom recurrent attacks of hypotension and diffuse swelling were initially attributed to staphylococcal toxic shock syndrome. With the additional finding of a monoclonal gammopathy, the diagnosis of systemic capillary leak syndrome was made. Recognition of this syndrome is important, as prophylactic treatment with terbutaline and theophylline may be beneficial in this life threatening syndrome.

Outcome in three groups of patients with typhoid fever in Indonesia between 1948 and 1990.

The outcome in three groups of patients with bacteriologically confirmed typhoid fever caused by Salmonella typhi, treated during three episodes between 1948 and 1990 in Java, Indonesia, was compared by retrospective analysis of hospital records. The study population consisted of three groups of patients. Group I (n = 50) was treated in Batavia (the present Jakarta) from 1948 to 1950, Group II (n = 61) in Yogyakarta from 1952 to 1956, Group III (n = 105) in Semarang from 1989 to 1990. Main outcome measures were days until defervescence, early relapses during hospitalization, duration of hospital stay, complications and mortality. Group I received supportive treatment only, Group II low doses of chloramphenicol (total 12.5 g) and Group III full doses of chloramphenicol (total 27 g); occasionally other antibiotics were used. In Group I, II and III the mean number of days until defervescence was 16, 8 and 6 and the mean number of days in hospital 43, 47 and 15, respectively. Mortality was 26%, 10% and 5% and complications occurred in 38%, 18% and 13%, respectively. Between Group I and Group II the differences in mortality and complications were statistically significant (P < 0.05). Compared to Group I the proportion of early relapses was higher in Group II, but was zero in Group III. There were significantly fewer gastrointestinal complications in Group II than in Group I (P < 0.01) and even fewer in Group III. When no antibiotic against S. typhi was available, typhoid fever had a protracted course, and only 74% of patients survived. Even with low dosages of chloramphenicol, defervescence was earlier and mortality and complications decreased dramatically, but early relapses were frequent. Full doses of chloramphenicol for a sufficient period of time only slightly reduced mortality and complications further, but eliminated early relapses completely.

Recombinant murine granulocyte colony-stimulating factor protects against acute disseminated Candida albicans infection in nonneutropenic mice.

The effect of recombinant granulocyte colony-stimulating factor (rG-CSF) on acute disseminated Candida albicans infection in nonneutropenic mice was investigated. Mice treated with a single dose of rG-CSF showed a significantly reduced mortality (28% vs. 90%; P < .001). The outgrowth of C. albicans from the kidneys, spleens, and livers of rG-CSF-treated mice was significantly reduced (log cfu/g of kidney, 5.54 vs. 7.13; P < .001), as were circulating tumor necrosis factor-alpha and interleukin-1beta. After rG-CSF, the kidneys showed fewer infectious infiltrates, enhanced granulocyte influx, and almost complete absence of hyphal outgrowth. During peritoneal C. albicans infection, rG-CSF enhanced influx of granulocytes to the site of infection, and exudate granulocytes showed increased oxygen radical production. These results indicate that rG-CSF enhances host resistance to disseminated candidiasis in nonneutropenic mice through activation of granulocytes and their recruitment to the site of infection.

Low plasma concentrations of indinavir are related to virological treatment failure in HIV-1-infected patients on indinavir-containing triple therapy.

All human immunodeficiency virus type 1 (HIV-1)-infected patients who started to use indinavir (800 mg three times a day) as part of their triple drug regimen were included in a study to determine the importance of low plasma concentrations of indinavir as a cause of virological treatment failure. The indinavir concentration and a number of patient characteristics at baseline were tested as risk factors for virological treatment failure (defined as a viral load above 200 copies/ml after 24 weeks of treatment) in univariate and multivariate analyses; 65 patients were included. Virological treatment failure occurred in 36.9% of the patients. Multivariate analysis showed that a low plasma concentration of indinavir (odds ratio 0.1), a high viral load at baseline (odds ratio 2.6) and pretreatment with another protease inhibitor (odds ratio 10.0) were independent factors related to virological treatment failure. Monitoring of indinavir plasma concentrations may be an important tool for the optimization of triple drug combination therapy.

A semi-quantitative reverse transcriptase polymerase chain reaction method for measurement of MRNA for TNF-alpha and IL-1 beta in whole blood cultures: its application in typhoid fever and exentric exercise.

Whole blood cultures are used to study cytokine stimulation and release ex vivo. In the present study this method was compared with a more direct approach and a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to assess mRNA expression for IL-1 beta and tumour necrosis factor alpha (TNF-alpha) and mRNA in whole blood. Stimulation of whole blood from normal donors with lipopolysaccharide (LPS) at various time intervals showed a parallel rise of immunogenic IL-1 beta and TNF-alpha as well as a rise of mRNA expression for IL-1 beta and TNF-alpha with peak levels for IL-1 beta after 4-6 h stimulation and for mRNA TNF-alpha expression after 2 h stimulation. These methods were used to explore cytokine production during the course of typhoid fever and after a 5 km run. In both conditions circulating cytokine concentrations were not influenced, but the TNF-alpha and IL-1 beta mRNA gene expression in circulating whole blood cells was increased in patients with typhoid fever. The LPS-stimulated production of TNF-alpha and IL-1 beta was decreased in both but there was no change for the mRNA content in whole blood for these cytokines. These findings demonstrate that RT-PCR is an attractive method to study the gene expression of cytokines in whole blood, an increased TNF-alpha and IL-1 beta gene expression is present in typhoid fever, and that the LPS stimulated downregulation of cytokines in exercise and typhoid fever may be mediated by post-transcriptional processes.

Phospholipase A2 is a circulating mediator in typhoid fever.

Circulating proinflammatory mediators have not been found in studies on typhoid fever, although the patients suffer from a systemic disease with characteristic protracted fever. The 14-kDa group II extracellular phospholipase A2 (PLA2) is induced by interleukin-1 and tumor necrosis factor and may mediate some of the effects of these cytokines. Circulating PLA2 concentrations were measured in 12 typhoid fever patients on various days after admission and after recovery. On admission, mean concentrations of PLA2 were elevated (1444 +/- 1560 ng/mL) and decreased gradually and significantly to day 14 (55 +/- 48 ng/mL). patients with complicated disease had significantly higher PLA2 levels on admission. PLA2 was not produced in a lipopolysaccharide-stimulated whole blood culture, indicating that PLA2 originates from other types of cells. These data indicate that PLA2 may be a mediator of disease in protracted inflammatory diseases such as thyroid fever.

Culture of Salmonella typhi and Salmonella paratyphi from blood and bone marrow in suspected typhoid fever.

We studied the yield of blood and bone marrow (BM) cultures in 145 patients clinically suspected of typhoid fever (TF) in Indonesia. The objectives were to compare the positivity of blood culture using 3 ml versus 10 ml of blood and to examine in how far specific antibiotic treatment for TF interfered with the positivity of BM culture. Blood for culture was collected before antibiotic treatment was initiated in hospital and BM 1 to 10 days after the start of treatment. Cultures were performed with Oxgall subcultured on SS agar. Seventy-nine per cent of patients was treated for 14 days or more with oral chloramphenicol, 18% with chloramphenicol followed by ampicillin or cotrimoxazol and 3% with other antibiotics. Cultures were positive for Salmonella typhi or S-paratyphi A in 57 of the 145 patients (39.3%) when 3 ml of blood was cultured and in 58 (40%) when 10 ml of blood was cultured. BM culture was positive despite antibiotic treatment in 70 patients (48.2%); this positivity was significantly greater than that of blood cultures (p < 0.05). When we considered the positivity of BM culture in relation to the number of days on antibiotics in hospital, the yield of BM culture remained apparently unchanged during the first 5 days of treatment. This may be the consequence of slow elimination of S.typhi or S.paratyphi by the antibiotics used and could be responsible for relapses.

Patterns of proinflammatory cytokines and inhibitors during typhoid fever.

Cytokines and inhibitors in plasma were measured in 44 patients with typhoid fever. Ex vivo production of the cytokines was analyzed in a whole blood culture system with and without lipopolysaccharide (LPS). Acute phase circulating concentrations of cytokines (+/- SD) were as follows: interleukin (IL)-1 beta, < 140 pg/mL; tumor necrosis factor-alpha (TNF alpha), 130 +/- 50 pg/mL; IL-6, 96 +/- 131 pg/mL; and IL-8, 278 +/- 293 pg/mL. Circulating inhibitors were elevated in the acute phase: IL-1 receptor antagonist (IL-1RA) was 2304 +/- 1427 pg/mL and soluble TNF receptors 55 and 75 were 4973 +/- 2644 pg/mL and 22,865 +/- 15,143 pg/mL, respectively. LPS-stimulated production of cytokines was lower during the acute phase than during convalescence (mean values: IL-1 beta, 2547 vs. 6576 pg/mL; TNF alpha, 2609 vs. 6338 pg/mL; IL-6, 2416 vs. 7713 pg/mL). LPS-stimulated production of IL-1RA was higher in the acute than during the convalescent phase (5608 vs. 3977 pg/mL). Inhibited production of cytokines during the acute phase may be due to a switch from a proinflammatory to an antiinflammatory mode.

[Usefulness of a physical examination upon return from the tropics]. / Nut van medisch onderzoek na terugkeer uit de tropen.

This study was undertaken to determine the usefulness of medical check-ups after return from the tropics by retrospective analysis of the data of the outpatient clinic for tropical medicine and imported diseases of the University Hospital of Nijmegen. During the years 1986-1990, 379 persons who had returned from the tropics and who were asymptomatic were subjected to a medical check-up (this group comprised 32% of the total of 1190 patients seen in the clinic during this period). In 230 persons (61%) no abnormality was detected. In 101 persons (27%) one or more diagnoses were made which were related to their stay in the tropics. For three-quarters of them treatment was indicated (77 patients). In the remaining 48 persons (13%) diagnoses were made which were neither related to the tropics nor required treatment (e.g. mild varices or minor kyphoscoliosis). Such diagnoses did not contribute to the usefulness of a medical check-up. In 200 persons a chest X-ray was made, either because they had stayed in the tropics for more than 3 years, or had had close contacts with the local population or because abnormalities were suspected on the basis of history or physical examination. While four X-rays revealed significant pathology, in only one of these did the patient benefit from its detection (early pulmonary tuberculosis). We conclude from our study that a medical check-up after return from the tropics is justifiable. The duration of the stay in the tropics by itself is no indication for a chest X-ray.(ABSTRACT TRUNCATED AT 250 WORDS)

Parasitological, clinical and haematological response of children with Plasmodium falciparum to 4-aminoquinolines and to pyrimethamine-sulfadoxine with quinine in western Kenya.

Children with Plasmodium falciparum infections in Western Province, Kenya, were studied in 1987 for their parasitological, clinical and haematological response to chloroquine, to amodiaquine and to pyrimethamine-sulfadoxine plus quinine. Ninety-eight children under 5 years of age were treated in 1 of 2 hospitals. Of the 56 patients treated with chloroquine base 25 mg/kg, 91% had resistant infections, with 36% having no significant decrease in parasitaemia (RIII resistance); however, 69% responded clinically within a week. Of the 27 patients treated with amodiaquine base 25 mg/kg, 67% had resistant infections, with 7% RIII resistant; 81% responded clinically. The parasites cleared in all 15 children given pyrimethamine-sulfadoxine plus 3 days of quinine. Only when parasites cleared did patients have improved haemoglobins and haematocrits. This study shows that parasitaemia in children hospitalized in western Kenya responds poorly to 4-aminoquinolines, although the patients improve clinically, at least during the first 7 days. Young children may need to clear parasites to avoid the risk of severe anemia and the need for blood transfusions.

Comparison of chloroquine, pyrimethamine and sulfadoxine, and chlorproguanil and dapsone as treatment for falciparum malaria in pregnant and non-pregnant women, Kakamega District, Kenya.

OBJECTIVE: To compare treatment and protection against falciparum malaria in pregnant and non-pregnant women with three drug regimens. DESIGN: Prospective intervention study with six weeks' follow up. Patients received one of three drug regimens in order of entry. SETTING: Primary care hospital and secondary girls' school in rural western Kenya. PATIENTS: 158 of 988 pregnant women (89 primigravid and 69 multigravid) in the third trimester and 105 of 1488 non-pregnant schoolgirls of reproductive age were parasitaemic (more than 500 asexual forms/microliter. These women were divided into three treatment groups by gravid state. INTERVENTIONS: Women were treated with chloroquine base 25 mg/kg over three days or pyrimethamine 75 mg and sulfadoxine 1500 mg as a single dose or chlorproguanil 1.2 mg/kg and dapsone 2.4 mg/kg as a single dose. MAIN OUTCOME MEASURES: Parasitaemia and haemoglobin concentrations measured at seven day intervals for six weeks. RESULTS: Primigravid women were more likely to be parasitaemic on follow up than multigravidas or nulligravidas, whose response was about the same. Parasites did not clear by day 7 in primigravidas in six (20%) of 30 who received chloroquine, three (8%) of 35 treated with pyrimethamine and sulfadoxine, and none of 23 treated with chlorproguanil and dapsone. At day 28, 83%, 19%, and 67% of primigravidas in these treatment groups were parasitaemic. Haemoglobin concentrations rose in all women, but improvement was sustained only in women who remained free of parasites. CONCLUSIONS: Clearance of parasites was better with either pyrimethamine and sulfadoxine or chlorproguanil and dapsone than with chloroquine. Longest protection was obtained with pyrimethamine and sulfadoxine.