Exotic viral hepatitis: A review on epidemiology, pathogenesis, and treatment.

Certain "exotic" viruses are known to cause clinical diseases with potential liver involvement. These include viruses, beyond regular hepatotropic viruses (hepatitis A, -B(D), -C, -E, cytomegalovirus, Epstein-Barr virus), that can be found in (sub)tropical areas and can cause "exotic viral hepatitis". Transmission routes typically involve arthropods (Crimean Congo haemorrhagic fever, dengue, Rift Valley fever, yellow fever). However, some of these viruses are transmitted by the aerosolised excreta of rodents (Hantavirus, Lassa fever), or via direct contact or contact with bodily fluids (Ebola). Although some exotic viruses are associated with high fatality rates, such as Ebola for example, the clinical presentation of most exotic viruses can range from mild flu-like symptoms, in most cases, right through to being potentially fatal. A smaller percentage of people develop severe disease with haemorrhagic fever, possibly with (fulminant) hepatitis. Liver involvement is often caused by direct tropism for hepatocytes and Kupffer cells, resulting in virus-mediated and/or immune-mediated necrosis. In all exotic hepatitis viruses, PCR is the most sensitive diagnostic method. The determination of IgM/IgG antibodies is a reasonable alternative, but cross-reactivity can be a problem in the case of flaviviruses. Licenced vaccines are available for yellow fever and Ebola, and they are currently under development for dengue. Therapy for exotic viral hepatitis is predominantly supportive. To ensure that preventive measures can be introduced to control possible outbreaks, the timely detection of these viruses is very important.

A case report of transfusion-transmitted Plasmodium malariae from an asymptomatic non-immune traveller.

BACKGROUND: The incidence of transfusion-transmitted malaria is very low in non-endemic countries due to strict donor selection. The optimal strategy to mitigate the risk of transfusion-transmitted malaria in non-endemic countries without unnecessary exclusion of blood donations is, however, still debated and asymptomatic carriers of Plasmodium species may still be qualified to donate blood for transfusion purposes. CASE DESCRIPTION: In April 2011, a 59-year-old Dutch woman with spiking fevers for four days was diagnosed with a Plasmodium malariae infection. The patient had never been abroad, but nine weeks before, she had received red blood cell transfusion for anaemia. The presumptive diagnosis of transfusion-transmitted quartan malaria was made and subsequently confirmed by retrospective PCR analysis of donor blood samples. The donor was a 36-year-old Dutch male who started donating blood in May 2006. His travel history outside Europe included a trip to Kenya, Tanzania and Zanzibar in 2005, to Thailand in 2006 and to Costa Rica in 2007. He only used malaria prophylaxis during his travel to Africa. The donor did not show any abnormalities upon physical examination in 2011, while laboratory examination demonstrated a thrombocytopenia of 126 × 109/L as the sole abnormal finding since 2007. Thick blood smear analysis and the Plasmodium PCR confirmed an ongoing subclinical P. malariae infection. Chloroquine therapy was started, after which the infection cleared and thrombocyte count normalized. Fourteen other recipients who received red blood cells from the involved donor were traced. None of them developed malaria symptoms. DISCUSSION: This case demonstrates that P. malariae infections in non-immune travellers may occur without symptoms and persist subclinically for years. In addition, this case shows that these infections pose a threat to transfusion safety when subclinically infected persons donate blood after their return in a non-endemic malaria region.Since thrombocytopenia was the only abnormality associated with the subclinical malaria infection in the donor, this case illustrates that an unexplained low platelet count after a visit to malaria-endemic countries may be an indicator for asymptomatic malaria even when caused by non-falciparum Plasmodium species.

Is paromomycin the drug of choice for eradication of Blastocystis in adults?

Blastocystis is a protozoan parasite of controversial clinical significance that is often detected in stools of patients with gastrointestinal complaints. Patients infected with Blastocystis and persistent, unexplained gastrointestinal complaints are often treated with the intention to eradicate Blastocystis. However, there is no consensus on the most effective drug. We performed a retrospective follow-up study with a large cohort of patients in which the natural disease course and efficacy of treatment with either paromomycin, clioquinol, or metronidazole were evaluated. With an eradication rate of 77 %, treatment with paromomycin appeared significantly more effective than treatment with clioquinol (38 %), metronidazole (38 %), or no treatment (22 %). This study showed that (1) Blastocystis was frequently observed in the stools of our patient group (34 %), (2) spontaneous clearance of Blastocystis infections occurred only in a small proportion of patients (22 %), and therefore (3) drug treatment is required for more efficient eradication of Blastocystis. Paromomycin exhibited superior performance in comparison to both metronidazole and clioquinol.

Facial paralysis due to a spitting cobra bite.

The global burden of snakebites is growing, particularly its nonfatal sequelae. Therefore, the World Health Organization reinstated snakebites to its list of Neglected Tropical Diseases. We describe the case of a 4.5-year-old boy who was bitten by a spitting cobra, resulting in considerable local swelling accompanied by a right-sided facial paralysis due to neurotoxicity by cobra venom. Presently, surgical methods to recover facial paralysis include nerve repair, nerve grafting, nerve transfers, static slings, muscle transfers, and functional muscle transplantations. However, mime therapy consisting of neuromuscular retraining resulted in a good functional result with a moderate contour deficiency of the right cheek and a subtle paresis of the zygomatic muscles at 1 year and 9 months follow-up. The natural history of facial paralysis in our case shows that this condition can be transient and may resolve with mime therapy as a conservative measure.

Efficacy and safety of exchange transfusion as an adjunct therapy for severe Plasmodium falciparum malaria in nonimmune travelers: a 10-year single-center experience with a standardized treatment protocol.

BACKGROUND: Even in circumstances where optimal antimalarial and supportive treatment is available, severe Plasmodium falciparum malaria is still associated with a significant case fatality. Although exchange transfusion (ET) has been considered as a controversial adjunct therapy, we have not encountered any case fatality since ET was introduced as a standard adjunct therapy for patients with severe malaria. STUDY DESIGN AND METHODS: In this retrospective cohort study of 25 patients with severe malaria, the efficacy and safety of ET as an adjunct to parenteral antimalarial treatment (which was implemented in our hospital starting in 1998) were evaluated and compared with 31 historical control patients who were treated with conventional parenteral antimalarial treatment in the period before ET was added to the standard of care for severe malaria (generally before 1997). RESULTS: The parasite clearance times (PCT)(25%), PCT(50%), PCT(75%) and PCT(90%) were all significantly shorter for patients treated with ET than for patients treated with parenteral quinine only. The shorter PCTs in the ET group were the result of a more rapid parasite clearance in the early phases after initiation of ET. CONCLUSION: No case fatalities were observed in the ET group. The complications that were observed with ET were more likely related either to the multiorgan dysfunction associated with severe malaria or to side effects of parenteral quinine rather than to the ET procedure. ET may be safely executed in a setting with intensive care facilities and availability of safe blood products and should be considered as a beneficial adjunct treatment to parenteral antimalarial therapy.

Human Plasmodium knowlesi infection detected by rapid diagnostic tests for malaria.

We describe a PCR-confirmed case of Plasmodium knowlesi infection with a high parasitemia level and clinical signs of severe malaria in a migrant worker from Malaysian Borneo in the Netherlands. Investigations showed that commercially available rapid antigen tests for detection of human Plasmodium infections can detect P. knowlesi infections in humans.

[Myocarditis, a treacherous condition]. / Myocarditis, een verraderlijk ziektebeeld.

Myocarditis, a treacherous condition It is important to recognize myocarditis at an early stage. To illustrate this, we present two male patients aged 39 and 51, respectively, who were admitted with febrile disease and signs of circulatory instability. Initially, myocarditis was not suspected in these patients. After the sudden death of the younger patient it was discovered that he had had fulminant myocarditis. Its nonspecific, heterogeneous clinical presentation, and potentially disastrous outcome make myocarditis a treacherous condition, which mainly affects younger adults. Although its aetiology is broad, the primary cause in the western world is a viral infection leading to lymphocytic myocarditis. Fulminant forms are rare, but this diagnosis needs to be considered in patients with an atypical illness and impaired haemodynamics or electrocardiogram (ECG) abnormalities. Early and liberal consultation of a cardiologist is important. Primary diagnostics include blood testing (e.g. troponin, creatinine kinase), ECG, echocardiography and exclusion of coronary ischaemia. The diagnosis can be confirmed by cardiovascular MRI or endomyocardial biopsy.

Aseptic abscesses: a study of 30 patients with or without inflammatory bowel disease and review of the literature.

Aseptic abscesses (AA) are characterized by deep, sterile, round lesions consisting of neutrophil that do not respond to antibiotics but improve dramatically with corticosteroids. We report the clinical, laboratory, and radiologic characteristics and the associated conditions of 29 patients from the French Register on AA plus 1 patient from the Netherlands.The mean age of patients at AA diagnosis was 29 years (SD = 14). The main clinical manifestations of AA were fever (90%), abdominal pain (67%), and weight loss (50%). Duration of symptoms was 4.7 months on average until abscesses were discovered. The abscesses involved the spleen in 27/29 patients (93%; the thirtieth patient had a personal history of splenectomy after a trauma). In 7 they were unifocal and in the others they were multifocal, involving in addition the abdominal lymph nodes in 14 (48%), liver in 12 (40%), lung in 5 (17%), pancreas in 2 (7%), and brain in 2 (7%). They were not splenic in 3, including 2 with abdominal lymph nodes and 1 with superficial lymph nodes and testicle and lung involvement. Twenty-two patients (70%) had elevated white blood cell and neutrophil count; antineutrophil cytoplasmic autoantibodies with a perinuclear, cytoplasmic or atypical pattern (negative for antiproteinase 3 and negative for antimyeloperoxidase except for 1) were positive in 21% of the 24 patients tested. Twenty-one patients had inflammatory bowel disease (IBD), which preceded the occurrence of abscesses in 7, was concomitant in 7, and appeared secondarily in 7. Six patients had neutrophilic dermatosis (20%), 3 had relapsing polychondritis as an associated condition, and 3 others had monoclonal gammopathy of undetermined significance. Three patients had no associated condition. Splenectomy was performed in 15 (52%) patients. All patients received steroid therapy. Thirteen (43%) were given additional immunosuppressive therapy, 1 immediately and the others after a relapse, of whom 3 were also treated by anti-tumor necrosis factor-alpha agents. Mean follow-up was 7 years. Eighteen (60%) patients experienced 1 or several relapses, but there was no death related to AA. Relapses occurred on immunosuppressive therapy in 2 patients and off immunosuppressive therapy in the others while corticosteroids were being tapered. We surveyed the literature and analyzed 19 additional cases. AA is an emergent and probably underrecognized entity. It represents an apparently noninfectious inflammatory disorder involving neutrophils that responds to corticosteroid therapy. AA mainly affects patients with IBD but also affects those with other conditions, or with no other apparent disease.

Distinguishing tropical sprue from celiac disease in returning travellers with chronic diarrhoea: a diagnostic challenge?

BACKGROUND: Within the present era of worldwide travel, it is important for all clinicians to consider the possibility of tropical sprue (TS) in returning patients with persistent diarrhoea after travel. The symptoms and histologic findings of TS can resemble but also be confused with celiac disease (CD). MATERIAL AND METHOD: Patients at our institute diagnosed with CD or TS in the period January 2000-December 2010 were eligible for inclusion. Of all patients, demographic, clinical, laboratory and endoscopy data on admission and in follow-up were collected retrospectively. RESULTS: 28 CD and 7 TS patients were included. There were no differences in baseline clinical characteristics, duration of stay in a tropical region or in laboratory findings on admission. However, in the majority of CD patients antibodies against endomysium (EMA) or tissue transglutaminase (tTG) were present at presentation but absent in all TS patients at presentation. CONCLUSIONS: In returning travellers with persistent diarrhoea, a diagnosis of CD is unlikely in case of absence of anti-EMA or anti-tTG antibodies but conversely increases the likelihood of TS. This distinct immunoserological profile may be of help in selecting the optimal treatment in returning travelers with chronic diarrhoea after staying in a tropical region.

Is paromomycin the drug of choice for eradication of Dientamoeba fragilis in adults?

Dientamoeba fragilis is a debated protozoan parasite that is often detected in stools of patients with chronic gastro-intestinal complaints. A retrospective follow-up study of a large cohort of patients was performed to better understand the natural course of the infection and possible treatment options. D. fragilis was spontaneously cleared in 41% of untreated cases. With an eradication rate of 98%, treatment with paromomycin appeared more effective than treatment with clioquinol (83%) or metronidazole (57%).

Early small bowel perforation and cochleovestibular impairment as rare complications of typhoid fever.

Two Indian migrant workers suffering from fever and malaise were admitted to the hospital directly after arrival in the Netherlands. The first patient was 25-year-old man who had fever and rigors on admission. The patient was treated for presumptive typhoid fever with ciprofloxacin. Cefotaxime was added the following day because of the possibility of a nalidixic-acid resistant strain of S. typhi. The clinical course was complicated by a small bowel perforation on the third day of the disease. Blood cultures grew a nalidixic acid resistant strain of Salmonella enterica serovar typhi. The patient recovered completely. The second patient, a 22-year-old man, suffered from fever, malaise and hearing loss. A sensorineural hearing loss with vestibular dysfunction was diagnosed. Cultures of blood and bone marrow aspirate showed a nalidixic acid resistant strain of S. typhi. Treatment with ciprofloxacin and ceftazidime improved the hearing loss significantly. The clinical features of typhoid fever are heterogeneous and rare complications may occur. The emergence of multidrug and nalidixic acid resistance may complicate further the treatment of this serious systemic infection.

[Tick-borne encephalitis after a holiday in Southern Germany]. / Teken-encefalitis na een vakantie in Zuid-Duitsland.

A 56-year-old man was admitted to hospital with complaints of headache, fever and photophobia, 3 weeks after being bitten by ticks in Southern Germany. Two weeks before admission he had experienced a short period of a flu-like illness, from which he spontaneously recovered. Based on the tick bites in Southern Germany and the biphasic course of the illness shortly afterwards, we made the diagnosis tick-borne encephalitis, Frühsommer-Meningoenzephalitis in German (FSME). The diagnosis was confirmed serologically. FSME is caused by a flavivirus, which is transmitted via tick bites. In 72-87% of cases the course is biphasic. The virus subtype and the degree of central nervous system involvement determine the prognosis. The patient may experience residual symptoms. The treatment is symptomatic. Active immunisation offers protection, but is only recommended to those who stay frequently or for a long period in areas where the virus is endemic.

Different perceptions of the burden of upper GI endoscopy: an empirical study in three patient groups.

BACKGROUND: Few studies have evaluated patients' perceived burden of cancer surveillance tests. Cancer screening and surveillance, however, require a large number of patients to undergo potentially burdensome tests with only some experiencing health gains from it. We investigated the determinants of patients' reported burden of upper gastrointestinal (GI) endoscopy by comparing data from three patient groups. PATIENTS AND METHODS: A total of 476 patients were included: 180 patients under regular surveillance for Barrett esophagus (BE), a premalignant disorder; 214 patients with non-specific upper GI symptoms (NS), and 82 patients recently diagnosed with upper GI cancer (CA). We assessed pain, discomfort and overall burden experienced during endoscopy, symptoms in the week afterwards and psychological distress over time (Hospital Anxiety and Depression scale and Impact of Event Scale). RESULTS: Two-thirds (66%) of patients reported discomfort and overall burden of upper GI endoscopy. Only 23% reported any pain. BE patients reported significantly less discomfort, pain and overall burden than the other patients: those with NS reported more discomfort, CA patients more pain, and both more overall burden. These differences could be statistically explained by the number of previous endoscopies and whether sedation was provided or not, but not by patient characteristics. CONCLUSION: The perception of upper GI endoscopy varies by patient group, due to potential adaptation after multiple endoscopies and aspects of the procedure.

Use of enzyme-linked immunosorbent assay and dipstick assay for detection of Strongyloides stercoralis infection in humans.

A homemade enzyme-linked immunosorbent assay (ELISA) (Academic Medical Center ELISA [AMC-ELISA]) and a dipstick assay for the detection of anti-Strongyloides stercoralis antibodies in serum were developed and evaluated together with two commercially available ELISAs (IVD-ELISA [IVD Research, Inc.] and Bordier-ELISA [Bordier Affinity Products SA]) for their use in the serodiagnosis of imported strongyloidiasis. Both commercially available ELISAs have not been evaluated previously. The sensitivities of the assays were evaluated using sera from 90 patients with parasitologically proven intestinal strongyloidiasis and from 9 patients with clinical larva currens. The sensitivities of the AMC-ELISA, dipstick assay, IVD-ELISA, and Bordier-ELISA were 93, 91, 89, and 83%, respectively, for intestinal strongyloidiasis. In all tests, eight of nine sera from patients with larva currens were positive. The specificity was assessed using a large serum bank of 220 sera from patients with various parasitic, bacterial, viral, and fungal infectious diseases; sera containing autoimmune antibodies; and sera from healthy blood donors. The specificities of AMC-ELISA, dipstick assay, IVD-ELISA, and Bordier-ELISA were 95.0, 97.7, 97.2, and 97.2%, respectively. Our data suggest that all four assays are sensitive and specific tests for the diagnosis of both intestinal and cutaneous strongyloidiasis.