Patrick Soentjens

A Schistosoma haematobium-Specific Real-Time PCR for Diagnosis of Urogenital Schistosomiasis in Serum Samples of International Travelers and Migrants

Background Diagnosis of urogenital schistosomiasis by microscopy and serological tests may be elusive in travelers due to low egg load and the absence of seroconversion upon arrival. There is need for a more sensitive diagnostic test. Therefore, we developed a real-time PCR targeting the Schistosoma haematobium-specific Dra1 sequence. Methodology/Principal Findings The PCR was evaluated on urine (n = 111), stool (n = 84) and serum samples (n = 135), and one biopsy from travelers and migrants with confirmed or suspected schistosomiasis. PCR revealed a positive result in 7/7 urine samples, 11/11 stool samples and 1/1 biopsy containing S. haematobium eggs as demonstrated by microscopy and in 22/23 serum samples from patients with a parasitological confirmed S. haematobium infection. S. haematobium DNA was additionally detected by PCR in 7 urine, 3 stool and 5 serum samples of patients suspected of having schistosomiasis without egg excretion in urine and feces. None of these suspected patients demonstrated other parasitic infections except one with Blastocystis hominis and Entamoeba cyst in a fecal sample. The PCR was negative in all stool samples containing S. mansoni eggs (n = 21) and in all serum samples of patients with a microscopically confirmed S. mansoni (n = 22), Ascaris lumbricoides (n = 1), Ancylostomidae (n = 1), Strongyloides stercoralis (n = 1) or Trichuris trichuria infection (n = 1). The PCR demonstrated a high specificity, reproducibility and analytical sensitivity (0.5 eggs per gram of feces). Conclusion/Significance The real-time PCR targeting the Dra1 sequence for S. haematobium-specific detection in urine, feces, and particularly serum, is a promising tool to confirm the diagnosis, also during the acute phase of urogenital schistosomiasis.

Syphilis reinfections pose problems for syphilis diagnosis in Antwerp, Belgium - 1992 to 2012

Persons with multiple syphilis reinfections may play an important role in syphilis transmission. We analysed all syphilis tests carried out for people attending the HIV/sexually transmitted infection (STI) clinic at the Institute of Tropical Medicine, Antwerp, Belgium, from 1992 to 2012 to evaluate the extent to which syphilis reinfections were contributing to the syphilis epidemic in Antwerp. We then characterised the features of the syphilis infections in individuals with five or more episodes of syphilis. A total of 729 syphilis episodes were diagnosed in 454 persons. The majority of syphilis episodes occurred in people who had more than one episode of syphilis (445/729; 61%). A total of 10 individuals had five or more episodes of syphilis diagnosed over this period. All were men who have sex with men, HIV positive and on antiretroviral therapy. They had a total of 52 episodes of syphilis diagnosed and treated. In 38/42 of the episodes of repeat syphilis in these 10 individuals, they presented without any signs or symptoms of syphilis. Given that the majority of cases of incident syphilis in our clinic were persons with reinfections and that they frequently presented without signs of symptoms of syphilis, there is a strong case for frequent and repeated screening in all persons with a diagnosis of syphilis.

Use of bacteriophages in the treatment of colistin-only-sensitive Pseudomonas aeruginosa septicaemia in a patient with acute kidney injury—a case report

Sepsis from Pseudomonas aeruginosa bacteraemia may be fatal, especially when no appropriate therapy can be given. In June 2016, a 61-year-old man was hospitalised for Enterobacter cloacae peritonitis and severe abdominal sepsis with disseminated intravascular coagulation, secondary to a diaphragmatic hernia with bowel strangulation. The patient had a prolonged hospital course complicated by gangrene of the peripheral extremities, resulting in the amputation of the lower limbs and the development of large necrotic pressure sores (Fig. 1). Three months after admission, the patient was transferred to the Queen Astrid military hospital for surgical management of the pressure sores. Wound cultures on admission revealed colonisation with, amongst others, multidrug-resistant P. aeruginosa. One month after admission, the patient developed septicaemia with colistin-only-sensitive P. aeruginosa. Intravenous colistin therapy was started. Ten days later, the patient developed acute kidney injury with rising serum creatinine and urea levels (Fig. 2), presumably sepsisand drug-induced. Antibiotic therapy was discontinued to prevent further kidney damage. Unfortunately, on 12 November, P. aeruginosa septicaemia re-emerged with rapid heart rate, low blood pressure, fever and high C-reactive protein (CRP) levels. On 14 November, the patient went into a coma with 9 scores (E2V2M5) on the Glasgow Coma Scale. Because of the risk of colistin nephrotoxicity and the family’s will to avoid intensive therapy interventions such as hemofiltration, bacteriophage therapy was initiated under the umbrella of Article 37 (Unproven Interventions in Clinical Practice) of the Declaration of Helsinki [1]. Fifty microlitres of purified bacteriophage cocktail BFC1 [2], containing two bacteriophages that showed in vitro activity against the patient’s P. aeruginosa

Toxocariasis Diagnosed in International Travelers at the Institute of Tropical Medicine, Antwerp, Belgium, from 2000 to 2013

Although infection with Toxocara canis or T. catis (commonly referred as toxocariasis) appears to be highly prevalent in (sub)tropical countries, information on its frequency and presentation in returning travelers and migrants is scarce. In this study, we reviewed all cases of asymptomatic and symptomatic toxocariasis diagnosed during post-travel consultations at the reference travel clinic of the Institute of Tropical Medicine, Antwerp, Belgium. Toxocariasis was considered as highly probable if serum Toxocara-antibodies were detected in combination with symptoms of visceral larva migrans if present, elevated eosinophil count in blood or other relevant fluid and reasonable exclusion of alternative diagnosis, or definitive in case of documented seroconversion. From 2000 to 2013, 190 travelers showed Toxocara-antibodies, of a total of 3436 for whom the test was requested (5.5%). Toxocariasis was diagnosed in 28 cases (23 symptomatic and 5 asymptomatic) including 21 highly probable and 7 definitive. All but one patients were adults. Africa and Asia were the place of acquisition for 10 and 9 cases, respectively. Twelve patients (43%) were short-term travelers (< 1 month). Symptoms, when present, developed during travel or within 8 weeks maximum after return, and included abdominal complaints (11/23 symptomatic patients, 48%), respiratory symptoms and skin abnormalities (10 each, 43%) and fever (9, 39%), often in combination. Two patients were diagnosed with transverse myelitis. At presentation, the median blood eosinophil count was 1720/μL [range: 510–14160] in the 21 symptomatic cases without neurological complication and 2080/μL [range: 1100–2970] in the 5 asymptomatic individuals. All patients recovered either spontaneously or with an anti-helminthic treatment (mostly a 5-day course of albendazole), except both neurological cases who kept sequelae despite repeated treatments and prolonged corticotherapy. Toxocariasis has to be considered in travelers returning from a (sub)tropical stay with varying clinical manifestations or eosinophilia. Prognosis appears favorable with adequate treatment except in case of neurological involvement.

Schistosomiasis in Belgian military personnel returning from the Democratic Republic of Congo.

The detection of schistosomiasis cases among Belgian military personnel returning from a mission in the Democratic Republic of Congo (DRC) prompted a nested case-control study of all military personnel deployed in the DRC between 2005 and 2008 to identify all infections and to start appropriate treatment. Of 197 patients exposed at Lake Tanganyika in the Kalemie area of DRC, 49 (24.9%) were diagnosed with schistosomiasis. Swimming was significantly more frequent than wading in the seropositive group than in the seronegative group (88.9% vs. 73.6%; odds ratio [OR], 2.86; 95% confidence interval [CI], 0.97-9.01). Thirty-one of 49 patients (63.3%) were symptomatic; including skin problems in 34.7%, respiratory symptoms in 12.2%, fever in 14.3%, and 51.0% with gastrointestinal problems. Median eosinophil counts were significantly higher in seropositive patients (375 vs. 138 per tL; Wilcoxon rank sum test [Ws] = 10,559.00; p < 0.01; r = -0.49). In total, 20 (40.8%) of the 49 patients were treated for symptomatic infections and the remainder for asymptomatic schistosomiasis. Our study emphasizes the need for active systematic post-tropical screening in military personnel after deployment to Schistosoma-endemic regions of the world.

Molecular Epidemiology and Clinical Impact of Acinetobacter calcoaceticus-baumannii Complex in a Belgian Burn Wound Center.

Multidrug resistant Acinetobacter baumannii and its closely related species A. pittii and A. nosocomialis, all members of the Acinetobacter calcoaceticus-baumannii (Acb) complex, are a major cause of hospital acquired infection. In the burn wound center of the Queen Astrid military hospital in Brussels, 48 patients were colonized or infected with Acb complex over a 52-month period. We report the molecular epidemiology of these organisms, their clinical impact and infection control measures taken. A representative set of 157 Acb complex isolates was analyzed using repetitive sequence-based PCR (rep-PCR) (DiversiLab) and a multiplex PCR targeting OXA-51-like and OXA-23-like genes. We identified 31 rep-PCR genotypes (strains). Representatives of each rep-type were identified to species by rpoB sequence analysis: 13 types to A. baumannii, 10 to A. pittii, and 3 to A. nosocomialis. It was assumed that isolates that belonged to the same rep-type also belonged to the same species. Thus, 83.4% of all isolates were identified to A. baumannii, 9.6% to A. pittii and 4.5% to A. nosocomialis. We observed 12 extensively drug resistant Acb strains (10 A. baumannii and 2 A. nosocomialis), all carbapenem-non-susceptible/colistin-susceptible and imported into the burn wound center through patients injured in North Africa. The two most prevalent rep-types 12 and 13 harbored an OXA-23-like gene. Multilocus sequence typing allocated them to clonal complex 1 corresponding to EU (international) clone I. Both strains caused consecutive outbreaks, interspersed with periods of apparent eradication. Patients infected with carbapenem resistant A. baumannii were successfully treated with colistin/rifampicin. Extensive infection control measures were required to eradicate the organisms. Acinetobacter infection and colonization was not associated with increased attributable mortality.

Analysis of delayed TBE-vaccine booster after primary vaccination

An open, uncontrolled single centre study was conducted in the Travel Clinic at the Military Hospital, Brussels. Eighty-eight subjects were recruited who had a primary series of tick-borne encephalitis (TBE) vaccine more than 5 years ago and who never received a booster dose afterwards. Response rate after booster vaccination was very high: 84 out of 88 subjects (95.5%) had neutralizing antibodies on plaque reduction neutralization test and all (100%) had IgG antibodies on ELISA, on Day 21-28 after booster vaccination. This study adds valuable information to the common situation of delayed booster interval. The results of our study indicate that in young healthy travellers (<50 years), one booster vaccination after a primary series of TBE vaccine in the past is sufficient to obtain protective antibodies, even if primary vaccination is much longer than the recommended booster interval of 5 years.

Low-Cost Intradermal Rabies Vaccination Is Indeed Very Promising

TO THE EDITOR—We read with great interest the recent article by Wieten et al in Clinical Infectious Diseases [1] and, being involved in ongoing research strictly related to this topic, we wish to bring our contribution to their reflections. First, we fully agree that a lower-dose, abbreviated intradermal preand postexposure vaccination schedule may constitute a valid, shorter, and cheaper alternative to the current intramuscular or intradermal 3to 4-week schedules. If proven to be effective, such a schedule would be highly advantageous both for prevention in international travelers and for expanding vaccination in resourcepoor endemic countries. We also agree that further studies are needed to determine precisely which intradermal preexposure regimen is ideal for life-long boostability and which intradermal postexposure regimen gives high effective serology titers at day 7 after exposure. In their literature review, Wieten et al selected 9 studies and described the effects of the different schedules [1]. They stated that direct comparisons of various studies was not possible because of the different timing, dosing, routes of administration, and, in our opinion, also because of the small sample size and of the differences in serologic testing. The 2 most promising intradermal studies were designed by Khawplod [2, 3]: In 5 of the 10 study arms, exclusively intradermal regimens (0.1 mL) were used, with a total dose between 0.4 mL and 0.8 mL. In 2 other studies, authors declared that a total dose of 0.4 mL or 0.6 mL, respectively, of preexposure rabies vaccine administered over a minimum of 2 visits gives an adequate antibody response, irrespective of the time interval since the last dose [4, 5]. Concerning serology, in fact, the World Health Organization guidelines recommend the use of either the rapid fluorescent focus inhibition test (RFFIT) or the fluorescent antibody virus neutralization test. In particular, an RFFIT titer of > 0.5 IU/mL after booster vaccination is considered to be the best surrogate marker to determine protection from rabies infection after an animal bite in endemic zones [6]. Thus, we suggest that studies using only the enzyme-linked immunosorbent assay (ELISA), although reliable as an alternative, should be excluded in future analyses assessing or comparing the boostability of preexposure and postexposure rabies vaccination schedules. For instance, a recent case

Selection of Potential Therapeutic Bacteriophages that Lyse a CTX-M-15 Extended Spectrum β-Lactamase Producing Salmonella enterica Serovar Typhi Strain from the Democratic Republic of the Congo

Recently, a Salmonella Typhi isolate producing CTX-M-15 extended spectrum β-lactamase (ESBL) and with decreased ciprofloxacin susceptibility was isolated in the Democratic Republic of the Congo. We have selected bacteriophages that show strong lytic activity against this isolate and have potential for phage-based treatment of S. Typhi, and Salmonella in general.

Clinical Utility of the NS1 Antigen Rapid Diagnostic Test in the Management of Dengue in Returning Travelers with Fever

Abstract Background Rapid diagnostic test (RDT) detecting the nonstructural 1 (NS1) antigen is increasingly used for dengue diagnosis in endemic and nonendemic settings, but its clinical utility has not been studied in travel clinic practice. Methods From August 2012 to July 2016, travelers returning from the tropics with fever were evaluated in the Institute of Tropical Medicine (Antwerp, Belgium) with the routine use of NS1 antigen RDT that provided results within 1 hour. We determined the diagnostic performance, assessed the management of patients with a positive RDT result, and compared it with that of historical cases of dengue diagnosed from 2000 to 2006, when only antibody detection assays were available. Results Of 335 travelers evaluated for fever, 54 (16%) were diagnosed with dengue, including 1 severe case. Nonstructural 1 antigen RDT was performed in 308 patients. It was truly positive in 43 of 52 tested dengue cases and falsely positive in only 1 of the 256 nondengue cases; therefore, sensitivity was 82.7% (95% confidence interval [CI], 74.4%–93.0%) and specificity was 99.6% (95% CI, 98.8%–100%). Only 3 (7%) of the 43 febrile travelers “immediately” diagnosed by RDT were admitted, and only 2 (5%) were given empirical antibacterial treatment, without adverse outcome. Admission and antibiotic prescription rates were significantly higher in the historical cases (n = 43) diagnosed by antibody detection (33%, P = .006 and 26%, P = .014, respectively), although the frequency of severe dengue was similar. Conclusions In our practice, the diagnostic performance of NS1 antigen RDT substantially contributed in withholding unnecessary hospitalization and antibiotherapy in dengue patients.