J. Clerinx

Incidence and Risk Factors of Serious Adverse Events during Antituberculous Treatment in Rwanda: A Prospective Cohort Study

Background Tuberculosis (TB) and TB-human immunodeficiency virus infection (HIV) coinfection is a major public health concern in resource-limited settings. Although TB treatment is challenging in HIV-infected patients because of treatment interactions, immunopathological reactions, and concurrent infections, few prospective studies have addressed this in sub-Saharan Africa. In this study we aimed to determine incidence, causes of, and risk factors for serious adverse events among patients on first-line antituberculous treatment, as well as its impact on antituberculous treatment outcome. Methods and findings Prospective observational cohort study of adults treated for TB at the Internal Medicine department of the Kigali University Hospital from May 2008 through August 2009. Of 263 patients enrolled, 253 were retained for analysis: median age 35 (Interquartile range, IQR 28–40), 55% male, 66% HIV-positive with a median CD4 count 104 cells/mm3 (IQR 44–248 cells/mm3). Forty percent had pulmonary TB, 43% extrapulmonary TB and 17% a mixed form. Sixty-four (26%) developed a serious adverse event; 58/167 (35%) HIV-infected vs. 6/86 (7%) HIV-uninfected individuals. Commonest events were concurrent infection (n = 32), drug-induced hepatitis (n = 24) and paradoxical reactions/TB-IRIS (n = 23). HIV-infection (adjusted Hazard Ratio, aHR 3.4, 95% Confidence Interval, CI 1.4–8.7) and extrapulmonary TB (aHR 2, 95%CI 1.1–3.7) were associated with an increased risk of serious adverse events. For TB/HIV co-infected patients, extrapulmonary TB (aHR 2.0, 95%CI 1.1–3.9) and CD4 count <100 cells/mm3 at TB diagnosis (aHR 1.7, 95%CI 1.0–2.9) were independent predictors. Adverse events were associated with an almost two-fold higher risk of unsuccessful treatment outcome at 6 months (HR 1.89, 95%CI 1.3–3.0). Conclusion Adverse events frequently complicate the course of antituberculous treatment and worsen treatment outcome, particularly in patients with extrapulmonary TB and advanced immunodeficiency. Concurrent infection accounts for most events. Our data suggest that deterioration in a patient already receiving antituberculous treatment should prompt an aggressive search for additional infections.

Selective ambulatory management of imported falciparum malaria: a 5-year prospective study

The ambulatory management of imported Plasmodium falciparum malaria is controversial because criteria for safe selection of patients are imprecise. The aim of the present study was to investigate the evolution and outcome of patients diagnosed with Plasmodium falciparum malaria at a Belgian referral institute in order to assess the safety of the institute’s current selective ambulatory management protocol. From 2000 to 2005, all patients diagnosed with P. falciparum infection at the Institute of Tropical Medicine and the University Hospital of Antwerp were enrolled prospectively. Ambulatory treatment was offered to nonvomiting patients if they exhibited none of the 2000 World Health Organization criteria of severity and had parasitemia below 1% at the initial assessment. The treatment of choice was quinine (plus doxycycline or clindamycin) for inpatients and atovaquone-proguanil for outpatients. P. falciparum malaria was diagnosed in 387 patients, of whom 246 (64%) were Western travelers or expatriates and 117 (30%) were already on antimalarial therapy. At diagnosis, 60 (15%) patients had severe malaria. Vital organ dysfunction was initially seen in 34 and developed later in five others. Five patients died. Of the 327 patients initially assessed as having uncomplicated malaria, 113 (35%) were admitted immediately; of these, 4 developed parasitemia ≥5% at a later stage but without any clinical consequence. None of the 214 individuals initially treated as outpatients experienced any malaria-related complications, including 10 who were admitted later. Vital organ dysfunction was observed in only 2 of the 214 patients with initial parasitemia <1% who had not taken antimalarial agents (both patients had impaired consciousness at presentation). Ambulatory treatment is safe in treatment-naive malaria patients with parasitemia <1% who do not vomit and who do not exhibit any criteria of severe malaria.

EPIDEMIOLOGY AND OUTCOME OF SHIGELLA, SALMONELLA AND CAMPYLOBACTER INFECTIONS IN TRAVELLERS RETURNING FROM THE TROPICS WITH FEVER AND DIARRHOEA

Abstract Introduction: During a study on fever after a stay in the tropics, we aimed at investigating the epidemiology and outcome of invasive bacterial enteritis due to Shigella, Salmonella or Campylobacter spp. in patients diagnosed with febrile traveller’s diarrhoea. Methods: From April 2000 to September 2006, we evaluated prospectively 594 travellers presenting with fever and diarrhoea within a month after a stay in the tropics. Patients not found with a systemic infection were assumed to have febrile traveller’s diarrhoea (TD). Invasive bacterial enteritis was confirmed by isolation of Shigella, Campylobacter or nontyphoidal Salmonella in stool cultures. Results: Systemic infections (mainly malaria) were diagnosed in 259 (44%) evaluated travellers. Invasive bacterial enteritis, either alone or with another infection, was confirmed in 114 (34%) of the 335 remaining patients with febrile TD. Aetiologies were distributed between Campylobacter jejuni (47, 41%), Shigella spp. (43, 38%), Salmonella spp. (22, 19%) and mixed Campylobacter-Salmonella infection (2, 2%). Invasive bacterial enteritis accounted for about a third of febrile TD cases occurring after a stay in sub-Saharan Africa, North Africa/Middle East or Latin America, and for half of those occurring after a travel to southern Asia (including 33% only due to C. jejuni). Resistance to fluoroquinolones was exclusively observed in C. jejuni isolates, but at an overall rate of 53%. Clinical failure occurred in 33% of the patients with C. jejuni infection empirically treated with a fluoroquinolone. Conclusion: Invasive bacterial enteritis was a frequent aetiology of febrile TD. C. jejuni was the leading pathogen after a travel to southern Asia, and was associated with high rate of resistance to fluoroquinolones and of clinical failure.

FEVER AFTER A STAY IN THE TROPICS Part 2 : common imported tropical diseases

Since world-wide travel and migration increased considerably in the last decades, physicians of industrialised countries may face various travel-related health problems or infectious diseases coming from all regions of the world. In 1997, about 650000 Belgian travellers had visited tropical and subtropical regions (1). After a short-term visit to developing countries, 15 % of 7886 Swiss travellers reported health problems, abroad or upon return, and 8 % consulted a doctor (2). In another study, up to 64 % of 784 American travellers experienced some illness during or after their travel, and febrile episodes were reported by 13 % of them (3). In travel clinics, fever represents the second cause of posttravel consultation after diarrhoea and has been reported by 20-37% of sick travellers in 2 observational studies (4,5). The diagnostic approach of fever in travellers usually challenges the attending clinician. First, the possible exposure to tropical pathogens broadens widely the differential diagnosis. In addition, fever and associated symptoms may not be specific enough to allow early diagnosis, or at least early distinction between a minor, self-limited process and a progressive, potentially lifethreatening illness. Finally, physicians of European countries may be unfamiliar with tropical infections that the patient may have encountered while travelling. As the possible causes of imported febrile illnesses are numerous and potentially severe, the clinician needs a logical approach in order to establish promptly an etiologic diagnosis. This article (part 1) describes the prevalence of the different illnesses reported in recent observational studies among travellers returning from the tropics, and discusses the required diagnostic work up for such patients. The second article (part 2) provides an updated knowledge of the most common tropical infections.

A CASE OF MULTIPLE AMOEBIC LIVER ABSCESSES: CLINICAL IMPROVEMENT AFTER PERCUTANEOUS ASPIRATION

Abstract Amoebic liver abscesses are by far the most common extra-intestinal manifestation of invasive amoebiasis. The classical clinical picture consists of fever, right upper quadrant pain and hepatomegaly. Ultrasound and serology make an early diagnosis possible. Amoebic liver abscesses usually appear singly and are normally situated in the right lobe of the liver. This case report refers to a white Belgian woman, living in an endemic area for amoebiasis, presenting with 25 amoebic liver abscesses, who did not improve clinically despite appropriate anti-amoebic therapy, is described. Only percutaneous drainage of the larger abscesses led to clinical recovery. Amoebic abscess aspiration and evacuation under ultrasonographic guidance is of limited risk, but in experienced hands may enhance clinical recovery, particularly in patients with large abscesses not responding to conservative medical treatment. Aspiration of large abscesses (> 5 cm) is rarely necessary but should be considered if there is no clinical improvement after 3 days of nitroimidazole treatment with amoebicides.