J. Van den Ende

Time delays in diagnosis of pulmonary tuberculosis: a systematic review of literature

BackgroundDelay in diagnosis of pulmonary tuberculosis results in increasing severity, mortality and transmission. Various investigators have reported about delays in diagnosis of tuberculosis. We aimed at summarizing the data on these delays in diagnosis of tuberculosis.MethodsA systematic review of literature was carried out. Literature search was done in Medline and EMBASE from 1990 to 2008. We used the following search terms: delay, tuberculosis, diagnosis, and help-seeking/health-seeking behavior without language restrictions. In addition, indices of four major tuberculosis journals were hand-searched. Subject experts in tuberculosis and authors of primary studies were contacted. Reference lists, review articles and text book chapters were also searched. All the studies were assessed for methodological quality. Only studies carried out on smear/culture-positive tuberculosis patients and reporting about total, patient and health-care system delays were included.ResultsA total of 419 potential studies were identified by the search. Fifty two studies qualified for the review. The reported ranges of average (median or mean) total delay, patient delay, health system delay were 25–185 days, 4.9–162 days and 2–87 days respectively for both low and high income countries. Average patient delay was similar to health system delay (28.7 versus 25 days). Both patient delay and health system delay in low income countries (31.7 days and 28.5 days) were similar to those reported in high income countries (25.8 days and 21.5 days).ConclusionThe results of this review suggest that there is a need for revising case-finding strategies. The reported high treatment success rate of directly observed treatment may be supplemented by measures to shorten the delay in diagnosis. This may result in reduction of infectious cases and better tuberculosis control.

Evaluation of two tests based on the detection of histidine rich protein 2 for the diagnosis of imported Plasmodium falciparum malaria.

The ParaSight-F dipstick test (Becton Dickinson, USA) and the ICT Malaria Pf test (ICT, Australia) both detect histidine rich protein 2 (HRP-2), a water-soluble antigen expressed by Plasmodium falciparum trophozoites. The present study compared the diagnostic performance of both tests in persons returning to Belgium from countries endemic for malaria. During a period of 18 months both tests were performed on all patients returning from the tropics with a positive malaria blood film. Patients with fever without an obvious cause were used as controls. For the ParaSight-F test, considering P. falciparum trophozoites only, sensitivity was 95% and specificity 90%. Considering trophozoites of all species of Plasmodium, sensitivity was 71% and specificity 87%. Finally, considering patients with clinical malaria, the sensitivity of the test was 72% and specificity 87%. For the ICT Malaria Pf test, sensitivity was 95% and specificity 89% for P. falciparum trophozoites only, 71% and 86% for trophozoites of all species, and 72% and 87% for clinical malaria. Both tests gave highly comparable results. However, antigen detection assays cannot replace conventional microscopy in diagnosing imported malaria. Thick blood film examination is more sensitive and more specific, it allows estimation of parasitaemia and distinction between parasite growth stages, and it covers all species. Moreover, with treated patients the use of antigen tests might lead to problems in determining the efficacy of therapy.

An algorithm to optimize viral load testing in HIV-positive patients with suspected first-line antiretroviral therapy failure in Cambodia.

Objective:To develop an algorithm for optimal use of viral load testing in patients with suspected first-line antiretroviral treatment (ART) failure. Methods:Data from a cohort of patients on first-line ART in Cambodia were analyzed in a cross-sectional way to detect markers for treatment failure. Markers with an adjusted likelihood ratio <0.67 or >1.5 were retained to calculate a predictor score. The accuracy of a 2-step algorithm based on this score followed by targeted viral load testing was compared with World Health Organization criteria for suspected treatment failure. Results:One thousand eight hundred three viral load measurements of 764 patients were available for analysis. Prior ART exposure, CD4 count below baseline, 25% and 50% drop from peak CD4 count, hemoglobin drop of ≥1 g/dL, CD4 count <100 cells per microliter after 12 months of treatment, new onset of papular pruritic eruption, and visual analog scale <95% were included in the predictor score. A score ≥2 had the best combination of sensitivity and specificity and required confirmatory viral load testing for only 9% of patients. World Health Organization criteria had a similar sensitivity but a lower specificity and required viral load testing for 24.9% of patients. Conclusion:An algorithm combining a predictor score with targeted viral load testing in patients with an intermediate probability of failure optimizes the use of scarce resources.

Exchange blood transfusion in severe falciparum malaria: retrospective evaluation of 61 patients treated with, compared to 63 patients treated without, exchange transfusion.

The rationale for exchange blood transfusion (ET) in severe falciparum malaria is threefold: reduction of parasitaemia, reduction of presumptive ‘toxic’ factors, and improvement of the rheological quality of the blood. We evaluated the records of 61 patients treated with ET to describe the present status of malaria treatment in Germany, Austria and Switzerland and to assess the efficacy of ET. Clinical data of 61 patients treated with ET were compared to data of 63 patients treated in 2 hospitals where ETs were generally not performed. We found that exchange transfusion is applied according to the clinician’s subjective impression rather than strict guidelines. Logistic regression analysis adjusting for the differences in clinical parameters between patients treated with or without ET did not identify treatment as a prognostic indicator (odds ratio for relative risk of death with ET: 1.3; 95% CI: 0.4–4.9). Exchange transfusion did not significantly improve the unfavourable prognosis in cases of severe falciparum malaria. However, failure to reach statistical significance may be due to the retrospective design of the study and therefore non‐systematic approach.

Intrathecal vs intramuscular administration of human antitetanus immunoglobulin or equine tetanus antitoxin in the treatment of tetanus: a meta-analysis

Background  Mortality caused by tetanus is still a serious health problem in developing countries. Apart from immunization, early treatment with equine antitetanus serum (ATS) or human tetanus immunoglobulin (TIG) is the real treatment that can avoid death. On pathophysiological grounds intrathecal administration would be preferred because of high concentrations of the antiserum in cerebrospinal fluid and thus around the nerve roots. Many studies concluded on its effectiveness whereas others did not find any superiority of this method. However, most of those studies were not random and/or had no sufficient weight.

Hyperreactive malaria in expatriates returning from sub-Saharan Africa

Summary The extreme presentation of hyperreactive malaria is hyperreactive malarial splenomegaly syndrome (HMS). Some patients present with a less pronounced syndrome. To investigate whether the degree of splenomegaly correlates with the degree of immune stimulation, whether prophylaxis or recent treatment play a role, and whether short therapy alone is effective, we examined retrospectively the medical records of expatriates with exposure to P. falciparum who attended our outpatient department from 1986 to 1997, particularly subacute symptoms or signs, strongly elevated malarial antibodies and elevated total serum IgM. We analysed duration of stay, prophlyaxis intake, spleen size, serum IgM levels and response to antimalarial treatment. Serum IgM levels were significantly higher in patients with larger splenomegaly. The use of chloroquine alone as treatment for presumptive or proved malaria attacks was correlated with larger spleen size. Short adequate antimalarial therapy resulted in marked improvement or complete recovery. In nine patients the hyperreactive response reappeared after re‐exposure, in four of them twice. We conclude that patients with subacute symptoms but without gross splenomegaly may have very high levels of IgM and malarial antibodies, and relapse on re‐exposure, suggesting the existence of a variant of the hyperreactive malarial splenomegaly syndrome without gross splenomegaly.

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.

A cluster of airport malaria in Belgium in 1995

In Europe 64 cases of airport malaria have been registered between 1969 and 1996, most of them in France, Switzerland and Belgium. In the summer of 1995 six cases of airport malaria occurred at the International airport of Brussels, Belgium. Of the six patients three were airport employees, three were occasional visitors. One patient died, the diagnosis was made by PCR amplification and DNA sequencing after exhumation. Two different species of Plasmodium were detected, and infections occurred on at least two different floors of the airport. An inquiry revealed that the cabin of airplanes is correctly sprayed, according to WHO recommendations, but that the inside of the hand luggage, the cargo hold, the animal compartment, the wheel bays and container flights remain possible shelters for infected mosquitoes. In a case of fever of unknown origin, airport malaria should be considered in the differential diagnosis, especially during hot summers, and when thrombocytopenia is present. Additional antimosquito measures should be generalised, encompassing highly exposed personnel, container content and handling buildings, animal cages, wheel bays, and the boundary between the sorting and the reception of luggage.

Kabisa: an interactive computer-assisted training program for tropical diseases

In Europe, tropical pathology is usually taught in special short courses, intended for those planning to practise in developing countries. The theoretical knowledge to be assimilated during this short period is considerable, and turning such newly acquired knowledge into competence is difficult.