When is rational to order a diagnostic test, or prescribe treatment: the threshold model as an explanation of practice variation.

BACKGROUND: The threshold model represents an important advance in the field of medical decision-making. It is a linchpin between evidence (which exists on the continuum of credibility) and decision-making (which is a categorical exercise - we decide to act or not act). The threshold concept is closely related to the question of rational decision-making. When should the physician act, that is order a diagnostic test, or prescribe treatment? The threshold model embodies the decision theoretic rationality that says the most rational decision is to prescribe treatment when the expected treatment benefit outweighs its expected harms. However, the well-documented large variation in the way physicians order diagnostic tests or decide to administer treatments is consistent with a notion that physicians' individual action thresholds vary. METHODS: We present a narrative review summarizing the existing literature on physicians' use of a threshold strategy for decision-making. RESULTS: We found that the observed variation in decision action thresholds is partially due to the way people integrate benefits and harms. That is, explanation of variation in clinical practice can be reduced to a consideration of thresholds. Limited evidence suggests that non-expected utility threshold (non-EUT) models, such as regret-based and dual-processing models, may explain current medical practice better. However, inclusion of costs and recognition of risk attitudes towards uncertain treatment effects and comorbidities may improve the explanatory and predictive value of the EUT-based threshold models. CONCLUSIONS: The decision when to act is closely related to the question of rational choice. We conclude that the medical community has not yet fully defined criteria for rational clinical decision-making. The traditional notion of rationality rooted in EUT may need to be supplemented by reflective rationality, which strives to integrate all aspects of medical practice - medical, humanistic and socio-economic - within a coherent reasoning system.

Intuitive weights of harm for therapeutic decision making in smear-negative pulmonary Tuberculosis: an interview study of physicians in India, Pakistan and Bangladesh.

BACKGROUND: To estimate the amount of regret and weights of harm by omission and commission during therapeutic decisions for smear-negative pulmonary Tuberculosis. METHODS: An interviewer-administered survey was done among young physicians in India, Pakistan and Bangladesh with a previously used questionnaire. The physicians were asked to estimate probabilities of morbidity and mortality related with disease and treatment and intuitive weights of omission and commission for treatment of suspected pulmonary Tuberculosis. A comparison with weights based on literature data was made. RESULTS: A total of 242 physicians completed the interview. Their mean age was 28 years, 158 (65.3%) were males. Median probability (%) of mortality and morbidity of disease was estimated at 65% (inter quartile range [IQR] 50-75) and 20% (IQR 8-30) respectively. Median probability of morbidity and mortality in case of occurrence of side effects was 15% (IQR 10-30) and 8% (IQR 5-20) respectively. Probability of absolute treatment mortality was 0.7% which was nearly eight times higher than 0.09% reported in the literature data. The omission vs. commission harm ratios based on intuitive weights, weights calculated with literature data, weights calculated with intuitive estimates of determinants adjusted without and with regret were 3.0 (1.4-5.0), 16 (11-26), 33 (11-98) and 48 (11-132) respectively. Thresholds based on pure regret and hybrid model (clinicians' intuitive estimates and regret) were 25 (16.7-41.7), and 2(0.75-7.5) respectively but utility-based thresholds for clinicians' estimates and literature data were 2.9 (1-8.3) and 5.9 (3.7-7.7) respectively. CONCLUSION: Intuitive weight of harm related to false-negatives was estimated higher than that to false-positives. The mortality related to treatment was eightfold overestimated. Adjusting expected utility thresholds for subjective regret had little effect.

Severe strongyloidiasis: a systematic review of case reports.

BACKGROUND: Strongyloidiasis is commonly a clinically unapparent, chronic infection, but immuno suppressed subjects can develop fatal disease. We carried out a review of literature on hyperinfection syndrome (HS) and disseminated strongyloidiasis (DS), in order to describe the most challenging aspects of severe strongyloidiasis. METHODS: We conducted a structured search using PubMed to collect case reports and short case series on HS/DS published from 1991 to 2011. We restricted search to papers in English, Spanish, Italian and French. Case reports were classified as HS/DS according to given definitions. RESULTS: Records screened were 821, and 311 were excluded through titles and abstract evaluation. Of 510 full-text articles assessed for eligibility, 213 were included in qualitative analysis. As some of them were short case series, eventually the number of cases analyzed was 244.Steroids represented the main trigger predisposing to HS and DS (67% cases): they were mostly administered to treat underlying conditions (e.g. lymphomas, rheumatic diseases). However, sometimes steroids were empirically prescribed to treat signs and symptoms caused by unsuspected/unrecognized strongyloidiasis. Diagnosis was obtained by microscopy examination in 100% cases, while serology was done in a few cases (6.5%). Only in 3/29 cases of solid organ/bone marrow transplantation there is mention of pre-transplant serological screening. Therapeutic regimens were different in terms of drugs selection and combination, administration route and duration. Similar fatality rate was observed between patients with DS (68.5%) and HS (60%). CONCLUSIONS: Proper screening (which must include serology) is mandatory in high - risk patients, for instance candidates to immunosuppressive medications, currently or previously living in endemic countries. In some cases, presumptive treatment might be justified. Ivermectin is the gold standard for treatment, although the optimal dosage is not clearly defined in case of HS/DS.

Is increasing complexity of algorithms the price for higher accuracy? virtual comparison of three algorithms for tertiary level management of chronic cough in people living with HIV in a low-income country.

BACKGROUND: The algorithmic approach to guidelines has been introduced and promoted on a large scale since the 1970s. This study aims at comparing the performance of three algorithms for the management of chronic cough in patients with HIV infection, and at reassessing the current position of algorithmic guidelines in clinical decision making through an analysis of accuracy, harm and complexity. METHODS: Data were collected at the University Hospital of Kigali (CHUK) in a total of 201 HIV-positive hospitalised patients with chronic cough. We simulated management of each patient following the three algorithms. The first was locally tailored by clinicians from CHUK, the second and third were drawn from publications by Médecins sans Frontières (MSF) and the World Health Organisation (WHO). Semantic analysis techniques known as Clinical Algorithm Nosology were used to compare them in terms of complexity and similarity. For each of them, we assessed the sensitivity, delay to diagnosis and hypothetical harm of false positives and false negatives. RESULTS: The principal diagnoses were tuberculosis (21%) and pneumocystosis (19%). Sensitivity, representing the proportion of correct diagnoses made by each algorithm, was 95.7%, 88% and 70% for CHUK, MSF and WHO, respectively. Mean time to appropriate management was 1.86 days for CHUK and 3.46 for the MSF algorithm. The CHUK algorithm was the most complex, followed by MSF and WHO. Total harm was by far the highest for the WHO algorithm, followed by MSF and CHUK. CONCLUSIONS: This study confirms our hypothesis that sensitivity and patient safety (i.e. less expected harm) are proportional to the complexity of algorithms, though increased complexity may make them difficult to use in practice.

Strict adherence to malaria rapid test results might lead to a neglect of other dangerous diseases: a cost benefit analysis from Burkina Faso.

BACKGROUND: Malaria rapid diagnostic tests (RDTs) have generally been found reliable and cost-effective. In Burkina Faso, the adherence of prescribers to the negative test result was found to be poor. Moreover, the test accuracy for malaria-attributable fever (MAF) is not the same as for malaria infection. This paper aims at determining the costs and benefits of two competing strategies for the management of MAF: presumptive treatment for all or use of RDTs. METHODS: A cost benefit analysis was carried out using a decision tree, based on data previously obtained, including a randomized controlled trial (RCT) recruiting 852 febrile patients during the dry season and 1,317 in the rainy season. Cost and benefit were calculated using both the real adherence found by the RCT and assuming an ideal adherence of 90% with the negative result. The main parameters were submitted to sensitivity analysis. RESULTS AND DISCUSSION: At real adherence, the test-based strategy was dominated. Assuming ideal adherence, at the value of 525 € for a death averted, the total cost of managing 1,000 febrile children was 1,747 vs. 1,862 € in the dry season and 1,372 vs. 2,138 in the rainy season for the presumptive vs. the test-based strategy. For adults it was 2,728 vs. 1,983 and 2,604 vs. 2,225, respectively. At the subsidized policy adopted locally, assuming ideal adherence, the RDT would be the winning strategy for adults in both seasons and for children in the dry season.At sensitivity analysis, the factors most influencing the choice of the better strategy were the value assigned to a death averted and the proportion of potentially severe NMFI treated with antibiotics in patients with false positive RDT results. The test-based strategy appears advantageous for adults if a satisfactory adherence could be achieved. For children the presumptive strategy remains the best choice for a wide range of scenarios. CONCLUSIONS: For RDTs to be preferred, a positive result should not influence the decision to treat a potentially severe NMFI with antibiotics. In the rainy season the presumptive strategy always remains the better choice for children.

Buffer substitution in malaria rapid diagnostic tests causes false-positive results.

BACKGROUND: Malaria rapid diagnostic tests (RDTs) are kits that generally include 20 to 25 test strips or cassettes, but only a single buffer vial. In field settings, laboratory staff occasionally uses saline, distilled water (liquids for parenteral drugs dilution) or tap water as substitutes for the RDT kit's buffer to compensate for the loss of a diluent bottle. The present study assessed the effect of buffer substitution on the RDT results. METHODS: Twenty-seven RDT brands were run with EDTA-blood samples of five malaria-free subjects, who were negative for rheumatoid factor and antinuclear antibodies. Saline, distilled water and tap water were used as substitute liquids. RDTs were also run with distilled water, without adding blood. Results were compared to those obtained with the RDT kit's buffer and Plasmodium positive samples. RESULTS: Only eight cassettes (in four RDT brands) showed no control line and were considered invalid. Visible test lines occurred for at least one malaria-free sample and one of the substitutes in 20/27 (74%) RDT brands (saline: n = 16; distilled water: n = 17; and tap water: n = 20), and in 15 RDTs which were run with distilled water only. They occurred for all Plasmodium antigens and RDT formats (two-, three- and four-band RDTs). Clearance of the background of the strip was excellent except for saline. The aspects (colour, intensity and crispness) of the control and the false-positive test lines were similar to those obtained with the RDT kits' buffer and Plasmodium positive samples. CONCLUSION: Replacement of the RDT kit's dedicated buffer by saline, distilled water and tap water can cause false-positive test results.

Malaria rapid diagnostic tests: Plasmodium falciparum infections with high parasite densities may generate false positive Plasmodium vivax pLDH lines.

BACKGROUND: Most malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum and an antigen common to the four species. Plasmodium vivax-specific RDTs target P. vivax-specific parasite lactate dehydrogenase (Pv-pLDH). Previous observations of false positive Pv-pLDH test lines in P. falciparum samples incited to the present study, which assessed P. vivax-specific RDTs for the occurrence of false positive Pv-pLDH lines in P. falciparum samples. METHODS: Nine P. vivax-specific RDTs were tested with 85 P. falciparum samples of high (>or=2%) parasite density. Mixed P. falciparum/P. vivax infections were ruled out by real-time PCR. The RDTs included two-band (detecting Pv-pLDH), three-band (detecting P. falciparum-antigen and Pv-pLDH) and four-band RDTs (detecting P. falciparum, Pv-pLDH and pan-pLDH). RESULTS: False positive Pv-pLDH lines were observed in 6/9 RDTs (including two- three- and four-band RDTs). They occurred in the individual RDT brands at frequencies ranging from 8.2% to 29.1%. For 19/85 samples, at least two RDT brands generated a false positive Pv-pLDH line. Sixteen of 85 (18.8%) false positive lines were of medium or strong line intensity. There was no significant relation between false positive results and parasite density or geographic origin of the samples. CONCLUSION: False positive Pv-pLDH lines in P. falciparum samples with high parasite density occurred in 6/9 P. vivax-specific RDTs. This is of concern as P. falciparum and P. vivax are co-circulating in many regions. The diagnosis of life-threatening P. falciparum malaria may be missed (two-band Pv-pLDH RDT), or the patient may be treated incorrectly with primaquine (three- or four-band RDTs).

Accuracy of a rapid diagnostic test on the diagnosis of malaria infection and of malaria-attributable fever during low and high transmission season in Burkina Faso.

BACKGROUND: Malaria management policies currently recommend that the treatment should only be administered after laboratory confirmation. Where microscopy is not available, rapid diagnostic tests (RDTs) are the usual alternative. Conclusive evidence is still lacking on the safety of a test-based strategy for children. Moreover, no formal attempt has been made to estimate RDTs accuracy on malaria-attributable fever. This study aims at estimating the accuracy of a RDT for the diagnosis of both malaria infection and malaria - attributable fever, in a region of Burkina Faso with a typically seasonal malaria transmission pattern. METHODS: Cross-sectional study. SUBJECTS: all patients aged > 6 months consulting during the study periods. Gold standard for the diagnosis of malaria infection was microscopy. Gold standard for malaria-attributable fever was the number of fevers attributable to malaria, estimated by comparing parasite densities of febrile versus non-febrile subjects. EXCLUSION CRITERIA: severe clinical condition needing urgent care. RESULTS: In the dry season, 186/852 patients with fever (22%) and 213/1,382 patients without fever (15%) had a Plasmodium falciparum infection. In the rainy season, this proportion was 841/1,317 (64%) and 623/1,669 (37%), respectively. The attributable fraction of fever to malaria was 11% and 69%, respectively. The RDT was positive in 113/400 (28.3%) fever cases in the dry season, and in 443/650 (68.2%) in the rainy season. In the dry season, the RDT sensitivity and specificity for malaria infection were 86% and 90% respectively. In the rainy season they were 94% and 78% respectively. In the dry season, the RDT sensitivity and specificity for malaria-attributable fever were 94% and 75%, the positive predictive value (PPV) was 9% and the negative predictive value (NPV) was 99.8%. In the rainy season the test sensitivity for malaria-attributable fever was 97% and specificity was 55%. The PPV ranged from 38% for adults to 82% for infants, while the NPV ranged from 84% for infants to over 99% for adults. CONCLUSIONS: In the dry season the RDT has a low positive predictive value, but a very high negative predictive value for malaria-attributable fever. In the rainy season the negative test safely excludes malaria in adults but not in children.

Rapid malaria diagnostic tests vs. clinical management of malaria in rural Burkina Faso: safety and effect on clinical decisions. A randomized trial.

OBJECTIVES: To assess if the clinical outcome of patients treated after performing a Rapid Diagnostic Test for malaria (RDT) is at least equivalent to that of controls (treated presumptively without test) and to determine the impact of the introduction of a malaria RDT on clinical decisions. METHODS: Randomized, multi-centre, open clinical trial in two arms in 2006 at the end of the dry and of the rainy season in 10 peripheral health centres in Burkina Faso: one arm with use of RDT before treatment decision, one arm managed clinically. Primary endpoint: persistence of fever at day 4. Secondary endpoints: frequency of malaria treatment and of antibiotic treatment. RESULTS: A total of 852 febrile patients were recruited in the dry season and 1317 febrile patients in the rainy season, and randomized either to be submitted to RDT (P_RTD) or to be managed presumptively (P_CLIN). In both seasons, no significant difference was found between the two randomized groups in the frequency of antimalarial treatment, nor of antibiotic prescription. In the dry season, 80.8% and 79.8% of patients with a negative RDT were nevertheless diagnosed and treated for malaria, and so were 85.0% and 82.6% negative patients in the rainy season. In the rainy season only, both diagnosis and treatment of other conditions were significantly less frequent in RDT positive vs. negative patients (48.3% vs. 61.4% and 46.2% vs. 59.9%, P = 0.00 and 0.00, respectively). CONCLUSION: Our study was inconclusive on RDT safety (clinical outcome in the two randomized groups), because of an exceedingly and unexpectedly low compliance with the negative test result. Further research is needed on best strategies to promote adherence and on the safety of a test based strategy compared with the current, presumptive treatment strategy.

Assessment of the prozone effect in malaria rapid diagnostic tests.

BACKGROUND: The prozone effect (or high doses-hook phenomenon) consists of false-negative or false-low results in immunological tests, due to an excess of either antigens or antibodies. Although frequently cited as a cause of false-negative results in malaria rapid diagnostic tests (RDTs), especially at high parasite densities of Plasmodium falciparum, it has been poorly documented. In this study, a panel of malaria RDTs was challenged with clinical samples with P. falciparum hyperparasitaemia (> 5% infected red blood cells). METHODS: Twenty-two RDT brands were tested with seven samples, both undiluted and upon 10 x, 50 x and 100 x dilutions in NaCl 0.9%. The P. falciparum targets included histidine-rich protein-2 (HRP-2, n = 17) and P. falciparum-specific parasite lactate dehydrogenase (Pf-pLDH, n = 5). Test lines intensities were recorded in the following categories: negative, faint, weak, medium or strong. The prozone effect was defined as an increase in test line intensity of at least one category after dilution, if observed upon duplicate testing and by two readers. RESULTS: Sixteen of the 17 HRP-2 based RDTs were affected by prozone: the prozone effect was observed in at least one RDT sample/brand combination for 16/17 HRP-2 based RDTs in 6/7 samples, but not for any of the Pf-pLDH tests. The HRP-2 line intensities of the undiluted sample/brand combinations with prozone effect (n = 51) included a single negative (1.9%) and 29 faint and weak readings (56.9%). The other target lens (P. vivax-pLDH, pan-specific pLDH and aldolase) did not show a prozone effect. CONCLUSION: This study confirms the prozone effect as a cause of false-negative HRP-2 RDTs in samples with hyperparasitaemia.

Weighing harm in therapeutic decisions of smear-negative pulmonary tuberculosis.

PURPOSE: To relate the intuitive weight of harm by commission and harm by omission in therapeutic decisions for pulmonary tuberculosis, and to compare it with a weight based on probabilities. METHODS: Clinicians were asked for an estimation of probabilities related with the outcome of treated and nontreated pulmonary tuberculosis and for the toll of wrong decisions. Three ratios of the weight of forgoing a treatment in false-negative patients against the weight of treating false-positives were calculated. The first was based on intuitive estimations, whereas the second and third were based on calculated, either through intuitive estimations of probabilities or through literature data. The association between experience and the difference between the intuitive and the calculated ratios was assessed. RESULTS: Eighty-one participants from Ecuador, Laos, Nepal, and Rwanda responded. The ratio of intuitive weights was 2.0 (interquartile range [IQR], 1.0-4.0) and the ratio of calculated weights based on intuitive probabilities was 64 (IQR, 25.0-169.6; P < 0.001). The ratio of calculated weight based on literature probabilities was 30 (IQR, 17.9-59.2). No association (R(2) = 0.03) was found between experience and accuracy in estimating the weight of errors. CONCLUSION: The weight of a false negative is more important than the weight of a false positive for therapeutic decisions in pulmonary tuberculosis. The ratio of the intuitively estimated weights was much lower than the calculation based on intuitively estimated influencing factors. Clinicians were accurate in estimating probabilities but failed to incorporate them into therapeutic decisions.

The threshold model revisited.

BACKGROUND: The threshold model represents one of the most significant advances in the field of medical decision-making, yet it often does not apply to the most common class of clinical problems, which include health outcomes as a part of definition of disease. In addition, the original threshold model did not take a decision-maker's values and preferences explicitly into account. METHODS: We reformulated the threshold model by (1) applying it to those clinical scenarios, which define disease according to outcomes that treatment is designed to affect, (2) taking into account a decision-maker's values. RESULTS: We showed that when outcomes (eg, morbidity) are integral part of definition of disease, the classic threshold model does not apply (as this leads to double counting of outcomes in the probabilities and utilities branches of the model). To avoid double counting, the model can be appropriately analysed by assuming diagnosis is certain (P = 1). This results in deriving a different threshold-the threshold for outcome of disease (Mt ) instead of threshold for probability of disease (Pt ) above which benefits of treatment outweigh its harms. We found that Mt  ≤ Pt , which may explain differences between normative models and actual behaviour in practice. When a decision-maker values outcomes related to benefit and harms differently, the new threshold model generates decision thresholds that could be descriptively more accurate. CONCLUSIONS: Calculation of the threshold depends on careful disease versus utility definitions and a decision-maker's values and preferences.

Tuberculous meningitis: does lowering the treatment threshold result in many more treated patients?

OBJECTIVE: To determine how many more patients would be treated when lowering the treatment threshold for tuberculous meningitis. METHODS: From 1989 to 2004 findings of patients with symptoms lasting more than 1 week and inflammatory changes of cerebrospinal fluid (CSF) were collected. Several models of latent class analysis were tested. Cumulative numbers of cases were plotted against different cut-offs for post-test probability. RESULTS: In a cohort of 232 patients the prevalence of tuberculous meningitis (TBM) was estimated at 79.8% (95% CI. 67,0-88,1); probabilities above 80% were reached in 73% of patients. Lowering this threshold from 80% to 20% would add 14% more patients to be treated, for a total of 87%. A further lowering of the threshold to 5% would imply 5% more patients to be treated, bringing the cumulative number to 92%. The difference of lowering the threshold from 80% to 5% was 19%. CONCLUSION: In this setting, at least 75% of patients showing suggestive symptoms for more than a week and CSF changes very probably had TBM. The number of patients that should be treated does not increase linearly when lowering the threshold.

Evaluation of the GIDEON expert computer program for the diagnosis of imported febrile illnesses.

OBJECTIVE: The authors evaluate the performance of the expert system Global Infectious Diseases and Epidemiology Network (GIDEON) in diagnosing febrile illnesses occurring after a stay in the tropics. METHODS: One investigator (E.B.) entered into the program the collected characteristics of 161 febrile travelers randomly extracted from a database of 1842 cases prospectively included during a study on imported fever. Accuracy was considered acceptable if the correct diagnosis appeared in the top 5 GIDEON ranking list. Interuser agreement was assessed by J.V.d.E. and J.M., who also entered the data of the first 50 sample cases with an established diagnosis. RESULTS: The sample was epidemiologically and clinically representative of the whole cohort. An infectious etiology had been established in 129 cases; diagnosis was unknown in 31 cases and non-infectious in 1 case. GIDEON generated a median of 29 diagnoses per case, including 23 with a probability lower than 1%. Accuracy was acceptable in 64% of the 129 fevers with infectious etiology. It tended to decrease when more than 3 findings were entered per case. Eleven (8%) severe conditions were rejected by GIDEON because non-disease-related characteristics had been introduced. In other cases, the posttest probability was inadequately affected by the insufficient weight of absent relevant findings. Interuser agreement was good for acceptable accuracy and final ranking (kappa=0.83 and 0.72, respectively). CONCLUSION: The performance of GIDEON in diagnosing imported fever is relatively good and reproducible but is impaired by some conceptual weaknesses. Its use might be hazardous for inexperienced physicians.

Sexual risk behavior of travelers who consulted a pretravel clinic.

OBJECTIVE: The objective of this study was to determine to which degree travelers who received pretravel advice at a travel clinic have protected or unprotected sexual contact with a new partner and what factors influence this behavior. METHOD: An anonymous questionnaire was sent to travelers who came to a pretravel clinic between June 1 and August 31, 2005. Risk factors for casual travel sex and predictors of protected sex were studied in a multivariate model. RESULTS: A total of 1,907 travelers were included (response rate 55%) in the study. Only 4.7% of the respondents had sexual contact with a new partner, and 63.1% of these new partners were from the country of destination. Of those who had casual travel sex, 52.4% did not expect this (women 75%), 30.9% did not always use condoms, and 41% were not protected against hepatitis B. Independent risk factors for casual travel sex were traveling without steady partner (OR 14.4), expecting casual travel sex (OR 9.2), having casual sexual contacts in the home country (OR 2.4), non-tourist journeys (OR 2.2), being male (OR 2.1), the fact that the information on sexually transmitted infections (STI) had been read (OR 2.0), and traveling to South and Central America (OR 2.0). Taking condoms along (OR 5.4) and reading the information on STI (OR 3.3) were identified as independent predictors of protected sex. CONCLUSIONS: Travelers have substantial sexual risk behavior. Casual sex is usually not expected, and the most important predictor is traveling without a steady partner. We would advice every client of a travel clinic who will travel without a steady partner to read the STI information, to take condoms along, and to be vaccinated against hepatitis B.

Clinical and microscopic predictors of Entamoeba histolytica intestinal infection in travelers and migrants diagnosed with Entamoeba histolytica/dispar infection.

BACKGROUND: Amebiasis is a protozoal infection caused by Entamoeba histolytica, while the morphologically indistinguishable E. dispar is considered as non-pathogenic. Polymerase chain reaction (PCR) assays are necessary to differentiate both species. The most common clinical presentations of E. histolytica disease are amebic colitis and amebic liver abscess, but asymptomatic infection is also possible. We assessed the frequency and pattern of clinical symptoms and microscopic features in travelers/migrants associated with E. histolytica intestinal infection and compared them to those found in individuals with E. dispar infection. METHODS: We conducted a retrospective study at the travel clinic of the Institute of Tropical Medicine, Antwerp, Belgium on travelers/migrants found from 2006 to 2016 positive for Entamoeba histolytica/dispar through antigen detection and/or through microscopy confirmed by PCR. All files of individuals with a positive PCR for E. histolytica (= cases) and a random selection of an equal number of Entamoeba dispar carriers (= controls) were reviewed. We calculated the sensitivity, specificity and likelihood ratios (LRs) of clinical symptoms (blood in stool, mucus in stool, watery diarrhea, abdominal cramps, fever or any of these 5 symptoms) and of microscopic features (presence of trophozoites in direct and in sodium acetate-acetic acid-formalin (SAF)-fixed stool smears) to discriminate between E. histolytica and E. dispar infection. RESULTS: Of all stool samples positive for Entamoeba histolytica/dispar for which PCR was performed (n = 810), 30 (3.7%) were true E. histolytica infections, of which 39% were asymptomatic. Sensitivity, specificity and positive LRs were 30%, 100% and 300 (p 0.007) for presence of blood in stool; 22%, 100% and 222 (p 0.03) for mucus in stool; 44%, 90% and 4.7 (p 0.009) for cramps and 14%, 97% and 4.8 (p = 0.02) for trophozoites in direct smears. For watery diarrhea, fever and for trophozoites in SAF fixated smears results were non-significant. CONCLUSIONS: E. histolytica infection was demonstrated in a small proportion of travelers/migrants with evidence of Entamoeba histolytica/dispar infection. In this group, history of blood and mucus in stool and cramps had good to strong confirming power (LR+) for actual E. histolytica infection. Trophozoites were also predictive for true E. histolytica infection but in direct smears only.

Fever after a stay in the tropics: diagnostic predictors of the leading tropical conditions.

Differential diagnosis of fever in travelers returning from the tropics is extremely diverse. Apart from the travel destination, other diagnostic predictors of tropical infections are poorly documented in returning travelers. From April 2000 to December 2005, we prospectively enrolled all patients presenting at our referral centers with fever within 1 year after visiting a tropical or subtropical area. For clinical relevance, the diagnostic predictors of the leading tropical conditions were particularly investigated in the febrile episodes occurring during travel or within 1 month after return (defined as early-onset fever). In total, 2071 fever episodes were included, occurring in 1962 patients. Most patients were western travelers (60%) or expatriates (15%). Regions of exposure were mainly sub-Saharan Africa (68%) and southern Asia/Pacific (14%). Early-onset fever accounted for 1619 episodes (78%). Most tropical infections were related to specific travel destinations. Malaria (mainly Plasmodium falciparum) was strongly predicted by the following features: enlarged spleen, thrombocytopenia (platelet count <150 x 10(3)/microL), fever without localizing symptoms, and hyperbilirubinemia (total bilirubin level >or=1.3 mg/dL). When malaria had been ruled out, main predictors were skin rash and skin ulcer for rickettsial infection (mainly African tick bite fever); skin rash, thrombocytopenia, and leukopenia (leukocyte count <4 x 10(3)/microL) for dengue; eosinophil count >or=0.5 x 10(3)/microL for acute schistosomiasis; and enlarged spleen and elevated alanine aminotransferase level (>or=70 IU/L) for enteric fever. The initial clinical and laboratory assessment can help in selecting appropriate investigations and empiric treatments for patients with imported fever.

Why are clinicians reluctant to treat smear-negative tuberculosis? An inquiry about treatment thresholds in Rwanda.

PURPOSE: The diagnosis of tuberculosis remains controversial between clinicians and public health officers. Public health officials fear to treat too many patients; clinicians fear that truly diseased will be denied treatment. We wondered whether an analysis of the treatment threshold could help making the often intuitive decision to treat smear-negative cases more evidence based. METHODS: Eighteen clinicians and 10 public health specialists were asked for an intuitive estimate of their treatment threshold for tuberculosis and of key determinant factors for this threshold: the magnitude and subjective weight of mortality and morbidity due to both the disease and the treatment and risk and cost of the latter. With these factors, the authors calculated treatment thresholds and compared them to the intuitive thresholds of the interviewees. A prescriptive threshold was calculated based on literature data, omitting cost and subjective factors. RESULTS: The median overall intuitive treatment threshold was 52.5%, the calculated 11.9%, and the prescriptive 2.7%. For 2 factors, public health officers provided significantly lower values than clinicians: cost of treatment (median = 20 dollars v. 300 dollars; U = 2.5; P = 0.0002); cost of life (median = 500 dollars v. 5000 dollars; U = 17.5; P = 0.009). CONCLUSION: These results suggest that clinicians and public health officers estimate wrongly the threshold even when using their own subjective estimate of influencing factors. Omitting treatment cost and subjective weight of provoked harm can result in a very low threshold. Sound training in threshold principles and providing tools to correctly assess data might help in making better decisions in tuberculosis in developing countries.