Causes of fever in Tanzanian adults attending outpatient clinics: a prospective cohort study.

OBJECTIVES: Exploring fever aetiologies improves patient management. Most febrile adults are outpatients, but all previous studies were conducted in inpatients. This study describes the spectrum of diseases in adults attending outpatient clinics in urban Tanzania. METHODS: We recruited consecutive adults with temperature ≥38°C in a prospective cohort study. We collected medical history and performed a clinical examination. We performed 27 364 microbiological diagnostic tests (rapid tests, serologies, cultures and molecular analyses) for a large range of pathogens on blood and nasopharyngeal samples. We based our diagnosis on predefined clinical and microbiological criteria. RESULTS: Of 519 individuals, 469 (89%) had a clinically or microbiologically documented infection and 128 (25%) were human immunodeficiency virus (HIV) -infected. We identified 643 diagnoses: 264 (41%) acute respiratory infections (36 (5.6%) pneumonia, 39 (6.1%) tuberculosis), 71 (11%) infections with another focus (31 (4.8%) gastrointestinal, 26 (4.0%) urogenital, 8 (1.2%) central nervous system) and 252 (39%) infections without focus (134 (21%) dengue, 30 (4.7%) malaria, 28 (4.4%) typhoid). Of the 519 individuals, 318 (61%), 179 (34%), 30 (6%) and 15 (3%), respectively, had a viral, bacterial, parasitic and fungal acute infection. HIV-infected individuals had more bacterial infections than HIV-negative (80/122 (66%) versus 100/391 (26%); p < 0.001). Patients with advanced HIV disease had a higher proportion of bacterial infections (55/76 (72%) if CD4 ≤200 cells/mm3 and 25/52 (48%) if CD4 >200 cells/mm3, p 0.02). CONCLUSIONS: Viral diseases caused most febrile episodes in adults attending outpatient clinics except in HIV-infected patients. HIV status and a low CD4 level strongly determined the need for antibiotics. Systematic HIV screening is essential to appropriately manage febrile patients.

A prospective multicentre study of healthcare provider preference in rapid HIV testing kits: Determine versus INSTI.

Rapid HIV testing may circumvent the practical barriers to HIV testing in several settings. User preference of the testing kits available has been relatively underexplored. We examined healthcare provider (HCP) ratings of two validated rapid testing kits in clinical practice. From 1 July to 1 December 2012 we prospectively recruited HCPs (clinic nurses) from three outpatient clinics linked to Lausanne University Hospital, Lausanne, Switzerland. The HCPs had experience in taking blood samples but varying experience in rapid HIV testing. Participating HCPs performed rapid HIV testing using Determine™ Combo (DETE) or INSTI™ (INSTI), according to a predefined randomization sequence, and rated practical aspects of each test using a Likert scale. Seventeen HCPs of 23 approached (74%) were eligible and agreed to participate, performing a total of 336 HIV tests. Globally, the testing procedure was rated as easy or very easy by 97% (DETE) to 99% (INSTI) of tests performed. Among experienced HCPs, DETE was rated easier than INSTI for kit storage (p < 0.001) and blood collection ( P = 0.012) while INSTI was rated easier than DETE for blood application ( P = 0.001) and test interpretation ( P = 0.005). Among less experienced HCPs, both tests performed equally with the exception of test interpretation ( P < 0.001) and overall ease of use ( P = 0.05) in favour of INSTI. Of all HCPs, 94% stated they would recommend INSTI over DETE based on the time to result, ease of test interpretation and overall ease of use. Rapid HIV testing was considered easy to perform, even by inexperienced nursing staff. Whilst both tests were considered easy to use, the HCPs in this study preferred INSTI to DETE overall, due to rapid time to result, ease of test interpretation and general ease of use.

Rapid diagnostic tests for non-malarial febrile illness in the tropics.

The recent roll-out of rapid diagnostic tests (RDTs) for malaria has highlighted the decreasing proportion of malaria-attributable illness in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of severe febrile illnesses in low resource settings. This review summarizes the current state of RDT development for several key infections, including dengue fever, enteric fever, leptospirosis, brucellosis, visceral leishmaniasis and human African trypanosomiasis, and highlights many remaining gaps. Most RDTs for non-malarial tropical infections currently rely on the detection of host antibodies against a single infectious agent. The sensitivity and specificity of host-antibody detection tests are both inherently limited. Moreover, prolonged antibody responses to many infections preclude the use of most serological RDTs for monitoring response to treatment and/or for diagnosing relapse. Considering these limitations, there is a pressing need for sensitive pathogen-detection-based RDTs, as have been successfully developed for malaria and dengue. Ultimately, integration of RDTs into a validated syndromic approach to tropical fevers is urgently needed. Related research priorities are to define the evolving epidemiology of fever in the tropics, and to determine how combinations of RDTs could be best used to improve the management of severe and treatable infections requiring specific therapy.

[Viral fevers from elsewhere]. / Fièvres virales d'ailleurs.

Some viruses are transmitted only in specific parts of the world and do not exist in Switzerland. However, the increase in intercontinental travels, the tendency of travelers to have activities in remote rural areas, the transportation (sometimes forbidden) of exotic animals, the climatic warming and the adaptation of viruses to new vectors produce an extension of viral diseases towards Northern countries. To improve the identification of these infections in travelers, but also in European autochthonous populations, it is necessary to know the clinical characteristics and the websites announcing the epidemics. Neurological or hemorrhagic signs should incite the clinician to suspect a viral hemorrhagic fever, diagnosis to be considered if the destination and chronology are compatible, strict isolation measures being necessary.

[Rapid diagnostic tests (RDT): the cure-all for the practitioner?]. / Tests diagnostiques rapides (TDR): la panacée pour le praticien?

Many rapid diagnostic tests (RDT) for the diagnosis of infectious diseases have been developed over the last 20 years. These allow (1) administering a treatment immediately in case of a potentially fatal disease, (2) prescribing a specific rather than presumptive treatment, (3) quickly introducing measures aimed at interrupting the transmission of the disease, (4) avoiding useless antibiotic treatments and (5) implementing a sequential diagnostic strategy to avoid extensive investigations. Using the example of malaria, a new strategy that includes a RDT as first-line emergency diagnostic tool and, when negative, delayed microscopy at the laboratory opening time is implemented in Lausanne since 1999. This strategy has been shown to be safe. Each TDR has its own characteristics that imperatively need to be known by the practitioner if he/she wants to use it in a rational way.

[Malaria: an endangered species?]. / Malaria: une espèce en voie de disparition?

The implementation at scale of preventive measures and the use of effective treatments in populations living in endemic areas has led to a drastic reduction of the burden of malaria in all continents. The considerable investment of international agencies to support local governments in the fight against malaria allows hoping to achieve the millennium goals for malaria and child mortality in several countries. Malaria elimination, and even eradication becomes a realistic objective, especially so because a vaccine may be soon available to complement the armamentarium. For travelers, the tendency will be to reduce the number of countries where chemoprophylaxis or stand-by treatment is recommended and to insist on the rigorous use of measures to prevent mosquito bites such as repellents and insecticide-impregnated bednets.

www.fevertravel.ch: an online study prototype to evaluate the safety and feasibility of computerized guidelines for fever in returning travellers and migrants.

Following the paper publication of practice guidelines for the management of febrile patients returning from the tropics, we constructed a consultation website that comprises a decision chart and specific diagnostic features providing medical diagnostic assistance to primary care physicians. We then integrated a research component to evaluate the implementation of these computerized guidelines. This study website has the same interface as the consultation website. In addition, one is able to record: (i) the pathway followed by the physician through the decision chart, (ii) the diagnostic tests performed, (iii) the initial and final diagnoses as well as outcome and (iv) reasons for non-adherence when the physician diverges from the proposed attitude. We believe that Internet technology is a powerful medium to reach physicians of different horizons in their own environment, and could prove to be an effective research tool to disseminate practice guidelines and evaluate their appropriateness. Here we describe the design, content, architecture and system implementation of this interactive study prototype aimed at integrating operational research in primary care practice.

[Travelers' diarrhea: resistance to antibiotics]. / Diarrhée des voyageurs: résistance aux antibiotiques.

There is a discrepancy between the recommendations developed by international organisations and infectious disease societies about the prescription of antibiotics for non severe diseases and those established by travel medicine experts for travelers' diarrhea. For the first ones, the prescription of antibiotics should be drastically reduced; for the second, antibiotics should be used by the vast majority of travelers with diarrhea. We believe that the latter recommendation goes against the general interest since 1) travelers' diarrhea is usually benign, 2) there is no recent study on the effectiveness of chemoprophylaxis or treatment in different countries with different level of antibiotic resistance of usual enteropathogens, 3) there is no data on travelers' perception of their illness and on their attitudes in case of diarrhea.

[HIV and travel]. / VIH et voyage.

Since the introduction of antiretroviral therapy (ART), persons living with HIV (PLHIV) are traveling more frequently and international travel has become much safer. Specific concerns include the safety of ART during travel, drug adherence and interactions. The simultaneous administration of ART and antimalarial drugs is a challenge, considering the lack of reliable data. Several travel-related infectious diseases are more frequent and/or more severe in PLHIV. Even with a CD4 count > 400/microl, some PLHIV experience lower immune responses to several vaccines. With avanced immunosuppression, complications following the administration of live vaccines can occur, and most of the responses to vaccine are clearly reduced. The consequences of reduced vaccine immunogenicity on their clinical effectiveness (protection against infection) are unclear.

[Diagnosis of malaria in general practice: dealing with uncertainty]. / Le diagnostic de malaria au cabinet: comment gérer t'incertitude ?

Malaria is the disease to exclude when dealing with a patient coming back from an endemic area with fever. We need reliable diagnostic tools with negative likelihood ratio (LR-) close to zero (-> high negative predictive value). Ideally, a microscopical examination (ME) (thick and thin film) should be done, with or without a rapid diagnostic test (RDT). When the ME is not immediately available, an RDT can be done in the practice office and the ME delayed for 6-12 hours, provided there is no danger sign or thrombopenia. Indeed, the LR- of RDT being of 0.08 (estimated in a meta-analysis of RDT in non-immune travelers), the probability of falciparum malaria is 1% after a negative RDT. When the RDT is positive, the patient should always be treated with an anti-malarial, even if the ME is negative.

[Infectious diarrhea]. / Diarrhées infectieuses.

Traveler's diarrhea is generally a benign condition which resolves spontaneously in 48 h. Information on dietary hygiene, severity of symptoms and dehydration, as well as their management, is essential. Chemoprophylaxis and antibiotic treatment are not recommended, except in very specific situations. The incidence of chronic diarrhea in HIV-positive patients has dramatically decreased since the introduction of HAART. In the absence of any correlation with the initiation of HAART, a stepwise diagnostic workup is indicated (bacteriological cultures and microscopic examination of fecal samples followed by ileocolonoscopy and gastroduodenoscopy). Specific treatment of any pathogens identified, and HAART in the case of microsporidiasis or cryptosporidiosis, constitute the mainstay of therapeutic management of chronic diarrhea in these patients.