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The exposure of a research team to chigger mites in southern Chile allowed the first identification of a trombiculid species as vector and reservoir of scrub typhus outside the tsutsugamushi triangle, providing unique insights into the ecology and transmission of this recently discovered rickettsial infection in South America.

Highlights • Due to the rapidly emerging SARS-CoV-2 pandemic and its tremendous public health challenges worldwide, there is a critical demand for rapid and easy to perform diagnostic assays. • The evaluated rapid antigen detection test had a high diagnostic sensitivity and specificity in respiratory samples obtained from patients who mainly presented during the first week of Covid-19. • Rapid antigen detection has the potential to become an important tool for the early diagnosis of SARS-CoV-2, particularly in situations with limited access to molecular methods., Objectives In the context of the Covid-19 pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. We evaluated a novel rapid antigen detection test (RDT) for SARS-CoV-2 in respiratory samples. Methods The fluorescence immunochromatographic SARS-CoV-2 antigen test (Bioeasy Biotechnology Co., Shenzhen, China) was evaluated using universal transport medium with nasopharyngeal (NP) and oropharyngeal (OP) swabs from suspected Covid-19 cases. Diagnostic accuracy was determined in comparison to SARS-CoV-2 real time (RT)-PCR. Results A total of 127 samples were included; 82 were RT-PCR positive. Median patients’ age was 38 years, 53.5% were male, and 93.7% were from the first week after symptom onset. Overall sensitivity and specificity were 93.9% (CI95% 86.5–97.4) and 100% (CI95% 92.1–100), respectively, with a diagnostic accuracy of 96.1% and Kappa coefficient of 0.9. Sensitivity was significantly higher in samples with high viral loads. Conclusions The evaluated RDT showed a high sensitivity and specificity in samples mainly obtained during the first week of symptoms and with high viral loads, despite the use of a non-validated sample material. The assay has the potential to become an important tool for early diagnosis of SARS-CoV-2, particularly in situations with limited access to molecular methods.

Background: Pet-related tick-borne infections constitute an emerging problem in human and veterinary medicine worldwide. In Chile, two pathogens of the Anaplasmataceae family, Anaplasma platys and Ehrlichia canis, have been identified in recent years in dogs and vectors. This epidemiological survey aimed to determine the human and canine seroprevalence of Anaplasma spp. in urban and rural areas of different regions in Chile and to analyze the factors associated with seropositivity. Methods: We performed a cross-sectional household-based study in four regions, where healthy adults and their household dogs were included. Households were chosen by double stratified random sampling in urban areas and by convenience sampling in rural areas. Anaplasma seroreactivity was determined by a commercial microimmunofluorescence assay using Anaplasma phagocytophilum antigens. A questionnaire survey was applied to assess risk factors for Anaplasma seropositivity. Results: A total of 1105 persons and 905 dogs were included. The overall seroprevalence in humans was 9.4%, ranging from 5.6% in central Chile to 13.7% in the extreme north; in dogs the overall prevalence was 44.0% and ranged from 37.2% in the northern region to 61.1% in central Chile. Risk factors for human seropositivity were lower education and external deworming of dogs, whereas canine seropositivity was associated to urban site, mixed-breed, older animals, and tick infestation. Conclusions: This cross-sectional study suggests a broad exposure of both dogs and dog owners to Anaplasma or related agents in Chile. Further epidemiological and clinical studies are necessary to understand the complete spectrum and epidemiology of tick-borne zoonotic infections in the different ecoclimatic regions of Chile.

Rickettsial diseases are a group of vector-borne bacterial infections that cause acute febrile illness with potentially severe or fatal complications. These vector-borne diseases are prevalent in tropical and subtropical regions worldwide and disproportionately affect poorer communities but are scientifically underrecognized. Despite this, they are not included in the World Health Organization’s list of neglected tropical diseases nor were they mentioned in Peter Hotez’s recent reflections on “What constitutes a neglected tropical disease?” in PLOS Neglected Tropical Diseases [1]. Here we present the case that rickettsial infections, as an overlooked cause of morbidity, mortality, and economic losses in marginalized populations, should be recognized as neglected tropical diseases. We describe how this oversight is the result of a number of factors and how it negatively impacts patient outcomes. We then propose measures to address the neglect of rickettsial infections in both scientific research and public health interventions.

Genital tract bleeding in prepubertal girls is a rare clinical condition, which can occur for multiple reasons. It frequently generates anxiety in the family and in health care professionals. A thorough anamnesis and careful genital inspection can give important diagnostic hints; however, there are cases in which the cause remains doubtful and a complete gynecological evaluation (including cultures and vaginoscopy) is necessary. Therefore, the attending physician should always consider less frequent diagnoses in order to perform the necessary studies in a sequential and rational manner. We present the case of a preschool girl with vaginal bleeding due to pinworm endometritis, which, to our knowledge, has never been reported before as a cause of genital bleeding in prepubertal girls.

Coccidioides is a primary pathogenic fungus, which infects humans through highly infectious arthroconidia, causing substantial morbidity including life-threatening disseminated infections. Due to the low infectious dose, laboratory personnel might become infected during diagnostic procedures. Accordingly, coccidioidomycosis is reported as the most frequent laboratory-acquired systemic mycosis worldwide. This risk is aggravated in non-endemic countries, where the diagnosis may not be suspected. We report on an inadvertent exposure of 44 persons to Coccidioides posadasii in a clinical microbiology laboratory in Chile, the measures of containment after rapid diagnosis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the lessons learnt in a non-endemic setting.

Background Healthcare workers (HCWs) are at high risk of exposure to SARS-CoV-2. Cross-sectional studies have provided variable rates of seroprevalence in HCWs. Longitudinal assessments of the serological response to Covid-19 among HCWs are crucial to understanding the risk of infection and changes in antibody titers over time. We aimed to investigate seroprevalence and risk factors associated with seroconversion in a prospective cohort of HCWs during the peak of the first wave of the Covid-19 pandemic. Methods We conducted a longitudinal study among 446 front-line HCWsin a tertiary-care hospital in Chile from April to July 2020. IgG was determined monthly using two different ELISAs in serum samples of HCWs, during the three-month period. In each visit, demographic data, symptoms, risk factors, and exposure risks were also assessed. Results The overall seroprevalence at the end of the study period was 24% (95% CI20.2–28.3), with 43% of seropositive HCWs reporting no prior symptoms. Seroconversion rates significantly differed over the study period, from 2.1% to as high as 8.8% at the peak of the epidemic. There were no statistically significant differences observed between HCWs in direct clinical care of patients with Covid-19 and those working in low risk areas. Antibody titers appeared to wane over time. Conclusions HCWs were severely affected with a high rate of seroconversion that appeared to mirror the local epidemiological situation. A significant amount of participants underwent an asymptomatic infection, highlighting the need for improved surveillance policies. Antibody titers appear to wane over time; further studies to understand this finding’s impact on the risk of reinfection are warranted.

Since Lyme borreliosis is endemic in the Northern Hemisphere, it is usually not in the spotlight of travel medicine. However, borreliosis is a relevant problem and diagnostic challenge in travelers from the Southern Hemisphere returning from trips to Europe and North America.

Background Understanding the characteristics of the Covid-19 pandemic in different geographical regions, ethnic and socioeconomic settings are of emerging importance. This study presents the demographic and clinical features of SARS-CoV-2 infected patients in a large private healthcare center in Santiago, Chile, during the first month of the pandemic. Methods We analyzed the demographics, laboratory and clinical characteristics including severity and outcome of all patients diagnosed with Covid-19 during the first month of the pandemic. SARS-2-CoV infection was confirmed by RT-PCR in nosopharyngeal samples. The primary outcome was a composite of ICU admission or all-cause, in-hospital mortality. Clinical and laboratory parameters of hospitalized patients were analyzed regarding their association with the primary outcome. Results From March 3 to April 4, 2020, 3679 individuals were tested for SARS-CoV-2 in our hospital. Of those, 381 had Covid-19 and were included into this analysis. Most patients (99.2%) were Chileans, 12% returning from recent travel. The median age was 39 years (IQR 31–49) and 52% were female. A total of 88 patients (23.1%) were hospitalized; 18 (3.7%) required ICU and/or died. The overall mortality was 0.7%. Increased body mass index (BMI) and elevated C-reactive protein (CRP) were independently associated with ICU care or death. Conclusion During the first weeks of the pandemic in Chile, most Covid-19 patients were young, with low rates of hospitalization, ICU requirement, and fatality. BMI and CRP on admission were predictors for severity. Our data provide important information on the clinical course and outcome of Covid-19 in a Latin American setting.

The evaluated SARS-CoV-2 antigen rapid fluorescence immunoassays reliably identified patients within the first 5 days of symptom onset, when respiratory secretions carried high viral loads. This high performance suggests that these tests might play an important role for future PCR-independent strategies to detect early or infective cases.

ObjectiveTo analyse the spectrum, vaccination needs and pretravel advice complexity of travellers presenting at a travel medicine clinic in Santiago, Chile.DesignCross-sectional study.SettingPretravel consultations in a private healthcare centre in Chile, an ‘emerging market’ country in South America.ParticipantsTravellers (n=1341) seeking pretravel advice at the Travel Medicine Program of Clínica Alemana, Santiago, from April 2016 to March 2018.Primary and secondary outcome measuresDemographical and travel characteristics, indications for travel vaccines and malaria prophylaxis, and complexity of travel consultations.ResultsOf 1341 travellers, 51% were female; the median age was 33 years. Most frequent travel reasons were tourism (67%) and business (20%). Median travel duration and time to departure were 21 days and 28 days, respectively. Most destinations were located in America (41%), followed by Asia (36%) and Africa (26%); 96% visited less developed countries, mostly in tropical regions, with risk of arboviral infections (94%) and malaria (69%). The indicated vaccine indications comprised hepatitis A (84%), yellow fever (58%), typhoid fever (51%), rabies (29%), polio (8%), Japanese encephalitis (6%) and meningococcal meningitis (5%). More than 60% of consultations were classified as complex.ConclusionThe studied population mostly visited less developed tropical regions, resulting in a high requirement of yellow fever and other travel-related vaccinations. Most consultations were complex and required a comprehensive knowledge and training in travel medicine.

IntroductionUnderstanding the clinical course and outcomes of patients with Covid-19 in underrepresented populations like Latin America is paramount. In this study, we report the clinical characteristics of Covid-19 in Chile, with a focus on subjects requiring hospitalization during the initial phases of the SARS-CoV-2 pandemic.MethodsThis is a single center study including all consecutive patients diagnosed with Covid-19 during the first month of the pandemic. Demographics, clinical characteristics and laboratory data were collected within 24 hours of admission. The primary outcome was a composite of ICU admission or all-cause, in-hospital mortality.ResultsDuring the first month of the pandemic, 381 patients were confirmed as positive for SARS-CoV-2 by molecular testing; 88 (23.1%) of them eventually required hospitalization. Median age of the cohort was 39 years (IQR 31-49). Overall mortality was 0.7% and 18 (3.7%) out of the 88 subjects who required hospitalization either died and/or required ICU. Increased body mass index (BMI), C-reactive protein levels (CRP) and the SaTO2/FiO2 index on admission were independently associated with a higher risk of ICU care or death.DiscussionThe lower mortality observed in our prospective cohort during the first month of SARS-Cov-2 pandemic was lower than previously reported. This finding could be due to a lower threshold for admission, a healthcare system not yet overburdened and a younger population, among other factors. BMI, CRP on admission were strong predictors for ICU care or all-cause, in-hospital mortality. Our data provide important information regarding the clinical course of Covid-19 in Latin America.

In the context of the Covid-19 pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. We compared the performance of four rapid antigen detection tests for SARS-CoV-2 in respiratory samples. Immunochromatographic SARS-CoV-2 assays from RapiGEN, Liming bio, Savant, and Bioeasy were evaluated using universal transport medium containing naso-oropharyngeal swabs from suspected Covid-19 cases. The diagnostic accuracy was determined in comparison to SARS-CoV-2 RT-PCR. A total of 111 samples were included; 80 were RT-PCR positive. Median patients’ age was 40 years, 55% were female, and 88% presented within the first week after symptom onset. The evaluation of the Liming bio assay was discontinued due to insufficient performance. The overall sensitivity values of RapiGEN, Liming bio, and Bioeasy tests were 62.0% (CI95% 51.0–71.9), 16.7% (CI95% 10.0–26.5), and 85.0% (CI95% 75.6–91.2), respectively, with specificities of 100%. Sensitivity was significantly higher in samples with high viral loads (RapiGEN, 84.9%; Bioeasy, 100%). The study highlighted the significant heterogeneity of test performance among evaluated assays, which might have been influenced by the use of a non-validated sample material. The high sensitivity of some tests demonstrated that rapid antigen detection has the potential to serve as an alternative diagnostic method, especially in patients presenting with high viral loads in early phases of infection. This is particularly important in situations with limited access to RT-PCR or prolonged turnaround time. Further comparative evaluations are necessary to select products with high performance among the growing market of diagnostic tests for SARS-CoV-2.

Background: In the context of the COVID-19 pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority to enable the required testing scale up in most countries. We evaluated a novel rapid antigen detection test (RDT) for SARS-CoV-2 in respiratory samples. Method: sA new fluorescence immunochromatographic SARS-CoV-2 antigen detection test (Bioeasy Biotechnology Co., Shenzhen, China) was evaluated in nasophayngeal (NP) and oropharyngeal (OP) swabs from patients with suspected COVID-19 in Santiago, Chile. Diagnostic accuracy was determined in comparison to SARS-CoV-2 real time (RT)-PCR, using the same material (universal transport medium with NP and OP swab). Findings: A total of 127 samples were included. The median patients’ age was 38 years (IQR 29·5–44), 53·5% were male, and 93·7% were in the first week after symptom onset. Among 82 RT-PCR positive specimens, 77 were correctly detected by RDT. All 45 RT-PCR negative samples were correctly identified. The overall sensitivity and specificity of the RDT were 93·9% (CI95% 86·5–97·4) and 100% (CI95% 92·1–100), respectively, with a diagnostic accuracy of 96·1% and Kappa coefficient of 0·9. Sensitivity was significantly higher in samples with increased viral loads. Interpretation: The antigen-based immunofluorescence RDT showed a high sensitivity and specificity in respiratory samples obtained from patients who mainly presented during the first week of COVID-19, despite the use of a non-validated sample. The assay was easy to use and provided results in a timely manner. It has the potential to become an important tool for early diagnosis of SARS-CoV-2, particularly in situations with limited access to molecular methods. Funding Statement: This work did not receive funding. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The study was approved by the local Institutional Review Board (Comite Etico Cientifico, Facultad de Medicina Clinica Alemana, Universidad del Desarrollo, Santiago, Chile) and need for informed consent was waived.

Resumen El tifus de los matorrales, causado por Orientia tsutsugamushi y transmitido por larvas de ácaros trombicúlideos de roedores silvestres es una rickettsiosis endémica en el Asia Pacífico. Luego del primer caso identificado en Chile en el año 2006, nuestro grupo ha identificado más de 30 casos a partir del año 2015. Los casos se han presentado con un marcado predominio en meses de verano, y su presentación clínica incluye fiebre, exantema y una mancha negra en el sitio de inoculación. Otros hallazgos frecuentes han sido cefalea intensa, sudoración nocturna, aumento de PCR, VHS y transaminasas hepáticas. La gran mayoría de los pacientes se han diagnosticado en el sur de Chile (principalmente la isla de Chiloé), pero recientemente también se han presentado casos en la Región Metropolitana, en personas volviendo de viajes al sur de Chile. Los médicos clínicos deben estar informados de esta enfermedad emergente en el país, de modo de sospecharla e iniciar terapia empírica con doxiciclina. La confirmación de estos casos con los métodos diagnósticos disponibles en Chile contribuirá a una mejor comprensión del rango epidemiológico y la relevancia clínica de esta infección nueva en el país.

Background Travelers to international mass gatherings may be exposed to conditions which increase their risk of acquiring infectious diseases. Most existing data come from single clinical sites seeing returning travelers, or relate to single events. Methods Investigators evaluated ill travelers returning from a mass gathering, and presenting to a GeoSentinel site between August 2015 and April 2019, and collected data on the nature of the event and the relation between final diagnoses and the mass gathering. Results Of 296 ill travelers, 51% were female and the median age was 54 years (range: 1–88). Over 82% returned from a religious mass gathering, most frequently Umrah or Hajj. Only 3% returned from the Olympics in Brazil or South Korea. Other mass gatherings included other sporting events, cultural or entertainment events, and conferences. Respiratory diseases accounted for almost 80% of all diagnoses, with vaccine preventable illnesses such as influenza and pneumonia accounting for 26% and 20% of all diagnoses respectively. This was followed by gastrointestinal illnesses, accounting for 4.5%. Sixty-three percent of travelers reported having a pre-travel encounter with a healthcare provider. Conclusions Despite this surveillance being limited to patients presenting to GeoSentinel sites, our findings highlight the importance of respiratory diseases at mass gatherings, the need for pre-travel consultations before mass gatherings, and consideration of vaccination against influenza and pneumococcal disease.

Background Real-Time Reverse-Transcription Polymerase Chain Reaction (RT-PCR) is currently the only recommended diagnostic method for SARS-CoV-2. However, rapid immunoassays for SARS-CoV-2 antigen could significantly reduce the COVID-19 burden currently weighing on laboratories around the world. Methods We evaluated the performance of two rapid fluorescence immunoassays (FIAs), SOFIA SARS Antigen FIA (Quidel Corporation, San Diego, CA, USA) and STANDARD F COVID-19 Ag FIA (SD Biosensor Inc., Gyeonggi-do, Republic of Korea), which use an automated reader. The study used 64 RT-PCR characterized clinical samples (32 positive; 32 negative), which consisted of nasopharyngeal swabs in universal transport medium. Results Of the 32 positive specimens, all from patients within 5 days of symptom onset, the Quidel and SD Biosensor assays detected 30 (93.8%) and 29 (90.6%) samples, respectively. Among the 27 samples with high viral loads (Ct ≤ 25), the two tests had a sensitivity of 100%. Specificity was 96.9% for both kits. Conclusion The high performance of the evaluated FIAs indicates a potential use as rapid and PCR-independent tools for COVID-19 diagnosis in early stages of infection. The excellent sensitivity to detect cases with viral loads above ~106 copies/mL (Ct values ≤ 25), the estimated threshold of contagiousness, suggests that the assays might serve to rapidly identify infective individuals.

Scrub typhus is a life-threatening zoonosis caused by Orientia tsutsugamushi organisms that are transmitted by the larvae of trombiculid mites. Endemic scrub typhus was originally thought to be confined to the so called "tsutsugamushi triangle" within the Asia-Pacific region. In 2006, however, two individual cases were detected in the Middle East and South America, which suggested that the pathogen was present farther afield. Here, we report three autochthonous cases of scrub typhus caused by O. tsutsugamushi acquired on Chiloé Island in southern Chile, which suggests the existence of an endemic focus in South America. (Funded by the Chilean Comisión Nacional de Investigación Científica y Tecnológica and the Wellcome Trust.).

Although pets provide physiological and psychological benefits to their owners, they are a potential source of zoonotic infections, especially for vulnerable individuals such as immunocompromised patients. During 1 year, we therefore performed a pilot project, which included 32 immunocompromised Chilean children and their family pets (35 dogs and 9 cats) with the aim of detecting, treating and preventing zoonotic infections. Children were examined by Infectious Diseases paediatricians and demographical and clinical information related to zoonotic infections were recorded. Pets were examined and sampled by veterinarians, who also administered missing routine vaccines and anti-parasitics. During family visits, all members were informed and educated about zoonoses and a satisfaction survey was performed. Visits also included vector control and indoor residual spraying with pyrethroids. Children were re-examined and re-tested according to the findings of their pets, and all detected zoonotic infections were treated both in children and pets. Physical examination revealed abnormalities in 18 dogs (51.4%) and three cats (33.3%). Twenty-eight (63.6%) of the pets were diagnosed with a zoonotic pathogen, and seven (15.9%) with a facultative pathogen. Most zoonotic agents were isolated from the pet's external ear and intestine. Bacteria with the highest pathogenic potential were Campylobacter jejuni and Brucella canis. In two children and their respective pets, the same zoonotic diseases were diagnosed (toxocariasis and giardiasis). Arthropods serving as potential vectors of zoonotic infections were found in 49% of dogs and 44% of cats. The pilot project was positively evaluated by the participating families. Our pilot project confirmed that pets are reservoir for various zoonotic agents in Chile and that the implementation of an integrated multidisciplinary programme was a valuable tool to prevent, diagnose and treat such zoonotic infections in vulnerable patients such as immunocompromised children.

BACKGROUND:Coinfections of HIV patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) are mayor public health problems, contributing to the emerging burden of HIV-associated hepatic mortality. Coinfection rates vary geographically, depending on various factors such as predominant transmission modes, HBV vaccination rates, and prevalence of HBV and HCV in the general population. In South America, the epidemiology of coinfections is uncertain, since systematic studies are scarce. Our study aimed to analyze rates of HBV and HCV infection in people living with HIV attending centers of the public and private health system in Chile. METHODS:We performed a cross-sectional study including a public university hospital and a private health center in Santiago, Metropolitan Region in Chile. Serum samples were used to determine serological markers of hepatitis B (HBsAg, anti-HBs, anti-HBc total, HBeAg, anti-HBe) and anti-HCV. Demographic, clinical and laboratory data were obtained from medical records. RESULTS:399 patients were included (353 from public, 46 from private health center). Most (92.8%) were male, with a median age of 38.3 years; 99.4% acquired HIV through sexual contact (75.0% MSM); 25.7% had AIDS and 90.4% were on ART. In 78.9%, viral loads were

Background: Chikungunya (CHIK) was introduced in The Americas in 2013, spreading rapidly. In 2014, the first imported case was diagnosed in Chile. Aim: To identify patients with clinical suspicion of CHIK and describe their clinical and laboratory characteristics. Patients and Methods: Patients with suspected CHIK were enrolled. All were confirmed by PCR, IgM or IgG CHIK. A structured survey was applied, which included demographic questions, travel characteristics, clinical manifestations, and laboratory results. Results: 21 patients were enrolled and CHIK was confirmed in 16, who were further analyzed; 12 were female (75%), average age 39 years (27- 52). The Caribbean and South Americawere the most frequent sites of exposure. In 63%, the initial symptom was arthralgia. Most frequent symptoms were myalgias, malaise (both 100%), fever, and polyarthralgia (both 94%). The median duration of arthralgias was 90 days (3-262); in 53% arthralgias lasted ≥ 3 months. Main joints involved were ankles, hands, and wrists; 87% reported invalidating pain. Arthritis lasted longer in men than in women (p < 0.001). 38% of patients presented lymphopenia and one patient mild thrombocytopenia. Two patients required hospitalization, one with severe headaches, the other with acute pyelonephritis. Conclusions: Chikungunya should be suspected in returning travelers presenting with fever and severe polyarthralgia. Travelers to endemic areas should apply prevention measures to avoid mosquito bites.

Instituto de Ciencias e Innovacion en Medicina (ICIM)/ Centro de Epidemiologia y Politicas de Salud

We report a cluster of imported vivax malaria in three of five Chilean travelers returning from Peru in March 2015. The cluster highlights the high risk of malaria in the Loreto region in northern Peru, which includes popular destinations for international nature and adventure tourism. According to local surveillance data, Plasmodium vivax is predominating, but Plasmodium falciparum is also present, and the incidence of both species has increased during recent years. Travelers visiting this region should be counseled about the prevention of malaria and the options for chemoprophylaxis.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy and safety of methylene blue for treating people with malaria.

Background Campylobacter is a leading cause of bacterial gastroenteritis, but sensitive diagnostic methods such as culture are expensive and often not available in resource limited settings. Therefore, direct staining techniques have been developed as a practical and economical alternative. We analyzed the impact of replacing Campylobacter staining with culture for routine stool examinations in a private hospital in Chile. Methods From January to April 2014, a total of 750 consecutive stool samples were examined in parallel by Hucker stain and Campylobacter culture. Isolation rates of Campylobacter were determined and the performance of staining was evaluated against culture as the gold standard. Besides, isolation rates of Campylobacter and other enteric pathogens were compared to those of past years. Results Campylobacter was isolated by culture in 46 of 750 (6.1 %) stool samples. Direct staining only identified three samples as Campylobacter positive and reached sensitivity and specificity values of 6.5 and 100 %, respectively. In comparison to staining-based detection rates of previous years, we observed a significant increase of Campylobacter cases in our patients. Conclusion Direct staining technique for Campylobacter had a very low sensitivity compared to culture. Staining methods might lead to a high rate of false negative results and an underestimation of the importance of campylobacteriosis. With the inclusion of Campylobacter culture, this pathogen became a leading cause of intestinal infection in our patient population.

A 28-year-old, otherwise healthy Chilean man presented in December 2015 with fever, headache, and myalgia. He had returned, 2 days ago, from a tourist trip to Colombia, where he had visited Bogota and the northern region including Cartagena de Indias, Santa Marta, and Tayrona National Park. During his return, he suffered nonspecific symptoms including sore throat, anorexia, and myalgia. A day later, he noted high grade fever and tender nodules behind his ears (Figure 1 ). Physical examination revealed fever (39.0°C), a maculopapular rash of the trunk and extremities (Figure 2 ), mild conjunctivitis, and a generalized lymphadenopathy with palpable tender axillary, cervical, and bilateral postauricular lymph nodes. After dengue and chikungunya virus infections were excluded by molecular methods, antigen detection, and IgM antibody testing, samples were sent to the national reference laboratory (Instituto de Salud Publica de Chile, Santiago, Chile), where Zika virus (ZIKV) nucleic acids were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) as previously described.1 The sample was also positive using a commercial RT-PCR assay for the detection of ZIKV (Zika Virus genesig® Advanced Kit; Primerdesign™ Ltd., Southampton, United Kingdom) in the clinical laboratory, Clinica Alemana, Santiago. The patient recovered rapidly and without complications. Figure 1. Bilateral tender postauricular lymphadenopathy in patient with Zika virus infection. Figure 2. Maculopapular rash on the patient's arm. Since 2015, ZIKV is rapidly emerging within the Americas, where it is disseminated by mosquitos of the Aedes genus. However, the virus is also transmitted by blood transfusion and, as recently suggested, by contact with infectious semen.2,3 Because of its possible association with fetal malformations and neurological complications, this epidemic has been declared a global public health emergency by the World Health Organization. The clinical presentation of the infection is similar to dengue including fever, rash, joint pain, conjunctivitis, myalgia, headache, and vomiting.4–6 Although lymphadenopathy has recently been described in patients with ZIKV infection in Brazil,7,8 it is usually not listed as a typical manifestation. Our case confirms that ZIKV might cause systemic lymphadenopathy including the posterior auricular lymph nodes. Because tender bilateral postauricular lymphadenopathy is a known clinical sign of postnatal rubella, it might mislead ZIKV diagnosis especially in pediatric patients.

The incidence of cutaneous and mucocutaneous Leishmaniasis (CL/MCL) is increasing globally, also in Germany, although the cases are imported and still low in number. The current evidence for the different therapies has many limitations due to lack of sufficient studies on the different Leishmania species with differing virulence. So far there is no international gold standard for the optimal management. The aim of the German joint working group on Leishmaniasis, formed by the societies of Tropical Medicine (DTG), Chemotherapy (PEG) and Dermatology (DDG), was to establish a guideline for the diagnosis and treatment of CL and MCL in Germany, based on evidence (Medline search yielded 400 articles) and, where lacking, on consensus of the experts. As the clinical features do not necessarily reflect the involved Leishmania species and, as different parasite species and even geographically distinct strains of the same species may require different treatments or varying dosages or durations of therapy, the guidelines suggest for Germany to identify the underlying parasite prior to treatment. Because of relevant differences in prognosis and ensuing therapy species should be identified in i) New World CL/MCL (NWCL/ MCL) to distinguish between L. mexicana-complex and subgenus Viannia, ii) in suspected infections with L. mexicana-complex to distinguish from L. amazonensis, and iii) in Old World CL (OWCL) to distinguish between L. infantum and L. major, L. tropica, or L. aethiopica. A state-of-the-art diagnostic algorithm is presented. For recommendations on localized and systemic drug treatment and physical procedures, data from the accessible literature were adjusted according to the involved parasite species and a clinical differentiation into uncomplicated or complex lesions. Systemic therapy was strictly recommended for i) complex lesions (e. g. > 3 infected lesions, infections in functionally or cosmetically critical areas such as face or hands, presence of lymphangitis), ii) lesions refractory to therapy, iii) NWCL by the subgenus Viannia or by L. amazonensis, iv) in MCL and v) in recalcitrant, or disseminating or diffuse cutaneous courses. In e. g. infection with L. major it encompasses miltefosine, fluconazole and ketoconazole, while antimony or allopurinol were here considered second choice. Local therapy was considered appropriate for i) uncomplicated lesions of OWCL, ii) L. mexicana-complex and iii) pregnant women. In e. g. infection with L. major it encompasses perilesional antimony, combined with cryotherapy, paromomycin 15 %/in methylbenzethoniumchlorid 12 % and thermotherapy. The group also stated that there is an urgent need for improving the design and the way of publishing of clinical trials in leishmaniasis.

The efficacy and safety of artemether-lumefantrine for the treatment of malaria in nonimmune populations are not well defined. In this study, 165 nonimmune patients from Europe and non-malarious areas of Colombia with acute, uncomplicated falciparum malaria or mixed infection including P. falciparum were treated with the six-dose regimen of artemether-lumefantrine. The parasitologic cure rate at 28 days was 96.0% for the per protocol population (119/124 patients). Median times to parasite clearance and fever clearance were 41.5 and 36.8 hours, respectively. No patient had gametocytes after Day 7. Treatment was well tolerated; most adverse events were mild to moderate and seemed to be related to malaria. There were few serious adverse events, none of which were considered to be drug-related. No significant effects on ECG or laboratory parameters were observed. In conclusion, the six-dose regimen of artemether-lumefantrine was effective and well tolerated in the treatment of acute uncomplicated falciparum malaria in nonimmune patients.

Summary Background Haiti has the highest prevalence of lymphatic filariasis ( Wuchereria bancrofti ) in the Western Hemisphere. Still, the risk of filarial infection for long-term visitors such as humanitarian aid workers or military personnel is uncertain. The presented study analyzed the exposure to W. bancrofti in Chilean participants of the UN Stabilization Mission in Haiti (MINUSTAH) in 2011. Methods Blood samples collected from 531 participants were screened for antifilarial antibodies by IgG ELISA, and, if positive, analyzed by immunofluorescence assay (IFA), IgG4 ELISA, Real-Time PCR, and circulating filarial antigen (CFA) card test. Results ELISA screening was positive in 10 cases. Seroconversion occurred in only two cases (0.38%) based on ELISA values determined in samples taken before and after deployment. Positive IgG ELISA values could not be confirmed by IFA and IgG4 ELISA. Real-Time PCR and CFA testing did not reveal the presence of filaria. Conclusions Our data indicate that in the examined cohort of MINUSTAH participants in 2011, the risk of filarial exposure or infection was low.

Data concerning the clinical and epidemiological features of travel-associated cryptosporidiosis are lacking. In order to investigate the impact of this disease on travellers' health, a retrospective study was conducted at the Institute of Tropical Medicine, Berlin. In total, 57 cryptosporidial infections were identified between 2000 and 2004, resulting in a prevalence of 2.9% in patients with travel-associated diarrhoea. Travel to south-central Asia, especially India, was associated with a higher prevalence of infection than was travel to other destinations. Clinically, the disease resembled giardiasis, but fever and arthralgias seemed to occur more frequently.

We evaluated the Rida Quick rotavirus/adenovirus Combi rapid immunochromatographic test (ICT) under field conditions with Ghanaian children with acute diarrhea. Compared to PCR results, sensitivities and specificities were 75% and 95% for rotavirus and 22% and 84% for adenovirus. In resource-poor settings, ICTs may help to overcome difficulties in the diagnosis of rotavirus infection.

Summary Objectives To analyze the prevalence of hepatitis B virus (HBV) co-infection and its influence on mortality and treatment outcome within a large AIDS cohort in Chile. Methods Clinical and epidemiological data from the Chilean AIDS Cohort were retrospectively analyzed. Adult patients tested for hepatitis B surface antigen (HBsAg) during the time period of October 2001 to October 2007 were included. Results Of 5115 cohort patients, 1907 met the inclusion criteria. The prevalence of HBV co-infection was 8.4%. Overall mortality rates were 2.15 and 1.77 per 100 person-years for HBsAg-positive and HBsAg-negative HIV patients, respectively, with a mortality rate ratio of 1.22 (95% confidence interval 0.58–2.54). Kaplan–Meier survival and Cox regression analysis did not show significant differences between the groups. Virological and immunological responses to antiretroviral therapy (ART) were not influenced by HBsAg status, but in co-infected patients, initial ART was more frequently changed. Conclusions The prevalence of hepatitis B co-infection was 8.4%, indicating a markedly elevated hepatitis B risk compared to the general population in Chile. Neither treatment outcome nor overall mortality was influenced by hepatitis B co-infection. Still, patients with hepatitis B co-infection had less stable ART regimens, which might be related to a higher risk of hepatotoxic drug effects.

A 27-year-old Chilean man presented with a 3 month history of cutaneous ulcers accompanied by intermittent fever, night sweats, dry cough, and weight loss. He had recently returned from a 10-month stay at the Yucatan Peninsula, Mexico, where his clinical problems had started with a skin lesion on his forehead, which he related to an insect bite. Samples of this lesion had been diagnosed in Mexico as cutaneous leishmaniasis. Shortly before returning to Chile, he was tested and found to be positive for HIV. On admission, he had various small maculopapular lesions on his chest and several skin ulcers on his shoulder and face (fi gure, A). CT scans showed several pulmonary nodular lesions and hepatosplenomegaly. His CD4 count was 75 cells per μL and his HIV viral load was 110 000 copies per mL; serology for toxoplasmosis, syphilis, Chagas disease, and Cryptococcus neoformans antigen were negative. Scrapings of the lateral margins of a skin ulcer were taken to confi rm the previous suspicion of cutaneous leish maniasis. Giemsa stains showed numerous intracellular and extracellular oval structures with a diameter of 2–4 μm (fi gure, B). Because kinetoplasts (densely stained rod-shaped structure representing mitochondrial DNA), which are pathognomonic for Leishmania spp parasites, were absent, histoplasmosis was suspected. This suspicion was verifi ed by Grocott-Gomori methenamine silver stain showing several numerous darkly stained yeast-like elements (fi gure, C). With antifungal treatment (amphotericin B, itraconazole) the fever subsided and the patient recovered; skin ulcers healed with scarring (fi gure, D). Oral itraconazole was continued for 12 months. Currently, the patient is still on his fi rst-line antiretroviral regimen (abacavir, lamivudine, raltegravir) and has undetectable viral loads. Although his CD4 count is maintained below 100 cells per μL, he is clinically stable and asymptomatic. Histoplasma capsulatum is an endemic fungal agent causing pulmonary infection after inhalation of spores. Immuno compromised patients might have life-threatening systemic infections, including cutaneous manifestations, which are more frequently reported from Latin America. Microscopic examination of tissue samples permits rapid diagnosis and initiation of therapy. However, in specimens of chronic skin ulcers, H capsulatum cells might easily be misdiagnosed as leishmania amastigotes because both microorganisms present as intracellular objects of the same size and shape.

Dear Sir: We read the comprehensive review of Steinhardt and colleagues on malaria prophylaxis for travelers to Latin America with great interest.1 Still, because this subject is controversial in Travel Medicine,2 we would like to add some information from Germany, a country not cited by the review. Primaquine is the only available drug that eradicates hepatic stages of malaria parasites including hypnozoites of Plasmodium vivax and Plasmodium ovale. It is licensed for radical cure after vivax or ovale malaria.3 Only the U.S. American guidelines published by the Centers for Disease Control and Prevention (CDC) (www.cdc.gov) recommend it as a first-line option for primary prophylaxis. Therefore, the conclusion by Steinhardt and colleges to name primaquine as a recommended option for certain regions of Latin America is not based on a broad international consensus. To our personal experience, the use of this drug is hampered by several factors: 1. There is a lack of data and experience with primaquine in primary prophylaxis of malaria. Although the daily travel medicine practice deals mainly with brief regimens, most trials with primaquine have only evaluated longer regimens of over 12 weeks of prophylaxis.4 Furthermore, the capacity to prevent falciparum malaria, which is the main goal of malaria chemoprophylaxis5 has not been evaluated in larger studies. This is of importance, because in most Latin American areas with P. vivax predominance, Plasmodium falciparum co-occurs.6 2. Because the drug is not licensed or recommended for primary prophylaxis in any country except the United States, the prescribing physician is liable for any damage caused by primaquine. Furthermore, in many countries, the drug is not easily available as it has to be imported from foreign countries. 3. The necessary testing for glucose-6-phosphate-dehydrogenase (G6PD) activity before taking the drug adds significant costs and together with the delay of G6PD activity reporting renders the prophylactic use of primaquine impractical in daily travel medicine practice. The incidence and mortality of autochthonous malaria in Latin America has declined dramatically since the early 2000s.6,7 During the years 2002–2010, six to 17 annual cases (average 13.0) of malaria imported from Latin American countries were notified to the German authorities (Robert Koch Institute, Berlin;www.rki.de). Absolute numbers were declining in recent years, but the relative share stayed stable with 2–4% of all imported malaria cases in Germany. For 2009, the German Federal Statistical Office reported more than 1.2 million German travelers to malaria-endemic countries in Latin America (www.destatis.de) resulting in six notified imported malaria cases from these countries (Brazil, 4; Honduras, 2), all caused by P. vivax (Schoneberg I, personal communication, Robert Koch Institute, Berlin). As a drawback to analysis, the proportion of German travelers to Latin America receiving chemoprophylaxis is unknown, but is expected to be very low in light of the German guidelines. The overall mortality rate for imported malaria in Germany in 2009 was 0.6% and is probably much lower for vivax malaria. Although the numbers might not be exact, they highlight the dimensions of the problem and confirm recent risk calculations based on endemicity data of malaria in the respective countries8: to prevent a single malaria case imported from Latin America to Germany, we have to use antimalarial drugs with their potentially severe side-effects in hundreds of thousands of travelers; to prevent a single fatal malaria case from Latin America in Germany, millions of travelers would have to use chemoprophylaxis. In Germany and Switzerland, chemoprophylaxis is only recommended for travelers to certain areas of Brazil (Acre, Rondonia, and Roraima) and all non-coastal regions in Guyana, Suriname, and French Guiana (www.dtg.org, www.safetravel.ch). For all other parts of Latin America, avoidance of mosquito bites and immediate consultation of a physician in case of fever during or after the journey is recommended. Travelers, who stay in areas where the diagnosis and treatment of malaria might not be possible in a timely manner, carry a drug for self-treatment (“stand-by emergency treatment”). This approach aims to avoid the broad use of chemoprophylaxis in areas of low malaria risk and therefore, from a medical and health economical point of view, might be a preferable option for tourists to many Latin America regions.

Introduccion: La hidatidosis es una enfermedad endemica en Chile. Se presenta la experiencia clinica de un hospital en Santiago, desde 1996 al 2010. Metodos: Los casos fueron identificados usando las bases de datos institucionales y se analizaron las caracteristicas clinicas y patologicas, el tratamiento y la evolucion en forma retrospectiva. Resultados: Se identificaron 23 pacientes intervenidos en 30 oportunidades. La mediana de edad fue de 40 anos (rango 5 a 73) y 76,5% visito o residia en zonas endemicas en Chile. Los quistes abdominales fueron predominantes (78,3%) y la mayor parte de los pacientes eran sintomaticos (73,9%). Un 42,9% de aquellos con quistes sintomaticos toracicos reporto eliminacion de vesiculas con la tos. Un 41,2% presento eosinofilia y 57,1% tuvo serologia positiva para hidatidosis. Todos los pacientes fueron tratados quirurgicamente, en 60,9% en combinacion con albendazol. La mayoria de los quistes hepaticos fueron tratados con cirugia radical (88,9%) y los pulmonares predominantemente con quistostomia y capitonaje (83,3%). Un 24% de los quistes eran fertiles. La morbilidad post-quirurgica fue frecuente (37,9%) y 13,3% de la serie requirio reingresos por esta causa. Cerca de 25% de los pacientes estuvo hospitalizado por mas de 14 dias, un fenomeno asociado con la presencia de fiebre por complicacion septica al ingreso (p < 0,05). No se registraron recurrencias en la fraccion de pacientes seguidos por mas de dos anos. Conclusiones: La hidatidosis afecta principalmente a adultos en su cavidad abdominal. Aunque los pacientes fueron tratados exitosamente con cirugia, las complicaciones, estadias prolongadas y reingresos por esta causa no fueron infrecuentes.

Neurocysticercosis (NCC) is not a notifiable disease in Chile and has received little attention on the national medical literature. In order to evaluate the relevance and clinical features of the disease, we performed a retrospective analysis in a general hospital of five cases of NCC during a 11 years period. Age ranged from 3 to 63 years and all had history of living or visiting southern Chile. Three patients had a solitary parenchymal cyst in vesicular or granulomatous stages and presented with generalized seizures. Their outcome was favorable after anticonvulsant and albendazole therapy and cysts reduced in size and calcified during follow-up. The other 2 patients had extra-parenchymal or mixed forms, including a pregnant woman with intraventricular cysts who developed endocraneal hypertension and recurrent dysfunction of her ventriculoperitoneal shunt. This patient died after discharge despite an initial favorable evolution with steroids and high-dose albendazole. This case series showed that NCC is still an epidemiological and clinical problem in Chile, affects patients within a wide range of age including children, requires multidisciplinary therapeutic interventions, and has two clinical presentations with different prognosis including one malignant form. To control this infection, a surveillance or reporting system should be initiated.

Las infecciones por metapneumovirus (MPVH) son poco conocidas en pacientes adultos y el objetivo de esta publicación es presentar una serie de 4 casos observados en pacientes hospitalizados durante el invierno de 2010. Los casos se identificaron por inmunofluorescencia directa en muestras respiratorias. Todos los pacientes fueron de sexo femenino con un rango de edad 79 a 95 años, dos de ellos postrados, uno con demencia y 3 con enfermedad pulmonar obstructiva crónica. La manifestación clínica correspondió a neumonía en 3 casos (2 de tipo intersticial y una con consolidación lobar) y bronquitis crónica reagudizada en el caso restante, con una duración sintomática de 3 a 7 días antes de la hospitalización. Un caso presentó co-infección con virus parainfiuenza 3. Las sibilancias estuvieron presentes en 3 casos y todos presentaron falla respiratoria hipoxémica o global con linfopenia (< 1.000/mm³). La hospitalización tuvo una duración de 5 a 20 días, marcada en los 3 casos que sobrevivieron por una signología obstructiva prolongada. Dos pacientes requirieron ventilación mecánica no invasora. Las infecciones por MPVH representan una causa de hospitalización por descompensación de patologías respiratorias crónicas en pacientes adultos ancianos, tienen una morbilidad prolongada con signología obstructiva marcada y pueden ocasionar la muerte. Human metapneumovirus infections are increasingly recognized among adult patients and the aim of this report is to present a series of 4 cases admitted during the winter of 2010. All were detected by direct fluorescence anti-bodies assay of respiratory samples and all were female patients with an age range of 79 to 95 years, including two bedridden cases, one with dementia and three with chronic obstructive pulmonary disease. One patient presented with parainfluenza 3 virus coinfection. Patients presented with pneumonía in 3 cases (interstitial pattern in 2 and lobar consolidation in the other) or acute exacerbation of chronic bronchitis in the remaining case. Symptoms were present for 3 to 7 days before admission and 3 have wheezing. All had hypoxemic or global respiratory failure and lymphopenia (< 1.000/mm³). Hospitalization lasted for 5 to 20 days, marked in the 3 cases that survived by prolonged bronchial obstructive manifestations. Two cases required non invasive mechanical ventilation. Human metapneumovirus infections can decompensate elderly patients with chronic respiratory diseases generating hospital admission and a prolonged morbidity marked by obstructive manifestations and sometimes can become into death.

Leishmaniasis is a rare, non-notifiable disease in Germany. Epidemiological and clinical data, therefore, are scarce. Most infections seen in Germany are contracted outside the country. The German surveillance network for imported infectious diseases (Surveillance Importierter Infektionen in Deutschland, or SIPMID) recorded 42 cases of imported leishmaniasis (16 visceral, 23 cutaneous, and 3 mucocutaneous) from January 2001 to June 2004. Although most infections were acquired in European Mediterranean countries, the risk of infection was highest for travelers to Latin America. HIV coinfection was observed significantly more often in patients with visceral leishmaniasis than in patients with cutaneous/mucocutaneous leishmaniasis (31 vs. 4%, p=0.02). The median time to a definitive diagnosis was 85 days in cases of visceral leishmaniasis and 61 days in cases of cutaneous/mucocutaneous leishmaniasis, reflecting the unfamiliarity of German physicians with leishmanial infections. Visceral leishmaniasis was treated most frequently with amphotericin B, whereas cutaneous/mucocutaneous leishmaniasis was treated with a variety of local and systemic therapies. The findings presented here should serve to increase awareness as well as improve clinical management of leishmaniasis in Germany.

aPrevious studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases.

Background Hydatidosis is a zoonotic disease of worldwide distribution caused by Echinococcus granulosus. Our study aimed to determine the prevalence of human and canine echinococcosis as well as the associated risk factors in a rural area of the Limarí province in northern Chile. Methodology/Principal Findings A cross-sectional study was conducted between August and November 2009 using a stratified sampling design in each of the five districts of the province. In the selected villages, up to 10 households were sampled. Serum and fecal samples from an adult family member and a dog were collected from each participating household. Risk factors were assessed by standardized questionnaires. Seroprevalence was assessed using a multi-step approach: an ELISA for screening, IFA, IHA and western blot for confirmation of results, respectively. The prevalence of echinococcal infection in dogs was determined by coproantigen genus specific ELISA. Chi-square, Fisher tests and logistic regressions were used to assess risk factors for human seropositivity and dog copropositivity. A seroprevalence of 2.6% (10/403) and coproprevalence of 28% (26/93) was recorded for humans and dogs respectively. Contact with dogs and dog feces were risk factors for human seropositivity while dog copropositivity was associated with home slaughter of livestock (OR = 3.35; CI 90%: 1.16–6.85) and households de-worming dogs (OR = 2.82; CI 90%: 1.33–8.43). Conclusions/Significance Echinococcal infection of humans and their dogs is common in Limarí province. Risk factors for human seropositivity were related to contact with domestic dogs and their feces, whereas those for dogs were home slaughter of livestock and the practice of de-worming dogs., Author Summary Hydatidosis is a hyperendemic zoonotic disease in Chile caused by the dog tapeworm, Echinococcus granulosus. In Chile as in many other countries in South America, this disease has been largely neglected with few exceptions. Chile's growing economy and the interest of health authorities has lead to an increase in the number of studies investigating the epidemiology of echinococcosis and the factors related to infections of the main definitive host, the domestic dog and humans. In this study, we determined the prevalence of human and canine echinococcosis as well as the associated risk factors in a rural area of the Limarí province in northern Chile. We undertook a household questionnaire survey in rural areas of the five municipalities of the Limarí province in Coquimbo region. For each household serum of an adult family member and fecal samples from a dog were taken. Results of our study indicate that infection occurs in 2.6% of humans and 28% of dogs and is primarily due to feeding of dogs with contaminated offal and high dog-human contact. As a result of this study, the Chilean Ministry of Health instigated a control program aimed to control the infection in dogs and avoid new infections to humans.

Objective: To assess HIV-1 isolate based resistance profiles from extensively pretreated patients and effects of a resistance guided switch of antiretroviral therapy. Methods: In a prospective study phenotypic and genotypic resistance analyses were performed on HIV infected individuals with failure of the current therapy and history of at least three antiretroviral regimens. Antiretroviral therapy was changed according to the results. Viral load and CD4 lymphocyte counts were measured at baseline, after 10 (SD 2), and 24 (2) weeks. Results: All patients (n=52) failed their actual regimen. Currently versus ever previously taking the specific drug, resistance associated mutations and phenotypic resistance to AZT and 3TC were found in over 80% of individuals; resistance to DDI and D4T was detected in less than 10% of cases. A resistance guided switch of therapy was followed by a median decrease of viral load of 0.5 log10 units after 24 weeks. Individuals resistant to two or more drugs compared with patients with resistance to less than two drugs of ongoing treatment, were switched to a regimen containing DDI, D4T, and a PI or NNRTI. After 10 (SD 2) weeks viral load decrease was pronounced in patients with resistance to at least two drugs in the previous regimen. Conclusions: Among different RTI, the profile of clinically relevant resistance indicates pronounced differences when looking at separate drugs. Regarding virological response, in the context of available drugs, resistance tested with currently used methods is of limited value in extensively pretreated patients and seems to have its value primarily in first or second switch of therapy.